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This article highlights the importance of Air Traffic Control in ensuring the security and efficiency of international aviation operations. Traditional RADAR systems face limitations in power consumption, coverage, and accuracy, leading to the development of innovative solutions like the Automatic Dependent Surveillance-Broadcast (ADS-B) system. However, the open nature of ADS-B's unencrypted signals poses security challenges, allowing attackers to intercept and manipulate data. To address this, the paper emphasizes the need for symmetric authentication, which uses shared secret keys through schemes like Message Authentication Codes and block cipher encryption. The choice between these methods depends on factors such as security, performance, and usability. Symmetric authentication is a practical solution, requiring robust shared keys and careful encryption algorithm selection. The research underscores the need for secure ADS-B systems and the trade-offs required in designing authentication schemes. [ABSTRACT FROM AUTHOR]

After sport-related concussion (SRC), immediate access to a certified athletic trainer (AT) is important to ensure proper treatment. However, resource allocation and coverage may differ between male and female youth sports. To compare resource allocation between male and female sports in the following areas: (1) rates of immediate on-field evaluation by an AT at the time of injury, (2) time to general health care presentation, and (3) time to SRC clinic presentation. Retrospective cohort study. Regional sports concussion center. Athletes aged 14 to 18 years who presented to a regional sports concussion center from November 2017 to April 2022. The primary exposure of interest was sex (male or female). The primary outcome was immediate on-field evaluation by an AT (yes or no). Secondary outcomes included time to general health care and SRC clinic presentation. Descriptive statistics, χ2 analyses, and linear regressions were performed. Covariates included age, history of prior concussions, and statistically significant demographics. A total of 832 patients with SRC were included (age = 16.2 ± 1.2 years, 66.5% male). Female athletes had lower rates of attention-deficit/hyperactivity disorder (χ2 = 10.404, P =.001) and higher rates of anxiety and depression (χ2 = 12.891, P <.001) compared with male athletes. The average time to presentation to general health care and the SRC clinic did not differ between males and females, but AT on-field evaluation occurred more in male (40.3%) than female (32.3%) athletes (χ2 = 8.677, P =.013). Multivariable linear regression found that AT on-field evaluation was a significant predictor of time to general health care presentation (β = −.085, P =.015) but not SRC clinic presentation (β = −.055, P =.099). History of prior concussions was a significant predictor of time to initial health care contact (β =.083, P =.018). History of anxiety and depression (β =.136, P <.001) and initial evaluation by emergency department or urgent care (β =.305, P <.001) were significant predictors of delayed time to SRC clinic presentation. Among 832 concussed youth athletes, female athletes were evaluated less frequently by an AT immediately after injury. Furthermore, not being evaluated by an AT on field was significantly associated with a longer time to health care presentation. Future investigations should elucidate resource equity among male and female athletes. [ABSTRACT FROM AUTHOR]

Nowadays, the utilization of Flexible Alternating Current Transmission System (FACTS) devices remains a better alternative for improving Available Transfer Capability (ATC), and it further minimizes the system loss in aggressive electrical power systems. It could minimize the cost of the new transmission line construction and also enhance the utilization rate. This paper introduces a new optimization-assisted ATC enhancement model by determining the optimal placement and compensation level of a Thyristor Controlled Series Capacitor (TCSC) device. As a novelty, a unique Improved Sea Lion Optimization (I-SLnO) model is established, which is an improved form of the conventional Sea Lion Optimization (SLnO) model. The evaluation is performed in IEEE-14 & IEEE-39 test bus systems to analyze the effectiveness of the suggested approach in terms of convergence analysis, ATC enhancement, and so on. [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]

One of the most significant factors that has contributed to the development of the electrical market is the deregulation of electricity transmission systems. This process is aimed at creating efficient markets and ensuring that the electricity supply is distributed fairly. However, open access can lead to system overload and can clog the network. It is essential to quickly determine the availability of a transmission network's transfer capability during a time-consuming activity in the system. This paper presents a variety of AI techniques that can help identify ATC, including deep learning, natural language processing, and machine vision. This study explores various methods and approaches that can be used to forecast the congestion in the transmission network. It also reviews the literature and examines the outcomes of different AI techniques when it comes to calculating ATC. [ABSTRACT FROM AUTHOR]

Opinion statement: Anaplastic thyroid cancer presents formidable challenges, particularly in cases of recurrence or metastasis. Timely BRAF V600E testing is imperative at diagnosis, initially through immunohistochemistry, followed by comprehensive genomic profiling encompassing genes such as NTRK, RET, ALK, and assessment of tumor mutation burden (TMB). FDA-approved treatment options include dabrafenib and trametinib for patients with BRAF mutations, while those exhibiting high TMB may benefit from pembrolizumab. Further therapeutic decisions hinge upon mutational profile, urgency of response required, airway integrity, and access to targeted therapies There is growing use of immunotherapy for ATC based on published reports of activity, but currently there is no FDA approved agent for ATC. The off-label utilization of "precision medicine" combinations imposes a considerable financial strain, underscoring the necessity for further clinical trials to elucidate promising therapeutic avenues for this orphan disease. There is a pressing need for the development and support of clinical trials investigating genomically driven and immune-based therapies for anaplastic thyroid cancer. [ABSTRACT FROM AUTHOR]

Objective: To assess the changes in survival outcomes among patients with anaplastic thyroid carcinoma in the US over the past two decades. Methods: Surveillance, Epidemiology, and End Results (SEER) database research data were reviewed, and patients with anaplastic thyroid carcinoma, who were diagnosed from 2004 to 2020 were evaluated. Kaplan-Meier survival estimates were conducted to examine differences in overall survival between three year-of-diagnosis groups (2004 to 2010; 2011 to 2016; and 2017 to 2020). Multivariable Cox regression analysis was then performed to explore the factors affecting overall survival. Results: A total of 1804 patients with anaplastic thyroid carcinoma were included. Using Kaplan-Meier survival estimates, overall survival was better among patients diagnosed from 2017 to 2020 versus those diagnosed at earlier periods (P < 0.001). One-year survival estimates were 25% among patients diagnosed from 2017 to 2020 versus 15% for patients diagnosed from 2011 to 2016, and 19%, for patients diagnosed from 2004 to 2010. Using the multivariable Cox regression model, an earlier year of diagnosis was associated with worse overall survival compared to the diagnosis year 2017 to 2020 (HR for diagnosis 2004 to 2010 versus diagnosis 2017 to 2020: 1.170; 95% CI: 1.029 to 1.331, and HR for diagnosis 2011 to 2016 versus diagnosis 2017 to 2020: 1.251; 95% CI: 1.103 to 1.419). Conclusions: While anaplastic thyroid carcinoma remains a deadly cancer, survival seems to be improving for the last few years compared to earlier years. There is still additional work to be done to improve the outcomes of those patients. [ABSTRACT FROM AUTHOR]

The rapid development of instant lifestyles has significantly impacted the air transportation system. The air transportation system involves many parties, for example, facilities, infrastructure, and human resources. One of the parties that plays important role in human resources is the Air Traffic Controller (ATC). ATC playing a crucial role in coordinating air traffic and providing assistance to pilots. By seeing the importance of an ATC's duties, particularly in communicating with pilots, which requires them to use English as an international language in the world of flight, this research sought to identify the factors influencing the English language proficiency of ATC Officers at Sultan Hasanuddin Makassar International Airport. The research used interviews, documentation, and data analysis methods to gather and analyze data. The research's findings demonstrated that factors influencing the English language proficiency of ATC Officers at Sultan Hasanuddin Makassar International Airport are: a. Writing skills: 1) interest factors and 2) environmental factors. b. Listening skill: 1) interest factor. 2) vocabulary factor; 3) concentration factor; and 4) interest in the topic factor. c. Speaking Skill: 1) psychological factors and 2) grammatical factors. d. Reading Skill: 1) motivational factors. 2) language complexity factor; and 3) vocabulary factor. [ABSTRACT FROM AUTHOR]

Featured Application: Within the context of the Medical Informatics Initiative (MII) funded by the Federal Ministry of Research and Education (BMBF), German academic medicine constructs a nationally harmonized, joint infrastructure enabling secondary use of patient data from heterogeneous clinical IT sources. The semantic annotation of such data is a prerequisite for cross-site usage. The approach and software described in and published jointly with this manuscript may not only facilitate a more efficient semantic annotation process but also promote fully interoperable semantic representations by catalyzing convergent user decisions in the presence of non-uniqueness of annotation choices. The cross-institutional secondary use of medical data benefits from structured semantic annotation, which ideally enables the matching and merging of semantically related data items from different sources and sites. While numerous medical terminologies and ontologies, as well as some tooling, exist to support such annotation, cross-institutional data usage based on independently annotated datasets is challenging for multiple reasons: the annotation process is resource intensive and requires a combination of medical and technical expertise since it often requires judgment calls to resolve ambiguities resulting from the non-uniqueness of potential mappings to various levels of ontological hierarchies and relational and representational systems. The divergent resolution of such ambiguities can inhibit joint cross-institutional data usage based on semantic annotation since data items with related content from different sites will not be identifiable based on their respective annotations if different choices were made without further steps such as ontological inference, which is still an active area of research. We hypothesize that a collaborative approach to the semantic annotation of medical data can contribute to more resource-efficient and high-quality annotation by utilizing prior annotational choices of others to inform the annotation process, thus both speeding up the annotation itself and fostering a consensus approach to resolving annotational ambiguities by enabling annotators to discover and follow pre-existing annotational choices. Therefore, we performed a requirements analysis for such a collaborative approach, defined an annotation workflow based on the requirement analysis results, and implemented this workflow in a prototypical Collaborative Annotation Tool (CoAT). We then evaluated its usability and present first inter-institutional experiences with this novel approach to promote practically relevant interoperability driven by use of standardized ontologies. In both single-site usability evaluation and the first inter-institutional application, the CoAT showed potential to improve both annotation efficiency and quality by seamlessly integrating collaboratively generated annotation information into the annotation workflow, warranting further development and evaluation of the proposed innovative approach. [ABSTRACT FROM AUTHOR]

Recently, artificial intelligence and data science have witnessed dramatic progress and rapid growth, especially Automatic Speech Recognition (ASR) technology based on Hidden Markov Models (HMMs) and Deep Neural Networks (DNNs). Consequently, new end-to-end Recurrent Neural Network (RNN) toolkits were developed with higher speed and accuracy that can often achieve a Word Error Rate (WER) below 10%. These toolkits can nowadays be deployed, for instance, within aircraft cockpits and Air Traffic Control (ATC) systems in order to identify aircraft and display recognized voice messages related to flight data, especially for airports not equipped with radar. Hence, the performance of air traffic controllers and pilots can ultimately be improved by reducing workload and stress and enforcing safety standards. Our experiment conducted at Tangier's International Airport ATC aimed to build an ASR model that is able to recognize aircraft call signs in a fast and accurate way. The acoustic and linguistic models were trained on the Ibn Battouta Speech Corpus (IBSC), resulting in an unprecedented speech dataset with approved transcription that includes real weather aerodrome observation data and flight information with a call sign captured by an ADS-B receiver. All of these data were synchronized with voice recordings in a structured format. We calculated the WER to evaluate the model's accuracy and compared different methods of dataset training for model building and adaptation. Despite the high interference in the VHF radio communication channel and fast-speaking conditions that increased the WER level to 20%, our standalone and low-cost ASR system with a trained RNN model, supported by the Deep Speech toolkit, was able to achieve call sign detection rate scores up to 96% in air traffic controller messages and 90% in pilot messages while displaying related flight information from ADS-B data using the Fuzzy string-matching algorithm. [ABSTRACT FROM AUTHOR]

The article provides an overview of train control and protection systems used on high-speed railways in given European and Asia-Pacific region countries. Particular attention is paid to currently operated and future means for the transmission of safetyrelated information to the trains. [ABSTRACT FROM AUTHOR]

Background: CDK4/6 inhibitors (CDK4/6i) have been established as standard treatment against advanced Estrogen Receptor-positive breast cancers. These drugs are being tested against several cancers, including in combinations with other therapies. We identified the T172-phosphorylation of CDK4 as the step determining its activity, retinoblastoma protein (RB) inactivation, cell cycle commitment and sensitivity to CDK4/6i. Poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinomas, the latter considered one of the most lethal human malignancies, represent major clinical challenges. Several molecular evidence suggest that CDK4/6i could be considered for treating these advanced thyroid cancers. Methods: We analyzed by two-dimensional gel electrophoresis the CDK4 modification profile and the presence of T172-phosphorylated CDK4 in a collection of 98 fresh-frozen tissues and in 21 cell lines. A sub-cohort of samples was characterized by RNA sequencing and immunohistochemistry. Sensitivity to CDK4/6i (palbociclib and abemaciclib) was assessed by BrdU incorporation/viability assays. Treatment of cell lines with CDK4/6i and combination with BRAF/MEK inhibitors (dabrafenib/trametinib) was comprehensively evaluated by western blot, characterization of immunoprecipitated CDK4 and CDK2 complexes and clonogenic assays. Results: CDK4 phosphorylation was detected in all well-differentiated thyroid carcinomas (n=29), 19/20 PDTC, 16/23 ATC and 18/21 thyroid cancer cell lines, including 11 ATC-derived ones. Tumors and cell lines without phosphorylated CDK4 presented very high p16CDKN2A levels, which were associated with proliferative activity. Absence of CDK4 phosphorylation in cell lines was associated with CDK4/6i insensitivity. RB1 defects (the primary cause of intrinsic CDK4/6i resistance) were not found in 5/7 tumors without detectable phosphorylated CDK4. A previously developed 11-gene expression signature identified the likely unresponsive tumors, lacking CDK4 phosphorylation. In cell lines, palbociclib synergized with dabrafenib/trametinib by completely and permanently arresting proliferation. These combinations prevented resistance mechanisms induced by palbociclib, most notably Cyclin E1-CDK2 activation and a paradoxical stabilization of phosphorylated CDK4 complexes. Conclusion: Our study supports further clinical evaluation of CDK4/6i and their combination with anti-BRAF/MEK therapies as a novel effective treatment against advanced thyroid tumors. Moreover, the complementary use of our 11 genes predictor with p16/KI67 evaluation could represent a prompt tool for recognizing the intrinsically CDK4/6i insensitive patients, who are potentially better candidates to immediate chemotherapy. [ABSTRACT FROM AUTHOR]

Flexible AC transmission systems (FACTS) are a viable way to improve power system performance because of the rapid advancement of power electronic technology. Improvement of dynamic and transient stability, voltage control, voltage stability improvement, power factor correction, enhancement of 'power profile, an increase in the transmission line's power transfer capabilities, and loss alleviation are all FACTS device applications in power system networks. But, optimal placement and sizing of the FACTS devices may cause the system to attain the objective at a reasonable cost. Hence, to find out the optimal location and compensation level of the FACTS device, an improved version of the Genetic algorithm (GA) had been introduced in the preceding version of this paper. Genetic Algorithm with Dual Mutation Probability (GADMP) was the term given to the improved version of GA since it included dual probabilities for the mutation operator. To ensure a fair comparison between the algorithms on FACTS localization and sizing, this paper subjects the GADMP and Traditional GA (TGA) to rigorous experimental investigation. Simulation experiments have been performed using three benchmark bus systems, IEEE 24 RTS, IEEE 30, and IEEE 57 to verify the performance of the adopted scheme. [ABSTRACT FROM AUTHOR]

In this paper, uncertainty is included in the extended framework of global air traffic both through the action of the wind and through the incomplete determination of the aerodynamic coefficients and the inevitable imprecision involved in the execution of ATC instructions. In order to study the air conflict detection process in detail, the possibility of potential conflicts must be evaluated, considering the current state of the international airspace, and taking into account the uncertainty in calculating the future position of the aircraft. A mathematical model for predicting potential aerial conflicts is necessary for this objective. In a probabilistic framework, the mathematical model thus created could be either an empirical distribution of future aircraft positions in space or a dynamic model, such as a stochastic differential equation, that describes the movement of the aircraft and implicitly defines a distribution for the position’s future of the aircraft/ future aircraft positions. Based on the prediction model, aircraft flight safety matrices can be evaluated. The mathematical methods applied in the Detection and Resolution of Air Traffic Conflicts - CDR involve a wide range of fields, but also the appropriate modeling of physical systems such as airplanes, the codification of mathematical algorithms for conflict detection, as well as the properly applied procedures for resolving potential air conflicts.

This study presents the flight plan data related to aircraft performance and is tested against the aircraft performance database. The Significant Meteorological Information Reports - SIGMET will be generated by the system according to the selected turbulence areas by attaching different AIS data to an exercise that can change the simulation objectives. The exercise must be assigned to one or more courses to be able to attach meteorological data when viewing a data recording; changes can be made to the aircraft as in a normal exercise run, while the other instructions will be loaded from the recorded data file. A data recording is airspace dependent, changing the airspace can make the data recording fail during playback. Video Recording is only available for the RADAR Simulator. A video recording can be made at any time during a simulation session; a data recording can be selected only at the beginning of the simulation session and cannot be started during the simulation session; if the simulator is integrated with the Voice Communication System and the audio channels, then a sound recording window will automatically pop-up. For this study, an ideal case, for the configuration presentation we will assume that the 3D Tower Simulator is composed of 4 LCD/Projectors to create the out-of-the-window view, 180 degrees, 2 Pseudo-Pilots, and 1 Supervisor/FEEDER Position. The 4 image generators will be provided by SIM01, SIM02, SIM03, and SIM04. The Pseudo-Pilots positions will be provided by SIM05 and SIM06. The Supervisor/Feeder Position will be provided by SIM07. For the Tower Controller Working Positions, we will provide the following information displays: DE – Flight Data Equipment/Clearance Delivery, MET – Meteorological Information, LCP –Lights Control Panel, and a RADAR Image. Station SIM08 will be used. Stations SIM01, SIM02, SIM03, and SIM04 are equipped with one large LCD Display or a Projector; Stations SIM05 and SIM07 are equipped with 2 monitors, one for the RADAR Image and the other one for the bird-eye view over the airport; Station SIM06 is equipped with one monitor for the bird-eye view over the airport; Station SIM08 is equipped with 4 monitors providing all necessary information for the Tower Controller Working Positions. SIM07, as presented above, is the FEEDER/SUPERVISOR for the RADAR Simulator, the approach sector is “TMA” and the application will be started on the second monitor, the first monitor is used for the 3D Tower Simulator. SIM07 is also FEEDER/SUPERVIZOR for the 3D Tower Simulator, the station function will be “3DTWR” and the sector will be the previously created 3D Tower configuration, “TOWER”. On SIM08 will add a RADAR Image for the Tower Controller Working Positions, sector is “TMA”, the application will be started on monitor 4, and the station function is “TWR”. Usually, for an aircraft departing from an airport inside an approach sector, the first owner will be the tower until passing the maximum flight level/ altitude for the tower, the second owner will be the approach sector and the third owner will be the en-route sector. In this case, the tower sector has power over the approach sector, and the en-route sector, the approach sector has power over the en-route sector. The outside FIR sectors will be used in the determination of the next en-route sector, for coordination purposes. If the VFR points do not appear on the RADAR Map after the “DRAW” button has been pushed, use the “MAP MENU” – “VFR” button. The aircraft performance database is not airspace structure dependent. When a new airspace structure is created the aircraft performance database will remain unchanged.

BackgroundCDK4/6 inhibitors (CDK4/6i) have been established as standard treatment against advanced Estrogen Receptor-positive breast cancers. These drugs are being tested against several cancers, including in combinations with other therapies. We identified the T172-phosphorylation of CDK4 as the step determining its activity, retinoblastoma protein (RB) inactivation, cell cycle commitment and sensitivity to CDK4/6i. Poorly differentiated (PDTC) and anaplastic (ATC) thyroid carcinomas, the latter considered one of the most lethal human malignancies, represent major clinical challenges. Several molecular evidence suggest that CDK4/6i could be considered for treating these advanced thyroid cancers.MethodsWe analyzed by two-dimensional gel electrophoresis the CDK4 modification profile and the presence of T172-phosphorylated CDK4 in a collection of 98 fresh-frozen tissues and in 21 cell lines. A sub-cohort of samples was characterized by RNA sequencing and immunohistochemistry. Sensitivity to CDK4/6i (palbociclib and abemaciclib) was assessed by BrdU incorporation/viability assays. Treatment of cell lines with CDK4/6i and combination with BRAF/MEK inhibitors (dabrafenib/trametinib) was comprehensively evaluated by western blot, characterization of immunoprecipitated CDK4 and CDK2 complexes and clonogenic assays.ResultsCDK4 phosphorylation was detected in all well-differentiated thyroid carcinomas (n=29), 19/20 PDTC, 16/23 ATC and 18/21 thyroid cancer cell lines, including 11 ATC-derived ones. Tumors and cell lines without phosphorylated CDK4 presented very high p16CDKN2A levels, which were associated with proliferative activity. Absence of CDK4 phosphorylation in cell lines was associated with CDK4/6i insensitivity. RB1 defects (the primary cause of intrinsic CDK4/6i resistance) were not found in 5/7 tumors without detectable phosphorylated CDK4. A previously developed 11-gene expression signature identified the likely unresponsive tumors, lacking CDK4 phosphorylation. In cell lines, palbociclib synergized with dabrafenib/trametinib by completely and permanently arresting proliferation. These combinations prevented resistance mechanisms induced by palbociclib, most notably Cyclin E1-CDK2 activation and a paradoxical stabilization of phosphorylated CDK4 complexes.ConclusionOur study supports further clinical evaluation of CDK4/6i and their combination with anti-BRAF/MEK therapies as a novel effective treatment against advanced thyroid tumors. Moreover, the complementary use of our 11 genes predictor with p16/KI67 evaluation could represent a prompt tool for recognizing the intrinsically CDK4/6i insensitive patients, who are potentially better candidates to immediate chemotherapy.

The behavior of four drugs from the family of nucleoside analog reverse-transcriptase inhibitors (zalcitabine, stavudine, didanosine, and apricitabine) in a membrane environment was traced using molecular dynamics simulations. The simulation models included bilayers and monolayers composed of POPC and POPG phospholipids. It was demonstrated that the drugs have a higher affinity towards POPG membranes than POPC membranes due to attractive long-range electrostatic interactions. The results obtained for monolayers were consistent with those obtained for bilayers. The drugs accumulated in the phospholipid polar headgroup region. Two adsorption modes were distinguished. They differed in the degree of penetration of the hydrophilic headgroup region. Hydrogen bonds between drug molecules and phospholipid heads were responsible for adsorption. It was shown that apricitabine penetrated the hydrophilic part of the POPC and POPG membranes more effectively than the other drugs. Van der Waals interactions between S atoms and lipids were responsible for this. [ABSTRACT FROM AUTHOR]

Observational research utilizes patient information from many disparate databases worldwide. To be able to systematically analyze data and compare the results of such research studies, information about exposure to drugs or classes of drugs needs to be harmonized across these data. The NLM's RxNorm drug terminology and WHO's ATC classification serve these needs but are currently not satisfactorily combined into a common system. Creating such system is hampered by a number of challenges, resulting from different approaches to representing attributes of drugs and ontological rules. Here, we present a combined ATC- RxNorm drug hierarchy, allowing to use ATC classes for retrieval of drug information in large scale observational data. We present the heuristic for maintaining this resource and evaluate it in a real world database containing drug and drug classification information. [ABSTRACT FROM AUTHOR]

Purpose: Anaplastic thyroid carcinoma (ATC) is an orphan disease with a fatal outcome. Surgery to the primary tumor in metastatic ATC is controversial. Determination of specific surgical techniques may help facilitate local control and, hence, beneficial overall and disease-specific survival. Methods: Using individualized patient data derived from our systematic review of literature and our single center study (n = 123), conducting a Surveillance, Epidemiology, and End Results register (SEER)-based study (n = 617) we evaluated surgery, its combination with systemic and local therapies in metastatic ATC. Results: Pooled cohort study showed surgery (p < 0.001), RT ≥ 30 Gy (p < 0.001), ChT (p < 0.001) and multimodal treatment (p = 0.014) to result in improved OS univariately. In the multivariate analysis, surgery (1.997 [1.162–3.433], p = 0.012) and RT ≥ 30 Gy (1.877 [1.232–2.843], p = 0.012) were independent predictors for OS. In SEER-based study of patients undergoing any tumor-directed treatment (n = 445) total thyroidectomy (p = 0.031), administration of ChT (p = 0.007), RT (p < 0.001), combination of surgery and RT ± ChT (p < 0.001) and multimodal treatment (p < 0.001) correlated with an improved DSS univariately. On the multivariate analysis, debulking surgery was an independent predictor for a worse outcome (HR 0.535, 95%CI 0.332–0.862, p = 0.010), whereas RT administration correlated with a longer DSS (HR 2.316, 95%CI 1.362–3.939, p = 0.002). Among operated patients from SEER register total thyroidectomy (p = 0.031), ChT (p = 0.007), RT (p < 0.001), combination of surgery and RT ± ChT (p < 0.001) and multimodal treatment (p < 0.001) correlated with an improved DSS in the univariate analysis, whereas debulking surgery was inversely correlated with the DSS (p < 0.001). On the multivariate analysis, debulking surgery was an independent predictor for a worse DSS (HR 0.535, 95%CI 0.332–0.862, p = 0.010), whilst RT administration correlated with a longer DSS (HR 2.316, 95%CI 1.362–3.939, p = 0.002). Conclusions: Surgery to the primary tumor with the aim of R0/R1 resection, but not debulking, is associated with a significant OS and DSS benefit even in systemically metastasized disease. [ABSTRACT FROM AUTHOR]

Introduction: According to the ATC system of drug classification, group R06 includes H1 antihistamines for systemic use, which are divided into drug groups of the 1st and 2nd generation. Aim: Since there are no national guidelines in Serbia, for treating most allergic diseases, our aim was to compare pharmaceutical products and treatment strategies of systemic antihistamines use in Serbia with that in the Nordic countries that have been recognized as countries with good pharmacoeconomic practice. Material and methods: Data on drug consumption in the Republic of Serbia, the Kingdom of Norway, the Republic of Finland, and the Kingdom of Denmark were collected from the publications of national drug regulatory agencies for the period from 2009 to 2019. Results: Loratadine was the most commonly consumed antihistamine in Serbia in 2009, making 72.32% of the total consumption of drugs in the R06 group. During observed period the consumption of cetirizine increased 21.8 times, levocetirizine increased 36.6 times, desloratadine increased 2.6 times. The most commonly used antihistamines in Serbia in 2016 were: loratadine with 34.86%, followed by desloratadine with 18.70%, and ketotifen with 14.52% of the total consumption of drugs in the R06 group. In 2019, the most commonly used antihistamines were levocetirizine, loratadine, desloratadine and cetirizine. In Norway as well as in Finland and Denmark, during all eleven years (2009-2019) cetirizine was the most consumed antihistamine with mild increase trend in consumption of 1.5-5.74-20.5%. The second most consumed antihistamine in Norway and in Finland was desloratadine and in Denmark, fexofenadine. A decrease in consumption was recorded in case of loratadine in all three Scandinavian countries. First generation antihistamines promethazine and dexchlorpheniramine showed a continuous but minimal downward trend. Conclusion: Unlike Norway, Sweden and Denmark, in Serbia in the last 11 years, the consumption trends of antihistamines have not been consistent and seem to depend on various factors such as price.

To explore asthma control in patients undergoing pharmacotherapy on studies in the last 20 years in Brazil. Asthma is a chronic airway inflammation disease with a high prevalence worldwide. Even with a variety of drug treatment improvements, attaining asthma control is challenging, since it should have a personalized approach. In Brazil, studies on the prevalence of asthma control are scarce and usually from a small sample size. A systematic review was performed to assess asthma control in Brazilian population. Terms related to "asthma", "asthma control" and "Brazil" were used in the search strategies in PubMed, BVSalud, Embase and Cochrane Library, including Brazilian Journal of Allergy and Immunology as data sources. A narrative synthesis was performed to report key outcome. In total, 23 studies were included. Most of them were conducted in the Southeastern and Northeast regions, in a short duration. Pediatric and non-pediatric population were assessed, with a higher proportion of female. In pediatric population, those with poorly controlled asthma usually had severe or persistent disease. In elderly, an increased asthma severity was found, although proper treatment might be effective. Most studies (70%) also described exacerbations, hospitalizations (48%), quality of life (39%), and emergency visits (30%). Despite heterogeneity of outcomes and population, studies show an important prevalence of uncontrolled asthma even in patients being treated, with better disease control with treatment improvements. Studies in Brazil have shown that asthma control remains a challenge and there is still a need for improvement on disease management. [ABSTRACT FROM AUTHOR]

This study presents the flight plan data related to aircraft performance and is tested against the aircraft performance database. The Significant Meteorological Information Reports - SIGMET will be generated by the system according to the selected turbulence areas by attaching different AIS data to an exercise that can change the simulation objectives. The exercise must be assigned to one or more courses to be able to attach meteorological data when viewing a data recording; changes can be made to the aircraft as in a normal exercise run, while the other instructions will be loaded from the recorded data file. A data recording is airspace dependent, changing the airspace can make the data recording fail during playback. Video Recording is only available for the RADAR Simulator. A video recording can be made at any time during a simulation session; a data recording can be selected only at the beginning of the simulation session and cannot be started during the simulation session; if the simulator is integrated with the Voice Communication System and the audio channels, then a sound recording window will automatically pop-up. For this study, an ideal case, for the configuration presentation we will assume that the 3D Tower Simulator is composed of 4 LCD/Projectors to create the out-of-thewindow view, 180 degrees, 2 Pseudo-Pilots, and 1 Supervisor/FEEDER Position. The 4 image generators will be provided by SIM01, SIM02, SIM03, and SIM04. The Pseudo-Pilots positions will be provided by SIM05 and SIM06. The Supervisor/Feeder Position will be provided by SIM07. For the Tower Controller Working Positions, we will provide the following information displays: DE - Flight Data Equipment/Clearance Delivery, MET - Meteorological Information, LCP -Lights Control Panel, and a RADAR Image. Station SIM08 will be used. Stations SIM01, SIM02, SIM03, and SIM04 are equipped with one large LCD Display or a Projector; Stations SIM05 and SIM07 are equipped with 2 monitors, one for the RADAR Image and the other one for the bird-eye view over the airport; Station SIM06 is equipped with one monitor for the bird-eye view over the airport; Station SIM08 is equipped with 4 monitors providing all necessary information for the Tower Controller Working Positions. SIM07, as presented above, is the FEEDER/SUPERVISOR for the RADAR Simulator, the approach sector is "TMA" and the application will be started on the second monitor, the first monitor is used for the 3D Tower Simulator. SIM07 is also FEEDER/SUPERVIZOR for the 3D Tower Simulator, the station function will be "3DTWR" and the sector will be the previously created 3D Tower configuration, "TOWER". On SIM08 will add a RADAR Image for the Tower Controller Working Positions, sector is "TMA", the application will be started on monitor 4, and the station function is "TWR". Usually, for an aircraft departing from an airport inside an approach sector, the first owner will be the tower until passing the maximum flight level/altitude for the tower, the second owner will be the approach sector and the third owner will be the en-route sector. In this case, the tower sector has power over the approach sector, and the en-route sector, the approach sector has power over the en-route sector. The outside FIR sectors will be used in the determination of the next en-route sector, for coordination purposes. If the VFR points do not appear on the RADAR Map after the "DRAW" button has been pushed, use the "MAP MENU" - "VFR" button. The aircraft performance database is not airspace structure dependent. When a new airspace structure is created the aircraft performance database will remain unchanged. [ABSTRACT FROM AUTHOR]

In this paper, uncertainty is included in the extended framework of global air traffic both through the action of the wind and through the incomplete determination of the aerodynamic coefficients and the inevitable imprecision involved in the execution of ATC instructions. In order to study the air conflict detection process in detail, the possibility of potential conflicts must be evaluated, considering the current state of the international airspace, and taking into account the uncertainty in calculating the future position of the aircraft. A mathematical model for predicting potential aerial conflicts is necessary for this objective. In a probabilistic framework, the mathematical model thus created could be either an empirical distribution of future aircraft positions in space or a dynamic model, such as a stochastic differential equation, that describes the movement of the aircraft and implicitly defines a distribution for the position's future of the aircraft/future aircraft positions. Based on the prediction model, aircraft flight safety matrices can be evaluated. The mathematical methods applied in the Detection and Resolution of Air Traffic Conflicts - CDR involve a wide range of fields, but also the appropriate modeling of physical systems such as airplanes, the codification of mathematical algorithms for conflict detection, as well as the properly applied procedures for resolving potential air conflicts. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid cancer (ATC) is the most aggressive type of thyroid cancer. This study aimed to identify specific long noncoding RNAs (lncRNAs) associated with ATC, and further investigated their biological functions and molecular mechanism underlying regulation of malignancy in ATC. We searched for lncRNAs associated with dedifferentiation and screened out specific lncRNAs significantly deregulated in ATC by using transcriptome data of dedifferentiation cancers from Fudan University Shanghai Cancer Center (FUSCC) and the Gene Expression Omnibus (GEO) database. The above lncRNAs were analyzed to identify a potential biomarker in thyroid cancer patients from the FUSCC, GEO, and The Cancer Genome Atlas, which was then investigated for its functional roles and molecular mechanism in ATC in vitro. The clinicopathological association analyses revealed that LINC00886 expression was significantly correlated with dedifferentiation and suppressed in ATC. In vitro, LINC00886 was confirmed to negatively regulate cell proliferation, and cell migration and invasion of ATC. LINC00886 physically interacted with protein kinase R (PKR) and affected its stability through the ubiquitin/proteasome-dependent degradation pathway in the ATC cell. Decreased PKR caused by downregulation of LINC00886 enhanced the activity of eukaryotic initiation factor 2α (eIF2α) via reducing phosphorylation of eIF2α and thus promoted protein synthesis to maintain ATC malignancy. Our findings identify LINC00886 as a novel biomarker of thyroid cancer and suggest that LINC00886/PKR/eIF2α signaling is a potential therapeutic target in ATC. [ABSTRACT FROM AUTHOR]

Recently, artificial intelligence and data science have witnessed dramatic progress and rapid growth, especially Automatic Speech Recognition (ASR) technology based on Hidden Markov Models (HMMs) and Deep Neural Networks (DNNs). Consequently, new end-to-end Recurrent Neural Network (RNN) toolkits were developed with higher speed and accuracy that can often achieve a Word Error Rate (WER) below 10%. These toolkits can nowadays be deployed, for instance, within aircraft cockpits and Air Traffic Control (ATC) systems in order to identify aircraft and display recognized voice messages related to flight data, especially for airports not equipped with radar. Hence, the performance of air traffic controllers and pilots can ultimately be improved by reducing workload and stress and enforcing safety standards. Our experiment conducted at Tangier’s International Airport ATC aimed to build an ASR model that is able to recognize aircraft call signs in a fast and accurate way. The acoustic and linguistic models were trained on the Ibn Battouta Speech Corpus (IBSC), resulting in an unprecedented speech dataset with approved transcription that includes real weather aerodrome observation data and flight information with a call sign captured by an ADS-B receiver. All of these data were synchronized with voice recordings in a structured format. We calculated the WER to evaluate the model’s accuracy and compared different methods of dataset training for model building and adaptation. Despite the high interference in the VHF radio communication channel and fast-speaking conditions that increased the WER level to 20%, our standalone and low-cost ASR system with a trained RNN model, supported by the Deep Speech toolkit, was able to achieve call sign detection rate scores up to 96% in air traffic controller messages and 90% in pilot messages while displaying related flight information from ADS-B data using the Fuzzy string-matching algorithm.

Automatic dependent surveillance-broadcast (ADS-B) is a key air surveillance technology and a critical component of next-generation air transportation systems. It significantly simplifies aircraft surveillance technology and improves airborne traffic situational awareness. Many types of mobile cockpit information systems (MCISs) are based on ADS-B technology. MCIS gives pilots the flight and traffic-related information they need. MCIS has two parts: an ADS-B transceiver and an electronic flight bag (EFB) application. The ADS-B transceivers transmit and receive the ADS-B radio signals while the EFB applications hosted on mobile phones display the data. Because they are cheap, lightweight, and easy to install, MCISs became very popular. However, due to the lack of basic security measures, ADS-B technology is vulnerable to cyberattacks, which makes the MCIS inherently exposed to attacks. Attacks are even more likely for the MCIS, because they are power, memory, and computationally constrained. This study explores the cybersecurity posture of various MCIS setups for both types of ADS-B technology: 1090ES and UAT978. Total six portable MCIS devices and 21 EFB applications were tested against radio-link-based attacks by transmission-capable software-defined radio (SDR). Packet-level denial of service (DoS) attacks affected approximately 63% and 37% of 1090ES and UAT978 setups, respectively, while many of them experienced a system crash. Our experiments show that DoS attacks on the reception could meaningfully reduce transmission capacity. Our coordinated attack and fuzz tests also reported worrying issues on the MCIS. The consistency of our results on a very broad range of hardware and software configurations indicate the reliability of our proposed methodology as well as the effectiveness and efficiency of our platform.

Aims: Automated checks for medication‐related problems have become a cornerstone of medication safety. In many clinical settings medication checks remain confined to drug–drug interactions because only medication data are available in an adequately coded form, leaving possible contraindicated drug–disease combinations unaccounted for. Therefore, we devised algorithms that identify frequently contraindicated diagnoses based on medication patterns related to these diagnoses. Methods: We identified drugs that are associated with diseases constituting common contraindications based on their exclusive use for these conditions (such as allopurinol for gout or salbutamol for bronchial obstruction). Expert‐based and machine learning algorithms were developed to identify diagnoses based on highly specific medication patterns. The applicability, sensitivity and specificity of the approach were assessed by using an anonymized real‐life sample of medication and diagnosis data excerpts from 3506 discharge records of geriatric patients. Results: Depending on the algorithm, the desired focus (i.e., sensitivity vs. specificity) and the disease, we were able to identify the diagnoses gout, epilepsy, coronary artery disease, congestive heart failure and bronchial obstruction with a specificity of 44.0–99.8% (95% CI 41.7–100.0%) and a sensitivity of 3.8–83.1% (95% CI 1.0–86.1%). Using only medication data, we were able to identify 123 (51.3%) of 240 contraindications identified by experts with access to medication data and diagnoses. Conclusion: This study provides a proof of principle that some key diagnosis‐related contraindications can be identified based on a patient's medication data alone, while others cannot be identified. This approach offers new opportunities to analyse drug–disease contraindications in community pharmacy or clinical routine data. [ABSTRACT FROM AUTHOR]

Robots operating with humans in highly dynamic environments need not only react to moving persons and objects but also to anticipate and adhere to patterns of motion of dynamic agents in their environment. Currently, robotic systems use information about dynamics locally, through tracking and predicting motion within their direct perceptual range. This limits robots to reactive response to observed motion and to short-term predictions in their immediate vicinity. In this paper, we explore how maps of dynamics (MoDs) that provide information about motion patterns outside of the direct perceptual range of the robot can be used in motion planning to improve the behaviour of a robot in a dynamic environment. We formulate cost functions for four MoD representations to be used in any optimizing motion planning framework. Further, to evaluate the performance gain through using MoDs in motion planning, we design objective metrics, and we introduce a simulation framework for rapid benchmarking. We find that planners that utilize MoDs waste less time waiting for pedestrians, compared to planners that use geometric information alone. In particular, planners utilizing both intensity (proportion of observations at a grid cell where a dynamic entity was detected) and direction information have better task execution efficiency.

The behavior of four drugs from the family of nucleoside analog reverse-transcriptase inhibitors (zalcitabine, stavudine, didanosine, and apricitabine) in a membrane environment was traced using molecular dynamics simulations. The simulation models included bilayers and monolayers composed of POPC and POPG phospholipids. It was demonstrated that the drugs have a higher affinity towards POPG membranes than POPC membranes due to attractive long-range electrostatic interactions. The results obtained for monolayers were consistent with those obtained for bilayers. The drugs accumulated in the phospholipid polar headgroup region. Two adsorption modes were distinguished. They differed in the degree of penetration of the hydrophilic headgroup region. Hydrogen bonds between drug molecules and phospholipid heads were responsible for adsorption. It was shown that apricitabine penetrated the hydrophilic part of the POPC and POPG membranes more effectively than the other drugs. Van der Waals interactions between S atoms and lipids were responsible for this.

The practical computations of enhancing available transfer capability (ATC) are evolving in the recent times. Most of the presently available techniques for enhancing ATC are being implemented; however, in many cases, they do not consider the impact of communications taking place in between the "power transfers, loop flows, non‐linearities, operating policies, and most importantly voltage collapse blackouts," respectively. Thus, the current research work aims to introduce a new hybrid method to solve the chaos in ATC in power system. The thyristor‐controlled series compensation (TCSC) that belongs to series flexible alternating current transmission system device is utilized for enhancing ATC. The introduced algorithm is termed as Lion Updated Moth Flame Optimization (LU‐MFO) to select the corresponding line for TCSC device to be connected. [ABSTRACT FROM AUTHOR]

This study provides a systematic synthesis of empirical research on mental workload (MWL) in air traffic control (ATC). MWL is a key concept in research on innovative technologies, because the assessment of MWL is crucial to the evaluation of such technologies. Our specific focus was on physiological measures of MWL. The used search strategy identified 39 peer-reviewed publications that analysed ATC tasks, examined different levels of difficulty of the ATC task, and considered at least one physiological measure of MWL. Positive relations between measures of MWL and task difficulty were observed most frequently, indicating that the measures indeed allowed the assessment of MWL. The most commonly used physiological measures were brain measures (EEG and fNIR) and heart rate measures. The review revealed a need for more precise descriptions of crucial experimental parameters in order to permit a transition of the field towards more interactive and dynamic types of analysis. Practitioner summary: Research on innovative technology in air traffic control (ATC) depends on assessments of mental workload (MWL). We reviewed empirical research on MWL in ATC. Brain and heart measures often allow assessments of MWL. Better descriptions of experiments are needed to allow comparisons among studies and more dynamic and interactive analyses. [ABSTRACT FROM AUTHOR]

Purpose: Anaplastic thyroid carcinoma (ATC) and primary squamous cell carcinoma of the thyroid (PSCCTh) have similar histological findings and are currently treated using the same approaches; however, the characteristics and prognosis of these cancers are poorly researched. The objective of this study was to determine the differences in characteristics between ATC and PSCCTh and establish prognostic models. Patients and Methods: All variables of patients with ATC and PSCCTh, diagnosed from 2004–2015, were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Percentage differences for categorical data were compared using the Chi-square test. Kaplan-Meier curves, log-rank test, and Cox-regression for survival analysis, and C-index value was used to evaluate the performance of the prognostic models. Results: After application of the inclusion and exclusion criteria, a total of 1164 ATC and 124 PSCCTh patients, diagnosed from 2004 to 2015, were included in the study. There were no differences in sex, ethnicity, age, marital status, or percentage of proximal metastases between the two cancers; however, radiotherapy, chemotherapy, incidence of surgical treatment, and presence of multiple primary tumors were higher in patients with ATC than those with PSCCTh. Further cancer-specific survival (CSS) of patients with PSCCTh was better than that of patients with ATC. Prognostic factors were not identical for the two cancers. Multivariate Cox model analysis indicated that age, sex, radiotherapy, chemotherapy, surgery, multiple primary tumors, marital status, and distant metastasis status are independent prognostic factors for CSS in patients with ATC, while for patients with PSCCTh, the corresponding factors are age, radiotherapy, multiple primary tumors, and surgery. The C-index values of the two models were both > 0.8, indicating that the models exhibited good discriminative ability. Conclusion: Prognostic factors influencing CSS were not identical in patients with ATC and PSCCTh. These findings indicate that different clinical treatment and management plans are required for patients with these two types of thyroid cancer. [ABSTRACT FROM AUTHOR]

The quality of work life is affected by the quality of the work environment. A positive work atmosphere will create a conducive work life. This study aims to determine the factors that affect the quality of life of air traffic controller at AirNav Surabaya. This is a quantitative research with a cross sectional study method. Interviews were conducted on 38 workers who were drawn based on the purposive sampling method. Then, from these results a logistic regression test was carried out which showed that blood pressure, position, and workload had a significant relationship. To determine the effect of individual characteristics, work fatigue and quality of life were measured using a questionnaire, blood pressure using a tensimeter and workload using an oximeter. Data were analyzed using the SPSS 25 application with the chi-square test. Results of the chi-square test analysis showed that there was a relationship between age and quality of life (p = 0.009), blood pressure with quality of life (p = 0.032), years of service with quality of life (p = 0.031), position and quality of life (p = 0.029), fatigue with quality of life (p = 0.012) and workload with quality of life (p = 0.005), while there was no relationship between sex and quality of life (0.279) and marital status with quality of life (p = 0.560). From these results, a logistic regression test was carried out which showed that blood pressure, position, and workload had a significant relationship. This research suggests AirNav Surabaya to pay more attention to the quality of life of air traffic controller, maintain the nutritional intake, exercise regularly, and pay attention to rest times. [ABSTRACT FROM AUTHOR]

Abstract Background Due to rising health care costs, in 2012 Switzerland introduced SwissDRG, a reimbursement system for hospitals based on lump sum per case. To circumvent possible negative consequences like reduction in length of stay, acute and transitional care (ATC) was anchored into the law (Federal act on health insurance) in 2011. ATC as a discharge option is applicable to patients who physicians deem will not fulfill rehabilitation criteria, but are unable to return home and are in need of temporary professional nursing care. ATC is associated with higher out of pocket costs to the patient than rehabilitation. Since social service workers are responsible for organizing discharge for patients with ongoing care needs after hospitalization, the aim of this study was to investigate how social service workers manage patient discharge in light of the new discharge option ATC. Methods Data was collected from 423 medical records of inpatients from Zurich’s municipal hospital, Triemli, discharged to ATC or rehabilitation, in 2016. We compared the two groups using inferential statistics and qualitatively analyzed written statements from social service workers. Results Our results showed that patients discharged to rehabilitation had a higher total number of discussions, but a shorter duration of discussions. Patients discharged to rehabilitation faced more delays, mainly due to unavailability of beds in rehabilitation centers. Conflicts concerning discharge arose mainly because of costs, discharge placement and too early discharge. Conclusions Our findings demonstrate how important social service workers are in providing information to patients about different discharge options. The newness of SwissDRG and ATC is still likely to cause longer discussion times and, consequently, more workload for social service workers. Only a small fraction of patients disagreed with their place of discharge, mostly due to financial reasons.

Abstract Background Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal malignancies. Long non-coding RNAs (lncRNAs) are being found to play crucial roles in ATC progression. Herein, we focused on the role of nuclear paraspeckle assembly transcript 1 (NEAT1) on ATC progression under hypoxia and underlying mechanisms governing it. Methods The expression levels of NEAT1, miR-206 and miR-599 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell migration and invasion abilities were detected using transwell assays. Glucose consumption and lactate production were determined using a corresponding commercial assay kit. Western blot was performed to evaluate the level of hexokinase 2 (HK2). The targeted interplays between NEAT1 and miR-206 or miR-599 were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model was established to observe the effect of NEAT1 on tumor growth in vivo. Results Our data indicated that NEAT1 was highly expressed in ATC tissues and cells, and hypoxia induced NEAT1 expression in ATC cells. NEAT1 depletion repressed ATC cell migration, invasion and glycolysis under hypoxia. Mechanistically, NEAT1 acted as a molecular sponge of miR-206 and miR-599. Moreover, the repressive effects of NEAT1 knockdown on ATC cell migration, invasion and glycolysis under hypoxia were mediated by miR-206 or miR-599. Additionally, NEAT1 knockdown weakened tumor growth in vivo. Conclusion In conclusion, our study suggested that a low NEAT1 expression suppressed the migration, invasion, and glycolysis in ATC cells under hypoxia at least partially through modulating miR-206 and miR-599, providing new therapeutic strategies for ATC treatment.

PurposeAnaplastic thyroid carcinoma (ATC) and primary squamous cell carcinoma of the thyroid (PSCCTh) have similar histological findings and are currently treated using the same approaches; however, the characteristics and prognosis of these cancers are poorly researched. The objective of this study was to determine the differences in characteristics between ATC and PSCCTh and establish prognostic models.Patients and MethodsAll variables of patients with ATC and PSCCTh, diagnosed from 2004–2015, were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Percentage differences for categorical data were compared using the Chi-square test. Kaplan-Meier curves, log-rank test, and Cox-regression for survival analysis, and C-index value was used to evaluate the performance of the prognostic models.ResultsAfter application of the inclusion and exclusion criteria, a total of 1164 ATC and 124 PSCCTh patients, diagnosed from 2004 to 2015, were included in the study. There were no differences in sex, ethnicity, age, marital status, or percentage of proximal metastases between the two cancers; however, radiotherapy, chemotherapy, incidence of surgical treatment, and presence of multiple primary tumors were higher in patients with ATC than those with PSCCTh. Further cancer-specific survival (CSS) of patients with PSCCTh was better than that of patients with ATC. Prognostic factors were not identical for the two cancers. Multivariate Cox model analysis indicated that age, sex, radiotherapy, chemotherapy, surgery, multiple primary tumors, marital status, and distant metastasis status are independent prognostic factors for CSS in patients with ATC, while for patients with PSCCTh, the corresponding factors are age, radiotherapy, multiple primary tumors, and surgery. The C-index values of the two models were both > 0.8, indicating that the models exhibited good discriminative ability.ConclusionPrognostic factors influencing CSS were not identical in patients with ATC and PSCCTh. These findings indicate that different clinical treatment and management plans are required for patients with these two types of thyroid cancer.

Objectives: Anaplastic thyroid cancer (ATC) is the most aggressive and fatal thyroid malignancy. Currently, there still exists a paucity of literature studying the relationship between available ATC-targeted therapy, immunotherapy, and survival. We aim to investigate how systemic therapies affect survival outcomes in ATC., Methods: A single-tertiary-institution chart review of patients diagnosed with advanced-stage ATC, and who underwent surgery as part of their treatment, was performed between 2000 and 2023, with 41 patients included. Demographics, clinical characteristics, and survival data were collected and analyzed via Kaplan-Meier and Cox proportional hazards analyses., Results: 54% of patients were female, and average age was 67.4 years old. The most common mutations identified were BRAF (15 patients), p53 (9 patients), and p63 (2 patients). A total of 18 patients utilized targeted or immunotherapy, with Trametinib and Dabrafenib (9 patients) as the most common agents used. Two-year overall survival was 24%, and 5-year overall survival was 23%, with median survival time of 7.6 months. Kaplan-Meier analysis demonstrated improved survival in patients who received chemotherapy (p = 0.048). Cox proportional hazards analysis demonstrated that patients treated with immunotherapy or targeted therapy had a statistically significant increase in survival compared with patients who did not receive these therapies (p = 0.016). Additionally, females and those with a p63 mutation demonstrated improved survival outcomes (p = 0.010, p = 0.001)., Conclusions: Targeted therapy and immunotherapy use should be strongly considered when treating patients with ATC. Further studies into novel drugs targeting immune checkpoints and combination therapy are needed to better optimize treatment of patients with ATC., Level of Evidence: 3 Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: The application of machine learning in health care often necessitates the use of hierarchical codes such as the International Classification of Diseases (ICD) and Anatomical Therapeutic Chemical (ATC) systems. These codes classify diseases and medications, respectively, thereby forming extensive data dimensions. Unsupervised feature selection tackles the "curse of dimensionality" and helps to improve the accuracy and performance of supervised learning models by reducing the number of irrelevant or redundant features and avoiding overfitting. Techniques for unsupervised feature selection, such as filter, wrapper, and embedded methods, are implemented to select the most important features with the most intrinsic information. However, they face challenges due to the sheer volume of ICD and ATC codes and the hierarchical structures of these systems., Objective: The objective of this study was to compare several unsupervised feature selection methods for ICD and ATC code databases of patients with coronary artery disease in different aspects of performance and complexity and select the best set of features representing these patients., Methods: We compared several unsupervised feature selection methods for 2 ICD and 1 ATC code databases of 51,506 patients with coronary artery disease in Alberta, Canada. Specifically, we used the Laplacian score, unsupervised feature selection for multicluster data, autoencoder-inspired unsupervised feature selection, principal feature analysis, and concrete autoencoders with and without ICD or ATC tree weight adjustment to select the 100 best features from over 9000 ICD and 2000 ATC codes. We assessed the selected features based on their ability to reconstruct the initial feature space and predict 90-day mortality following discharge. We also compared the complexity of the selected features by mean code level in the ICD or ATC tree and the interpretability of the features in the mortality prediction task using Shapley analysis., Results: In feature space reconstruction and mortality prediction, the concrete autoencoder-based methods outperformed other techniques. Particularly, a weight-adjusted concrete autoencoder variant demonstrated improved reconstruction accuracy and significant predictive performance enhancement, confirmed by DeLong and McNemar tests (P<.05). Concrete autoencoders preferred more general codes, and they consistently reconstructed all features accurately. Additionally, features selected by weight-adjusted concrete autoencoders yielded higher Shapley values in mortality prediction than most alternatives., Conclusions: This study scrutinized 5 feature selection methods in ICD and ATC code data sets in an unsupervised context. Our findings underscore the superiority of the concrete autoencoder method in selecting salient features that represent the entire data set, offering a potential asset for subsequent machine learning research. We also present a novel weight adjustment approach for the concrete autoencoders specifically tailored for ICD and ATC code data sets to enhance the generalizability and interpretability of the selected features., (©Peyman Ghasemi, Joon Lee. Originally published in JMIR Medical Informatics (https://medinform.jmir.org).)

Background: Multimorbidity is a significant public health concern, characterized by the coexistence and interaction of multiple preexisting medical conditions. This complex condition has been associated with an increased risk of COVID-19. Individuals with multimorbidity who contract COVID-19 often face a significant reduction in life expectancy. The postpandemic period has also highlighted an increase in frailty, emphasizing the importance of integrating existing multimorbidity details into epidemiological risk assessments. Managing clinical data that include medical histories presents significant challenges, particularly due to the sparsity of data arising from the rarity of multimorbidity conditions. Also, the complex enumeration of combinatorial multimorbidity features introduces challenges associated with combinatorial explosions., Objective: This study aims to assess the severity of COVID-19 in individuals with multiple medical conditions, considering their demographic characteristics such as age and sex. We propose an evolutionary machine learning model designed to handle sparsity, analyzing preexisting multimorbidity profiles of patients hospitalized with COVID-19 based on their medical history. Our objective is to identify the optimal set of multimorbidity feature combinations strongly associated with COVID-19 severity. We also apply the Apriori algorithm to these evolutionarily derived predictive feature combinations to identify those with high support., Methods: We used data from 3 administrative sources in Piedmont, Italy, involving 12,793 individuals aged 45-74 years who tested positive for COVID-19 between February and May 2020. From their 5-year pre-COVID-19 medical histories, we extracted multimorbidity features, including drug prescriptions, disease diagnoses, sex, and age. Focusing on COVID-19 hospitalization, we segmented the data into 4 cohorts based on age and sex. Addressing data imbalance through random resampling, we compared various machine learning algorithms to identify the optimal classification model for our evolutionary approach. Using 5-fold cross-validation, we evaluated each model's performance. Our evolutionary algorithm, utilizing a deep learning classifier, generated prediction-based fitness scores to pinpoint multimorbidity combinations associated with COVID-19 hospitalization risk. Eventually, the Apriori algorithm was applied to identify frequent combinations with high support., Results: We identified multimorbidity predictors associated with COVID-19 hospitalization, indicating more severe COVID-19 outcomes. Frequently occurring morbidity features in the final evolved combinations were age>53, R03BA (glucocorticoid inhalants), and N03AX (other antiepileptics) in cohort 1; A10BA (biguanide or metformin) and N02BE (anilides) in cohort 2; N02AX (other opioids) and M04AA (preparations inhibiting uric acid production) in cohort 3; and G04CA (Alpha-adrenoreceptor antagonists) in cohort 4., Conclusions: When combined with other multimorbidity features, even less prevalent medical conditions show associations with the outcome. This study provides insights beyond COVID-19, demonstrating how repurposed administrative data can be adapted and contribute to enhanced risk assessment for vulnerable populations., (©Dayana Benny, Mario Giacobini, Alberto Catalano, Giuseppe Costa, Roberto Gnavi, Fulvio Ricceri. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 18.07.2024.)

Architectural Terracotta (ATC) is one of the most common materials in excavations from the Roman period. These ceramic building materials are an essential component of construction. Some of these pieces show potter´s marks, of different categories, that allow access to the production world of these materials. This investigation is a first typological classification of the 1216 marks from ATC materials, collected from 41 archaeological sites in Bracara Augusta (Braga, Portugal). Most of the marks were collected from the domus of Carvalheiras, one of the most emblematic archaeological sites of the city, currently under a musealization process. With this work it was possible to correlate the studied marks with specific terracotta types (shapes), context distribution and associated chronologies. The results suggested an organized and dynamic production, and an open-market, supported by numerous officinae, certainly of different sizes. Some of them were located near the housing area and reveal the presence of a large number of workers, including women and children. Further approaches on mineralogical, chemical and technological characterization of ATC, linked with stratigraphy, are under development. [ABSTRACT FROM AUTHOR]

Summary: Wind farm (WF) power output is not constant due to the intermittent nature of wind speed, wind direction, and wind turbine (WT) wake effect. The integration of WF into large power systems affects the transmission system's available transfer capability (ATC). In this paper, WF power output is calculated by a proposed formula that considers the wind direction and wake effect of WT. The battery energy storage system (BESS) has been installed in the system, and charging/discharging criteria have been created to enhance the ATC value of the system. The clusters/zones are created according to transmission congestion distribution factor (TCDF) values. The average TCDF (ATCDF) value is proposed to select the optimal position of WF and BESS. The proposed approach increases ATC significantly. The results are simulated in the IEEE‐30 bus system. [ABSTRACT FROM AUTHOR]

Summary: As essential components in the energy hub, the multi‐energy devices are diverse, and their working conditions are complex. The relevant energy efficiency level of devices in the energy hub is also an important factor for the long‐term operation of the energy systems. The device efficiency is always considered constant in modeling the energy hub. However, it is necessary to study the efficiency variation and optimization of devices under off‐design working conditions. In this paper, we propose a coordinated dispatch method of the multi‐energy system considering the device off‐design characteristics in the energy hub. The energy efficiency optimization is included in the dispatch process. Then, we use the analysis target cascade (ATC) to obtain the optimal solution. The method is tested in the system, including distribution network, natural gas network, and energy hub. Compared to the traditional method, the proposed method can describe the operation of the whole system more authentically and thereby prove the effectiveness of energy efficiency optimization. The corresponding nonlinear constraints are linearized by piecewise linearization. Besides, we discuss the results of energy efficiency optimization at different load levels and capacity combinations, which is of guiding significance to optimize system working conditions. [ABSTRACT FROM AUTHOR]

Adjoint‐based shape optimization using unsteady solvers is costly and/or memory demanding. When mild unsteadiness is present or the flow in/around the optimized shape is not expected to be time‐varying, steady primal and adjoint solvers can be used instead. However, in such a case, convergence difficulties caused by flow unsteadiness must properly be treated. In this article, the steady primal and the corresponding (continuous) adjoint solvers are both stabilized by implementing the recursive projection method (RPM). This is carried out in the adjointOptimisation library of OpenFOAM, developed, and made publicly available by the group of authors. Upon completion of the optimization using steady solvers, unsteady re‐evaluations of the optimized solutions confirm a reduction in the time‐averaged objective function. In complex cases, in which the RPM may not necessarily ensure convergence of the adjoint solver on its own, the controlled damping of the adjoint transposed‐convection (ATC) term is additionally implemented. This is demonstrated in the shape optimization of a motorbike fairing where averaged primal fields over a number of iterations of the steady flow solver are used for the solution of the adjoint equations. Cases in which the RPM is, on its own, sufficient in ensuring convergence of the adjoint solver are additionally studied by using a controlled ATC damping, to assess its impact on the computed sensitivity derivatives. Comparisons show that controlled/mild ATC damping is harmless and greatly contributes to robustness. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated thyroid carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors are highly proliferative, with frequently increased tumor mutational burden (TMB) compared with differentiated thyroid carcinomas, and elevated programmed death ligand 1 (PD-L1) levels. These tumor properties implicate responsiveness to antiangiogenic and antiproliferative multikinase inhibitors such as lenvatinib, and immune checkpoint inhibitors such as pembrolizumab. Patients and Methods: In a retrospective study, we analyzed six patients with metastatic ATC and two patients with PDTC, who received a combination therapy of lenvatinib and pembrolizumab. Lenvatinib was started at 14–24 mg daily and combined with pembrolizumab at a fixed dose of 200 mg every three weeks. Maximum treatment duration with this combination was 40 months, and 3 of 6 ATC patients are still on therapy. Patient tumors were characterized by whole-exome sequencing and PD-L1 expression levels (tumor proportion score [TPS] 1–90%). Results: Best overall response (BOR) within ATCs was 66% complete remissions (4/6 CR), 16% stable disease (1/6 SD), and 16% progressive disease (1/6 PD). BOR within PDTCs was partial remission (PR 2/2). The median progression-free survival was 17.75 months for all patients, and 16.5 months for ATCs, with treatment durations ranging from 1 to 40 months (1, 4, 11, 15, 19, 25, 27, and 40 months). Grade III/IV toxicities developed in 4 of 8 patients, requiring dose reduction/discontinuation of lenvatinib. The median OS was 18.5 months, with three ATC patients being still alive without relapse (40, 27, and 19 months) despite metastatic disease at the time of treatment initiation (UICC and stage IVC). All patients with long-term (>2 years) or complete responses (CRs) had either increased TMB or a PD-L1 TPS >50%. Conclusions: Our results implicate that the combination of lenvatinib and pembrolizumab might be safe and effective in patients with ATC/PDTC and can result in complete and long-term remissions. The combination treatment is now being systematically examined in a phase II clinical trial (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab [ATLEP]) in ATC/PDTC patients. [ABSTRACT FROM AUTHOR]

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