Search Results (14)

Background/Objectives: Current evidence suggests that patients with unresectable non-small cell lung cancer (NSCLC) whose tumours harbour driver mutations do not benefit from immune checkpoint inhibition. Kirsten rat sarcoma virus mutations (KRASmts), however, seem to be the exceptions to the rule. To this end, we compared KRASmt patients who were treated with immunotherapy to those without. Methods: ALLSTAR is a nationwide registry for patients with histologically verified non-operable NSCLC aged 18 or older having a curative treatment option. This report presents a subcohort of KRASmt patients who were recruited between 2020/03 and 2023/04. The diagnostic work-up included ¹⁸F-FDG-PET-CT scan and contrast-enhanced cranial CT or—preferably—MRI. Patients were treated with chemoradiotherapy (CRT) either followed by immune checkpoint inhibition (ICI) or not. Results: Thirty-two KRASmt patients with a median follow-up of 25.9 months were included in this analysis. After CRT, 27/32 (84%) patients received ICI. The 2-year overall survival rate in KRASmt patients who received immunotherapy was significantly better compared to those without ICI (N = 32; 84% versus 20%; p < 0.001). Likewise, the 2-year progression-free-survival with immunotherapy was also significantly better than in those without ICI (N = 32; 75% versus 20%; p < 0.001). Of the 12/32 patients (38%) who had received radiation doses > 66 Gy, none had a locoregional relapse, whereas in the other 20 patients, 5 (25%) events occurred (p-value = 0.116). Conclusions: Since KRASmt patients could benefit from ICI treatment, immunotherapy should be offered to these patients, similar to those without actionable genetic drivers. Additionally, radiation dose escalation > 66 Gy may also improve locoregional control in this subset of patients. Full article

Culture consists of material and spiritual values and tools that a nation has accumulated in the historical process. In addition to the most basic contexts such as language and religion, contexts such as sporting activities, art, public medicine, and the public calendar are also important environments that reveal their own cultural elements. Among these contexts, religion is very effective in shaping the daily life of the individual and, thus, society through the rules it enjoins. Religion does not dominate only the world of belief of the individual. Through the world of belief, it also directs their relations with the social institutions they are involved in. Sport is one of the most important activities and social institutions that stand out with various functions in daily life, with wrestling being one of the branches of sports that have emerged as a result of the imitation of the struggle of human beings with nature and other creatures with which they share nature. In particular, those involved in the nomadic way of life had to hunt in order not to starve and fight in order to survive. Wrestling, which emerged as a result of these obligations, held an important place among all Turks in the world for a period of time, especially in the transition periods of life, such as birth, marriage, and death. One of the conditions set forth by women as a condition of marriage was that their suitor defeated them in wrestling. Examples of this condition are also observed in literary texts belonging to different periods when Turks were not yet acquainted with Islam and the concepts of halal and haram, which entered their lives together with Islam. According to the provisions of the Holy Qur’an, right/unprohibited thoughts and actions are associated with the words good and halal, while wrong/prohibited thoughts and actions are associated with the words sin and haram. In this study, the social and cultural phases of wrestling as a sports branch among Turks in the historical process will be evaluated on the basis of the history of religions and religious references, in addition to the literary texts belonging to historical periods when Turks were members of different religions, in the context of two events that have been experienced and reported in the news. The study was carried out using the method of document analysis, a method of qualitative research, and the data obtained by this method were evaluated using content analysis. The narratives of Alıp Manaş, Alpamış, Alpamıs, Alıpmenşen, and Bamsı Beyrek, which are evaluated in this context, belong to the periods when the Turks had not been introduced to Islam or had only recently been introduced to it. Alıp Manaş was collated from different Turkic tribes such as the Altais, Alpamış from the Uzbeks, Alpamıs the Kazakhs/Karakalpaks, Alıpmenşen the Bashkirs/Tatars, and Bamsı Beyrek the Oghuz Turks. The narratives of Kirmanshah, Köse Kenan-Dânâ Hanım, Bey Böyrek, Shah Ismail, and Yaralı Mahmut, which are evaluated in the study, belong to the periods when the Turks became Muslim en masse, and are related only among the Oghuz Turks. These narratives are included in the study because they are similar to Alıp Manaş, Alpamış, Alpamıs, Alıpmenşen, and Bamsı Beyrek and they belong to the period when Islam was largely established among the Turkish masses in Anatolia. The effect of the new religion on wrestling, which is a branch of sport, will be revealed through these narratives belonging to different tribes and religious periods. Once more, an event that occurred in recent history, and was the subject of the news, was subjected to document analysis, and content analysis was carried out through the text of the news and evaluated in the context of the study. This study aims to explain the effect of religious rules on sports branches with theological, folkloric, and sociological references based on ancient literary texts belonging to the Turks and two incidents which were experienced. Full article

Survival analysis is widely used in fields such as medical research and reliability engineering to analyze data where not all subjects experience the event of interest by the end of the study. It requires dedicated methods capable of handling censored cases. This paper extends the collection of techniques applicable to censored data by introducing a novel algorithm for interpretable recommendations based on a set of survival action rules. Each action rule contains recommendations for changing the values of attributes describing examples. As a result of applying the action rules, an example is moved from a group characterized by a survival curve to another group with a significantly different survival rate. In practice, an example can be covered by several induced rules. To decide which attribute values should be changed, we propose a recommendation algorithm that analyzes all actions suggested by the rules covering the example. The efficiency of the algorithm has been evaluated on several benchmark datasets. We also present a qualitative analysis of the generated recommendations through a case study. The results indicate that the proposed method produces high-quality recommendations and leads to a significant change in the estimated survival time. Full article

A series of heterocyclic chloroquine hybrids, containing a chain of two carbon atoms at position four of the quinolinic chain and acting as a link between quinoline and several benzoyl groups, is synthesized and screened in vitro as an inhibitor of β-hematin formation and in vivo for its antimalarial activity against chloroquine-sensitive strains of Plasmodium berghei ANKA in this study. The compounds significantly reduced haeme crystallization, with IC₅₀ values < 10 µM. The values were comparable to chloroquine’s, with an IC₅₀ of 1.50 ± 0.01 µM. The compounds 4c and 4e prolonged the average survival time of the infected mice to 16.7 ± 2.16 and 14.4 ± 1.20 days, respectively. We also studied the effect of the compounds 4b, 4c, and 4e on another important human parasite, Leishmania mexicana, which is responsible for cutaneous leishmaniasis, demonstrating a potential leishmanicidal effect against promasigotes, with an IC₅₀ < 10 µM. Concerning the possible mechanism of action of these compounds on Lesihmania mexicana, we performed experiments demonstrating that these three compounds could induce the collapse of the parasite mitochondrial electrochemical membrane potential (Δφ). The in vitro cytotoxicity assays against mammalian cancerous and noncancerous human cell lines showed that the studied compounds exhibit low cytotoxic effects. The ADME/Tox analysis predicted moderate lipophilicity values, low unbound fraction values, and a poor distribution for these compounds. Therefore, moderate bioavailability was expected. We calculated other molecular descriptors, such as the topological polar surface area, according to Veber’s rules, and except for 2 and 4i, the rest of the compounds violated this descriptor, demonstrating the low antimalarial activity of our compounds in vivo. Full article

Infrastructure development requires various considerations to maintain its continuity. Some public facilities cannot survive due to human indifference and irresponsible actions. Unfortunately, the government has to spend a lot of money, effort, and time to repair the damage. One of the destructive behaviors that can have an impact on infrastructure and environmental problems is littering. Therefore, this paper proposes a device as an alternative for catching littering rule violators. The proposed device can be used to monitor littering and provide warnings to help officers responsible for capturing the violators. In this innovation, the data obtained by the camera are sent to a mini-PC. The device will send warning information to a mobile phone when someone litters. Then, a speaker will turn on and issue a sound warning: “Do not litter”. The device uses pose detection and a recurrent neural network (RNN) to recognize a person’s activity. All activities can be monitored in a more distant place using IoT technology. In addition, this tool can also monitor environmental conditions and replace city guards to monitor the area. Thus, the municipality can save money and time. Full article

Breast cancer (BC) is one of the most frequent types of cancer that affect women. Human epidermal growth factor receptor-2 (HER2) is responsible for 20% of all BC cases. The use of anti-HER2 natural compounds in the cure of BC that is HER2-positive patients has resulted in significant increases in survival in both early and advanced stages. The findings of in-silico research support the use of ligands as possible HER2 inhibitors, and molecules with high free energy of binding may have considerable anti-BC action, making them candidates for future drug development. The inhibitory activity of selected ligands like ZINC43069427 and ZINC95918662 against HER2 was found to be −11.0 and −8.50 kcal/mol, respectively. The amino acid residues Leu726, Val734, Ala751, Lys753, Thr798, Gly804, Arg849, Leu852, Thr862, and Asp863 were found in common interaction as compared to the control compound Lapatinib. Molecular dynamics study calculations of these selected potent inhibitors were conducted and found to be stable over the 50 ns simulation time in terms of root mean square deviation (RMSD), root-mean square fluctuation (RMSF), radius of gyration (Rg), and solvent accessible surface area (SASA). In addition, there are several parameters such as absorption, distribution, metabolism, and excretion toxicity (ADMET), physicochemical, and drug-likeness that were checked and found in good range to be potential lead-like molecules. Several drug-likeness rules like Lipinski, Ghose, Veber, Egan, and Muegge were checked and found to be positive for these rules. Based on these calculations and different parameters, these top two selected natural compounds can be used as potential candidates for anti-HER2 for the management of BC. Full article

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones. The probability of cytoprotective action was assessed by measuring cell viability using two tests (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones under the conditions of our experiment had a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones also fully satisfy Lipinski’s rule of five (RO5), which increases their chances for possible use as orally active drugs with good absorption ability and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones as having a relatively high cytoprotective potential. Full article

The adoption of the United Nations Sustainable Development Goal 5 on gender equality and the growth in the number of women entrepreneurs in the MENA region is likely to change the rules of the game. A growing body of research is addressing this and the factors pertaining to this growth, including digital entrepreneurship. However, little remains known about the growth and resilience of women-owned digital microbusinesses during adverse social and economic disruptions, such as the COVID-19 pandemic, in Saudi Arabia. Hence, this study explores the impact of emotions on the resilience of women entrepreneurs in “Saudi Arabia in transformation”, to explore the impact this has on shaping the digital entrepreneurship journeys of women entrepreneurs. A qualitative longitudinal approach was utilized to capture the processual nature of entrepreneurship during crises, and the broaden-and-build theory offered the theoretical framing for the study. Of the eight women-owned digital microbusinesses participating in this study, six survived the COVID-19 pandemic. The findings show that digital entrepreneurship contributed to sustaining microbusinesses during adversity, and entrepreneurs motivated by passion are also infused with positive emotions and positive thoughts and actions, empowering their resilience, despite the adversity. Full article

With the advent of the COVID-19 pandemic, companies had to adapt quickly to survive in the market. During this time, employers played a key role, along with employees involved in Occupational Health and Safety (OHS) activities, as they were responsible for implementing the recommendations of the European Commission. There is no unambiguous definition of OHS in Polish legislation. It is assumed that it is a set of rules defining the manner of performing work, and above all, a method of providing employees with working conditions so that their performance is safe and hygienic. Responsibility for the health and safety in the workplace is imposed on the employer by the legislature. Thus, effective health and safety training is an essential element of the success of any properly operating company. In the literature, no studies have been identified that evaluate the effectiveness of actions during the COVID-19 outbreak. The aim of the article is to present the actions of Polish employers along with their effectiveness assessment related to the protection of employees during the COVID-19 outbreak. The article presents a proposal for conducting remote OHS (Occupational Health and Safety) training using the platform Moodle. The created course was implemented during OHS training conducted in a selected manufacturing company. At its end, an evaluation of the course was carried out, and the collected opinions of training participants allowed the formulation of interesting conclusions, which became the contribution of this paper. The authors pay special attention to three main points of the work. The first is the form of training, which gives the possibility to conduct training at a distance while maintaining its effectiveness. The second important point is the mandatory feedback of the trainees, ensuring the possibility of continuous improvement and quality enhancement of both the program and the form of training. The evaluation was developed on the basis of the extended Kirkpatrick model, which is a completely new approach to OHS training evaluation. The third point emphasized by the authors is the possibility of precise adaptation of the training to other plants and even industries. Therefore, it can be concluded that the course developed by the authors is a very interesting and practical didactic tool with great implementation potential. Full article

A data-driven method to identify frequent sets of course failures that students should avoid in order to minimize the likelihood of their dropping out from their university training is proposed. The overall probability distribution of the dropout is determined by survival analysis. This result can only describe the mean dropout rate of the undergraduates. However, due to the failure of different courses, the chances of dropout can be highly varied, so the traditional survival model should be extended with event analysis. The study paths of students are represented as events in relation to the lack of completing the required subjects for every semester. Frequent patterns of backlogs are discovered by the mining of frequent sets of these events. The prediction of dropout is personalised by classifying the success of the transitions between the semesters. Based on the explored frequent item sets and classifiers, association rules are formed providing the estimates of the success of the continuation of the studies in the form of confidence metrics. The results can be used to identify critical study paths and courses. Furthermore, based on the patterns of individual uncompleted subjects, it is suitable to predict the chance of continuation in every semester. The analysis of the critical study paths can be used to design personalised actions minimizing the risk of dropout, or to redesign the curriculum aiming the reduction in the dropout rate. The applicability of the method is demonstrated based on the analysis of the progress of chemical engineering students at the University of Pannonia in Hungary. The method is suitable for the examination of more general problems assuming the occurrence of a set of events whose combinations may trigger a set of critical events. Full article

The interpretation of the evolutionary theory prevailing in sport, based on the approach that the strongest survive, varies with the rules inherent in the criminal world, forbidding to “take out” negative information about interrelationships, in this case, outside the team or group. Such traditionally established culture puts pressure on athletes to suffer from bullying and follow the “silence law”. In the long run, this turns into a precondition for unsafe environment for athletes, which, due to negative consequences for the individual, can be identified as threats to social sustainability at the individual level. Such a situation is also indirectly approved by the heads and coaches of organizations. The latter, who lack competencies to resolve conflict situations, are left to solve arising problems on their own and do not receive any support from the management of organizations. Therefore, the aim of this research is to reveal the factors determining the specificity, emergence, and development of bullying and harassment in sport as threats to social sustainability at the individual level. The research was conducted using a semi-structured interview method with eight coaches representing team, individual, and duel sport branches. Inductive content analysis served as the basis for the data analysis. Research results disclosed factors determining the specificity of emergence of bullying and harassment in sport and hindering the entrenchment of social sustainability in sport at the individual level. The results revealed the euphemisms distinguished by coaches, which, in sport, have a positive connotation, such as “combativeness” and “sports anger” instead of the term “aggression”. It was identified that coaches named aggressors as “harder players”, “confident players”, “active persons”, “players-torpedoes”, “emotional players”, and “competitive players”. Sports competition is justified in various forms. The emergence of bullying and harassment is grounded on “mastery differences”, it is stated that abusive actions are experienced by “physically weak” players, while physical actions used by athletes are called “mischief”; verbal actions are “raillery”. In addition, inadequate preparation of Lithuanian coaches to respond to bullying and harassment in their trained teams or groups on time and appropriately was identified. It turned out that sports organizations are not particularly interested in organizing trainings for prevention of destructive interrelations and intervention. Such kind of in-service training is left to the coach’s initiative. Full article

This paper presents a part of the work of the Department of Traditional Settlements and Listed Buildings (Department of T. S. & L. B.) of the Ministry of Interior (sector of Macedonia and Thrace) which concerns to the specialized legislative policy for the protection and designation of architectural culture, giving a brief reference on major designation processes of properties from the region of Macedonia and Thrace. The Department of T. S. & L. B. is responsible, since 1986, for identifying and protecting the architectural heritage of Northern Greece, by preserving buildings and areas or settlements from inappropriate changes or destruction, thus recognizing them as listed buildings or traditional settlements according to specific administrative procedure. Formal designation helps to protect traditional properties as listed buildings from inappropriate changes or destruction; meanwhile, the establishment of specific protection terms and restrictions of construction, the approval of architectural plans for restorations, interventions, uses or additions contribute that all listed buildings survive and prosper as “live shells”, along with other monuments. Additionally, in cases of traditional areas and settlements, other actions, e.g., modification of city plans, establishment of building rules, etc. have created a holistic protection framework preserving the architectural, urban and aesthetic character of significant historical areas of the city. Full article

Background: The need to advance and achieve success is deeply ingrained in human evolution. As a species, humans developed instincts that allowed them to survive and transmit their genes along generations. The will to win is an instinct that has been maintained in the species for millions of years. Sport is an activity as old as humans themselves and is subject to rules; Objective: The proposal of this work is to explore some of the most recurrent practices to achieve the athletes’ goals, and the origins and historical use of methods or substances to improve performance and its regulation, as well as to review the impact of new technologies on achieving better results and to make a proposal of what actions should be takenin order to prevent bad practices; Methods: A narrative literature review of ethical sports issues and decision-making was performed in the English language; Results: Practically all behavior with regards to the theme of sports is regulated by ethical codes that must be followed by sportspersons, as well as by everyone involved in the athlete’s healthcare and in the athlete’s administrative, marketing, and business aspects. Notwithstanding this, winning and reaping glory implies a reward far greater than fame and fortune, which can lead to poor ethical practices in athletes, as well as in interested parties who detract from the intrinsic value of the spirit of sports. The will to win could exceed the limits of what is permitted in fair-play, like the use of prohibited methods or substances; Conclusions: In this work, we review some of the bioethical aspects ofsports. Additionally, recommendations are offered for good practices and to prevent falling into poor ethical behavior. Full article

The ruling Chinese Communist Party (CCP) abolished its total ban on religious activities in 1982. However, the distrust that the CCP feels for religions remains obvious today, and the religious restrictions in contemporary China remain tight. Conventional wisdom tells us that the official atheist ideology of Marxism-Leninism is the main reason behind the CCP’s distrust for, and restriction of, religion. However, taking a historical institutionalist perspective, this paper argues that the religious restrictions in contemporary China are in fact rooted in the fierce political struggles of the country’s two major revolutions in the first half of the twentieth century. Without the support of religious groups, the Nationalist Republicans would have found it difficult to survive and succeed in overthrowing the Qing Dynasty during the Chinese Republican Revolution in the first decade of the twentieth century. Likewise, without cooperating with a wide range of religious groups, the CCP would have struggled to defeat the Nationalist regime and the Japanese invaders in the Chinese Communist Revolution between 1920s and 1940s. Thanks to the collaborations and struggles with various religious groups during the two revolutions which lead to its eventual ascent to power, the CCP thoroughly understands the organisational strength and mobilising capability embedded within religious groups. The tight restrictions on religious affairs in contemporary China is therefore likely to stem from the CCP’s worry that prospective competitors could mobilise religious groups to challenge its rule through launching, supporting, or sponsoring collective actions. Full article