Search

Background: Nintedanib is a triple-angiokinase inhibitor with potential activity in patients with advanced thyroid cancers, as radioiodine refractory differentiated thyroid cancer (RAIR DTC) and medullary thyroid cancer (MTC). Design: EORTC-1209 (NCT01788982) was a double-blind randomized (2:1 ratio) placebo-controlled phase II, multi-cohort study exploring the efficacy and safety of nintedanib in patients with progressive, locally advanced, and/or metastatic RAIR DTC and MTC. The primary endpoint was progression-free survival (PFS) in the per-protocol (PP) population for both cohorts. Secondary endpoints included response rate, duration of response, overall survival (OS), and safety. Results: RAIR DTC cohort: Seventy out of the 75 planned patients with RAIR DTC (median age, 66 years; 39 women) who had progressed after one (76%) or two lines (24%) of previous systemic therapy were randomized to receive either nintedanib (N = 45) or placebo (N = 25). Of these, 69 patients started treatment and 56 met all inclusion criteria (PP). At data cutoff, the median duration of follow-up was 26.3 months in the nintedanib arm and 19.8 months in the placebo arm. In the PP population, themedian PFS was 3.7 months [80% confidence interval (CI), 1.9-6.5] in the nintedanib arm and 2.9 months (80% CI, 2.0-5.6) in the placebo arm(HR = 0.65; 80% CI, 0.42-0.99; one-sided log-rank test P = 0.0947). No objective response was observed. The median OS was 29.6 months [80% CI, 15.2-not reached (NR)] in the nintedanib arm and not reached in the placebo arm. Grade 3-4 adverse events of any attribution occurred in 50% of patients receiving nintedanib and in 36% of patients receiving placebo. MTC cohort: Thirty-one out of the 67 planned patients with MTC (median age, 57 years; eight women) who had progressed after one (68%) or two (32%) lines of previous systemic therapy were randomized to receive either nintedanib (N = 22) or placebo (N = 9). Of these, 20 patients (15 in the nintedanib arm and five in the placebo arm) started treatment and met all inclusion criteria (PP). The median PFS was 7.0 months (80% CI, 1.9-8.7) in the nintedanib arm and 3.9 months (80% CI, 3.0-5.5) in the placebo arm (HR = 0.49; 95% CI, 0.16-1.53). No objective response was reported. The median OS was 16.4 months (80% CI, 12.1-24.9) in the nintedanib arm and 12.3 months (80% CI, 7.1-NR) in the placebo arm. Grade 3-4 adverse events of any attribution during the blinded period occurred in 59.1% of patients receiving nintedanib and in 33.3% of patients receiving placebo. Conclusion: This study did not suggest a clinically significant improvement of PFS with nintedanib over placebo in patients with pretreated RAIR DTC and MTC. [ABSTRACT FROM AUTHOR]

BACKGROUND Thyroid cancer is the most common malignant endocrine cancer worldwide. The diagnosis and distinction between benign and malignant thyroid neoplasm, especially in follicular patterned thyroid lesions is still difficult. Of the various immuno histochemical markers, Galectin-3 was most reliable in diagnosis of thyroid carcinoma. AIM To study diagnostic utility of Galectin-3 in thyroid neoplasm. METHODS This was laboratory based diagnostic study, where 92 cases of thyroid neoplasm (48-malignant and 44 benign) were analyzed for Galectin-3 expression. The Galectin-3 staining was quantitatively evaluated as percentage of positive tumor cells and qualitatively for intensity of staining. When membrane ± cytoplasmic immunoreactivity of Galectin-3 was present in more than 10% of tumor cells was considered as positive staining. RESULTS Galectin 3 expression was significantly higher in thyroid cancer as compared to benign thyroid neoplasm (p<0.001). 33/35 cases of PTC were positive for Galectin-3 expression. Galectin-3 expression was significantly higher in FTC as compared to FA (p <0.01). Galectin-3 was also useful to differentiate between FVPTC and FTC (p<0.01) and FVPTC from other benign neoplasm (<0.01).The sensitivity, specificity, positive predictive value and negative predictive value in differentiating benign and malignant thyroid neoplasm were 83.33%, 100%,100%, 84.62% respectively. CONCLUSION Galectin-3 is a potential marker in differentiating benign and malignant thyroid neoplasm. It can used as sole marker for differentiating PTC and benign thyroid neoplasm and also useful to differentiate between FVPTC and FTC. [ABSTRACT FROM AUTHOR]

The problems of the North–South Transport Corridor development are directly interrelated with the integration of the regional infrastructure of the countries participating in this project. The importance of this corridor currently affects not only the economic sphere, but also the geopolitics of the world community as a whole, as the power balancing issues in the world economy are engaged. Based on the results of the statistical data study from open sources, the analysis of extensive periodical literature, the pros and cons of the North–South Multimodal Transport Corridor (MTC) project are substantiated, and the promising ways of implementing and improving its effectiveness are identified. Political pressure on a number of participating countries and an asymmetry of interests are highlighted as factors that hinder the active implementation of the project (the most interested participants are Iran and Russia, other parties may have negative geopolitical and economic consequences from participating in the project). There are major challenges concerning the infrastructure development and the insufficient degree of harmonization of the institutional conditions within which the transport corridor operates. On the other hand, the greatest advantages of the North–South Transport Corridor are reducing dependence on other transport routes, including those passing through competitive countries, increasing national security and sovereignty of Russia, consolidating Eurasian integration, improving foreign policy links with the countries in Asia and Africa. In order to maximize the potential of the North–South MTC and increase its competitiveness in comparison with other transport hubs, the following ways are proposed: 1. One-time solution to a set of tasks: modernization of infrastructure, primarily, port infrastructure in Russia, railway infrastructure in Iran; full digitalization of the transport and logistics sphere in all the participating countries; harmonization of institutional conditions for the project implementation in the domain of legislation, customs procedures, business processes, management. 2. More active use of free economic zones and special economic zones. 3. Formation of a special supranational organizational structure that will directly deal with the development of the North– South International Transport Corridor.

The paradigm of the Next Generation cellular network (6G) and beyond is machine-type communications (MTCs), where numerous Internet of Things (IoT) devices operate autonomously without human intervention over wireless channels. IoT's autonomous and energy-intensive characteristics highlight effective energy efficiency (EEE) as a crucial key performance indicator (KPI) of 6G. However, there is a lack of investigation on the EEE of random arrival traffic, which is the underlying platform for MTCs. In this work, we explore the distinct characteristics of F -composite fading channels, which specify the combined impact of multipath fading and shadowing. Furthermore, we evaluate the EEE over such fading under a finite blocklength regime and QoS constraints where IoT applications generate constant and sporadic traffic. We consider a point-to-point buffer-aided communication system model, where (1) an uplink transmission under a finite blocklength regime is examined; (2) we make realistic assumptions regarding the perfect channel state information (CSI) available at the receiver, and the channel is characterized by the F -composite fading model; and (3) due to its effectiveness and tractability, application data are found to have an average arrival rate calculated using Markovian sources models. To this end, we derive an exact closed-form expression for outage probability and the effective rate, which provides an accurate approximation for our analysis. Moreover, we determine the arrival and required service rates that satisfy the QoS constraints by applying effective bandwidth and capacity theories. The EEE is shown to be quasiconcave, with a trade-off between the transmit power and the rate for maximising the EEE. Measuring the impact of transmission power or rate individually is quite complex, but this complexity is further intensified when both variables are considered simultaneously. Thus, we formulate power allocation (PA) and rate allocation (RA) optimisation problems individually and jointly to maximise the EEE under a QoS constraint and solve such a problem numerically through a particle swarm optimization (PSO) algorithm. Finally, we examine the EEE performance in the context of line-of-sight and shadowing parameters. [ABSTRACT FROM AUTHOR]

Metastatic lung neuroendocrine carcinomas provide diagnostic challenges in identifying the cell of origin. High level calcitonin expression is not pathognomonic for medullary thyroid cancer. Tumor mutation analysis may provide essential clues regarding tissue origin and treatment targets. Oncogenic RET gene fusions have been identified in non-small cell lung cancer and non- medullary thyroid cancers, whereas RET point mutations are the key genetic finding in both inherited and sporadic MTC. Patients who receive radiation for the treatment of other cancers have an increased risk of developing a second malignancy, including a neuroendocrine carcinoma. Herein, we present a case of calcitonin-rich neuroendocrine carcinoma emerging on a background of prior radiation and chemotherapy for the treatment of Hodgkin's disease. Identification of a RET gene rearrangement (KIF5B-RET) led to initial successful treatment with selpercatinib, with eventual resistance associated with an activating mutation involving the MEK1 protein (MAP2K1 p. E102-I103 del) that led to relapse and progression of the disease. [ABSTRACT FROM AUTHOR]

BackgroundNintedanib is a triple-angiokinase inhibitor with potential activity in patients with advanced thyroid cancers, as radioiodine refractory differentiated thyroid cancer (RAIR DTC) and medullary thyroid cancer (MTC).DesignEORTC-1209 (NCT01788982) was a double-blind randomized (2:1 ratio) placebo-controlled phase II, multi-cohort study exploring the efficacy and safety of nintedanib in patients with progressive, locally advanced, and/or metastatic RAIR DTC and MTC. The primary endpoint was progression-free survival (PFS) in the per-protocol (PP) population for both cohorts. Secondary endpoints included response rate, duration of response, overall survival (OS), and safety.ResultsRAIR DTC cohort: Seventy out of the 75 planned patients with RAIR DTC (median age, 66 years; 39 women) who had progressed after one (76%) or two lines (24%) of previous systemic therapy were randomized to receive either nintedanib (N = 45) or placebo (N = 25). Of these, 69 patients started treatment and 56 met all inclusion criteria (PP). At data cutoff, the median duration of follow-up was 26.3 months in the nintedanib arm and 19.8 months in the placebo arm. In the PP population, the median PFS was 3.7 months [80% confidence interval (CI), 1.9–6.5] in the nintedanib arm and 2.9 months (80% CI, 2.0–5.6) in the placebo arm (HR = 0.65; 80% CI, 0.42–0.99; one-sided log-rank test P = 0.0947). No objective response was observed. The median OS was 29.6 months [80% CI, 15.2–not reached (NR)] in the nintedanib arm and not reached in the placebo arm. Grade 3–4 adverse events of any attribution occurred in 50% of patients receiving nintedanib and in 36% of patients receiving placebo. MTC cohort: Thirty-one out of the 67 planned patients with MTC (median age, 57 years; eight women) who had progressed after one (68%) or two (32%) lines of previous systemic therapy were randomized to receive either nintedanib (N = 22) or placebo (N = 9). Of these, 20 patients (15 in the nintedanib arm and five in the placebo arm) started treatment and met all inclusion criteria (PP). The median PFS was 7.0 months (80% CI, 1.9–8.7) in the nintedanib arm and 3.9 months (80% CI, 3.0–5.5) in the placebo arm (HR = 0.49; 95% CI, 0.16–1.53). No objective response was reported. The median OS was 16.4 months (80% CI, 12.1–24.9) in the nintedanib arm and 12.3 months (80% CI, 7.1–NR) in the placebo arm. Grade 3–4 adverse events of any attribution during the blinded period occurred in 59.1% of patients receiving nintedanib and in 33.3% of patients receiving placebo.ConclusionThis study did not suggest a clinically significant improvement of PFS with nintedanib over placebo in patients with pretreated RAIR DTC and MTC.

This article presents a case study of a 12-year-old boy with multiple papules on his lips and tongue. The patient also exhibited other symptoms, including constipation, a disproportionate upper body segment, an enlarged lower lip, and joint laxity. The diagnosis was determined to be multiple endocrine neoplasia type 2B syndrome, a rare genetic disorder that affects various endocrine glands. The article discusses the clinical manifestations, genetic mutations, and screening methods associated with this syndrome. Early detection and appropriate management are crucial for patients with this condition. [Extracted from the article]

Purpose: Compared with other types of thyroid carcinoma, patients with medullary thyroid carcinoma (MTC) are more likely to develop cervical lymph node metastasis. This study was conducted to clarify the risk factors for cervical lymph node metastasis (central lymph node metastasis or lateral cervical lymph node metastasis) in MTC by meta-analysis, and to provide evidence-based basis for the treatment and prognosis of MTC. Methods: The literatures related to cervical lymph node metastasis in medullary thyroid carcinoma were searched in PubMed, Embase, Web of Science, Cochrane, CNKI and Wanfang databases, and statistical analysis was performed using Revman 5.3 and Stata 14.0 software. Results: A total of 28 papers were included in this paper, and meta-analysis showed that the occurrence of central lymph node metastasis (CLNM) in MTC patients was significantly associated with tumor size (OR = 3.07, 95%CI: 2.04–4.63, P < 0.00001), multifocality (OR = 0.29, 95%CI: 0.19–0.44, P < 0.00001), bilaterality (OR = 3.75, 95% CI: 1.95–7.14, P < 0.0001), capsular invasion (OR = 9.88, 95% CI: 5.93–16.45, P < 0.00001) and extrathyroidal extension (OR = 5.48, 95% CI: 2.61–11.51, P < 0.00001). While the occurrence of lateral cervical lymph node metastasis (LLNM) in MTC patients was strongly correlated with gender (OR = 2.97, 95%CI: 2.46–3.58, P < 0.00001), tumor size (OR = 3.88, 95%CI: 1.90–7.92, P = 0.0002 < 0.05), multifocality (OR = 0.43, 95%CI: 0.35–0.51, P < 0.00001), bilaterality (OR = 2.93, 95% CI: 1.72–4.98, P < 0.0001), capsular invasion (OR = 8.44, 95% CI: 6.11–11.64, P < 0.00001), extrathyroidal extension (OR = 7.04, 95% CI: 5.54–8.94, P < 0.00001), margin of the tumor (OR = 4.47, 95% CI: 2.37–8.44, P < 0.00001), shape of the tumor (OR = 6.81, 95% CI: 3.64–12.73, P < 0.00001), preoperative calcitonin level (SMD = 1.39, 95% CI: 0.98–1.80, P < 0.00001), preoperative carcinoembryonic antigen level (SMD = 0.97, 95% CI: 0.74–1.20, P < 0.00001) and CLNM (OR = 19.70, 95% CI: 14.16–27.43, P < 0.00001). Conclusion: Tumor size, multifocality, bilaterality, capsular invasion and extrathyroidal extension are the main risk factors for developing CLNM in MTC patients; And risk factors for developing LLNM in MTC patients include: gender, tumor size, multifocality, bilaterality, capsular invasion, extrathyroidal extension, margin of the tumor, shape of the tumor, preoperative calcitonin level, preoperative carcinoembryonic antigen level and central lymph node metastasis. These risk factors can guide the individualized treatment plan and improve the prognosis of MTC patients. [ABSTRACT FROM AUTHOR]

Oceans are increasingly warming through climate change. Fish and invertebrate ectotherms respond to ocean warming through poleward and depth‐related migrations, a consequence of which is disruption of fisheries catch compositions. Mean temperature of the catch (MTC) is an index of change in catch composition, from colder to warmer water species. MTC is widely applied as an easily parameterised variable using readily available data (catch and species preferred temperature), but few studies underscore situations that might mask the "true" MTC trend. Here, we use fisheries catch in the Arabian‐Persian Gulf ("Gulf") to highlight, for the first time, how abrupt changes in market demand can strongly influence catch composition and thereby mask a trend in MTC, and discuss the implications of the unmasked MTC trend to fisheries in the region. We found that a recent sharp decline in MTC from 27 to 26°C, despite a gradual increase in sea surface temperature, coincided with an escalated demand for the largehead hairtail (Trichiurus lepturus), a relatively cold‐water species in the Gulf, that caused catch to dramatically increase for export to overseas markets. Our findings suggest that the change in MTC reflected a fishery response to satisfy increased international market demand, rather than reflecting warming‐driven changes in catch composition. When excluding the effect of T. lepturus catch, the Gulf MTC trend was stable over time and consistent with a trend in many tropical and subtropical waters. Our findings highlight that an MTC change can be masked by factors unrelated to warming‐driven changes in catch composition, and that catch‐only MTC trends should be examined cautiously. [ABSTRACT FROM AUTHOR]

Simple Summary: The usefulness of calcitonin measurement in fine needle aspiration (FNA-CT) for the diagnosis of medullary thyroid carcinoma (MTC) has been confirmed by several authors. During the review process of records of our patients with thyroid nodules (TNs) and elevated serum CT, we focused our attention on 11 patients with TNs showing at histology thyroid neoplasms other than MTC, as compared with a MTC patients' group. We showed that a high FNA-CT concentration is not only found in MTC but may also be observed in benign/malignant TNs coexisting with diffuse C-cells hyperplasia (CCH) due to contamination of the needle through the CCH area. Since diffuse CCH may cause false positive FNA-CT results, we propose a cautious use of FNA-CT in patients with TNs with increased serum CT and high FNA-CT values to avoid unnecessary surgery. Purpose: The FNA-CT is useful for the diagnosis of MTC. The aim of this study was to evaluate the performance of FNA-CT in TNs coexisting with CCH. Methods: This study retrospectively reviewed the records of 11 patients with TNs submitted to thyroidectomy on the basis of elevated basal and/or stimulated serum CT values, which at histology were not confirmed to be MTC. The results obtained in this group were compared with those of a previously reported group of histologically proven MTC patients submitted to an identical presurgical evaluation. All patients, negative for known mutations in the RET proto-oncogene, were preoperatively submitted to neck ultrasound, FNA-cytology, and FNA-CT. Results: Approximately 6 of 11 patients showed increased (>36 ng/mL, as established in previous studies not involving patients with CCH) FNA-CT. All these patients showed diffuse CCH at histology in the thyroid lobe submitted to FNA; 5 of them were benign at histology, while only one was malignant (papillary thyroid carcinoma, PTC). The remaining 5 of 11 patients had low FNA-CT (<36 ng/mL), and all of them showed only focal CCH in the lobe submitted to FNA; three of them were malignant (2 PTC, 1 follicular carcinoma), while two were benign. Conclusions: Employing the currently proposed cut-off values, false-positive FNA-CT results may be observed in benign/malignant TNs with coexisting diffuse CCH. FNA-CT must therefore be cautiously used in the diagnostic approach for patients with TNs and a slightly increased basal or stimulated serum CT concentration in order to avoid unnecessary surgery. [ABSTRACT FROM AUTHOR]

The authors analyze the forms of interaction between the United States and Latin America in the military sphere. The relevance of studying this issue is due to the aggravation of relations between the collective West and Russia, as well as between the United States and China, within the framework of which Latin America acts as a zone of competition between the world powers. In this regard, the analysis of Latin American vector of US policy in the military aspect from the point of view of Russia’s strategic interests is particularly important. The lack of domestic scientific research on this problem greatly adds to its relevance. As for the novelty, based on the review of the world market of arms and military equipment (AME), this article determines the dynamics and the share of the American producer in the total volume of arms trade. In the context of military-technical cooperation (MTC), the authors also consider the peculiarities of the American military power projection on Latin America, which is a zone of exclusive interests of the United States. Among the key formats of interaction and projection of influence, the authors include the following: arms and military-technical supplies to the armies and security services of the states of the region; training of military personnel in Latin American countries; financing of armies and military units; cooperation programs to optimize the managerial and organizational functions of the Latin American armed forces, establishment and maintenance of various types of military bases, conducting joint military exercises. Using new factual material, we examine each of the listed forms and show the systematic and geostrategic nature of the US influence on the Latin American region in the military aspect. As for military trade, the authors identify the main partners of the United States in South America.

Metastatic lung neuroendocrine carcinomas provide diagnostic challenges in identifying the cell of origin. High level calcitonin expression is not pathognomonic for medullary thyroid cancer. Tumor mutation analysis may provide essential clues regarding tissue origin and treatment targets. Oncogenic RET gene fusions have been identified in non-small cell lung cancer and non-medullary thyroid cancers, whereas RET point mutations are the key genetic finding in both inherited and sporadic MTC. Patients who receive radiation for the treatment of other cancers have an increased risk of developing a second malignancy, including a neuroendocrine carcinoma. Herein, we present a case of calcitonin-rich neuroendocrine carcinoma emerging on a background of prior radiation and chemotherapy for the treatment of Hodgkin’s disease. Identification of a RET gene rearrangement (KIF5B-RET) led to initial successful treatment with selpercatinib, with eventual resistance associated with an activating mutation involving the MEK1 protein (MAP2K1 p. E102-I103 del) that led to relapse and progression of the disease.

The paradigm of the Next Generation cellular network (6G) and beyond is machine-type communications (MTCs), where numerous Internet of Things (IoT) devices operate autonomously without human intervention over wireless channels. IoT’s autonomous and energy-intensive characteristics highlight effective energy efficiency (EEE) as a crucial key performance indicator (KPI) of 6G. However, there is a lack of investigation on the EEE of random arrival traffic, which is the underlying platform for MTCs. In this work, we explore the distinct characteristics of F-composite fading channels, which specify the combined impact of multipath fading and shadowing. Furthermore, we evaluate the EEE over such fading under a finite blocklength regime and QoS constraints where IoT applications generate constant and sporadic traffic. We consider a point-to-point buffer-aided communication system model, where (1) an uplink transmission under a finite blocklength regime is examined; (2) we make realistic assumptions regarding the perfect channel state information (CSI) available at the receiver, and the channel is characterized by the F-composite fading model; and (3) due to its effectiveness and tractability, application data are found to have an average arrival rate calculated using Markovian sources models. To this end, we derive an exact closed-form expression for outage probability and the effective rate, which provides an accurate approximation for our analysis. Moreover, we determine the arrival and required service rates that satisfy the QoS constraints by applying effective bandwidth and capacity theories. The EEE is shown to be quasiconcave, with a trade-off between the transmit power and the rate for maximising the EEE. Measuring the impact of transmission power or rate individually is quite complex, but this complexity is further intensified when both variables are considered simultaneously. Thus, we formulate power allocation (PA) and rate allocation (RA) optimisation problems individually and jointly to maximise the EEE under a QoS constraint and solve such a problem numerically through a particle swarm optimization (PSO) algorithm. Finally, we examine the EEE performance in the context of line-of-sight and shadowing parameters.

ABSTRACT Microbial volatile metabolite 2-methylisoborneol (2-MIB) causes odor and taste issues in drinking water, making it unappealing for human consumption. It has been suggested that 2-MIB biosynthesis consists of two main steps, namely, methylation of geranyl diphosphate into 2-methyl geranyl diphosphate by geranyl diphosphate methyl transferase (GPPMT) and subsequent cyclization into 2-MIB by 2-MIB synthase (MIBS). Pseudanabaena foetida var. intermedia is a 2-MIB-producing cyanobacterium whose GPPMT and MIBS enzymes are encoded by adjacent mtf and mtc genes. The present study identified a 2-MIB-related gene cluster composed of cnbA, mtf, mtc, and cnbB genes in P. foetida var. intermedia. The two homologous cyclic nucleotide-binding protein genes, cnbA and cnbB, were detected adjacent to the mtf and mtc genes, respectively. The nucleotide sequence of the cnbA-mtf-mtc-cnbB gene cluster showed 99.55% identity with 2-MIB synthesis-associated gene cluster of Pseudanabaena sp. dqh15. RT-PCR results revealed that mtf and mtc genes are co-expressed, while cnbA and cnbB genes are expressed independently in P. foetida var. intermedia. To investigate whether only mtf and mtc genes are sufficient for 2-MIB synthesis, the two-gene unit (mtf-mtc) was introduced into Escherichia coli strain JM109 via overexpression vector pYS1C. Gas chromatograph-mass spectrometry results showed that the E. coli strain transformed with mtf-mtc was able to produce 2-MIB. The intracellular 2-MIB level in P. foetida var. intermedia was higher than the extracellular 2-MIB level, while the transformed E. coli strain showed an opposite trend. Growth inhibition was observed in the 2-MIB-producing transformed E. coli strain. IMPORTANCE Contamination of drinking water with odiferous microbial metabolite 2-MIB is a worldwide concern. Removal of 2-MIB from drinking water burdens the water purification process. Therefore, it is important to search for alternative methods, such as suppressing the production of 2-MIB by aquatic microorganisms. For that, it is necessary to expand the current knowledge about the mechanism of 2-MIB synthesis at the genetic level. This study revealed that mtf and mtc genes of the 2-MIB-related gene cluster are transcribed as a single unit in P. foetida var. intermedia, and the expression of both mtf and mtc genes is essential and sufficient for 2-MIB synthesis in E. coli heterologous gene expression system.

Radical ring‐opening polymerization (RROP) of cyclic ketene acetals allows for the synthesis of functional and biodegradable polyesters. To gain a better understanding of RROP, kinetic studies of this reaction method are thus essential but still rare. In here we conducted kinetic experiments on RROP of 2‐methylene‐1,3,6‐trioxocan (MTC) for the first time. In line with earlier findings, the kinetic behavior could be distributed into a chain growth, stationary and step growth behavior probably caused by dominating branching and recombination reactions impacting the polymerization with increasing conversion. The impact of reaction conditions, such as monomer concentration, reaction temperature and source of energy input (Oil bath, microwave, UV light) were varied systematically. All of these factors were studied towards their influence on polymerization rate constant, density of branches (DB), polymer dispersity and molar mass. While each of these factors were impacted by the reaction conditions, the DB was only depending on monomer conversion. Elution fractionation of PMTC samples with high conversion proved decreasing DB with increasing molar mass. Altogether, this study gives a holistic insight into the kinetics of MTC under various means of free RROP, paving the way for developing a more hydrophilic polyester with adjustable DB and molecular weight. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) arises from parafollicular cells in the thyroid gland, and although rare, it represents an aggressive type of thyroid cancer. MTC is recognized for its low mutational burden, with point mutations in RET or RAS genes being the most common oncogenic events. MTC can be resistant to cytotoxic chemotherapy, and multitarget kinase inhibitors (MKIs) have been considered a treatment option. They act by inhibiting the activities of specific tyrosine kinase receptors involved in tumor growth and angiogenesis. Several tyrosine kinase inhibitors are approved in the treatment of advanced MTC, including vandetanib and cabozantinib. However, due to the significant number of adverse events, debatable efficiency and resistance, there is a need for novel RET-specific TKIs. Newer RET-specific TKIs are expected to overcome previous limitations and improve patient outcomes. Herein, we aim to review MTC signaling pathways, the most recent options for treatment and the applications for personalized medicine. [ABSTRACT FROM AUTHOR]

This article aims to calculate and analyze the reactivity coefficients of a SLOWPOKE-2 reactor under different temperature conditions using the OpenMC code and two cross-sectional libraries, JENDL4.0 and the version VIII.0 of the ENDF/B library. The study focuses on the effect of temperature on the reactivity coefficients, specifically the Fuel Temperature Coefficient (FTC), Moderator Temperature Coefficient (MTC), and Moderator Density Coefficient (MDC), as well as the neutron flux. Through full-core calculations using the three-dimensional Monte Carlo method, the reactivity coefficients and neutron flux for both normal and accidental operating conditions of the SLOWPOKE-2 reactor are determined. The reactor employs Low Enriched Uranium Dioxide (LEU-UO2) with a 19.89% enrichment level. The results of the calculations provide valuable insights into the behavior of the SLOWPOKE-2 reactor under varying temperature conditions. Furthermore, the neutron flux distribution is analyzed, providing information on the spatial distribution of neutrons within the reactor core. The obtained results contribute to the existing knowledge on the thermal behavior of the SLOWPOKE-2 reactor, which is essential for optimizing its performance and ensuring safe operation. Also, the findings can guide future design improvements and safety enhancements in similar research reactor systems. [ABSTRACT FROM AUTHOR]

Purpose: MTC has varying clinical course. In cases with metastatic disease (meta-MTC) further therapeutic modalities (locoregional and/or Tyrosine-Kinase-Inhibitors, TKIs) are needed. Clinical features, disease progression, response to therapy and possible factors predisposing to TKIs response-resistance in meta-MTCs were investigated. Methods: Out of 338 MTC patients 54 had meta-MTC and were followed for 0.7–46 years (median 10.5); therapeutic interventions and response to therapy were recorded retrospectively. Results: Of 54 meta-MTC patients, 34/54 were men, 44/54 sporadic (age-at-diagnosis 47 ± 17.4 years, range: 5–78). Distant metastases at diagnosis were present in 12/54 (≥2 loci in 8/12), 7/12 received TKIs; During follow-up metastases occurred in 42/54 (within 0.6–25 years from diagnosis, median 5 yrs). Locoregional therapies were administered to 44/54 (81.5%) and TKIs to 40/54 (74.1%). Vandetanib was administered in 30 patients (24 as first-line therapy). The median progression-free-survival, PFS) was 48 months (range 4–120), partial response (PR): 26.7%, stable disease (SD): 23.3%, progressive disease (PD): 50.0%, cancer-specific survival: 44.8%, (16 in ongoing-therapy). More favorable disease course was recorded in familial-MTC compared to sporadic (p = 0.02) and in those patients with serious-adverse-events (SAEs) under treatment (p = 0.027). Those with biochemical progression under vandetanib, later showed more frequently structural progression (p = 0.007). Ten patients received cabozantinib (8/10 as second-line therapy, median PFS:11 months (3–36 months), 8/10 died). Three RET-mutant patients received selpercatinib; all showed PR. Within the total follow-up period, the response to therapy was: PR: 8/54 (14.8%), SD: 15/54 (27.8%), PD: 31/54 (57.4%), cancer-specific survival 46.3%. Mortality was higher in older patients (≥60 years) compared to younger ones (<60 yrs) (83.3 vs 45.2%, p = 0.021). Outcome was better in familial-MTC vs sporadic (PR: 50 vs 6.8%, SD: 20 vs 29.5%, PD: 30 vs 59.1%, p = 0.007). Conclusions: Meta-MTCs treatment results in disease stabilization in 42.6% during a median 10.5 year follow-up. Combination of locoregional and systemic therapies may result in more favorable PFS. Family history, younger age, SAEs may predict better response; biochemical escape under TKI needs to be followed-up closely as it may indicate disease progression. [ABSTRACT FROM AUTHOR]

In order to optimize elevated kidney retention of previously reported minigastrin derivatives, we substituted (R)-DOTAGA by DOTA in (R)-DOTAGA-rhCCK-16/-18. CCK-2R-mediated internalization and affinity of the new compounds were determined using AR42J cells. Biodistribution and µSPECT/CT imaging studies at 1 and 24 h p.i. were carried out in AR42J tumor-bearing CB17-SCID mice. Both DOTA-containing minigastrin analogs exhibited 3- to 5-fold better IC50 values than their (R)-DOTAGA-counterparts. natLu-labeled peptides revealed higher CCK-2R affinity than their natGa-labeled analogs. In vivo, tumor uptake at 24 h p.i. of the most affine compound, [19F]F-[177Lu]Lu-DOTA-rhCCK-18, was 1.5- and 13-fold higher compared to its (R)-DOTAGA derivative and the reference compound, [177Lu]Lu-DOTA-PP-F11N, respectively. However, activity levels in the kidneys were elevated as well. At 1 h p.i., tumor and kidney accumulation of [19F]F-[177Lu]Lu-DOTA-rhCCK-18 and [18F]F-[natLu]Lu-DOTA-rhCCK-18 was high. We could demonstrate that the choice of chelators and radiometals has a significant impact on CCK-2R affinity and thus tumor uptake of minigastrin analogs. While elevated kidney retention of [19F]F-[177Lu]Lu-DOTA-rhCCK-18 has to be further addressed with regard to radioligand therapy, its radiohybrid analog, [18F]F-[natLu]Lu-DOTA-rhCCK-18, might be ideal for positron emission tomography (PET) imaging due to its high tumor accumulation at 1 h p.i. and the attractive physical properties of fluorine-18. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) methylation of RNA by the methyltransferase complex (MTC), with core components including METTL3–METTL14 heterodimers and Wilms’ tumor 1-associated protein (WTAP), contributes to breast tumorigenesis, but the underlying regulatory mechanisms remain elusive. Here, we identify a novel cleaved form METTL3a (residues 239–580 of METTL3). We find that METTL3a is required for the METTL3–WTAP interaction, RNA m6A deposition, as well as cancer cell proliferation. Mechanistically, we find that METTL3a is essential for the METTL3–METTL3 interaction, which is a prerequisite step for recruitment of WTAP in MTC. Analysis of m6A sequencing data shows that depletion of METTL3a globally disrupts m6A deposition, and METTL3a mediates mammalian target of rapamycin (mTOR) activation via m6A-mediated suppression of TMEM127 expression. Moreover, we find that METTL3 cleavage is mediated by proteasome in an mTOR-dependent manner, revealing positive regulatory feedback between METTL3a and mTOR signaling. Our findings reveal METTL3a as an important component of MTC, and suggest the METTL3a–mTOR axis as a potential therapeutic target for breast cancer.

Introduction: MEN 2B syndrome is distinguished by the occurrence of medullary thyroid cancer, pheochromocytoma, mucosal neuromas, marfanoid features, and skeletal anomalies, including kyphoscoliosis, joint laxity, pes cavus, and, in a smaller number of cases, slipped capital femoral epiphysis (SCFE). Case report: We describe a case report of a 15-years-old patient with the diagnosis of the MEN2B syndrome with a rare manifestation of Slipped Capital Femoral Epiphysis (SCFE). A 15-year-old female presented to the orthopedics out-patient department (OPD) with complaints of pain around the right hip and knee and walking with a limp for approximately four months. Additionally, the feeling of enlarged thyroid gland was reported. X-ray confirmed the presence of the SCFE, while thyroid biopsy revealed the presence of medullary thyroid cancer (MTC). Thus, the diagnosis of MEN2B was made. Conclusion: Slipped capital femoral epiphysis (SCFE) can occasionally be a manifestation of MEN 2B syndrome. It is important for physicians to be aware of this association, as it can contribute to the early detection of a potentially life-threatening condition.

N6-methyladenosine (m6A), the most abundant mRNA modification, is deposited in mammals/insects/plants by m6A methyltransferase complexes (MTC) comprising a catalytic subunit and at least five additional proteins. The yeast MTC is critical for meiosis and was known to comprise three proteins, of which two were conserved. We uncover three novel MTC components (Kar4/Ygl036w-Vir1/Dyn2). All MTC subunits, except for Dyn2, are essential for m6A deposition and have corresponding mammalian MTC orthologues. Unlike the mammalian bipartite MTC, the yeast MTC is unipartite, yet multifunctional. The mRNA interacting module, comprising Ime4, Mum2, Vir1, and Kar4, exerts the MTC’s m6A-independent function, while Slz1 enables the MTC catalytic function in m6A deposition. Both functions are critical for meiotic progression. Kar4 also has a mechanistically separate role from the MTC during mating. The yeast MTC constituents play distinguishable m6A-dependent, MTC-dependent, and MTC-independent functions, highlighting their complexity and paving the path towards dissecting multi-layered MTC functions in mammals.

With the rapid development of the internet of things (IoT), the application of machine type communication (MTC) in life has grown substantially, and the deployment of machine type devices (MTD) has become more and more intensive.In this case, if there is an unexpected situation such as a power outage and a network failure, a large-scale MTD will initiate access to the base station at the same time when the device is powered on.When the device accesses the base station, it needs to complete the downlink synchronization, system message receiving, random access (RA) and other processes.However, the preamble resources that can be allocated by the base station are limited and cannot meet such a huge access demand, which causes network congestion and affects the access probability and access delay of the device.In order to alleviate the access conflict of RA, a dynamic random access occasion (RO) adjustment scheme was proposed based on the uplink and downlink subframes and physical random access channel (PRACH) configuration, and time-based part of the MTD with high delay requirements allocates specific preamble resources.The simulation results show that this scheme can effectively improve the throughput of the system and reduce the access delay of the device.

“Machine-to-machine (M2M) is a kind of application and service based on intelligent interaction and networking among machine terminals, which is also called machine-type communications (MTC)”. Here, this paper intends to develop an enhanced secure MTC in LTE Network that takes place under two phases namely, (i) coarse grained attack detection system and (ii) fine grained attack detection system. Initially, the clustering of nodes takes place using LEACH approach and followed by that cluster head (CH) selection takes place by considering the constraints like distance, penalty, energy, and delay. The penalty determined may ensure the secured CH selection results from optimized Neural Network (NN) model. If penalty is assigned as one, particular node is forbidden, which cannot be selected as head node (simply dropped from network). Nodes information is transmitted in Blocks of block chain to authenticate the nodes with the support of Cluster Head (CH) and to ensure the integrity of the block chain. Further, fine grained attack detection system is carried out that authenticate the selected CH to assure attack free network. As a major contribution, the training of NN is carried out by means of a novel algorithm named as Whale with Tri-level Update (WTU). Finally, the superiority of the adopted scheme is analyzed over existing schemes in terms of correlation.

Neuroendocrine tumors (NETs) occur in various regions of the body and present with complex clinical and biochemical phenotypes. The molecular underpinnings that give rise to such varied manifestations have not been completely deciphered. The management of neuroendocrine tumors (NETs) involves surgery, locoregional therapy, and/or systemic therapy. Several forms of systemic therapy, including platinum-based chemotherapy, temozolomide/capecitabine, tyrosine kinase inhibitors, mTOR inhibitors, and peptide receptor radionuclide therapy have been extensively studied and implemented in the treatment of NETs. However, the potential of immune checkpoint inhibitor (ICI) therapy as an option in the management of NETs has only recently garnered attention. Till date, it is not clear whether ICI therapy holds any distinctive advantage in terms of efficacy or safety when compared to other available systemic therapies for NETs. Identifying the characteristics of NETs that would make them (better) respond to ICIs has been challenging. This review provides a summary of the current evidence on the value of ICI therapy in the management of ICIs and discusses the potential areas for future research. [ABSTRACT FROM AUTHOR]

Medullary thyroid cancer (MTC) accounts for only 4% of thyroid carcinomas but 15% of thyroid cancer deaths. MTC is a tumour of the calcitonin secreting parafollicular C cells in the thyroid which can occur sporadically or be hereditary in multiple endocrine neoplasias type 2 syndromes due to germline RET mutations. Sporadic forms of MTC can also be caused by mutations in the RET protooncogene. MTC commonly presents in a late stage, with 70% of patients presenting with local nodal metastasis. Currently, the only curative treatment for MTC is surgical removal. The aim of this paper is to describe the current guidelines and progressions of the surgical management of MTC and to highlight up-and-coming chemotherapies. A database literature review was completed utilizing PubMed to cumulate the extant literature, screening for most recent guidelines and publications regarding the management of MTC. Current guidelines were described by the American Thyroid Association in 2015. Controversial publications continue to present supporting evidence for varying degrees of thyroidectomy and neck dissections. Recently, researchers have been exploring non-surgical options including external beam radiotherapy and multikinase inhibitors such as vandetanib and cabozantinib for the treatment of MTC. Surgical management of MTC remains controversial and varies significantly dependent on the extent of disease. Chemotherapeutic options have undetermined effects on survival to date. [ABSTRACT FROM AUTHOR]

Abstract Background To evaluate the diagnostic value of American College of Radiology (ACR) score and ACR Thyroid Imaging Report and Data System (TI-RADS) for benign nodules, medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) through comparing with Kwak TI-RADS. Methods Five hundred nine patients diagnosed with PTC, MTC or benign thyroid nodules were included and classified into the benign thyroid nodules group (n = 264), the PTC group (n = 189) and the MTC group (n = 56). The area under the curve (AUC) values were analyzed and the receiver operator characteristic (ROC) curves were drawn to compare the diagnostic efficiencies of ACR score, ACR TI-RADS and KWAK TI-RADS on benign thyroid nodules, MTC and PTC. Results The AUC values of ACR score, ACR TI-RADS and Kwak TI-RADS for distinguishing malignant nodules from benign nodules were 0.914 (95%CI: 0.886–0.937), 0.871 (95%CI: 0.839–0.899) and 0.885 (95%CI: 0.854–0.911), respectively. In distinguishing of patients with MTC from PTC, the AUC values of ACR score, ACR TI-RADS and Kwak TI-RADS were 0.650 (95%CI: 0.565–0.734), 0.596 (95%CI: 0.527–0.664), and 0.613 (95%CI: 0.545–0.681), respectively. The AUC values of ACR score, ACR TI-RADS and Kwak TI-RADS for the discrimination of patients with MTC, PTC or benign nodules from patients without MTC, PTC or benign nodules were 0.899 (95%CI: 0.882–0.915), 0.865 (95%CI: 0.846–0.885), and 0.873 (95%CI: 0.854–0.893), respectively. Conclusion The ACR score performed the best, followed ex aequo by the ACR and Kwak TI-RADS in discriminating patients with malignant nodules from benign nodules and patients with MTC from PTC.

The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.Methods: The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.Results: The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.Conclusion: The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management.Graphical abstract: The recently developed metabolically more stable minigastrin derivative, DOTA-CCK-66, displayed promising preclinical data when labeled either with 68Ga or 177Lu. First positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Ga-DOTA-CCK-66 in two patients suffering from medullary thyroid carcinoma (MTC) displayed a favorable biodistribution profile. Here, we aim to investigate the therapeutic potential of [225Ac]Ac-DOTA-CCK-66 as a targeted α-therapy (TAT) agent in a comparative treatment study of [177Lu]Lu- versus [225Ac]Ac-DOTA-CCK-66.Treatment studies were performed (3 groups, n = 5, AR42J tumor-bearing 394-NOD SCID mice). Control group animals were injected with [68Ga]Ga-DOTA-CCK-66 (1.1 MBq, PET/CT imaging), while treatment group animals received a single dose of either [177Lu]Lu-DOTA-CCK-66 (37 MBq, radioligand therapy (RLT)) or [225Ac]Ac-DOTA-CCK-66 (37 kBq, TAT). All animals' tumor volume and body weight were monitored twice a week until end-point criteria were reached. Blood samples were evaluated (VetScan VS2, Abaxis) once mice were sacrificed.Upon treatment, an initial decline in tumor volume, followed by a significantly delayed tumor growth of treated cohorts, was observed. Mean survival of 177Lu- as well as 225Ac-treated animals was increased by 3- (37 ± 3 d) and 4.5-fold (54 ± 6 d), respectively, when compared to non-treated animals (12 ± 3 d). Blood sample analysis did not indicate toxic side effects to the liver, kidney, or stomach upon 177Lu and 225Ac-treatment.We demonstrated a substantial therapeutic efficacy of 177Lu- and 225Ac-labeled DOTA-CCK-66. As expected, treatment with the latter resulted in the highest mean survival rates. These results indicate a high therapeutic potential of 225Ac-labeled DOTA-CCK-66 for TAT in MTC patient management. [ABSTRACT FROM AUTHOR]

Radical ring opening polymerisation (RROP) of cyclic ketene acetals (CKAs) is an attractive technique to synthesize branched, (bio)degradable polyesters. However, CKAs as monomers of RROP suffer from hydrolysis lability, making aqueous heterogeneous precipitation polymerisations challenging. In order to explore the precipitation polymerisation of 2-methylene-1,3,6-trioxocane (MTC) and avoid the hydrolysis of monomer, kinetic studies in supercritical CO 2 (scCO 2) were performed. Tuning the reaction pressure and temperature allowed for synthesis in varying viscosity domains. Importantly, we describe the precipitation polymerisation of low T g PMTC (−65 °C) in scCO 2. In contrast to literature, where a particle-driven polymerisation mechanism has been described for high T g polymers, a slurry-like precipitation polymerisation was observed for PMTC. Depending on the reaction temperature, polymers with either (i) a defined density of branches (DB) and a scattering of molar mass values, or (ii) a scattering of DB values and relatively defined molar mass were prepared. [Display omitted] • First comprehensive study of RROP in scCO2. • Polymerisation in scCO2 leads to precipitation polymerisation. • Molar mass can be regulated by the reaction temperature. • Dispersity and branching largely independent of reaction pressure. • Use of scCO2 green solvent enhances RROP as sustainable polymerisation. [ABSTRACT FROM AUTHOR]

H 2 production due to zirconium hydration was the primary source of explosion in the Fukushima Daiichi nuclear accident. To improve accident tolerance of the new reactor designs, advanced fuel and cladding materials are being extensively investigated. Neutronic evaluation at both the pin-cell and assembly levels are performed for the conventional UO 2 and the candidate UN/U 3 Si 2 fuels with traditional cladding (Zr) as well as the accident tolerant claddings (SiC and advanced powder metallurgic ferritic, APMT). The neutronic performance, plutonium inventory, cycle length, radial and pin power distribution, spectrum distribution, spatial self-shielding analysis, plutonium radial distribution, and reactivity coefficients are evaluated and analyzed. Combination of UN/U 3 Si 2 and APMT produces 68% and 66 % more 239Pu and 135Xe than the UO 2 and APMT systems. In overall, the reactivity change versus burnup and other main neutronic parameters of SiC cladding are quite similar to the current Zr cladding. Using SiC resulted in an average increase of 0.85 % in reactivity in comparison to Zr conventional cladding (without any change in the enrichment of the fuel). Compared with the traditionally used UO 2 fuel assembly, the UN/U 3 Si 2 fuel assembly exhibit a higher (0.2 % at BOC and 0.4 % at EOC) pin power peak value in an assembly, which should be a concern from safety aspects. The negativity of FTC and MTC for the proposed UN/U 3 Si 2 is higher than that of UO 2 fuel. These higher and enhanced FTC and MTC values of UN fuels mean an improved inherent safety feature of UN-like high U density fuels. • The concentration of Pu239 in the UO 2 –Zr fuel clad combination reaches the maximum point at 57.1 GWd/te. • For 0.0253 eV, flux peak is 12% higher in SiC and Zr fuel pins than in APMT pins. • The APMT exhibited higher negative FTC, MTC and VRC at the BOC but lower at the intermediate and EOC. • The FTC, MTC, and VRC values of UN/U 3 Si 2 fuels are stronger than those of conventional UO 2 fuel. [ABSTRACT FROM AUTHOR]

Abstract Purpose Marital status has emerged as an important influence on several cancer outcomes, but its role in medullary thyroid cancer (MTC) remains unclear. This study was to explore the effects of marital status on the prognosis of MTC patients and to determine whether its effects vary by age. Patients and methods We retrospectively extracted 1344 eligible patients diagnosed with MTC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the marital status, we divided those patients into married and unmarried groups. We compared the difference in overall survival (OS) and cancer‐specific survival (CSS) between married and unmarried via the Kaplan–Meier analysis. Univariate and multivariate Cox proportional models were performed to identify the prognostic factors of OS and CSS. Results There were 1344 MTC eligible patients in a total of which 883 (65.7%) were married and 461 (34.3%) were unmarried. The comparison observed between married and unmarried patients was as follows: male (45.2% vs. 28.0%), age (≥52 years) (55.9% vs. 44.6%), White (86.7% vs. 78.7%), and undergo surgery (97.7% vs. 93.3%). Multivariate analysis revealed unmarried status as a risk factor independently associated with worse OS (HR: 2.15, 95% CI: 1.59–2.92) rate and CSS (HR: 1.70, 95% CI: 1.17–2.47) rate. In a further analysis stratified by age, there was no significant difference in OS and CSS between married and unmarried patients younger than 52 years. For the remaining group with 52 years old and higher, unmarried patients showed significantly higher risk of OS and CSS than married patients at all stages of the pathology except M1 stage. Conclusion Married patients with MTC have a better prognosis than unmarried ones. Age can affect the association between marital status and the survival of MTC, and married elders may benefit more than youngers.

A new control method for the determination of the malting barley susceptibility to gushing was developed. The method is based on the modified Carlsberg test (MCT) after prior stimulation of barley with substances that promote the germination process. Barleys from the harvest of 2020 and malts produced from them were used to develop and verify the method. The selection of barleys was based on the results of gushing potential detected in the produced malts. To optimise and verify the method, the barley variety Sunshine with a high gushing potential of both barley (139±33 g) and malt (144±13 g), and the barley variety Pionier with zero gushing potential of both barley and malt were used. Malt was produced from the Lodestar barley variety with a high content of the mycotoxin deoxynivalenol. Gushing of the malt was 127±10 g. The gushing potential in barley was determined by the MCT method after prior stimulation of germination. For comparison, the gushing potential was also determined by the MCT method without stimulation of germination. It was proved that stimulation of germination is a key process for correct determination of the susceptibility of barley to gushing. The newly developed method was used for the determination of the gushing potential of five barleys from the harvests of 2020 and 2021. Control gushing determination of five malt samples was performed using the MCT method. An agreement between the measured data was found.

• The study optimizes the current expressway toll station guidance signs in China. • Four guidance signage plans are designed and tested using a driving simulator. • The Complete MTC guidance sign plans have more safety benefits than the others. • Adding voice warning on the Complete MTC guidance plan does not offer extra benefits. Although ETC (Electronic Toll Collection) has been widely implemented in vehicles in China in recent years, the channel guidance signage system on expressways has not been updated accordingly. Late lane-changing occurs when drivers are confused about the correct channel to enter, leading to increased crash risks and traffic congestion in front of the toll. The paper aims to optimize the current guidance signage systems, given the high proportion of ETC vehicles on Chinese expressways, and evaluate its effects on the drivers' lane-changing behavior when passing through the expressway toll channels. A driving simulator experiment was conducted to test four scenarios: Original sign plan, Partial Manual Toll Collection (MTC) sign plan, Complete MTC sign plan and Complete MTC sign with Voice warning plan. Forty participants with a valid driver's license completed the four scenarios, and their behavior performances (e.g., decision-making of lane-changing, response time, average speed and deceleration) in the main lane in front of the toll booth were analyzed. The results showed that compared to the Original sign plan and Partial MTC sign plans, the Complete MTC sign plans (with and without voice warning) played a significant role in improving the MTC vehicle drivers' lane-changing behaviors. The improvement included earlier initiated lane-changing, shortened response time, lower deceleration rate and extended lane-changing duration distance. The findings of this study have important implications for expressway designers and relevant management departments to optimize the current guidance signage and enhance traffic safety and efficiency at the toll plaza. [ABSTRACT FROM AUTHOR]

Ocean warming has been affecting marine ecosystems over the past few decades. The signature of ocean warming in global fisheries catch data has been identified through a variety of methods, one of which is the mean temperature of the catch (MTC) index. The MTC is derived from the average temperature preference of fished species weighted by their contribution to annual catches. Here, we used MTC to explore the fisheries catch responses to warming, from 1950 to 2016, along a latitudinal gradient in the western Pacific Ocean, from 37° N, via 2.5° S in the central western Pacific, to 36° S. The tropicalization of catches in a given geographic space, i.e., the increased catch of species with affinity to warmer waters, as a result of increasing sea temperature and the associated poleward migration of species, rather than any large-scale oceanographic variability, was apparent through the increasing MTC at higher latitudes. In particular, MTC in temperate Japan increased by 0.33 °C per decade over the time series. The MTC in subtropical/temperate southeast Australia increased by 0.24 °C per decade over the full time period and by 1.24 °C per decade after 2002. The observed MTC increase was caused by the increasing dominance of thermophilous (preferring warmer waters) over psychrophilous (preferring cooler waters) taxa in the catches in these waters. On the other hand, the MTC in tropical Indonesian waters, as well as the ratio of thermophilous to psychrophilous taxa, showed a gentle yet consistent decrease of 0.05 °C per decade over the full time period. This finding supports the tropicalization hypothesis, given the limited scope for further tropicalization of catches in the already tropical ecosystem of Indonesia. Ocean warming has indeed been altering the distribution of marine organisms, particularly in temperate ecosystems as thermophilous taxa become more abundant, while psychrophilous taxa abundance decreases. Tropicalization impacts fisheries and catch composition and is, therefore, expected to cause conflicts among fishers and challenge fisheries management. [ABSTRACT FROM AUTHOR]

This paper describes the prototype and tests carried out to demonstrate the feasibility of implementing 4G/5G systems based on mobile network operators (MNOs) to transmit signalling critical data for railway systems as part of a possible solution for the Future Railway Mobile Communication System (FRMCS). This communication system design is performed from a protocol-stack perspective, introducing the KPIs for the physical layer (RSRP, RSRQ and SINR), network layer (latency and jitter) and application layer (signalling communication timeout). The analysis focuses on the characterisation of signalling critical railway data to assess the data traffic behaviour in a telecommunications laboratory. Finally, the study validates the approach in a realistic railway environment. [ABSTRACT FROM AUTHOR]

Grade, based on proliferative activity and tumor necrosis, has recently been shown to be prognostic in medullary thyroid carcinoma (MTC) in multivariate analysis. The aim of this study was to evaluate the interobserver reproducibility of assessed grade in MTC. Three groups (each group included one resident/fellow and one attending pathologist) independently evaluated a cohort of 44 sporadic MTC. For each case, all available tumor slides were reviewed, and mitotic count and the presence of tumor necrosis were recorded. Ki-67 was performed, and the Ki-67 proliferative index was determined in the area of highest proliferative activity. Tumors were graded according to the recently published International Medullary Thyroid Carcinoma Grading System (IMTCGS). Kappa statistics were calculated for each individual criterion (mitotic count, Ki-67 proliferative index, and necrosis) and for assigned IMTCGS grade. For our cohort of 44 MTCs, the kappa statistic for mitotic count, Ki-67 proliferative index, and necrosis was 0.68, 0.86, and 0.89, respectively. The kappa statistic for assigned IMTCGS grade was 0.87. Our findings indicate that there was a strong level of agreement for assessment of grade in our cohort of MTC, indicating that grade as assessed by the IMTCGS is not only prognostic but also reproducible. [ABSTRACT FROM AUTHOR]

Blood iron levels play a vital role in oxygen metabolism and energy generation whilst transporter protein, transferrin, binds and delivers iron to the transferrin receptor of endosomal compartments of cells. Consequently, the iron-binding capacity of transferrin is an important indicator for many diseases, and its measurements are used in the diagnosis and treatment of anaemias. Various assays, including Total Iron Binding Capacity (TIBC), Unsaturated Iron-Binding Capacity (UIBC) and Transferrin Saturation (TS), were developed to assess the iron-binding capacity of transferrin. Clinically, UIBC is measured in serum by a multi-step liquid ferrozine method and subjected to interference from conditions such as haemolysis and lipemia. Here, we report a quick method that directly measures the concentration of apotransferrin in EDTA-treated plasma, theoretically equivalent to UIBC. Importantly, this supramolecular assembly-based method is more time-efficient, cost-effective and insensitive to serum cation fluctuations. With additional colorimetric property, this method also provides a visual indicator for abnormal health conditions with extreme transferrin statuses such as those found in cancers. Its minimal requirement for equipment would be particularly useful for diagnosis in remote and under-developed regions. [ABSTRACT FROM AUTHOR]

Background: We performed a bibliometric study to identify the most-cited publications in MTC research and demonstrate how they highlight the most important historical developments in this area., Methods: Bibliometric data from papers published on the topic of MTC until December 31, 2022 was extracted from the Web of Science database. Analysis was performed utilizing Bibliometrix and VOSViewer software., Results: There has been a gradual increase in the number of publications on the topic of MTC over the years. The most cited publications focused on the underlying genetic basis for MTC, the use of targetted therapy, and guidelines. Recent research frontiers have focused on management, guidelines, and tyrosine kinase inhibitors., Conclusion: Bibliometric study of the topic of MTC has allowed for identification, characterization and appreciation of many of the key historical developments in this field. Bibliometric analysis can also be helpful in identifying research frontiers., Competing Interests: Declaration of competing interest The authors do not report any conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)