The identification of numerous gene alterations in the past decade had a major impact on the treatment of Non Small Cell Lung Cancer (NSCLC). These driver mutations lead to specific biochemical pathways, which further promote growth and survival of cancer cells. There are several important mutations which represent well establish targets in the treatment of NSCLC. The first discovered drug-sensitive mutation in NSCLC was Epidermal Growth Factor Receptor (EGFR). The inhibition of EGFR has led the way for targeted therapy in the treatment of NSCLC. Erlotinib, the first anti-EGFR antibody was first approved in 2004. At first, the approval was referred to unselected patients after failure of chemotherapy, but was later proven to be superior in comparison with chemotherapy as first-line treatment of metastatic NSCLC with sensitizing EGFR mutations. Today, there are a variety of other anti-EGFR antibodies, such as gefitinib, afatinib, osimertinib or dacomitinib. The analyzes of phase 3 randomized trial FLAURA, showed superiority of osimertinib in first-line therapy with osimertinib in metastatic NSCLC with EGFR mutations regardless of T790M status. Antoher dirver mutation, found in approximately 5% of patients with NSCLC is ALK gene rearrangemet, also known as ALK fusion. This mutation is not routinely found in patients with squamous cell carcinoma, and therefore it is recommended to test for ALK fusions in patients with metastatic non-squamous NSCLC, based on the data showing efficacy of different kinase inhibitors, such as alectinib, brigatinib, ceritinib and crizotinib. ROS1 gene rearrangements (also known as ROS1 fusions) occur in about 1% to 2% of patients with NSCLC. There are different fusion partners that can be detected in NSCLC: CD74, SLC34A2, CCDC6 and FIG. The benefit of crizotinib, ceritinib and entrectinib for patients with ROS1 fusions was shown in different trials. Aditionally, there are others gene alterations, such as BRAF V600E mutation. These patients have a significant benefit in the treatment with combination of BRAF and MEK inhibitors dabrafenib and trametinib. Detection of RET rearrangements is predictive for the treatment with TKIs selpercatinib and pralsetinib. Furthermore, NTRK, METex14, KRAS mutations are proven to be very efficacious molecular biomarkers in the treatment of NSCLC. Testing for the expression of immune biomarker PD-L1 is crucial predictive biomarker for the treatment with immune checkpoint inhibitors. IHC testing for PD-L1 expression should be performed before first-line treatment in all patients with metastatic NSCLC. There are different checkpoint inhibitors (pembrolizumab, atezolizumab, nivolumab, ipilimumab, cemiplimab), which showed efficacy alone or in combination with other treatment regimens. Testing of lung cancer specimens for these alterations is important for identification of potentially efficacious targeted therapies, as well as avoidance of therapies unlikely to provide clinical benefit. With the invention of targeted therapies and antibodies directed against tyrosine kinases and other specific driver mutations, the treatment options in lung cancer changed from histology-based to molecular and biomarker-based treatment. These changes in the treatment of NSCLC put in spotlight the significance of the cooperation between oncology and pathology. Brain metastases occur in about 30- 50% of patients with HER2 positive and 40% of patients with triple negative breast cancer. Occurrence of CNS metastases is a marker of aggressive disease. Median overall survival of patients with brain metastases is 13 – 19 months in patients with HER2 positive disease and 4.4 months in patients with triple negative disease. Regarding radiotherapy, breast cancer brain metastases are treated the same as metastases from all other tumor sites. When setting up an indication for local treatment, crucial is to have information about the control of extracranial disease, possibility of further systemic therapy lines and patient’s performance status. Local therapy consists of surgical treatment, with or without consolidation stereotactic radiotherapy and radiotherapy as a sole modality. Preferred method of radiotherapy would be stereotactic radiotherapy (SRT), in patients with up to 10-15 metastases, limiting factor being the volume of the disease (up to 15 mL). With STR local control can be achieved in up to 60% of patients. Fractionated stereotactic radiotherapy (FSRT), delivered in 3 to 12 fractions provides 1- year local control rate in up to 80% of patients. In case stereotactic radiotherapy is not available or possible, patients with good performance status and extracranial disease control could be referred to whole brain radiotherapy (WBRT), which palliates symptoms in about 60% of patients. Both stereotactic and whole brain radiotherapy are connected with cognitive impairment, which is more often after WBRT. WBRT induced cognitive toxicity can be lowered by using hippocampal sparing radiation techniques. WBRT after SRT or neurosurgical procedure improves local control but has no effect on overall survival and can also lead to cognitive impairment. Therefore, WBRT is not indicated after these procedures. Upon neurosurgical operation, SRT of resection cavity should be performed, as it lowers the risk if intracranial relapse of the disease. There are several ongoing trials exploring different radiotherapy techniques (SRT or WBRT), and their timing and combination with various systemic agents in breast cancer patients with brain metastases, such as lapatinib, trastuzumab emtansine, pembrolizumab. In patients with low performance status, loss of extracranial disease control and short life expectancy, it would be reasonable to omit whole brain radiotherapy since it has no effect on survival or quality of life and the same palliative effect can be achieved with corticosteroids use only. Immunotherapy has evolved recently as very promising and possibly effective treatment of several tumor types. Immunotherapy has dramatically changed treatment landscape of some entities, but benefit in colorectal cancer was so far very modest due to fact that only up to 5% of patients with mCRC have high microsatelite instability and mismatch-repair deficient genes. These features are considered as biologic markers for tumors which we expect to respond to immunotherapy. According to data obtained from early clinical studies (phase II) and last year presented phase III study, KEYNOTE-177, led to FDA-approval of pembrolizumab in first line treatment of metastatic colorectal cancer in June 2020. KEY-NOTE-177 was a randomized, open-label study enrolling 307 treatment-naive patients with microsatelite instability-high/mismatch repair-deficient (MSI-H/dMMR) mCRC. Randomization was 1:1 to treatment with pembrolizumab or investigator’s choice of doublet chemotherapy (n=154) meaning standard of care. Dual primary endpoint were PFS and OS, and crossover was permitted at disease progression. This is very important trial, since it was the first randomized- trial evaluating first-line pembrolizumab in patients with metastatic colorectal cancer. This was especially critical for Europe, because pembrolizumab was not approved. It is worth to mention that about 25% of patients had BRAF V600E-mutant tumor sin the trial. Median PFS2 was not reached in the pembrolizumab group and was 23.5 months in the chemotherapy group (HR:0.63)(ASCO GI 2021). The 12-month rate was PFS2 76% for pembrolizumab and 67% for chemotherapy. The same tendency was at 24-month PFS2. The rate of adverse events (AEs) and treatment-related AEs was similar in both treatment arms. Grade ≥ 3 treatment-related AEs were much more common in the chemotherapy group, affecting 66% of the patients compared with 22% of the patients receiving pembrolizumab. Grade ≥ 3 diarrhea, fatigue, and neutropenia also were significantly higher in the chemotherapy group. These results were expected, as pembrolizumab is generally well-tolerated. Generally, quality of life did not decrease in pembrolizumab group (QoL scores), and pain and appetite loss also improved with pembrolizum vs chemotherapy. So, there was a clear benefit in both PFS and QoL for the use of pembrolizumab over chemotherapy. The rate of adverse events (AEs) and treatment-related AEs was similar in both treatment arms. Grade ≥ 3 treatment-related AEs were much more common in the chemotherapy group, affecting 66% of the patients compared with 22% of the patients receiving pembrolizumab. Grade ≥ 3 diarrhea, fatigue, and neutropenia also were significantly higher in the chemotherapy group. These results were expected, as pembrolizumab is generally well-tolerated. Although this results put immunotherapy as very attractive treatment modality, there are many questions still to be answered in the future. We still don’t know the relationship between KRAS-mutant phenotype and immunotherapy, as well as the meaning of other biomarkers. After all, some patients do not respond to immunotherapy, so in the near future we should define which patients would be optimal for immunotherapy in first line setting and which would benefit from chemotherapy, nevertheless. Bacground : Hepatocellular carcinoma is fourth leading cause of death among cancer patients. This cancer is four to eight times more common in the male population and is usually associated with chronic liver damage (hepatitis B (HBV), hepatitis C (HCV) and alcoholic cirrhosis). Cirrhosis, regardless of the cause, is present in 70-80% of HCC cases. Chronic infection with HBV and cirrhosis increases the possibility of HCC up to 100 times. 5-30% of patients with HCV infection develop chronic liver disease, > 30% progress to cirrhosis, and in that population, 1-2% of them develop HCC annually. Co-infection with HBV further increases the risk of developing the disease. Other risk factors are: alcohol abuse, autoimmune diseases (autoimmune hepatitis and primary biliary cirrhos

Abstract This chapter summarizes IRACON contributions related to the application of IoT in healthcare. It consists of the following three sections. Section 8.1 presents the measurement campaigns and the related statistical analysis to obtain various channel models for wearable and implantable devices. In addition, the importance of physical human-body phantoms used for channel, Specific Absorption Rate (SAR), and Electromagnetic (EM) exposure measurements are examined. Methodologies to improve the accuracy of these phantoms for various frequency bands are also discussed. Section 8.2 outlines methodologies to improve the medium access control (MAC) and networking layers of a body area networks along with possible architectures for remote health monitoring. Several applications such as localization, activity recognition, and crowdsensing and their corresponding technical challenges are also presented in this section. Finally, Section 8.3 introduces the concept of nanocommunications which can be considered as the nano-scale limit of the IoT technology spectrum. It provides an overview of the promising mechanisms that can establish data communication at molecular levels inside the human body as well as various interfacing techniques with macro-scale devices. It also highlights the revolutionary healthcare applications that could be enabled by this technology.

Journal of Anthropology and Archaeology is a peer-reviewed international journal, which publishes original papers promoting theoretical, methodological and empirical developments in the discipline of socio-cultural anthropology.

The choice of the appropriate variety of fruit is one of the most important factors in establishing new orchards. It is necessary to choose the variety that will give the best results in meeting the investment goals. This paper offered an innovative decision support model for plum variety selection, based on expert decision making and fuzzy logic. The fuzzy MARCOS (Measurement Alternatives and Ranking according to COmpromise Solution) method was used. The research was conducted with the aim of improving plum production in Bosnia and Herzegovina (BiH). To achieve this, the knowledge of experts from the Republic of Serbia was used, because this country is currently the third in the world in plum production and have branded many plum varieties. The results obtained using this model showed that two plum varieties stand out - Cacanska rodna and Stanley. These results were also confirmed by the performed sensitivity analysis. The worst results were obtained by the Sumadijka variety. These results will help in the selection of plum varieties when establishing new orchards in BiH to achieve the best results in Bosnian plum production.

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), persists as a threat to global health and continues to be a rapidly evolving condition. Although COVID19 is negatively correlated with the existing comorbidities in terms of the clinical outcome, the ability of SARS-CoV-2 to mediate the novel, or to exacerbate the existing autoimmune conditions, has generated considerable interest, due to its potential implications both with regard to patients suffering from autoimmune conditions, as well as to the long-term consequences of the disease. However, although molecular mimicry has been postulated as a potential causative factor in post-COVID19 autoimmunity and multi-organ damage, a substantial body of research needs to emerge in order to achieve a more definitive conclusion. We investigated the possibility of SARS-CoV-2 peptide sequences behaving as molecular mimics with a potential to trigger an autoimmune response. Thus, on the basis of analysis in silico, we were able to develop a plausible case for the molecular mimicry as a potential aetiological mechanism of SARS-CoV-2-mediated autoimmunity, both in a multi-organ damage context or outside of the viral phase of infection. Interestingly, this is the first time that the peptide sequence of MACROD1 has been implicated in the COVID-19 autoimmunity. Additionally, we also confirm that PARP9 and PARP14 may be involved in the process.

For validation and demonstration of high accuracy ranging and positioning algorithms and systems, a wideband radio signal generation and acquisition testbed, tightly synchronized in time and frequency, is needed. The development of such a testbed requires solutions to several challenges. Tight time and frequency synchronization, derived from a centrally distributed time-frequency reference signal, needs to be maintained in the hardware of the transmitter and receiver nodes, and wideband signal acquisition requires sustainable data throughput between the receiver and host PC as well as data storage at GB level. This article presents a testbed for wideband radio signal acquisition, for validation and demonstration of high accuracy ranging and positioning. It consists of multiple Ettus X310 universal software radio peripherals (USRPs) and supports high accuracy (<100 ps) time-deterministic, sustainable signal transmission and acquisition, with a bandwidth up to 320 MHz (in dual channel mode) and frequencies up to 6 GHz. Generation and processing of wideband arbitrary signal waveforms is done offline. To realize these features, radio frequency on chip (RFNoC) compatible HDL units were developed for integration in the X310 SDR platform. Wideband transmission and signal acquisition at a lower duty cycle is applied to reduce the data offloading throughput to the host’s personal computer (PC). Benchmarking of the platform was performed to demonstrate sustainable long duration dual channel acquisition. Indoor range measurements with the synchronous operation of the testbed show a decimeter-level accuracy.

The main intention of this paper is to explore the possibility of positioning the discourse on adult identity formation within the context of higher education. To this end, first formational potential of higher education is revisited. Further on, Eriksonian psychosocial theoretical approach and Arnett's concept of emerging adulthood are proposed as the referential framework for conceptualizing adult identity formation processes. It is concluded that by offering instituzionalized moratorium and the possibility for the extended transition from adolescence to adulthood, higher education context provides intensive identity work opportunities. However, in dominant discourses, higher education's humanistic ends have been suppressed by economistic and utilitarian objectives. Therefore, this paper also urges revitalizing higher education's humanistic values by exploring personal growth posibilities.

that the air sacs. The morphology of the air sacs system has been described in many domestic and wild bird Abstract | The research was conducted with the aim to investigate the morphology of air sacs system in Crimson Rosella ( Platycercus elegans ) parrots. Five adult birds, two males and three females were used in this study. The lungs and air sac system were injected via trachea with 26% solution of Vinylite mass. The obtained cast showed that these parrots have nine air sacs. The clavicular air sac was the only unpaired, while the cervical, cranial thoracic, caudal thoracic and abdominal air sacs were paired. The morphology of the air sacs was generally similar to that reported in other bird species, however, some specific features were identified. As most prominent among them were a partial fusion of the cervical air sacs, communication between the left and right subpectoral and perirenal diverticula and connection between the claviclar and cranial thoracic air sacs. The present investigation provided detailed and comprehensive data about the morphology of air sacs system in these parrot species and these findings will be very useful for future clinical examination and treatment of this birds.

The aim of this study is to investigate how various elements of digital content impact the behavioural engagement of the content’s users in the setting of Southeast Europe, which has recently experienced turbulence in its political and social interrelationships. Using the stimulus-organism-response (S-O-R) theory we develop a model that considers two types of stimuli: digital content tone (consisting of positive and negative valence) and digital content substance, as well as two types of behavioural responses: opens and clicks on the content. Research is conducted in six countries over a period of three years, investigating objective users’ behavioural indicators for a regional newsletter. The results show digital content tone impacts users’ response in terms of opens and that this effect differs across the region. Furthermore, we show that the digital content substance is significantly related to number of clicks on the newsletter content and that this effect is curvilinear for the number of news features and number of calls, while it is positive and linear for the stakeholder/keywords mentions. Theoretical and managerial implications of the study are elaborated and discussed.