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Machine type communication devices proposed as one of the substantial data collections in the 5G of wireless networks. However, the existing mobile communication network is not designed to handle massive access from the MTC devices instead of human type communication. In this context, we propose the device-to-device communication assisted a mobile terminal (smartphone) on data computing, focusing on data generated from a correlated source of machine type communication devices. We consider the scenario that the MTC devices after collecting the data will transmit to a smartphone for computing. With the limitation of computing resources at the smartphone, some data are offloaded to the nearby mobile edge-computing server. By adopting the sensing capability on MTC devices, we use a power exponential function to compute a correlation coefficient existing between the devices. Then we propose two grouping techniques K-Means and hierarchical clustering to combine only the MTC devices, which are spatially correlated. Based on this framework, we compare the energy consumption when all data processed locally at a smartphone or remotely at mobile edge computing server with optimal solution obtained by exhaustive search method. The results illustrated that; the proposed grouping technique reduce the energy consumption at a smartphone while satisfying a required completion time. [ABSTRACT FROM AUTHOR]

"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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background A thymoma with chest pain and multilocular thymic cysts (MTCs) is very rare. Case presentation A 49-year-old man presented to another hospital complaining of an anterior chest pain. Chest computed tomography (CT) showed an anterior mediastinal tumor 60 × 30 × 55 mm in size. The boundary with the pericardium or left brachiocephalic vein seemed to be partially unclear while enhanced by the contrast medium, and so the tumor could have invaded them. No definitive diagnosis of myasthenia gravis was made although the serum anti-acetylcholine receptor antibody count was high. We performed an extended thymectomy with combined partial resection of left brachiocephalic vein, left upper lobe, and left phrenic nerve. He was discharged with no chest pain and no complications post-surgery. The tumor was pathologically type B2 thymoma with hemorrhage necrosis and MTCs, and we diagnosed Masaoka stage II because of no histological infiltration to the organs. Conclusions We speculated that hemorrhagic necrosis due to infarction in tumor caused the inflammation to spread to the surrounding organs, which was related to the chest pain and the development of MTCs.

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.

Purpose: Accurate recognition of medullary thyroid carcinoma (MTC) is of great importance in medical diagnosis, as MTC is rare but second‐most malignant thyroid cancers with a high case‐fatality ratio.1 But there is a lower recognition rate on distinguishing MTC from other thyroid nodules in ultrasound images, even by experienced experts. This paper introduces the computer‐aided method to tackle the challenge of recognizing MTC from ultrasound images, including limited MTC samples, and ambiguities among MTC, benign nodules, and papillary thyroid carcinoma (PTC). Methods: The recognition of MTC based on large MTC samples of ultrasound images has never been explored, as only one existing work presented a relevant dataset with a limited 21 MTC samples. This study proposes a novel method for primarily differentiating MTC samples from benign nodules and PTC that is the most common thyroid cancer. Our method is a two‐stage schema with two important components including a cascaded coarse‐to‐fine segmentation network and a knowledge‐based classification network. The cascaded coarse‐to‐fine segmentation network incorporates two U‐Net++ networks for improving the segmentation results of thyroid nodules. Meanwhile, our knowledge‐based classification network extracts and fuses semantic features of solid tissues and calcification for better recognizing the segmented nodules from the ultrasound images. In our experiments, dice similarity coefficient (DSC), intersection over union (IoU), precision, recall, and Hausdorff distance (HD) are adopted for evaluating the segmentation results of thyroid nodules, and accuracy, precision, recall, and F1‐score are used for classification evaluation. Results: We present a well‐annotated dataset including samples of 248 MTC, 240 benign nodules, and 239 PTC. For thyroid nodule segmentation, our designed cascaded segmentation network attains values of 0.776 DSC, 0.689 IoU, 0.778 precision, and 0.821 recall, respectively. By incorporating prior knowledge, our method achieves a mean accuracy of 82.1% in classifying thyroid nodules of MTC, PTC, and benign ones. Especially, our method gains the higher performance in recognizing MTC with an accuracy of 86.8%, compared to nearly 70% diagnosis accuracy of experienced doctors. The experimental results on our Fujian Provincial Hospital dataset further validate the efficiency of our proposed method. Conclusions: Our proposed two‐stage method incorporates pipelines of thyroid nodules segmentation and classification of MTC, individually. Quantitative and qualitative results indicate that our proposed model achieves accurate segmentation of thyroid nodules. The results also validate that our learning‐based framework facilitates the recognition of MTC, which gains better classification accuracy than experienced doctors. [ABSTRACT FROM AUTHOR]

The ciliate phylum is a group of protists noted for their unusual membrane trafficking system and apparent environmental ubiquity; as highly successful microbial predators, they are found in all manner of environments and the ability for specific species to adapt to extremely challenging conditions makes them valued as bioindicators. Ciliates have also been used for many years as cell biological models because of their large cell size and ease of culturing, and for many fundamental cell structures, particularly membrane‐bound organelles, ciliates were some of the earliest organisms in which these were observed via microscopy. In this study, we carried out a comparative genomic survey of selected membrane trafficking proteins in a pan‐ciliate transcriptome and genome dataset. We observed considerable loss of membrane trafficking system (MTS) proteins that would indicate a loss of machinery that is generally conserved across eukaryotic diversity, even after controlling for potentially incomplete genome representation. In particular, the complete DSL1 complex was missing in all surveyed ciliates. This protein complex has been shown as involved in peroxisome biogenesis in some model systems, and a paucity of DSL1 components has been indicative of degenerate peroxisome. However, Tetrahymena thermophila (formerly Tetrahymena pyroformis) was one of the original models for visualizing peroxisomes. Conversely, the AP3 complex essential for mucocyst maturation in T. thermophila, is poorly conserved despite the presence of secretory lysosome‐related organelles across ciliate diversity. We discuss potential resolutions for these apparent paradoxes in the context of the heterogenous distribution of MTS machinery across the diversity of ciliates. [ABSTRACT FROM AUTHOR]

Mission critical Machine-type Communication (mcMTC), also referred to as Ultra-reliable Low Latency Communication (URLLC), has become a research hotspot. It is primarily characterized by communication that provides ultra-high reliability and very low latency to concurrently transmit short commands to a massive number of connected devices. While the reduction in physical (PHY) layer overhead and improvement in channel coding techniques are pivotal in reducing latency and improving reliability, the current wireless standards dedicated to support mcMTC rely heavily on adopting the bottom layers of general-purpose wireless standards and customizing only the upper layers. The mcMTC has a significant technical impact on the design of all layers of the communication protocol stack. In this paper, an innovative bottom-up approach has been proposed for mcMTC applications through PHY layer targeted at improving the transmission reliability by implementing ultra-reliable channel coding scheme in the PHY layer of IEEE 802.11a standard bearing in mind short packet transmission system. To achieve this aim, we analyzed and compared the channel coding performance of convolutional codes (CCs), low-density parity-check (LDPC) codes, and polar codes in wireless network on the condition of short data packet transmission. The Viterbi decoding algorithm (VA), logarithmic belief propagation (Log-BP) algorithm, and cyclic redundancy check (CRC) successive cancellation list (SCL) (CRC-SCL) decoding algorithm were adopted to CC, LDPC codes, and polar codes, respectively. Consequently, a new PHY layer for mcMTC has been proposed. The reliability of the proposed approach has been validated by simulation in terms of Bit error rate (BER) and packet error rate (PER) vs.signal-to-noise ratio (SNR). The simulation results demonstrate that the reliability of IEEE 802.11a standard has been significantly improved to be at PER = 10-5 or even better with the implementation of polar codes. The results also show that the general-purpose wireless networks are prominent in providing short packet mcMTC with the modification needed. [ABSTRACT FROM AUTHOR]

Purpose: Medullary thyroid carcinoma (MTC) originates from thyroid parafollicular C-cells and represents <5% of all thyroid cancers. Serum Calcitonin (CTn) is considered the most sensitive marker of persistent or recurrent disease and is measured in association to CEA. According to the American Thyroid Association (ATA) guidelines, following initial surgery when CTn level remains below 150 pg/mL, follow-up may rely on repeated serum marker determinations and on neck ultrasonography (US). When CTn level exceeds 150 pg/ml, additional imaging is required. In this review, we provide an overview of available imaging tools to monitor MTC course and propose an effective imaging strategy for MTC patients according to their clinical situation. Methods: A literature search focusing on available imaging tools to monitor MTC provided the currently available information for this review. Recent evidence-based reports and reviews were considered as priority over older evidence. Results: For MTC patients with detectable CTn levels and disease recurrence, PET/CT imaging with 18F-DOPA or 68Ga-DOTA-peptides present the best sensitivity for lesion detection. 18F FDG PET/CT represents a prognostic tool and is useful in case of aggressive disease. Neck ultrasound, chest CT scan and MRI of the liver and of the axial skeleton represent complementary techniques. Beyond the diagnostic accuracy, the clinical impact of imaging is variable according to different disease settings and tumor marker levels. Finally, other applications of imaging such as response to focal and systemic treatments and new promising PET tracers should be further investigated. Conclusion: The role of imaging in MTC patients improved, especially with the use of 18F-DOPA PET/CT that provides high quality diagnostic images. However, the impact on therapeutic management should be further evaluated in the different disease settings and in proper prospective trials. [ABSTRACT FROM AUTHOR]

Abstract The relevant role of long non-coding RNAs (lncRNAs) in cancer is currently a matter of increasing interest. Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor (2–5% of all thyroid cancer) derived from the parafollicular C-cells which secrete calcitonin. About 75% of all medullary thyroid cancers are believed to be sporadic medullary thyroid cancer (sMTC), whereas the remaining 25% correspond to inherited cancer syndromes known as Multiple Endocrine Neoplasia type 2 (MEN2). MEN2 syndrome, with autosomal dominant inheritance is caused by germline gain of function mutations in RET proto-oncogene. To date no lncRNA has been associated to MEN2 syndrome and only two articles have been published relating long non-coding RNA (lncRNA) to MTC: the first one linked MALAT1 with sMTC and, in the other, our group determined some new lncRNAs in a small group of sMTC cases in fresh tissue (RMST, FTX, IPW, PRNCR1, ADAMTS9-AS2 and RMRP). The aim of the current study is to validate such novel lncRNAs previously described by our group by using a larger cohort of patients, in order to discern their potential role in the disease. Here we have tested three up-regulated (RMST, FTX, IPW) and one down-regulated (RMRP) lncRNAs in our samples (formalin fixed paraffin embedded tissues from twenty-one MEN2 and ten sMTC patients) by RT-qPCR analysis. The preliminary results reinforce the potential role of RMST, FTX, IPW and RMRP in the pathogenesis of MTC.

Machine Type Communication (MTC) becomes one of enablers of the internet of things, it faces many challenges in its integration with human-to-human (H2H) communication methods. To this aim, the Long Term Evolution (LTE) needs some adaptation in the scheduling algorithms that assign resources efficiently to both MTC devices (MTCDs) and H2H users. The minimum amount of LTE resources that can be assigned to one user is much larger than the requirements of a single MTCD. In this paper, a QoS-enabled algorithm is proposed to aggregate MTCD traffic coming from many sources at the Relay Node (RN) that classifies and aggregates the MTCD traffic based on the source type and delay requirements. In this study, three types of MTCD and one H2H sources will be considered. Each type of MTCD traffic will be grouped into a separate queue, and will be served with the appropriate priority. Resources are then assigned to the aggregated MTC traffic instead of an individual assignment for each MTCD, while the H2H users will be directly connected to the LTE. Two schemes of resource partitioning and sharing between the MTCDs and the H2H users will be considered: one proportional and the other moving-boundary. Simulation models will be built to evaluate the proposed algorithms. While the obtained results for the first scheme showed a clear improvement in LTE resource utilization for the MTCDs, a negative effect was noticed in the performance of the H2H users. The second scheme achieved a positive improvement for both MTCDs and H2H users.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and life-threatening hypersensitivity reaction. It is characterized by fever, skin lesions, and internal organ involvement. Sorafenib is a tyrosine kinase inhibitor that is used for the treatment of certain cancers such as hepatocellular, renal cell, and thyroid cancer. Case Presentation: The case is a 40 years old man who presented with fever, generalized skin rash, and pruritus. The patient has received sorafenib for the treatment of medullary thyroid cancer (MTC) from 3 weeks ago. Following presentation, the drug was discontinued and causality was assessed by scoring system RegiSCAR and Naranjo scale that showed a probable DRESS. There was no internal organ involvement based on the laboratory evaluations. The considerable abnormality was eosinophilia among patient's laboratory tests. Antihistamines and topical and systemic corticosteroids were utilized for the management of the symptoms. Conclusion: To the best of our knowledge, this is the first case report of DRESS syndrome by sorafenib in the patients with MTC. Clinicians should be aware of sign and symptoms suggesting DRESS syndrome of sorafenib. [ABSTRACT FROM AUTHOR]

Summary: The International Telecommunications Union defines in its IMT‐2020 recommendations three types of use of 5G services: mMTC (massive Machine‐type Communications), eMBB (enhanced Mobile Broadband), and uRLLC (ultra‐Reliable Low Latency Communications). The mMTC service allows a considerable number of machines and devices to communicate while guaranteeing a good quality of service. The eMBB service allows very high data throughput, even at the cell border. The uRLLC service is used for ultra‐reliable communication for critical needs requiring very low latency. These services are provided separately in a given cell. However, the number of connected objects is starting to increase rapidly as well as the bit rates and energy consumption. The 5G network must make it possible to provide access to a vast number of users of its different service categories. Call admission control (CAC) techniques focus more on availability in terms of bit rate and coverage. In this article, we suggest an algorithm for modeling CAC in an area served by the three categories of services in a 5G access network, mainly based on minimum energy consumption. This technique will allow connected objects that consume low energy to connect to the network with an adequate quality of service and enable the development of the Internet of Things. [ABSTRACT FROM AUTHOR]

Effective resource allocation has always been one of the serious challenges in wireless communication. A considerable number of machine type communication (MTC) devices in 5G with variable quality of service (QoS) aggravates this challenge even further. Existing Resource allocation schemes in MTC are usually considering signal to noise ratio (SNR), which provides preference to MTC devices based on distance rather than their QoS requirements. This paper proposes a resource allocation scheme with dynamic priorities for MTC devices with multiple radio access technologies (RATs). The proposed resource allocation scheme has two main parts namely medium access and resource allocation. The medium access leverages the broadcast nature of wireless signal and MTC devices' wait time to assign priorities using capillary band in a secure and integral way. At resource allocation, SNR, total induced transmission delay, and transmission-awaiting MTC devices are used to assign resources in the cellular band. The rumination of two-staged dynamic priorities in the proposed scheduling scheme brings significant performance improvements in outage and success probabilities. Compared to SNR-based schemes, the proposed mechanism performs well by expressively improving the outage and success probability by 20% and 30%, respectively.

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.

Background: A thymoma with chest pain and multilocular thymic cysts (MTCs) is very rare. Case presentation: A 49-year-old man presented to another hospital complaining of an anterior chest pain. Chest computed tomography (CT) showed an anterior mediastinal tumor 60 × 30 × 55 mm in size. The boundary with the pericardium or left brachiocephalic vein seemed to be partially unclear while enhanced by the contrast medium, and so the tumor could have invaded them. No definitive diagnosis of myasthenia gravis was made although the serum anti-acetylcholine receptor antibody count was high. We performed an extended thymectomy with combined partial resection of left brachiocephalic vein, left upper lobe, and left phrenic nerve. He was discharged with no chest pain and no complications post-surgery. The tumor was pathologically type B2 thymoma with hemorrhage necrosis and MTCs, and we diagnosed Masaoka stage II because of no histological infiltration to the organs. Conclusions : We speculated that hemorrhagic necrosis due to infarction in tumor caused the inflammation to spread to the surrounding organs, which was related to the chest pain and the development of MTCs. [ABSTRACT FROM AUTHOR]

Current communication networks are mainly designed for Human-to-Human (H2H) communication requirements. However, future Internet of Things (IOT) and fifth-generation mobile communications system (5G) will connect a lot of mechanical equipment. Therefore, this paper proposes a priority-based predictive resource scheduling algorithm that integrates the predictive method and priority scheduling for the uplink of Massive Machine Type Communication (mMTC). The predictive method is used to reduce the delay of a device sent scheduling request to the eNodeB to obtain the approved resources for data transmission. This is combined with a priority ranking sequence to develop the optimal resource allocation strategy to reduce the total delay time, and improve the transmission success rate and resource utilization. Simulation results show that the proposed algorithm can effectively reduce delay and increase the transmission success rate, compared with the existing methods. [ABSTRACT FROM AUTHOR]

Coexistence of Human-Type Communications (HTCs) and Machine-Type Communications (MTCs) is inevitable. Ultra-Dense Networks (UDNs) will be efficacious in supporting both types of communications. In a UDN, a massive number of low-power and low-cost Small Cells (SCs) are deployed with density higher than that of the HTC users. In such a scenario, the backhaul capacities constitute an intrinsic bottleneck for the system. Hence, we propose a multiple association scheme where each HTC user associates to and activates multiple SCs to overcome the backhaul capacity constraints mainly encountered in the downlink. In addition, having more active cells allows for more MTC devices to be supported by the network. Using tools from stochastic geometry, we formulate a novel mathematical framework investigating the performance of HTC in both downlink and uplink as well as the uplink MTC. Stretched Exponential Path Loss (SEPL) model is considered to practically reflect the UDN environment. Extensive simulations were conducted to verify the accuracy of the mathematical analysis under different system parameters. Results show the existence of an optimum number of SCs to which an HTC user may connect under backhaul capacity constraints. Besides, the proposed multiple-association scheme improves the performance of MTC in terms of both ASE and density of supported devices. [ABSTRACT FROM AUTHOR]

Abstract Background Medullary thyroid carcinoma (MTC) is a rare subtype of thyroid cancer. Other than gain‐of‐function RET mutations, no other genetic, lifestyle or environmental risk associations have been established for MTC. Several case‐control studies and meta‐analysis have examined the risk association of different SNPs with MTC in different populations but with contradictory or inconclusive results. Methods In a large cohort of 438 Indian MTC cases and 489 gender and ethnicity matched healthy controls from 1000 genome project, a comprehensive risk association of 13 SNPs of three pathways—detoxification, cell cycle regulation and RET was performed along with meta‐analysis of RET SNPs. Results Multivariate logistic regression analysis identified a protective risk association of CDKN1ASer31Arg SNP with both hereditary (OR 0.26; 95% confidence interval [CI] 0.13‐0.55; P

Poupak Fallahi,1 Silvia Martina Ferrari,2 Giusy Elia,2 Francesca Ragusa,2 Sabrina Rosaria Paparo,2 Ilaria Ruffilli,2 Armando Patrizio,2 Gabriele Materazzi,3 Alessandro Antonelli21Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 2Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 3Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Pisa, ItalyCorrespondence: Alessandro AntonelliDepartment of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi, 10, Pisa I-56126, ItalyTel +39 05 099 2318Fax +39 05 099 3472Email alessandro.antonelli@med.unipi.itAbstract: Medullary thyroid cancers (MTCs) are neuroendocrine tumors, which secrete calcitonin and carcinoembryonic antigen, both of which can serve as tumor markers. Extensive and accurate surgical resection is the primary treatment for MTC, whereas the use of external beam radiotherapy is limited. Moreover, since MTC is derived from thyroid parafollicular cells or C cells, it is not responsive to either radioiodine or thyroid-stimulating hormone suppression, and therefore, they cannot be considered as treatment strategies. Traditional therapies for advanced or metastatic progressive medullary thyroid cancer (pMTC) are poorly effective. Among the new approaches tested in clinical trials, targeted chemotherapies with tyrosine kinase inhibitors (TKIs) are now available and they represent effective interventions for progressive disease, with additional investigational options emerging. This paper reviews the efficacy and safety of vandetanib in patients with a pMTC, as it has been shown to improve progression-free survival (30.5 vs 19.3 months in controls). Vandetanib is approved by the FDA and EMA for symptomatic or progressive MTC in patients with unresectable locally advanced or metastatic disease in adults, adolescents, and children older than 5 years. The most common adverse events in vandetanib-treated patients are diarrhea, rash, folliculitis, nausea, QTc prolongation, hypertension, and fatigue. More data are required to deepen our knowledge on molecular biology of tumor and host defense, with the aim to achieve better prognosis and higher quality of life for affected patients.Keywords: MTC, pediatric MTC, vandetanib, RET, VEGFR, AEs

Abstract Background Different pathogenic germline mutations in the RET oncogene are identified in MEN 2, a hereditary syndrome characterized by medullary thyroid carcinoma (MTC) and other endocrine tumors. Although genetic predisposition is recognized, not all RET mutation carriers will develop the disease during their lifetime or, likewise, RET mutation carriers belonging to the same family may present clinical heterogeneity. It has been suggested that a single germline mutation might not be sufficient for development of MEN 2-associated tumors and a somatic bi-allelic alteration might be required. Here we investigated the presence of somatic second hit mutation in the RET gene in MTC. Methods We integrated Multiplex Ligation-dependent Probe Amplification (MLPA) and whole exome sequencing (WES) to search for copy number alteration (CNA) in the RET gene in MTC samples and medullary thyroid cell lines (TT and MZ-CR-1). We next found reads spanning exon-exon boundaries on RET, an indicative of retrocopy. We subsequently searched for RET retrocopies in the human reference genome (GRCh37) and in the 1000 Genomes Project data, by looking for reads reporting joined exons in the RET locus or distinct genomic regions. To determine RET retrocopy specificity and recurrence, DNA isolated from sporadic and MEN 2-associated MTC (n = 37), peripheral blood (n = 3) and papillary thyroid carcinomas with RET fusion (n = 10) samples were tested using PCR-sequencing methodology. Results Through MLPA we have found evidence of CNA in the RET gene in MTC samples and MTC cell lines. WES analysis reinforced the presence of the CNA and hinted for a retroposed copy of RET not found in the human reference genome and 1.000 Genomes Project. Extended analysis confirmed the presence of a somatic MTC-related retrocopy of RET in both sporadic and hereditary tumors. We further unveiled a recurrent (28%) novel point mutation (p.G548 V) found exclusively in the retrocopy of RET. The mutation was also found in cDNA of mutated samples, suggesting it might be functional. Conclusion We here report a somatic specific RET retroposed copy in MTC samples and cell lines. Our results support the idea that generation of retrocopies in somatic cells is likely to contribute to MTC genesis and progression.

The machine-type communication (MTC) plays an essential role in the mobile network society and it has demonstrated its effectiveness to generate significant revenues for mobile network operators. The MTC has become the main communication paradigm for several emerging smart services, such as public safety, health care, industrial automation, drones/robotics, utilities, and transportation. The MTC requires a major model change to cope with the improvement in 5G and imposes various requirements on the enabling technology, such as ultra-reliability, low latency, and availability. The scheme that fulfills such requirements are called a mission-critical MTC (mcMTC). However, the mcMTC is still in the early-standardization phase of 5G new radio and it needs a lot of research efforts to be improved. This paper presents an extensive review and evaluations to highlight diverse challenges and future aspects of mcMTC on 5G-enabling technologies. A number of research opportunities from both academic communities and industrial partners are given as examples for encouragement purposes.

Jes Sloth Mathiesen,1,2 Jens Peter Kroustrup,3 Peter Vestergaard,3,4 Kirstine Stochholm,5,6 Per Løgstrup Poulsen,6 Åse Krogh Rasmussen,7 Ulla Feldt-Rasmussen,7 Sten Schytte,8 Stefano Christian Londero,8 Henrik Baymler Pedersen,9 Christoffer Holst Hahn,10 Jens Bentzen,11 Sören Möller,2,12 Mette Gaustadnes,13 Maria Rossing,14 Finn Cilius Nielsen,14 Kim Brixen,2 Anja Lisbeth Frederiksen,2,15 Christian Godballe1 On behalf of the Danish Thyroid Cancer Group (DATHYRCA) 1Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark; 2Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark; 4Steno Diabetes Center North Jutland, Aalborg, Denmark; 5Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Aarhus, Denmark; 6Center for Rare Diseases, Aarhus University Hospital, Aarhus, Denmark; 7Department of Medical Endocrinology, Copenhagen University Hospital, Copenhagen, Denmark; 8Department of ORL Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark; 9Department of ORL Head & Neck Surgery, Aalborg University Hospital, Aalborg, Denmark; 10Department of ORL Head & Neck Surgery, Copenhagen University Hospital, Copenhagen, Denmark; 11Department of Oncology, Herlev Hospital, Herlev, Denmark; 12Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark; 13Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; 14Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark; 15Department of Clinical Genetics, Odense University Hospital, Odense, Denmark Background: The completeness of REarranged during Transfection (RET) testing in patients with medullary thyroid carcinoma (MTC) was recently reported as 60%. However, the completeness on a population level is unknown. Similarly, it is unknown if the first Danish guidelines from 2002, recommending RET testing in all MTC patients, improved completeness in Denmark. We conducted a nationwide retrospective cohort study aiming to evaluate the completeness of RET testing in the Danish MTC cohort. Additionally, we aimed to assess the completeness before and after publication of the first Danish guidelines and characterize MTC patients who had not been tested.Methods: The study included 200 patients identified from the nationwide Danish MTC cohort 1997–2013. To identify RET tested MTC patients before December 31, 2014, the MTC cohort was cross-checked with the nationwide Danish RET cohort 1994–2014. To characterize MTC patients who had not been RET tested, we reviewed their medical records and compared them with MTC patients who had been tested.Results: Completeness of RET testing in the overall MTC cohort was 87% (95% CI: 0.81–0.91; 173/200). In the adjusted MTC cohort, after excluding patients diagnosed with hereditary MTC by screening, completeness was 83% (95% CI: 0.76–0.88; 131/158). Completeness was 88% (95% CI: 0.75–0.95; 42/48) and 81% (95% CI: 0.72–0.88) (89/110) before and after publication of the first Danish guidelines, respectively. Patients not RET tested had a higher median age at diagnosis compared to those RET tested. Median time to death was shorter in those not tested relative to those tested.Conclusion: The completeness of RET testing in MTC patients in Denmark seems to be higher than reported in other cohorts. No improvement in completeness was detected after publication of the first Danish guidelines. In addition, data indicate that advanced age and low life expectancy at MTC diagnosis may serve as prognostic indicators to identify patients having a higher likelihood of missing the compulsory RET test. Keywords: RET testing, medullary thyroid carcinoma, Denmark

There is a growing interest in the transition from 4-step random access to 2-step random access in machine-type communication (MTC), since 2-step random access is well-suited to short message delivery in various Internet of Things (IoT) applications. In this paper, we study a 2-step random access approach that uses code division multiple access (CDMA) to form multiple channels for data packet transmissions with a spreading factor less than the number of channels. As a result, the length of data transmission phase in 2-step random access can be shorter at the cost of multiuser interference. To see how the decrease of the length of data transmission phase can improve the spectral efficiency, we derive the throughput as well as the spectral efficiency. From the results of analysis, we can show that the 2-step CDMA-based random access approach can have a higher spectral efficiency than conventional 2-step approach with orthogonal channel allocations, which means that the performance of MTC can be improved by successfully transmitting more data packets per unit time using CDMA. This is also confirmed by simulation results. [ABSTRACT FROM AUTHOR]

Purpose: To develop a fast, quantitative 3D magnetization transfer contrast (MTC) framework based on an unsupervised learning scheme, which will provide baseline reference signals for CEST and nuclear Overhauser enhancement imaging. Methods: Pseudo‐randomized RF saturation parameters and relaxation delay times were applied in an MR fingerprinting framework to generate transient‐state signal evolutions for different MTC parameters. Prospectively compressed sensing–accelerated (four‐fold) MR fingerprinting images were acquired from 6 healthy volunteers at 3 T. A convolutional neural network framework in an unsupervised fashion was designed to solve an inverse problem of a two‐pool MTC Bloch equation, and was compared with a conventional Bloch equation–based fitting approach. The MTC images synthesized by the convolutional neural network architecture were used for amide proton transfer and nuclear Overhauser enhancement imaging as a reference baseline image. Results: The fully unsupervised learning scheme incorporated with the two‐pool exchange model learned a set of unique features that can describe the MTC–MR fingerprinting input, and allowed only small amounts of unlabeled data for training. The MTC parameter values estimated by the unsupervised learning method were in excellent agreement with values estimated by the conventional Bloch fitting approach, but dramatically reduced computation time by ~1000‐fold. Conclusion: Given the considerable time efficiency compared to conventional Bloch fitting, unsupervised learning‐based MTC–MR fingerprinting could be a powerful tool for quantitative MTC and CEST/nuclear Overhauser enhancement imaging. [ABSTRACT FROM AUTHOR]

Background: Preoperative diagnosis of medullary thyroid carcinoma (MTC) is often difficult, given the poor sensitivity of fine‐needle aspiration (FNA) cytology for MTC. This study investigates this issue and presents recommendations for improving preoperative diagnostic paradigms in MTC cases. Design/Method: Histopathologically confirmed MTC patients with preoperative cytologic assessment of index nodules were enrolled. FNA diagnosis, final pathology, and surgery details were collected. Results: Out of 71 patients, 49 (69%) were diagnosed by FNA as either definitive MTC (35, 49%) or suspected MTC (14, 20%) and 22 (31%) patients had no indication of MTC on FNA. Conclusion: In a tertiary‐care setting, one‐third of subjects had an FNA interpretation that did not suggest the possibility of MTC. The limitations of preoperative diagnosis are especially problematic for MTC as they can cause delayed or incomplete treatment. Additional testing is proposed to improve preoperative diagnosis and surgical care of MTC patients. [ABSTRACT FROM AUTHOR]

Semisolid magnetization transfer contrast (MTC) and chemical exchange saturation transfer (CEST) MRI based on MT phenomenon have shown potential to evaluate brain development, neurological, psychiatric, and neurodegenerative diseases. However, a qualitative MT ratio (MTR) metric commonly used in conventional MTC imaging is limited in the assessment of quantitative semisolid macromolecular proton exchange rates and concentrations. In addition, CEST signals measured by MTR asymmetry analysis are unavoidably contaminated by upfield nuclear Overhauser enhancement (NOE) signals of mobile and semisolid macromolecules. To address these issues, we developed an MTC-MR fingerprinting (MTC-MRF) technique to quantify tissue parameters, which further allows an estimation of accurate MTC signals at a certain CEST frequency offset. A pseudorandomized RF saturation scheme was used to generate unique MTC signal evolutions for different tissues and a supervised deep neural network was designed to extract tissue properties from measured MTC-MRF signals. Through detailed Bloch equation-based digital phantom and in vivo studies, we demonstrated that the MTC-MRF can quantify MTC characteristics with high accuracy and computational efficiency, compared to a conventional Bloch equation fitting approach, and provide baseline reference signals for CEST and NOE imaging. For validation, MTC-MRF images were synthesized using the tissue parameters estimated from the deep-learning method and compared with experimentally acquired MTC-MRF images as the reference standard. The proposed MTC-MRF framework can provide quantitative 3D MTC, CEST, and NOE imaging of the human brain within a clinically acceptable scan time.

In this paper, we report the design, synthesis and biological evaluation of a novel S-allyl-l-cysteine (SAC) and gallic acid conjugate S-(4-fluorobenzyl)-N-(3,4,5-trimethoxybenzoyl)-l-cysteinate (MTC). We evaluate the effects on ischemia-reperfusion-induced PC12 cells, primary neurons in neonatal rats, and cerebral ischemic neuronal damage in rats, and the results showed that MTC increased SOD, CAT, GPx activity and decreased LDH release. PI3K and p-AKT protein levels were significantly increased by activating PI3K/AKT pathway. Mitochondrial pro-apoptotic proteins Bax and Bim levels were reduced while anti-apoptotic protein Bcl-2 levels were increased. The levels of cleaved caspase-9 and cleaved caspase-3 were also reduced in the plasma. The endoplasmic reticulum stress (ERS) was decreased, which in turns the survival rate of nerve cells was increased, so that the ischemic injury of neurons was protected accordingly. MTC activated the MEK-ERK signaling pathway and promoted axonal regeneration in primary neurons of the neonatal rat. The pretreatment of MEK-ERK pathway inhibitor PD98059 and PI3K/AKT pathway inhibitor LY294002 partially attenuated the protective effect of MTC. Using a MCAO rat model indicated that MTC could reduce cerebral ischemia-reperfusion injury and decrease the expression of proinflammatory factors. The neuroprotective effect of MTC may be due to inhibition of the over-activation of the TREK-1 channel and reduction of the current density of the TREK1 channel. These results suggested that MTC has a protective effect on neuronal injury induced by ischemia reperfusion, so it may have the potential to become a new type of neuro-ischemic drug candidate.

Wireless networks beyond 5G will mostly be serving myriads of sensors and other machine-type communications (MTC), with each device having different requirements in respect to latency, error rate, energy consumption, spectral efficiency or other specifications. Multiple-input multiple-output (MIMO) systems remain a central technology towards 6G, and in cases where massive antenna arrays or cell-free networks are not possible to deploy and only moderately large antenna arrays are allowed, the detection problem at the base-station cannot rely on zero-forcing or matched filters and more complex detection schemes have to be used. The main challenge is to find low complexity, hardware feasible methods that are able to attain near optimal performance. Randomized algorithms based on Gibbs sampling (GS) were proven to perform very close to the optimal detection, even for moderately large antenna arrays, while yielding an acceptable number of operations. However, their performance is highly dependent on the chosen “temperature” parameter (TP). In this paper, we propose and study an optimized variant of the GS method, denoted by triple mixed GS, and where three distinct values for the TP are considered. The method exhibits faster convergence rates than the existing ones in the literature, hence requiring fewer iterations to achieve a target bit error rate. The proposed detector is suitable for symmetric large MIMO systems, however the proposed fixed complexity detector is highly suitable to spectrally efficient adaptively modulated MIMO (AM-MIMO) systems where different types of devices upload information at different bit rates or have different requirements regarding spectral efficiency. The proposed receiver is shown to attain quasi-optimal performance in both scenarios.

The relevant role of long non-coding RNAs (lncRNAs) in cancer is currently a matter of increasing interest. Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor (2-5% of all thyroid cancer) derived from the parafollicular C-cells which secrete calcitonin. About 75% of all medullary thyroid cancers are believed to be sporadic medullary thyroid cancer (sMTC), whereas the remaining 25% correspond to inherited cancer syndromes known as Multiple Endocrine Neoplasia type 2 (MEN2). MEN2 syndrome, with autosomal dominant inheritance is caused by germline gain of function mutations in RET proto-oncogene. To date no lncRNA has been associated to MEN2 syndrome and only two articles have been published relating long non-coding RNA (lncRNA) to MTC: the first one linked MALAT1 with sMTC and, in the other, our group determined some new lncRNAs in a small group of sMTC cases in fresh tissue (RMST, FTX, IPW, PRNCR1, ADAMTS9-AS2 and RMRP). The aim of the current study is to validate such novel lncRNAs previously described by our group by using a larger cohort of patients, in order to discern their potential role in the disease. Here we have tested three up-regulated (RMST, FTX, IPW) and one down-regulated (RMRP) lncRNAs in our samples (formalin fixed paraffin embedded tissues from twenty-one MEN2 and ten sMTC patients) by RT-qPCR analysis. The preliminary results reinforce the potential role of RMST, FTX, IPW and RMRP in the pathogenesis of MTC. [ABSTRACT FROM AUTHOR]

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Long-Term Evolution-Advanced (LTE-A) networks have been regarded as having great potential to support the Internet of Things (IoT). However, the high probability of preamble collisions when massive numbers of IoT devices try to access the network within a short period has become a significant problem. In this paper, we propose a new scheme to efficiently handle the initial access contention for massive numbers of IoT devices in LTE-A networks. The proposed scheme divides an entire preamble set into $k$ subgroups; then, contention resolution is performed in each subgroup independently in a parallel and pipelined manner. Simulation results show that our scheme leads to considerable improvement in terms of average access delay and standard deviation of access delays without increasing blocking probability. Moreover, utilization of preamble resources is greatly improved by reducing the number of random access slots, where only a few devices participate in preamble selection.

This paper focuses on edge-enabled cloud radio access network architecture to achieve ultra-reliable communication, a crucial enabler for supporting mission-critical machine-type communication networks. We propose coordinated multi-point transmission schemes taking advantage of diversity mechanisms in interference-limited downlink cellular networks. The network scenario comprises spatially distributed multiple remote radio heads (RRHs) that may cooperate through silencing, or by using more elaborated diversity strategies such as maximum ratio transmission or transmit antenna selection to serve user equipment in the ultra-reliable operation regime. We derive an exact closed-form expression for the outage probabilities and expected values of signal-to-interference ratio for silencing, transmit antenna selection and maximum ratio transmission schemes. We formulate rate control and energy efficiency under reliability constraints to test the performance and resource usage of the proposed schemes. Furthermore, we study the impact on average system sum throughput with throughput-reliability trade-off under cooperative communication. Extensive numerical analysis shows the feasibility of ultra-reliable communication by implementing diversity schemes with RRHs cooperation.

In this paper, we identify issues and possible solutions in the key area of large-scale antenna systems, also know as Massive Multiple Input Multiple Output (MIMO) systems. Additionally, we propose the use of Massive MIMO technology as a means to tackle the uplink mixed-service communication problem. Under the assumption of an available physical narrowband shared channel (PNSCH), the capacity of the MTC network and, in turn, that of the whole system, can be increased by grouping Machine-Type Communication (MTC) devices into clusters and letting each cluster share the same time-frequency physical resource blocks. We study the feasibility of applying sub-optimal linear detection to the problem of detecting a large number of MTC devices sharing the same time-frequency resources at the uplink of a base station (BS) equipped with a large number of antennas, M. In our study, we derive the achievable lower-bound rates for the studied sub-optimal linear detectors and show that the transmitted power of each MTC device can be reduced as M increases, which is a very important result for power-constrained MTC devices running on batteries. Our simulation results suggest that, as M is made progressively larger, the performance of sub-optimal linear detection methods approach the matched filter bound, also known as perfect interference-cancellation bound. [ABSTRACT FROM AUTHOR]

The People's Republic of China (PRC) is a world power that has repositioned itself in the international system and in this process has sought to re-signify and internationalize its ancient culture. The objective of this article is to understand the process of resignificance and internationalization of Traditional Chinese Medicine (TCM) as a central element of its culture, through the analysis of the strategic communication used by the Asian giant to show its use in the fight against the SARS epidemic and the COVID-19 pandemic. Chinese journalistic sources such as Xinhua, People's Daily and China Hoy are used, contrasted with other international agencies, as well as official sources like the White Paper on TCM and the document "Guidelines for using acupuncture and moxibustion to treat COVID-19" analyzed with a qualitative approach. It is proposed, at a hypothetical level, that Covid-19 pandemic has given new impetus to China's efforts to internationalize its traditional medicine, which it had already tried with the SARS epidemic in the Hu Jintao government. Through strategic communication, which emphasizes the positive effects of its use, it seeks to make it clear that, as stated by President Xi Jinping, TCM is a treasure of Chinese scientific heritage and therefore a sample of legacy of the Chinese civilization to the development of humankind in the "new era". [ABSTRACT FROM AUTHOR]