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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, 135:478–484, 2025 [ABSTRACT FROM AUTHOR]

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]

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive thyroid malignancy typically comprised of undifferentiated tumor cells with various histologic morphologies, which makes the diagnosis challenging. These tumors commonly show loss of thyroglobulin and TTF1 with preservation of cytokeratin (67%) and Paired Box Gene 8 (PAX8) (55%) expression. Identification of a sensitive immunohistochemical stain to aid in the diagnosis of ATC would be beneficial. Immunohistochemistry (IHC) against special AT-rich sequence-binding protein 2 (SATB2) protein is a sensitive and specific marker expressed in colorectal adenocarcinoma and bone or soft tissue tumors with osteoblastic differentiation. However, SATB2 is also expressed in other sarcomatous/undifferentiated neoplasms lacking osteoblastic differentiation. Using quantitative reverse transcription PCR (RT-qPCR) we showed that there is variable expression of SATB2 mRNA expression in ATCs. To evaluate the role of SATB2 protein expression in ATC, we performed PAX8, SATB2, pancytokeratin (AE1/AE3 & CAM5.2), claudin-4 and TTF1 immunostaining on 23 cases. ATCs showed retained expression of PAX8 in 65% (15/23); SATB2 was detected in 74% (17/23); pancytokeratin was expressed in 65% (15/23); claudin-4 was expressed in 35% (8/23) and TTF1 showed expression in 13% (3/23) of cases. Furthermore, 83% (5/6) of ATCs which lacked SATB2 expression, retained PAX8 expression, while 88% (7/8) of the tumors without PAX8 expression were positive for SATB2. Differentiated follicular cell-derived thyroid cancers (n = 30), differentiated high grade thyroid carcinoma (n = 3), and poorly differentiated thyroid carcinoma (n = 8) were negative for SATB2 immunoreactivity. Next-generation selected cases detected the commonly identified oncogenic variants including those in BRAF, RAS, TP53, and TERT promoter. Overall, we hereby demonstrate that SATB2 IHC may be used to support the diagnosis of ATC. [ABSTRACT FROM AUTHOR]

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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]

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]

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]

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]

To analyze the relationship between coagulation and fibrinolysis indicators and acute traumatic coagulopathy (ATC) after traumatic brain injury (TBI) and their predictive efficacy for cerebrocardiac syndrome ( CCS ). 80 patients withTBI admitted to our hospital from January 2020 to December 2022 were selected as the research objects. The levels of prothrombin time(PT), activated partial thromboplastin time (APTT), D-dimer (D-D), thrombin-antithrombin complex (TAT), plasminogen-α2 plasmino-gen inhibitor complex (PIC), international normalized ratio (INR) and TAT / PIC ratio were detected and calculated in non-ATC patientsand ATC patients, non-CCS patients and CCS patients, respectively. Bivariate Spearman correlation was used to test the correlation between coagulation and fibrinolysis indicators. Multivariate Logistic model was established to analyze the influencing factors of ATC andTBI combined with CCS after TBI, and the predictive efficacy of coagulation and fibrinolysis indicators on TBI combined with CCS wasanalyzed. The incidence of ATC in 80 TBI patients was 27. 50 %. Compared with the non-ATC group, the levels of PT, APTTand D-D in the ATC group were higher, and the TAT / PIC ratio was lower (P<0. 05). PT, APTT and D-D were positively correlated withATC after craniocerebral injury, and TAT / PIC was negatively correlated with ATC. Multivariate logistic analysis showed that TAT /PIC was an independent risk factor for ATC after craniocerebral injury (P<0. 05). The incidence of CCS in 80 TBI patients was 20. 00 %. Compared with the non-CCS group, the levels of PT, APTT and D-D in the CCS group were higher, and the TAT / PIC ratio was lower(P<0. 05). Multivariate logistic analysis showed that PT, APTT, D-D and TAT / PIC were independent risk factors for TBI combined with CCS (P<0. 05). In the prediction of TBI combined with CCS, the ACU of PT, APTT and D-D were all > 0. 70, and TAT / PIC > 0. 85. TAT / PIC is associated with ATC after TBI, and can also predict the occurrence of CCS, which has guiding significance in the prognosis prediction of TBI 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]

Background: In last 2 decades, there have been substantial changes in the utilization patterns of antihypertensive medicines following new clinical trials and the introduction of new treatment guidelines. The aim of this study was to analyze utilization and prescribing patterns regarding antihypertensive medicines in the Republic of Srpska, Bosnia and Herzegovina during an 11-years follow-up according to national and European treatment guidelines. Methods: In this retrospective, observational study, medicine utilization data were analyzed between 2009-2019 period using the ATC/DDD methodology and expressed as the number of DDD/1,000 inhabitants/day (DID/TID). The medicine utilization 90% (DU90%) method was used for determine the quality of prescribing. Results: During the observed period, the use of antihypertensive medicines increased more than 3-times (125.97 DDD/TID in 2009 vs 414.95 DDD/TID in 2019), corresponding to a rise in the prevalence of hypertensive patients from 91.7/1,000 to 186.3/1,000 in the same period. This was mainly driven by increased use of angiotensin converting enzyme inhibitors with 241.69%, beta blockers with 146.87%, calcium channel blockers with 251.55%, and diuretics with 178.95%. Angiotensin receptor blockers were the fastest growing group of antihypertensive medicines in this period and their utilization increased nearly 40 times. Conclusions: The overall antihypertensive medicines utilization was largely influenced by national and ESH/ESC guidelines and strongly corresponded to the positive medicine list of the national health insurance fund. Antihypertensive medicines utilization is comparable with medicine utilization trends in other countries.

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]

Production scheduling is one of the most important tasks in manufacturing systems since it allows the allocation of jobs with a certain number of available resources. In the production and service industries, meeting the established commitments with the different customers and production deadlines can lead to higher levels of satisfaction and market competitive advantages. On the other hand, one of the main industries worldwide is the coffee industry. Indeed, coffee is the second most traded commodity in the world. Therefore, this research addresses the optimization of the total tardiness in the scheduling of jobs in parallel machines for a case study in a coffee roaster. This is an NP-hard problem where each job requires the roasting process and, in addition, has an associated delivery time. Each job's processing time depends on the machine that is designated and not all machines can run all jobs. We present the mathematical model to describe the problem using mixed integer linear programming and then it is implemented in Python. Additionally, a mate heuristic model based on the ATC heuristic is proposed in order to reduce the computation time and to reach solutions close to the optimum. This model was evaluated with one thousand instances of real data from the roasting process. The Gurobi optimizer was used to solve the problem. The exact method shows high computational times, so we proposed to first perform the sequencing of jobs and then assign them to the machines by means of a simplified mathematical model. By using the proposed mate heuristic model, an average reduction of 53.98% of the execution time is achieved and with respect to the solution delay, this model achieves a median of 0.0% with respect to the optimum. [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]

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.

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]

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]

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.

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.

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]

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.

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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]

Introduction: The World Health Organization global standard for representing drug data is the Anatomical Therapeutic Chemical (ATC) classification. However, it does not represent ingredients and other drug properties required by clinical decision support systems. A mapping to a terminology system that contains this information, like RxNorm, may help fill this gap. This work evaluates and compares the completeness of mappings from the chemical substance level (5th-level) ATC classes to RxNorm ingredient concepts in the OHDSI Standardized Vocabularies (OSV) and the Unified Medical Language System (UMLS) Metathesaurus., Methods: To check the concordance between OSV and UMLS we compared the included contents of ATC and RxNorm not only in OSV and UMLS but also in BioPortal and the National Library of Medicine (NLM) repository. For each repository, we determined the number of 5th-level ATC concepts, RxNorm ingredient concepts, missing classes and concepts, and the ATC categories with the most missing concepts. The mappings from ATC to RxNorm in OSV and UMLS were compared, and we determined the number of mappings in common, and the mapping differences, which we categorized. We applied the mappings from OSV and UMLS on a sample of Electronic Health Record (EHR) data., Results: NLM contained the most ATC and RxNorm concepts. UMLS contained more missing mappings (null mappings) than OSV, 1949 versus 916. Most mapping differences were in the "unknown ingredient in the ATC label" category, for which UMLS provided no mappings. UMLS had a higher coverage of mappings in the sample EHR data than OSV, 96.5% versus 91%., Discussion: In conclusion, opting for OSV rather than UMLS is generally preferable for an ATC to RxNorm mapping since OSV provides more mappings. However, the results of the sample data show that UMLS can have fewer null mappings in concrete applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Anaplastic thyroid cancer (ATC) is a highly lethal form of thyroid cancer. lysine acetyltransferase 5 (KAT5) has been found to promote ATC development via c-Myc stabilization by previous study. We thus designed experiments to confirm the anti-tumor effect of a KAT5 inhibitor (MG149) in ATC., Methods: Western blotting assessed the level of KAT5, c-Myc, and epithelial-mesenchymal transition (EMT)-related proteins in ATC cells and xenograft tumor tissues. Cell counting kit-8, flow cytometry, wound healing, and transwell assays revealed the effect of MG149 on cell proliferation, apoptosis, migration, and invasion in ATC cell lines. Immunofluorescence detected the level of E-cadherin and N-cadherin in ATC cell lines. The effect of MG149 on KAT5-mediated c-Myc stabilization was detected using co-immunoprecipitation assay. Tumor volume and tumor weight in ATC xenograft models were evaluated. H&E staining showed the effect of MG149 on lung metastasis in vivo. We further investigated whether MG149 can enhance the sensitivity of ATC to cisplatin (CDDP)., Results: MG149 inhibited cell proliferation and increased the apoptosis of cells. MG149 suppressed the migratory and invasive ability of ATC cells. The EMT in CAL-62 and 8505C cells was significantly inhibited by MG149. MG149 suppressed the KAT5-mediated c-Myc acetylation. MG149 inhibited tumor growth and lung metastasis in vivo. Additionally, MG149 potentiated the sensitivity to CDDP in ATC cells in vitro and in vivo., Conclusion: MG149 suppresses ATC progression and metastasis by inhibiting the acetylation of c-Myc mediated by KAT5., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Anaplastic thyroid cancer (ATC) is the most lethal tumor arising from thyroid follicular epithelium. Lenvatinib is an off-label use option for ATC patients in many countries but an approved prescription in Japan. However, lenvatinib resistance is a substantial clinical challenge. Clinical ATC samples including lenvatinib-resistant tumors are used to build patient-derived cells and patient-derived xenografts. High-throughput drug screening and synergy analyses are performed to identify an effective combination partner for lenvatinib. Cellular functions are detected by cell senescence, apoptosis, cell cycle, cell viability and colony formation assays. CDK2 inhibition showed the significant synthetic lethality with lenvatinib via inhibiting G1/S transition and inducing cell senescence in ATC. High expression of CDK2 is associated with lenvatinib resistance and poor clinical outcomes of ATC patients. Lenvatinib increased protein expression of CDK2 in lenvatinib-resistant ATC cells. Mechanistically, lenvatinib inhibited protein degradation of CDK2 via reducing CDK2's interaction with the RACK1-FBW7 complex, which is involved in ubiquitination and subsequent proteasomal degradation of CDK2. Combination of CDK2 inhibitors in clinical trials (Dinaciclib or PF-07104091) and lenvatinib markedly suppressed growth of xenograft tumors from the lenvatinib-resistant patient. The findings support the combination therapy strategy of lenvatinib and CDK2 inhibitor for lenvatinib-resistant ATC patients with high CDK2 expression., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

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.

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]