Precise Diagnosis of Histological Type of Lung Carcinoma: The First Step in Personalized Therapy

This chapter is a combination of personal experience of a pulmonary pathologist and available references in the diagnosis of non-small cell lung cancer (NSCLC) types. The morphological appearance of poorly differentiated lung carcinoma is not characteristic, so immunohistochemical staining is used for further differentiation. In order to save tumor tissue from paraffin blocks, the most rational way is to use only two antibodies, p40 for squamous cell carcinoma and TTF-1 for adenocarcinoma of the lung, and if necessary or if cancer growth is organoid, also one of two neuroendocrine markers (CD56 or Synaptophysin) can be used. If there is enough tumor tissue in the paraffin block to confirm the diagnosis, NapsinA, p63, Cytokeratin5/6 or Cytokeratin5 can be used. It should be kept in mind that no antibody is highly specific for one histological type of carcinoma or its origin and if the immunohistochemical finding is unspecific, it should be concluded that this is “not otherwise specified” (NOS) carcinoma. The rest of tissue must be preserved for current and future molecular testing and predictive immunohistochemical staining for the purpose of personalized NSCLC therapy

SCOPE AND QUALITY OF LEGAL PROTECTION AFFORDED TO COMPUTER PROGRAMS AS OBJECT OF INTELLECTUAL PROPERTY

Computer programs are basic components of the usage of digital technology in all aspects of modern life, so the question arises as to how can current legal rules follow the development of digital technology  i.e. computer programs as well as modalities of its usage. The use of digital technology, especially via creation of computer programs, affects the law, and, consequently, leads to the need for adjusting already established legal mechanisms or for creating new ones for this aspect of legal relations. Since creation and usage of computer programs is basically result of human creative activity (intellectual property), the need arises to position and classify, as well as to define rights, obligations and legal protection of subjects and objects involved in these legal relations. Computer program, in the context of the law of Republic of Serbia, is treated as an object of copyright, while comparative law analyses shows different legal treatments in national laws in the region. Having in mind that computer technology develops far more faster than legal regulation can follow, question arises as to what is current scope and quality of legal protection of computer programs, as object of intellectual property. Defined issues will be analyzed within legal systems of the states in the region – Republic of Serbia, Republic of Croatia, Republic of Montenegro and Bosnia and Herzegovina, as well as in the wider context of the law of the European Union and the process of harmonization of national laws with community law

WRAP CONTRACTS AND THEIR INFLUENCE ON THE CONTRACT LAW

The basis of the digital economy is electronic commerce (e-commerce), based on contracting which increasingly relies on the use of a digital technology. A contract represents the basis of legal obligation, as well as the foundation of the validity and legitimacy of legal rules, dating back to the theory of the social contract. The functioning of the digital society and digital economy has introduced the process of digitization into the scope of the Contract Law and contracting practice. On the example of wrap contracts, as a kind of online contracts by access (adhesion contracts), the author shows how new practices in contracting affect the traditional obligation law institutes

Predicitve significance of PI3K/Akt signaling pathway and transport pumps involved in the development of drug resistance in patients with non small cell lung cancer

Uvod: Karcinom pluća je najčešći uzrok smrti od maligniteta globalno. Oko 80% svih karcinoma pluća su nesitnoćelijski karcinomi (NSCLC) kod kojih preovladavaju adenokarcinom (ADC) i skvamocelularni karcinom (SCC). Mada je hirurška resekcija najpovoljnija terapijska procedura u lečenju pacijenata sa nesitnoćelijskim karcinomom pluća, relaps tumora je i dalje visok, tako da je neoadjuvantna hemoterapija (NAC) prihvatljiv terapijski modalitet. Cilj: Istražiti da li neki od ključnih molekula uključenih u RAS/RAF/MEK/ERK i PI3K/Akt/mTOR signaline puteve kao i transportne pumpe uključene u razvoj rezistencije na lekove mogu imati prediktivni i prognostički značaj u aplikaciji NAC kod bolesnika sa nemikrocelularnim karcinomom pluća. Metod: Ispitalivali smo status PTEN, pAkt, pERK, P-gp, MDR1 i BCRP proteinske ekspresije i gubitak heterozigotnosti PTEN-a u dve grupe pacijenata sa NSCLC, onih koji su primali i onih koji nisu primali NAC. Rezultati: Utvrđeno je da LOH PTEN-a i niska pERK ekspresija koreliše sa dužim preživljavanjem pacijenata sa SCC odnosno ADC, koji su primali NAC. MRP1 ekspresija je statistički značajno povišena kod pacijenata koji nisu primali neoadjuvantnu hemoterapiju, što znači da su posedovali urođenu rezistenciju na hemoterapiju i pre započinjanja iste. Takođe, MRP1 je značajno povišen kod pacijenata koji nisu primali neoadjuvantnu hemoterapiju i imali su I ili II stadijum bolesti. BCRP je značajno viši kod pacijenata koji nisu primali terapiju i nisu imali tumorske promene u limfnim čvorovima. Pacijenti koji nisu primali neoadjuvantnu hemoterapiju i koji su imali smanjenu P-gp ekspresiju živeli su značajno duže od pacijenata koji su primali terapiju sa istom P-gp ekspresijom. Pored toga, pacijenti sa SCC, bez NAC i sa smanjenom P-gp ekspresijom živeli su značajno duže od pacijenata sa NAC. Zaključak: Primena NAC je korisna kod pacijenata sa NSCLC i specifičnim molekularnim promenama koje ubuduće mogu pomoći da se poboljšaju stalna istraživanja za terapeutskim metama koje se koriste u personalizovanoj terapiji.Introduction: Lung cancer is the most common cause of neoplasia-related death worldwide. Approximately 80% of all lung carcinomas are the non-small cell lung carcinoma (NSCLC) with predominance of adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although surgical resection is the most favorable treatment for patients with NSCLC, relapse is still high, so neoadjuvant chemotherapy (NAC) is an accepted treatment modality. Aim: To investigate whether some of the key molecules associated with the RAS/RAF/MEK/ERK and PI3K/Akt/mTOR signaling pathways as well as efflux pumps P-gp, MRP1 and BCRP could have predictive and prognostic value for the NAC application in patients with NSCLC. Method: We examined the expression status of PTEN, pAKT, pERK, P-gp, MRP1 and BCRP proteins and loss of heterozygosity (LOH) of PTEN gene in two groups of NSCLC patients, those who received and those who did not receive NAC. Results: LOH PTEN and low pERK expression are shown to be correlated with the longest survival of patients with SCC and ADC, respectively, who received NAC. MRP1 expression is significantly higher in patients who did not receive NAC, which means that they had intrinsic resistance to chemotherapy. Also, MRP1 is significantly higher in patients who did not receive NAC and had I or II stage of the disease. BCRP was significantly higher in patients who did not receive neoadjuvant chemotherapy and were without lymph node invasion. Patients who did not receive NAC band had lower P-gp expression lived significantly longer than patients who received this therapy and had the same P-gp expression. Besides, patients with SCC, without NAC and with lower P-gp expression lived significantly longer than patients with NAC. Conclusion: Application of NAC is beneficial in the NSCLC patients with specific molecular alterations which could further help to improve constant search for the molecular targets used in personalized therapy

National responsibility of the European Union in the light of the international law rules on the responsibility of international organizations

Предмет истраживања у овој докторској дисертацији јесте да ли се на Европску унију и њене државе чланице, имајући у виду посебност саме Уније и њеног поретка, могу применити општа правила о међународној одговорности садржана у Нацрту правила о међународној одговорности међународних организација Комисије за међународно право, или се може дефинисати посебно правило, у смислу lex specialis-а које би се могла применити на Унију. Овако дефинисан предмет спада у област права међународних организација, као уже области међународног јавног права, али у значајној мери обухвата и европско (комунитарно) право. Проблем одговорности међународних организација је данас све актуелније питање, о чему сведочи и брз развој ове гране међународног права на светским и европским правним факултетима, као и рад Комисије за међународно право Уједињених нација на кодификацији правила о одговорности међународних организација. Две су основне хипотезе на којима се заснива истраживање у овом раду. Прво, полази се од посебности Европске уније у односу на традиционалан концепт међународних организација. У том смислу, након приказа актуелних кодификованих правила о међународној одговорности међународних организација, у раду се анализира Унија као међународне организације, и њен поредак, у односу на уобичајене карактеристике међународних организација у међународном праву. Друга хипотеза тврди да је могуће из досадашње праксе утврђивања међународне одговорности Европске уније пред различитим форумима издвојити правило које би се могло применити у форми lex specialis-а, посебно у случајевима одговорности Уније и чланица проистеклих из „децентрализованости имплементације комунитарног поретка“. У циљу потврде ове хипотезе, истраживање обухвата спорове у којима је учествовала Европска унија пред различитим судским телима која су одлучивала о њеној одговорности.The research subject of this doctoral thesis is whether general rules on international responsibility of international organizations, as defined by International Law Commission, in Draft Articles on responsibility of international organizations (hereinafter: Draft), can be applied to European Union and member states, bearing in mind specificity of the Union and its order, or special rule can be defined in terms of lex specialis. Thus defined, the research subject falls within the area of the law of international organizations, as specific branch of public international law, but to a significant extent, also within European (communitarian) law. Responsibility of international organizations represents increasingly significant topic in contemporary international law, as evidenced by rapid development of this branch of international law in international and European law schools study programs, and also by the work of the International Law Commission of the United Nations on the codification of rules on the responsibility of international organizations. This research in based upon two hypothesis. Firstly, European Union is considered special in relation to the traditional concept of international organizations. Thus, after presenting codified rules on international responsibility of international organizations, author analyzes the Union as an international organization, and its order in relation to the common characteristics of international organizations in international law. The second hypothesis argues that it is possible, based on the current jurisprudence on the international responsibility of the European Union before various forums, to define a rule that could be applied in the form of lex specialis, especially in cases of responsibility of the Union and its Member States stemming from "the decentralized implementation of the Community legal order." In order to confirm this hypothesis, the study includes cases before various judicial bodies in which participated the European Union and which have decided on its responsibility

Stavovi studenata prema primjeni mobilne proširene stvarnosti u visokom obrazovanju

Virtual (VR) and augmented reality (AR) have emerged from the framework of academic and industrial laboratories and have acquired global attention. Currently, the focus shifted from the technologies themselves to finding adequate teaching and learning applications. In this paper, the students\u27 attitudes toward the application of mobile AR (MAR) in higher education (HE) were researched (with a focus on augmented textbooks). The results showed that the students have a mostly positive attitude, and it is concluded that there was no statistically significant difference between the STEM (science, technology, engineering, and mathematics) and non-STEM students\u27 opinions regarding this topic. Based on the results, the further research and integration of this technology into HE settings can be suggested.Virtualna i proširena stvarnost izašle su iz okvira akademskih i industrijskih laboratorija i stekle su globalnu pozornost. Trenutačno se fokus pomaknuo sa samih tehnologija prema pronalaženju odgovarajuće primjene u poučavanju i učenju. U ovom radu istraživani su stavovi studenata o primjeni mobilne proširene stvarnosti u visokom obrazovanju (s naglaskom na augmentiranim udžbenicima). Rezultati su pokazali da studenti imaju uglavnom pozitivan stav, a zaključeno je i da ne postoji statistički značajna razlika u mišljenju između STEM (znanost, tehnologija, inženjerstvo i matematika) i ne-STEM studenata o ovoj temi. Na temelju rezultata istraživanja mogu se predložiti daljnja istraživanja i integracija ove tehnologije u postavke visokog obrazovanja

Učinak dipping profila gestacijske hipertenzije na majčine simptome i fizikalne nalaze, porođajnu težinu i prijevremeni porođaj

The study aimed to determine if the non-dipping pattern of blood pressure (BP) influences preterm delivery in gestational hypertension (GH), but also maternal clinical findings and birth weight. Sixty women with GH, i.e. 30 women with a dipping BP profile (control group) and 30 non-dippers (study group), were included in the study. Echocardiography was performed in all subjects, as well as ambulatory blood pressure monitoring (ABPM) during third trimester. ABPM was repeated 6-8 weeks after delivery. Thirteen women with preterm delivery were classified as non-dippers and only four as dippers (p=0.01). The average and peak systolic and diastolic night-time BP had negative linear correlation with birth weight (p<0.0005). Total vascular resistance (p<0.0005) and mass index (p=0.014) were significantly higher as compared with women with term delivery, while ejection fraction (EF) (p=0.007) and circumferential systolic velocity (p=0.042) were significantly reduced in the preterm delivery group. Multivariate binary logistic regression identified the average night-time systolic BP, left ventricular mass index and EF as independent predictors of preterm delivery. Study results suggested a relationship of the non-dipping BP pattern in GH with preterm delivery, birth weight, and maternal clinical findings.Cilj ovoga istraživanja bio je utvrditi povezanost non-dipping profila krvnog tlaka (KT) s prijevremenim porođajem, porođajnom težinom novorođenčeta te kliničkim i ehokardiografskim parametrima kod žena s gestacijskom hipertenzijom (GH). Istraživanje je obuhvatilo 60 žena s GH, 30 s dipping profilom KT (kontrolna skupina) i 30 non-dippera (ispitna skupina). Sve žene podvrgnute su kompletnoj ehokardiografiji i 24-satnom ambulantnom praćenju krvnog tlaka (ambulatory blood pressure monitoring, ABPM) tijekom trećeg trimestra, a ABPM je ponovljen 6-8 tjedana nakon porođaja. Ukupno 17 žena imalo je prijevremeni porođaj. Trinaest žena s prijevremenim porođajem imalo je non-dipping profil KT, dok su samo četiri žene imale dipping profil KT (0,01). Prosječni i maksimalni sistolički i dijastolički noćni KT imali su negativnu linearnu korelaciju s porođajnom težinom (p<0,0005). Ukupna vaskularna rezistencija (p<0,0005) i indeks mase miokarda lijeve klijetke (p=0,014) bili su znatno viši u skupini žena s prijevremenim porođajem, dok su parametri sistoličke funkcije, tj. ejekcijska frakcija (EF) (p=0,007) i brzina cirkumferentnog skraćenja miokarda lijevog ventrikla (p=0,042) bili statistički značajno sniženi u skupini žena s prijevremenim porođajem. Multivarijatna regresijska analiza pokazala je da su prosječni noćni sistolički KT, indeks mase lijevog ventrikla i EF identificirani kao nezavisni prediktori prijevremenog porođaja. Rezultati istraživanja pokazali su da postoji povezanost između non-dipping profila KT s prijevremenim porođajem, porođajnom težinom novorođenčeta i poremećajem hemodinamskog statusa majke u GH

Teachers’ views of inclusive education in Serbian schools

This study was conducted to determine the attitudes of teachers concerning inclusion in schools all over Serbia. The respondents were teachers of different subjects who were tasked to anonymously complete the provided closed-type questionnaire (970 respondents). Primary and secondary school teachers from urban and rural areas of the Republic of Serbia participated in the research. The results indicate that the teachers are supportive of inclusion. Despite significant differences in respondents’ answers, the results of the research show that there are many similarities in teacher responses toward inclusive education. The results show that it is still necessary to work on the implementation of inclusive education in Serbia, especially to educate the teaching staff and involve experts in the planning and development of individual educational plans.Keywords: attitudes; inclusive education; Serbia; teacher