Pairing statistics and melting of random DNA oligomers: Finding your partner in superdiverse environments.

Understanding of the pairing statistics in solutions populated by a large number of distinct solute species with mutual interactions is a challenging topic, relevant in modeling the complexity of real biological systems. Here we describe, both experimentally and theoretically, the formation of duplexes in a solution of random-sequence DNA (rsDNA) oligomers of length L = 8, 12, 20 nucleotides. rsDNA solutions are formed by 4L distinct molecular species, leading to a variety of pairing motifs that depend on sequence complementarity and range from strongly bound, fully paired defectless helices to weakly interacting mismatched duplexes. Experiments and theory coherently combine revealing a hybridization statistics characterized by a prevalence of partially defected duplexes, with a distribution of type and number of pairing errors that depends on temperature. We find that despite the enormous multitude of inter-strand interactions, defectless duplexes are formed, involving a fraction up to 15% of the rsDNA chains at the lowest temperatures. Experiments and theory are limited here to equilibrium conditions.

Changes in Urinary Iodine Levels Following Bariatric Surgery.

OBJECTIVE: Obesity has become an epidemic in the United States. Although bariatric surgery can effectively achieve weight loss by altering the gastrointestinal tract, it commonly results in micronutrient deficiency, requiring supplementation. Iodine is an essential micronutrient for the synthesis of thyroid hormones. We aimed to investigate changes in urinary iodine concentrations (UIC) in patients following bariatric surgery. METHODS: 85 adults who underwent either laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass surgery were enrolled. At baseline and 3 months after surgery, we evaluated spot UIC and serum thyroid stimulating hormone (TSH), vitamin D, vitamin B12, ferritin, and folate levels. Participants provided a 24-hour diet recall for iodine-rich foods and information about multivitamin use at each time point. RESULTS: There was a significant increase in median UIC (201 [120.0 - 288.5] vs 334.5 [236.3 - 740.3] µg/L; P < .001), a significant decrease in mean body mass index (44.0 ± 6.2 vs 35.8 ± 5.9; P < .001) and a significant decrease in TSH levels (1.5 [1.2 - 2.0] vs 1.1 [0.7 - 1.6] uIU/mL; P < .001) at 3 months postoperatively compared to baseline. Body mass index, UIC, and TSH levels before and after surgery did not differ based on the type of weight loss surgery. CONCLUSION: In an iodine-sufficient area, bariatric surgery does not cause iodine deficiency nor clinically significant changes in thyroid function. Different surgical procedures with different anatomical alterations in the gastrointestinal tract do not significantly affect iodine status.

Publisher Correction: Image Data Resource: a bioimage data integration and publication platform.

This paper was originally published under standard Nature America Inc. copyright. As of the date of this correction, the Resource is available online as an open-access paper with a CC-BY license. No other part of the paper has been changed.

Total Thyroidectomy Versus Lobectomy for Thyroid Cancer: Single-Center Data and Literature Review.

BACKGROUND: Controversies remain about the ideal risk-based surgical approach for differentiated thyroid cancer (DTC). METHODS: At a single tertiary care institution, 370 consecutive patients with low- or intermediate-risk DTC were submitted to either lobectomy (LT) or total thyroidectomy (TT) and were followed up. RESULTS: Event-free survival by Kaplan-Meier curves was significantly higher after TT than after LT for the patients with either low-risk (P = 0.004) or intermediate-risk (P = 0.032) tumors. At the last follow-up visit, the prevalence of event-free patients was higher in the TT group than in the LT low-risk group (95% and 87.5%, respectively; P = 0.067) or intermediate-risk group (89% and 50%; P = 0.008). No differences in persistence prevalence were found among microcarcinomas treated by LT or TT (low risk, P = 0.938 vs. intermediate-risk, P = 0.553). Nevertheless, 15% of the low-risk and 50% of the intermediate-risk microcarcinomas treated by LT were submitted to additional treatments. On the other hand, macrocarcinomas were significantly more persistent if treated with LT than with TT (low-risk, P = 0.036 vs. intermediate-risk, P = 0.004). Permanent hypoparathyroidism was more frequent after TT (P = 0.01). After LT, thyroglobulin (Tg)/thyroid-stimulating hormone (TSH) had shown decreasing trend in 68% of the event-free patients and an increasing trend in the persistent cases. CONCLUSIONS: Lobectomy can be proposed for low-risk microcarcinomas, although in a minority of cases, additional treatments are needed, and a longer follow-up period usually is required to confirm an event-free outcome compared with that for patients treated with TT. On the other hand, to achieve an excellent response, TT should be favored for intermediate-risk micro- and macro-DTCs despite the higher frequency of postsurgical complications.

The Image Data Resource: A Bioimage Data Integration and Publication Platform.

Access to primary research data is vital for the advancement of science. To extend the data types supported by community repositories, we built a prototype Image Data Resource (IDR) that collects and integrates imaging data acquired across many different imaging modalities. IDR links data from several imaging modalities, including high-content screening, super-resolution and time-lapse microscopy, digital pathology, public genetic or chemical databases, and cell and tissue phenotypes expressed using controlled ontologies. Using this integration, IDR facilitates the analysis of gene networks and reveals functional interactions that are inaccessible to individual studies. To enable re-analysis, we also established a computational resource based on Jupyter notebooks that allows remote access to the entire IDR. IDR is also an open source platform that others can use to publish their own image data. Thus IDR provides both a novel on-line resource and a software infrastructure that promotes and extends publication and re-analysis of scientific image data.

Set-Up and Validation of a High Throughput Screening Method for Human Monoacylglycerol Lipase (MAGL) Based on a New Red Fluorescent Probe.

Monoacylglycerol lipase (MAGL) is a serine hydrolase that has a key regulatory role in controlling the levels of 2-arachidonoylglycerol (2-AG), the main signaling molecule in the endocannabinoid system. Identification of selective modulators of MAGL enables both to provide new tools for investigating pathophysiological roles of 2-AG, and to discover new lead compounds for drug design. The development of sensitive and reliable methods is crucial to evaluate this modulatory activity. In the current study, we report readily synthesized long-wavelength putative fluorogenic substrates with different acylic side chains to find a new probe for MAGL activity. 7-Hydroxyresorufinyl octanoate proved to be the best substrate thanks to the highest rate of hydrolysis and the best Km and Vmax values. In addition, in silico evaluation of substrates interaction with the active site of MAGL confirms octanoate resorufine derivative as the molecule of choice. The well-known MAGL inhibitors URB602 and methyl arachidonylfluorophosphonate (MAFP) were used for the assay validation. The assay was highly reproducible with an overall average Z' value of 0.86. The fast, sensitive and accurate method described in this study is suitable for low-cost high-throughput screening (HTS) of MAGL modulators and is a powerful new tool for studying MAGL activity.

Correction to: Radioiodine ablation with 1,850 MBq in association with rhTSH in patients with differentiated thyroid cancer.

Unfortunately, the fourth author's middle name was missed out in the original publication of this article. The complete correct name should read as follows.

Hyperthyroidism.

Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves' disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves' disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. ß blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment.

Fetal cell microchimerism in papillary thyroid cancer: A role in the outcome of the disease.

Fetal cell microchimerism (FCM) is defined as the persistence of fetal cells in maternal organs and circulation without any apparent rejection and it was hypothesized to protect toward the onset of some neoplastic diseases. To verify the role of FCM in papillary thyroid cancer (PTC), we enrolled 87 parous women with PTC and at least one male pregnancy preceding the diagnosis (PTC-P), 66 healthy women with 1 or more male children (HC-P) and 57 nonparous women with PTC (PTC-NP). The presence of circulating male DNA was assessed by the amplification of the Y chromosome-specific gene SRY, with a sensitivity of 1 male cell/1 million female cells. A significantly higher frequency of FCM was found in HC-P than PTC-P women (63.6% vs. 39.1%, p = 0.004). Among PTC-P patients, those positive for the presence of FCM (FMC+ve) had a lower prevalence of extrathyroidal extension (p = 0.027) and lymph node metastases (p = 0.044) than those without FCM (FMC-ve). Moreover, FMC+ve patients were more frequently in remission than FMC-ve cases (94.1 vs. 67.9%, p = 0.009). Interestingly, we showed for the first time that the positive effect on tumor presentation and outcome is specifically related to FCM and it is not an effect of pregnancy. In conclusion, circulating FCM is significantly more frequent in healthy parous women than in women with PTC. Moreover, the presence of circulating fetal male cells is associated with a significantly lower extrathyroidal extension and a good prognosis, suggesting a protective role of this phenomenon toward both the onset and the progression of thyroid cancer.

OMERO: flexible, model-driven data management for experimental biology.

Data-intensive research depends on tools that manage multidimensional, heterogeneous datasets. We built OME Remote Objects (OMERO), a software platform that enables access to and use of a wide range of biological data. OMERO uses a server-based middleware application to provide a unified interface for images, matrices and tables. OMERO's design and flexibility have enabled its use for light-microscopy, high-content-screening, electron-microscopy and even non-image-genotype data. OMERO is open-source software, available at http://openmicroscopy.org/.

BioBlend.objects: metacomputing with Galaxy.

SUMMARY: BioBlend.objects is a new component of the BioBlend package, adding an object-oriented interface for the Galaxy REST-based application programming interface. It improves support for metacomputing on Galaxy entities by providing higher-level functionality and allowing users to more easily create programs to explore, query and create Galaxy datasets and workflows. AVAILABILITY AND IMPLEMENTATION: BioBlend.objects is available online at https://github.com/afgane/bioblend. The new object-oriented API is implemented by the galaxy/objects subpackage.

Targeting of GSK3ß promotes imatinib-mediated apoptosis in quiescent CD34+ chronic myeloid leukemia progenitors, preserving normal stem cells.

The targeting of BCR-ABL, a hybrid oncogenic tyrosine (Y) kinase, does not eradicate chronic myeloid leukemia (CML)-initiating cells. Activation of ß-catenin was linked to CML leukemogenesis and drug resistance through its BCR-ABL-dependent Y phosphorylation and impaired binding to GSK3ß (glycogen synthase kinase 3ß). Herein, we show that GSK3ß is constitutively Y(216) phospho-activated and predominantly relocated to the cytoplasm in primary CML stem/progenitor cells compared with its balanced active/inactive levels and cytosolic/nuclear distribution in normal cells. Under cytokine support, persistent GSK3ß activity and its altered subcellular localization were correlated with BCR-ABL-dependent and -independent activation of MAPK and p60-SRC/GSK3ß complex formation. Specifically, GSK3ß activity and nuclear import were increased by imatinib mesylate (IM), a selective ABL inhibitor, but prevented by dasatinib that targets both BCR-ABL- and cytokine-dependent MAPK/p60-SRC activity. SB216763, a specific GSK3 inhibitor, promoted an almost complete suppression of primary CML stem/progenitor cells when combined with IM, but not dasatinib, while sparing bcr-abl-negative cells. Our data indicate that GSK3 inhibition acts to prime a pro-differentiative/apoptotic transcription program in the nucleus of IM-treated CML cells by affecting the ß-catenin, cyclinD1, C-EBPα, ATF5, mTOR, and p27 levels. In conclusion, our data gain new insight in CML biology, indicating that GSK3 inhibitors may be of therapeutic value in selectively targeting leukemia-initiating cells in combination with IM but not dasatinib.

Radioiodine ablation with 1,850 MBq in association with rhTSH in patients with differentiated thyroid cancer.

PURPOSE: The aim of this study was to evaluate the efficacy of post-operative radioiodine ablation with 1,850 MBq after recombinant human thyrotropin (rhTSH) administration in patients with differentiated thyroid carcinoma (DTC). We also aimed to assess the prognostic role of several patient features on the outcome of ablation. METHODS: We retrospectively analyzed data from a total of 125 patients with DTC who underwent post-operative radioiodine ablation with 1,850 MBq of ¹³¹I after preparation with rhTSH. One injection of 0.9 mg rhTSH was administered on each of two consecutive days; ¹³¹I therapy was delivered 24 h after the last injection, followed by a post-therapy whole-body scan. Successful ablation was assessed 6-12 months later and defined as an rhTSH-stimulated serum thyroglobulin (Tg) level ≤1.0 ng/ml and a normal neck ultrasound. RESULTS: Patients were stratified according to the American Thyroid Association (ATA) Management Guidelines for Differentiated Thyroid Cancer. Successful ablation was achieved in 82.4 % of patients, with an ablation rate of 95.1 % in low-risk patients and 76.2 % in intermediate-risk patients. Analyzing the correlation between ablation outcome and patient characteristics, we found a statistically significant association between failure to ablate and class of risk based on ATA guidelines (p = 0.025) and a stimulated Tg value at ablation of above 5 ng/ml (p < 0.001). CONCLUSION: The use of 1,850 MBq post-operative radioiodine thyroid remnant ablation in association with rhTSH is effective for low- and intermediate-risk patients. Moreover, in our study, we found a statistical correlation between failure to ablate and class of risk based on ATA guidelines for DTC and a stimulated Tg value at ablation.

Viable eco-efficiency targets for waste collection communities.

Waste management is crucial for advancing the circular economy, and Italy has begun to address this issue by organizing municipalities into collaborative communities of municipalities, named ATOs. In this paper, we propose a quantitative approach based on conditional efficiency analysis to estimate viable eco-efficiency targets for these waste collection communities. The proposed targets are both eco-efficient, because they reflect optimal resource allocation within the eco-efficiency framework, and viable, because they consider the unique specificities of each waste community. The methodology determines a pathway or direction for municipalities to reach the eco-efficiency frontier based on specific external factors, ensuring that each municipality is benchmarked against others with similar contexts within the same community. Our analysis focuses on 89 Italian municipalities within the ATO "Città metropolitana di Roma Capitale" in 2021, revealing that size and economic development significantly contributed to viable eco-efficiency within the community during this period. The proposed approach is general and flexible and can be applied to other municipalities in Italy or across Europe. It can also be extended to meso (regional) or macro (country) levels of analysis.

Impact of systemic treatments for advanced thyroid cancer on the adrenal cortex.

Background: Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption, or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI). Aim: The objective was to assess the entire adrenal function in patients on systemic treatments. Methods: ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, six on vandetanib, and five on selpercatinib). ACTH stimulation tests were performed in 26 cases. Results: After a median treatment period of 7 months, we observed an increase in ACTH values in 80-100% of patients and an impaired cortisol response to the ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-androstenedione and 17-OH progesterone levels were below the median of normal values in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of normal values in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the normal values in most cases, whilst renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI. Conclusion: Our data confirm that systemic treatments for advanced thyroid cancer can lead to impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been first reported and should be considered in the more appropriate management of these fragile patients.

Vitamin D levels and lipid profile in children and adolescents: a tight correlation.

INTRODUCTION: Vitamin D is an essential hormone for humans, playing an important role in musculoskeletal and calcium homeostasis. Its deficiency/insufficiency seems to contribute to the development of cardiometabolic diseases in adults: this correlation appears less clear for children and adolescents. The aim of this paper was to review literature data on the relationship between vitamin D and lipid profile alterations in pediatric population. EVIDENCE ACQUISITION: We carried out a comprehensive research in electronic databases, including MEDLINE and PubMed up to December 2022, for cross-sectional or prospective studies that investigated the correlation between serum vitamin D levels and lipid profile in children and adolescents. At the end of the process, 37 articles were included in this review. EVIDENCE SYNTHESIS: According to our findings, vitamin D deficiency/insufficiency is strongly associated with lower high-density lipoprotein (HDL) cholesterol levels and higher levels of triglycerides and total cholesterol. Data about low-density lipoproteins (LDL) cholesterol are inconsistent. The potential role of vitamin D supplements for the prevention of cardiometabolic disease currently remains a speculation. CONCLUSIONS: An increasing number of studies shows how hypovitaminosis D in the pediatric age may play a role in the pathogenesis of metabolic disorders and lipid profile alterations. Data regarding the potential role of vitamin D supplements for the prevention of cardiometabolic disease are currently controversial. Further studies are needed to evaluate the causality of this association and to assess the underlying pathogenetic mechanisms.

Toward a common standard for data and specimen provenance in life sciences.

Open and practical exchange, dissemination, and reuse of specimens and data have become a fundamental requirement for life sciences research. The quality of the data obtained and thus the findings and knowledge derived is thus significantly influenced by the quality of the samples, the experimental methods, and the data analysis. Therefore, a comprehensive and precise documentation of the pre-analytical conditions, the analytical procedures, and the data processing are essential to be able to assess the validity of the research results. With the increasing importance of the exchange, reuse, and sharing of data and samples, procedures are required that enable cross-organizational documentation, traceability, and non-repudiation. At present, this information on the provenance of samples and data is mostly either sparse, incomplete, or incoherent. Since there is no uniform framework, this information is usually only provided within the organization and not interoperably. At the same time, the collection and sharing of biological and environmental specimens increasingly require definition and documentation of benefit sharing and compliance to regulatory requirements rather than consideration of pure scientific needs. In this publication, we present an ongoing standardization effort to provide trustworthy machine-actionable documentation of the data lineage and specimens. We would like to invite experts from the biotechnology and biomedical fields to further contribute to the standard.

Endocrine-related adverse conditions induced by tyrosine kinase inhibitors.

Tyrosine kinase inhibitors (TKIs) have improved outcome for many tumors. Although better tolerated than cytotoxic chemotherapy, they may cause several adverse events (AEs) and various endocrine-related toxicities have been reported under TKI treatment. The toxicity profile varies between the different TKI compounds. This review focuses on the main endocrinopathies caused by TKIs. Thyroid dysfunction and, in particular, hypothyroidism are the most frequent and best described. Several potential mechanisms have been hypothesized, including thyroid gland dysfunction, hormone metabolism impairment and hypothalamus-pituitary-thyroid axis imbalance. TKIs have been reported to influence almost all glands. In particular, they are associated with adrenal insufficiency, growth retardation due to growth hormone (GH) and/or insulin-like growth factor-1 (IGF1) deficiency, hypogonadism, and male and female fertility impairment. TKIs may affect bone metabolism, in particular decreasing osteoclastogenesis and bone turnover and, in turn, they may cause secondary hyperparathyroidism. Hypocalcemia has been reported under lenvatinib and vandetanib treatment and parathyroid hormone (PTH)-dependent and PTH-independent mechanisms have been hypothesized. Metabolic alterations during TKI treatment range from hypoglycemia with imatinib and dasatinib to hyperglycemia with nilotinib; dyslipidemia improved with imatinib and worsened with nilotinib, sunitinib, pazopanib, sorafenib, and famitinib. Endocrine-related AEs should be managed by dedicated endocrinologists. Hormone deficiencies are easily managed by replacement therapy, while endocrine hyperfunction may be improved by symptomatic treatment. Severe situations should be managed in coordination with the oncologist, trying to limit the need for TKI dose reduction or interruption.

An integrated dataset providing a landscape of the Italian Universities.

We provide data describing all the largest Italian Universities from several perspectives, including scientific research, administrative and economic point of view. In particular, associated with each University, we have the following data. (a) The list of the most representative research keywords (single words and bigrams), automatically extracted from titles, abstracts and other possible metadata of all the research publications available for that University in Scopus database at October 2022. (b) The Extended_name of the University, Status, University_Type, State_status, number of Managerial and Administrative Staff, Teaching Staff and Researchers, Phd Diplomas, Phd Enrollments, Enrolled Undergraduates, Enrolled Graduates, Graduates, Master I Lv Graduates, Enrolled Master's Degree I Lv, Master II Lv, Graduates Enrolled, Master II Lv, Graduates Specialistic Schools and Enrolled Specialistic Schools were extracted from USTAT database for the years 2016-2018. (c) The data of Educational Income, Income from Commissioned Research and Technology Transfer, Income from Research with competitive funding, Own Income, Contributions from others (private), Contributions from others (public), Contributions from universities, Contributions from the European Union and the Rest of the World, Contributions from other local governments, Contributions Regions and Autonomous Provinces, MIUR and other central government grants, Operating Costs, Current Management Costs, Managerial and administrative personnel costs, Research and teaching staff cost, Cost of Lecturers and Researchers, Cost Scientific Collaborators, Cost of Contract Teachers, Cost of Language Experts, Other research and teaching personnel costs, Personnel Costs, Scientific equipment, Concessions, licenses and trademarks, Patent rights are extracted from the unique University Balance Sheet of each university for the years 2016-2018. These data were of difficult availability; they have been extracted from several heterogeneous sources and have been automatically checked, cleaned from errors, integrated, and missing values have been imputed as much as possible. However, due to large missing portions in the sources, they still contain several missing parts. Nonetheless, they represent a powerful snapshot of the Italian Universities, and can be of interest to researchers for many analyses of the Italian academic world. All the sources of the openly available data are provided.