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The associated publication reports proteogenomic analysis of non-small cell lung cancer, where we identified molecular subtypes with distinct immune evasion mechanisms and therapeutic targets, and validated our classification method in separate clinical cohorts. This protocol describes histological, tertiary lymphoid structure (TLS), and immunohistochemical evaluation of clinical samples. Specifically, immunohistochemistry was performed for PD-L1, CD3, and CD8 on tumor microarrays (TMAs) derived from formalin-fixed paraffin embedded (FFPE) samples.

The associated publication reports proteogenomic analysis of non-small cell lung cancer (NSCLC), where we identified molecular subtypes with distinct immune evasion mechanisms and therapeutic targets, and validated our classification method in separate clinical cohorts. This protocol describes sections of the bioinformatics analysis of the multi-omics data, namely, data analysis and processing for panel sequencing, identification of cancer- and driver-related proteins in proteomics data, proteogenomics search, and machine learning-based classifiers for NSCLC subtyping. Specifically, a cohort classifier was built using support-vector machine-recursive feature elimination (SVM-RFE) algorithm applied to in-depth proteomics data from a cohort of 141 samples. The classifier was then validated in three external datasets. Another classifier, suitable for single-sample subtyping, was built using k-top scoring pairs (k-TSP) algorithm applied to label-free data from a cohort of 136 samples. The k-TSP-based classifier was validated in two independent cohorts and an additional external dataset.

The associated publication reports proteogenomic analysis of non-small cell lung cancer (NSCLC), where we identified molecular subtypes with distinct immune evasion mechanisms and therapeutic targets, and validated our classification method in separate clinical cohorts. The in-depth proteomic analysis pointed to a potential role of STK11 inactivation in liver-specific signaling and subsequent cancer growth and immune evasion mechanisms. This protocol describes in vitro validation of the downstream effects of STK11-AMPK signaling on HNF1A and FGL1 in a liver and two lung cancer cell lines.

The associated publication reports proteogenomic analysis of non-small cell lung cancer, where we identified molecular subtypes with distinct immune evasion mechanisms and therapeutic targets, and validated our classification method in separate clinical cohorts. This protocol describes the sample preparation and mass spectrometry (MS)-based in-depth and rapid proteomic analyses of tumor and biopsy samples. We deployed single-pot solid-phase-enhanced sample preparation (SP3). For the in-depth analysis, we used TMT labeling, followed by high-resolution isoelectric focusing (HiRIEF) prefractionation and LC-MS with data-dependent acquisition (DDA). The reported protocol achieved analytical depth of close to 14,000 quantified proteins and almost 10,000 across the entire cohort of 141 samples. The rapid analysis was label-free, based on LC-MS with data-independent acquisition (DIA). The median number of identified proteins was 3,967 and 3,552 in two independent cohorts of tumor samples (n = 141 and 208, respectively), and 2,494 in another cohort of biopsy material (n = 84).

Despite major advancements in lung cancer treatment, long-term survival is still rare and a deeper understanding of molecular phenotypes would allow the identification of specific cancer dependencies and immune-evasion mechanisms. Here we performed in-depth mass-spectrometry-based proteogenomic analysis of 141 tumors representing all major histologies of non-small cell lung cancer (NSCLC). We identified six distinct proteome subtypes with striking differences in immune cell composition and subtype-specific expression of immune checkpoints. Unexpectedly, high neoantigen burden was linked to global hypomethylation and complex neoantigens mapped to genomic regions, such as endogenous retroviral elements and introns, in immune-cold subtypes. Further, we linked immune evasion with LAG-3 via STK11 mutation-dependent HNF1A activation and FGL1 expression. Finally, we develop a data-independent acquisition mass-spectrometry-based NSCLC subtype classification method, validate it in an independent cohort of 208 NSCLC cases and demonstrate its clinical utility by analyzing an additional cohort of 84 late-stage NSCLC biopsy samples. Lehtio and colleagues perform proteogenomic analysis of non-small cell lung cancer and identify molecular subtypes with distinct immune-evasion mechanisms and therapeutic targets and validate their classification method in separate clinical cohorts.

If our time is stressful, than protecting and promoting of our mental health is imperative of the time that is coming.In modern literature there is a huge interest for the determination of the mental health of the emotional intelligence, which is treated as a factor for it’s keeping and development. This paper is based on the assumption that the emotional intelligence has considerable contribution for understanding the relationship between psychosocial stress and mental health, seen through three important variables: self-confidence, depression and aggressiveness. In the research were included 72 people, and for variables’ measurement are used: questionnaire for measuring emotional intelligence (PК-45), stress inventory and questionnaire for emotional structure of the person- Profile index of emotions. The results from the regressive analyses showed that stress is connected to the three indicators of the mental health. People with low emotional intelligence react with lower self-confidence and high depression and aggressiveness in stressful situations. The two competencies of emotional intelligence (EI) - self consciousness and social consciousness statistically are different from the other relevant measures which show that EI is important thing in understanding the relationship between the stress and mental health.

Modern education considers schools and faculties for institutions whose goals have a broader scope than just an academic competence. Educational institutions have an obligation to completely prepare young people for adulthood and improve their optimal functioning and well being. This paper shows how the application of the positive psychology in the education can help schools and faculties to develop and maintain optimal functioning of the students and the employees. Educational institutions should approach strategically in the creation of positive educational programs that include elements of positive psychology, which positively reflects on the well-being and positive educational climate. The empirical findings of this paper confirm the role of positive psychology in education for improving the subjective dimensions of students: happiness, optimism, self-confidence, social and emotional competence. Students who attended educational programs with elements of positive psychology, have shown higher personal, emotional, social achievements and general well-being, which are prerequisites for realizing their potential. These findings imply the need to expand the arsenal of education through a positive education that includes the development of positive emotions that promote happiness and well-being.

Introduction: The Eustachian valve (EV) remnant, when present in adults, is usually rudimentary. However, in echocardiographic examinations, it may appear as a mobile long structure in the right atrium, and it rarely protrudes into the right ventricle. When it is quite large, the EV remnant could be misdiagnosed as a right atrial tumor, thrombus, or vegetation. Case Presentation: An 83-year-old patient was referred to the surgical ward for the excision of a gastric adenocarcinoma. In the course of preoperative assessment, transthoracic echocardiography showed a right atrial mobile filamentous mass that was protruding into the right ventricle. Differential diagnosis included a tumor or thrombus. After a precise evaluation through multiple views, the mass was demonstrated to be a giant EV, 7.3 cm in length. Conclusions: The giant EV remnant can persist in adults and is often diagnosed incidentally via echocardiography. Transthoracic echocardiography is a reliable noninvasive method for the diagnosis of the EV remnant and could help avoid its misdiagnosis as a tumor or thrombus. Nevertheless, sometimes transesophageal echocardiography is necessary to confirm the diagnosis or to demonstrate the existence of an additive clot on it.

Introduction: Left atrial thrombi are present in one third of patients with severe rheumatic mitral stenosis and atrial fibrillation. A left atrial mass can be diagnosed as a thrombus by transthoracic echocardiography in the presence of the predisposing factors for a thrombus such as mitral stenosis and atrial fibrillation. The sensitivity of transthoracic echocardiography for detecting left atrial appendage thrombi is low, and only a few case reports have been described in the literature. Case Presentation: This report describes the case of a 65-year-old female with severe rheumatic mitral stenosis and chronic atrial fibrillation presenting with congestive heart failure. This patient was shown, by means of transthoracic echocardiography, to have a large immobile left atrium cavity mass (6.5 × 3.4 × 2.3 cm) and a large left atrial appendage mass (1.7 cm) identified as a thrombus. Contrast computed tomography of the chest confirmed the diagnosis. Conclusions: Transthoracic echocardiography was sufficient to establish the diagnosis and to decide its management.