AI Aided Design of Epitope-Based Vaccine for the Induction of Cellular Immune Responses Against SARS-CoV-2.

The heavy burden imposed by the COVID-19 pandemic on our society triggered the race toward the development of therapies or preventive strategies. Among these, antibodies and vaccines are particularly attractive because of their high specificity, low probability of drug-drug interaction, and potentially long-standing protective effects. While the threat at hand justifies the pace of research, the implementation of therapeutic strategies cannot be exempted from safety considerations. There are several potential adverse events reported after the vaccination or antibody therapy, but two are of utmost importance: antibody-dependent enhancement (ADE) and cytokine storm syndrome (CSS). On the other hand, the depletion or exhaustion of T-cells has been reported to be associated with worse prognosis in COVID-19 patients. This observation suggests a potential role of vaccines eliciting cellular immunity, which might simultaneously limit the risk of ADE and CSS. Such risk was proposed to be associated with FcR-induced activation of proinflammatory macrophages (M1) by Fu et al. (2020) and Iwasaki and Yang (2020). All aspects of the newly developed vaccine (including the route of administration, delivery system, and adjuvant selection) may affect its effectiveness and safety. In this work we use a novel in silico approach (based on AI and bioinformatics methods) developed to support the design of epitope-based vaccines. We evaluated the capabilities of our method for predicting the immunogenicity of epitopes. Next, the results of our approach were compared with other vaccine-design strategies reported in the literature. The risk of immuno-toxicity was also assessed. The analysis of epitope conservation among other Coronaviridae was carried out in order to facilitate the selection of peptides shared across different SARS-CoV-2 strains and which might be conserved in emerging zootic coronavirus strains. Finally, the potential applicability of the selected epitopes for the development of a vaccine eliciting cellular immunity for COVID-19 was discussed, highlighting the benefits and challenges of such an approach.

Elective lung resection increases spatial QRS-T angle and QTc interval.

BACKGROUND: Lung resection changes intra-thoracic anatomy, which may affect electrocardiographic results. While postoperative cardiac arrhythmias have been recognized after lung resection, no study has documented changes in vectorcardiographic variables in patients undergoing this surgery. The purpose of this study was to analyse changes in spatial QRS-T angle (spQRS-T) and corrected QT interval (QTc) after lung resection. METHODS: Adult patients undergoing elective lung resection under general anaesthesia were studied. The patients were allocated into four groups: those undergoing (1) left lobectomy (LL); (2) left pneumonectomy (LP); (3) right lobectomy (RL); and (4) right pneumonectomy (RP). The spQRS-T angle and QTc interval were measured one day before surgery (baseline) and 24, 48 and 72 h after surgery. RESULTS: Seventy-one adult patients (47 men and 24 women) aged 47-80 (65 ± 7) years were studied. In the study group as a whole, lung resection was associated with significant increases in spQRS-T (p < 0.001) and QTc (p < 0.05 at 24 and 48 h and p < 0.01 at 72 h). The greatest changes were noted in patients undergoing LP. Postoperative atrial fibrillation (AF) was noted in 6.4% of patients studied, in whom the widest spQRS-T angle and the most prolonged QTc intervals were also noted. CONCLUSIONS: Lung resection widens the spQRS-T angle and prolongs the QTc interval, especially in patients undergoing LP. While postoperative AF was a relatively rare complication after lung resection in this study, it was associated with the widest spQRS-T angles and most prolonged QTc intervals.

The presence and clinical implications of α-2,6-galactose-linked sialic acids in non-small-cell lung cancer brain metastases--preliminary study.

Brain metastases (BM) in non-small-cell lung cancer (NSCLC) patients present an increasing clinical challenge. Identifying biomarkers which specifically identify patients at high risk of BM may improve their early diagnosis, which is crucial for surgical and radiotherapeutic treatment outcome. Alpha-2,6-sialyltransferase (α-2,6-ST) and the primary product of its activity, alpha-2,6-galactose-linked sialic acids (α-2,6-GalSA) have been found responsible for the adhesion of tumor cells to the brain vessels' endothelium and enabling their transmigration through the blood-brain barrier in brain metastatic tumors. The aim of the study was to investigate by histochemical method the presence and possible role of α-2,6-GalSA in the formation of brain metastasis in NSCLC. In the screening phase 76 metastatic brain tumors were stained for α-2,6-GalSA and the second phase involved an identical staining of 20 primary tumors of patients who had their primary tumors treated with surgery or definite radiochemotherapy yet who later developed BM. The results were compared to a control group of 22 patients treated with surgery for NSCLC and who survived 5 years without the recurrence of disease. Alpha-2,6-GalSA presence was found to be down-regulated in poorly differentiated tumor types, whereas majority of differentiated tumors overexpressed it. This was statistically significant for both BM and the primary tumors. The expression of α-2,6-GalSA remained stable in primary and metastatic tumor pairs, however, no statistically significant differences were observed between study and control groups. Within the study group, a higher α-2,6-GalSA expression was associated with better overall survival, but not all statistical models found this result significant. Further studies are recommended to validate these findings.

Urban vs. rural patients. Differences in stage and overall survival among patients treated surgically for lung cancer.

INTRODUCTION: Besides the undoubted influence of risk factors on morbidity and survival time, there are also other environmental factors, such as awareness of the prevalence of risk factors and the availability of modern diagnosis and treatment methods. OBJECTIVE: To evaluate differences in lung cancer 5-year overall survival rates between urban and rural patients hospitalized in the Department of Thoracic Surgery of the Medical University in Lublin, Poland, and possible influence of several risk factors on these rates. MATERIALS AND METHODS: The analysis was based on 125 lung cancer patients who underwent surgical procedures in years 2006-2007 and who agreed to take part in the survey. The study aimed at recognition of the health situation and selected demographic traits of people who had been treated surgically for lung cancer. The differences were evaluated between rural and urban inhabitants in gender, age, lung function, smoking habits, exposure to risk factors at work, family history of cancer, staging of the disease, histological type of cancer, post-surgical treatment, and their possible influence on overall survival. RESULTS: The results showed that the only noted differences between urban and rural population were in tobacco smoking and lung function. Survival rates were very similar and did not differ from the European average. CONCLUSIONS: The assumption that Polish rural patients are presenting with later cancer stages at the time of diagnosis, and have worse chances for survival, has become invalid in modern times.

[Active and passive smoking among students of Polish high schools]. / Aktywne i bierne palenie wsród uczniów polskich szkól srednich.

The survey was conducted among 29540 students in different secondary schools. All interviewers were 17.42 +/- 1.14 years old. The aim od this work was to define the relation between smoking adolescent and their health. The group of smokers consisted of 5112 (60.26%) men and 3370 (33.70%) women. The main causes of initiating smoking reported by respondents included curiosity--(47.91%) followed by stress (39.82%) and alcohol (6.77%). Smoking tobacco by parents at home results in inspiring by their children the unwholesome ingredients of tobacco smoke. Frequent staying among tobacco smokers significantly influences decision of starting or giving up smoking tobacco (59.24%). The obtain results may be helpful in preparing effective educational and preventive project among students, which can eliminate or lower the influence of factors predisposing to start and continue smoking tobacco. Special programs should be worked out for children showing early health consequences of smoking cigarettes. Giving up smoking is possible for "young" smokers, if they have not developed the symptoms of addiction.

[Smoking among secondary school students in Stalowa Wola]. / Rozpowszechnienie palenia tytoniu wsróds stalowowolskich gimnazjalistów.

Smoking is recognized as major, the most prevalent, and at the same time the only removable factor of many diseases. The major causes of starting smoking are: stress, curiosity and staying among people who smoke tobacco. The research was conducted among students of secondary school in Stalowa Wola in the form of an anonymous poll. The sample group included 2763 people. The group of smokers included 334 people (12.09%). Results of the research were subjected to a precise statistical analysis. The fact that 24.55% young age smokers smoke more than 20 cigarettes a day is worth stressing. In spite of short time of tobacco smoking, the investigated group has reported some negative health ailments. An attempt was made to identify the combination of features affecting smoking, including sex, origin, company of smokers, economic conditions (p < 0.05). The statistical analysis revealed a significant correlation between the number of cigarette smoked, economic conditions and the intention to stop smoking (p < 0.05). The obtained results may be helpful in preparing effective educational and preventive project among students, which can eliminate or lower the influence of factors predisposing to start and continue smoking tobacco.