Dysregulation of transcripts SMAD4-209 and SMAD4-213 and their respective promoters in colon cancer cell lines.

Background: The pervasive role of alternative promoters in context-specific isoform expression and the importance of promoter choice over its level of transcriptional activity have been recently implied based on pan-cancer in silico studies. We aimed to explore this phenomenon at the cellular level on the example of a major tumor suppressor SMAD4 in search of molecular mechanisms in colorectal cancer that could be exploited for novel biomarkers or therapeutic approaches. Methods: Multi-omics technologies, in silico tools and in vitro functional assays were applied to analyze the transcripts expression and the alternative promoters' function of the SMAD4 gene in colon cell lines HCEC-1CT, HCT116, DLD-1, SW480 and SW620. Results: High expression of the transcript SMAD4-213 emerged as a hallmark of colon cancer cells, while in silico tools point to its possible additional role and potential for sponging miRNAs. Based on the observed dysregulation of SMAD4-209 and SMAD4-213 in malignant vs. non-malignant colon cells, we propose that their expression ratio might be a solid biomarker candidate for colorectal cancer detection. Conclusions: A differential pattern of the respective promoters' activity was observed that corresponds to the expression of transcripts, confirming the role of alternative promoters in context-specific isoform expression. The investigated SMAD4 promoters and transcripts harbor translational potential that should be further investigated.

Characteristics of Akinetic and Dyskinetic Left Ventricular Aneurysms in the Context of Echocardiographic Diagnosis and Treatment Selection.

Background and Objectives. Distinct pressure curve differences exist between akinetic (A-LVA) and dyskinetic (D-LVA) aneurysms. In D-LVA, left ventricular (LV) ejection pressure decreases relative to the aneurysm size, whereas A-LVA does not impact pressure curves, indicating that the decrease in stroke volume (SV) and cardiac output is proportional to the size of dyskinesia. This study aimed to assess the frequency of A-LVA and D-LVA, determine aneurysm size parameters (volume and surface area), and evaluate predictive parameters using echocardiography in A-LVA and D-LVA. Furthermore, it aimed to compare individual echocardiographic parameters, according to ejection fraction (EF) and SV, with hemodynamic events shown in experimental models of A-LVA and D-LVA and their significance in everyday clinical practice. Materials and Methods. This clinical study included patients with post-infarction left ventricular aneurysm (LVA) admitted to the cardiovascular institute ''Dedinje", Serbia. Echocardiographic volume and surface area of LV and LVA were determined (by the area-length method) along with EF (by Simpson's method). Results. A-LVA was present in 62.9% of patients, while D-LVA was present in 37.1%. Patients with D-LVA had significantly higher systolic aneurysm volume (LVAVs) (94.07 ± 74.66 vs. 51.54 ± 53.09, p = 0.009), systolic aneurysm surface area (LVAAs) (23.22 ± 11.73 vs. 16.41 ± 8.58, p = 0.018), and end-systolic left ventricular surface areas (LVESA) (50.79 ± 13.33 vs. 42.76 ± 14.11, p = 0.045) compared to patients with A-LVA. The ratio of LVA volume to LV volume was higher in the D-LVA in systole (LVAVs/LVESV). The end-diastolic volume of LV (LVEDV) and end-systolic volume of LV (LVESV) did not significantly differ between D-LVA and A-LVA. EF (21.25 ± 11.92 vs. 28.18 ± 11.91, p = 0.044) was significantly lower among patients with D-LVA. Conclusions. Differentiating between A-LVA and D-LVA using echocardiography is crucial since D-LVA causes greater hemodynamic disturbances in LV function, and thus surgical resection of the aneurysm or LV reconstruction must have a positive effect regardless of myocardial revascularization surgery.

Markers of Epithelial-Mesenchymal Transition and Mucinous Histology Are Significant Predictors of Disease Severity and Tumor Characteristics in Early-Onset Colorectal Cancer.

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial-mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. This study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had significantly higher Mucin-1 (p < 0.001) and cytoplasmic E-cadherin (p = 0.043) scores; they were significantly less differentiated (p = 0.007), more advanced (p = 0.027), and predominately affected right the colon (p = 0.039) compared to non-mucinous tumors. Epithelial tumors were significantly better differentiated (p = 0.034) and with less prominent tumor budding (p < 0.001) than mesenchymal tumors. Mucin-1 and Vimentin were independent predictors of tumor differentiation (p = 0.006) and budding (p = 0.001), respectively. Mucinous histology and EMT markers are significant predictors of disease severity and tumor characteristics in early-onset colorectal cancer.

A Morphology-Preserving Algorithm for Denoising of EMG-Contaminated ECG Signals.

Goal: Clinical interpretation of an electrocardiogram (ECG) can be detrimentally affected by noise. Removal of the electromyographic (EMG) noise is particularly challenging due to its spectral overlap with the QRS complex. The existing EMG-denoising algorithms often distort signal morphology, thus obscuring diagnostically relevant information. Methods: Here, a new iterative regeneration method (IRM) for efficient EMG-noise suppression is proposed. The main hypothesis is that the temporary removal of the dominant ECG components enables extraction of the noise with the minimum alteration to the signal. The method is validated on SimEMG database of simultaneously recorded reference and noisy signals, MIT-BIH arrhythmia database and synthesized ECG signals, both with the noise from MIT Noise Stress Test Database. Results: IRM denoising and morphology-preserving performance is superior to the wavelet- and FIR-based benchmark methods. Conclusions: IRM is reliable, computationally non-intensive, fast and applicable to any number of ECG channels recorded by mobile or standard ECG devices.

Manufacture of Low-Na White Soft Brined Cheese: Effect of NaCl Substitution with a Combination of Na-K Salts on Proximate Composition, Mineral Content, Microstructure, and Sensory Acceptance.

All over the world, especially in Western societies, table salt intake that is inordinately higher than the acceptable level has been observed. An excess of Na in the human diet, mostly from processed foods, is becoming the "number one killer", leading to increased blood pressure. Therefore, the food industry is faced with a need to reduce Na in human nutrition in an effort to raise public health protection to a higher level. In this study, a commercially available combination of Na/K salts (COMB) at different concentrations was used as a NaCl substitute in the production of a modified, healthier, Na-reduced cheese. Samples of the modified low-Na white soft-brined cheese (WSBC) were produced by adding four different concentrations of COMB to production lots PL-1 to PL-4, and the control (CON) samples were prepared by salting with the usual, non-reduced concentration of NaCl. The effects of NaCl replacement on the physical-chemical parameters, major- and micro-elements, and microstructural and sensory properties of the WSBC were investigated. The obtained results indicated that there was no significant influence on the ash content, pH, and aw. The Na and K levels differed among treatments (p < 0.001). The lowest Na level in this study was recorded in PL-4 (only COMB was added) and was 334.80 ± 24.60 mg/100 g. According to the Na content, WSBC PL4 can be labeled with the nutrient claim "reduced amount of Na". A significant difference (p < 0.05) was noticed in overall acceptance between the CON and PL-4, with no statistically significant difference found amongst other WSBC production lots. The replacement of NaCl resulted in a slightly greater firmness of the WSBC. The results confirm the possibility of producing low-Na WSBC when optimal amounts of a suitable mineral salt are used as a substitute for NaCl, thus reducing the risk of high Na intake in the human body through the consumption of evaluated cheese.

Chronic stress alters hepatic metabolism and thermodynamic respiratory efficiency affecting epigenetics in C57BL/6 mice.

Chronic stress episodes increase metabolic disease risk even after recovery. We propose that persistent stress detrimentally impacts hepatic metabolic reprogramming, particularly mitochondrial function. In male C57BL/6 mice chronic variable stress (Cvs) reduced energy expenditure (EE) and body mass despite increased energy intake versus controls. This coincided with decreased glucose metabolism and increased lipid ß-oxidation, correlating with EE. After Cvs, mitochondrial function revealed increased thermodynamic efficiency (ƞ-opt) of complex CI, positively correlating with blood glucose and NEFA and inversely with EE. After Cvs recovery, the metabolic flexibility of hepatocytes was lost. Reduced CI-driving NAD+/NADH ratio, and diminished methylation-related one-carbon cycle components hinted at epigenetic regulation. Although initial DNA methylation differences were minimal after Cvs, they diverged during the recovery phase. Here, the altered enrichment of mitochondrial DNA methylation and linked transcriptional networks were observed. In conclusion, Cvs rapidly initiates the reprogramming of hepatic energy metabolism, supported by lasting epigenetic modifications.

Confronting Views of Companies and Authorities on Food Safety Issues-A Cross-Country Survey.

This study investigated food safety issues as perceived by food companies and food safety authorities in six countries in Europe and Central Asia. A total of 66 companies and 16 authorities participated in the survey. The results provide important insights related to what the main food safety priorities are, how they are addressed in the countries that participated in the survey, and what the role of the main stakeholders is in the food value chain. Almost 50% of food companies identified 'food fraud' as the most influential food safety attribute. One-third of food safety authorities recognized 'food safety management system' as the most influential food safety attribute. Principal component analysis separated food safety statements into two dimensions named 'food safety hazards and risks' and 'food safety system'. Although there are slight differences in food safety statements between the two stakeholders, i.e., food companies and food safety authorities, it is the country of origin that plays a more important role in understanding their views. Food companies will need to implement a systemic approach and transform the entire food value chain continuum while considering new food safety challenges. It is expected that food safety authorities will have to play a more proactive role in the future.

Catheter Ablation of Atrial Tachycardia after Pulmonary Vein Isolation in a Patient with Common Ostium of Inferior Pulmonary Veins: Case Report.

Background and Objectives: Atrial fibrillation (AF), a prevalent cardiac arrhythmia, significantly impacts the quality of life of those affected. The preferred treatment for symptomatic AF, particularly when pharmacological methods fall short, is catheter ablation with pulmonary vein isolation (PVI). While common pulmonary vein (PV) anatomical variants, such as the right accessory pulmonary vein and the common ostium of left pulmonary veins (LCPV), have been studied extensively, their impact on the long-term outcome of PVI is known to be minimal. However, data on less common anomalies, like the common ostium of the left and right inferior pulmonary vein (CIPV), remain scarce in the medical literature. This report aims to shed light on the challenges and outcomes of catheter ablation in a patient with a rare CIPV anomaly. By presenting this case, we contribute to the limited knowledge about the management of such unique anatomical variations in AF treatment and discuss the importance of individualized treatment approaches. Case Presentation: We present a case involving a 56-year-old male diagnosed with AF in 2018. Initial PVI treatment was successful, but the patient experienced symptom recurrence after three years. A preprocedural CT scan before the second ablation revealed a CIPV anomaly. During the repeat procedure, a right superior pulmonary vein (RSPV) reisolation was performed due to identified gaps in the previous ablation line. Post-procedure, the patient maintained a sinus rhythm and reported no further symptoms. Conclusions: This case highlights the importance of recognizing rare PV anatomies like CIPV in the effective management of AF. Tailored ablation strategies, accounting for unique anatomical conditions, can lead to successful long-term outcomes, reinforcing the need for personalized approaches in AF treatment, especially in cases involving complex anatomical variations.

A Database of Simultaneously Recorded ECG Signals With and Without EMG Noise.

Goal: Noise on recorded electrocardiographic (ECG) signals may affect their clinical interpretation. Electromyographic (EMG) noise spectrally coincides with the QRS complex, which makes its removal particularly challenging. The problem of evaluating the noise-removal techniques has commonly been approached by algorithm testing on the contaminated ECG signals constructed ad hoc as an additive mixture of a noise-free ECG signal and noise. Consequently, there is an absence of a unique/standard database for testing and comparing different denoising methods. We present a SimEMG database recorded by a novel acquisition method that allows for direct recording of the genuine EMG-noise-free and -contaminated ECG signals. The database is available as open source.

Transcript CD81-215 may be a long noncoding RNA of stromal origin with tumor-promoting role in colon cancer.

The role of tetraspanin CD81 in malignant transformation is best studied in colorectal cancer, and it appears that other transcripts beside the fully coding mRNA may also be dysregulated in malignant cells. Recent data from a comprehensive pan-cancer transcriptome analysis demonstrated differential activity of two alternative CD81 gene promoters in malignant versus nonmalignant gut mucosa. The promoter active in gut mucosa gives rise to transcripts CD81-203 and CD81-213, while the promoter active in colon and rectal cancer gives rise to transcripts CD81-205 and CD81-215. Our study aimed to explore the biomarker potential of the transcripts from the alternative CD81 gene promoters in colon cancer, as well as to investigate their structure and potential function using in silico tools. The analysis of the transcripts' expression in several colon cell lines cultivated in 2D and 3D and a set of colon cancer and healthy gut mucosa samples by qPCR and RNA sequencing suggested their low expression and stromal origin. Expression patterns in tumor and nontumor tissue along with in silico data suppose that the transcript CD81-215 may be a noncoding RNA of stromal origin with possible involvement in signaling related to malignant transformation.

The utility of serum amyloid A and other acute-phase reactants determination in ambulatory care COVID-19 patients.

Background: The unpredictable course of Coronavirus Disease 19 (COVID-19) is making good severity assessment tools crucial. This study aimed to assess the usefulness of serum amyloid A (SAA) and other acute-phase reactants (APRs) in ambulatory care COVID-19 patients and identified relationships between these markers and disease outcomes. Methods: From August to November 2020, patients seen in the outpatient department of the Clinic for Infectious and Tropical Diseases (Belgrade, Serbia) with confirmed COVID-19 were included. Patients were classified into mild, moderate, and severe disease groups based on World Health Organization criteria. SAA, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), ferritin, fibrinogen, D-dimer, albumin, and transferrin were measured. The median values of all APRs were compared between COVID-19 severity groups, hospitalized and non-hospitalized patients, and survivors and non-survivors. The Receiver operator characteristic (ROC) curve analysis was used for the classification characteristics assessment of individual APRs for the severity of illness, hospitalization, and survival.

Smartphone addiction, sleep quality, depression, anxiety, and stress among medical students.

Introduction: Studies consistently link excessive smartphone use to poor sleep quality, depression, anxiety, and stress. This study specifically aimed to investigate these associations among medical students in Belgrade and Nis (Central Serbia). Materials and methods: The cross-sectional study included a sample of 761 students, who were selected from both the Faculties of Medicine at the University of Belgrade and the University of Nis. Questionnaires, including the International Physical Activity Questionnaire - Short Form (IPAQ-SF), Smartphone Addiction Scale - Short Version (SAS-SV), the Pittsburgh Sleep Quality Index (PSQI), and the Depression, Anxiety, and Stress Scale - 21 items (DASS-21), were completed by the participants. Statistical analysis techniques, such as the Chi-square test, student's t-test, and logistic regression, were employed to examine the relationship between smartphone addiction, physical activity, sleep quality, depression, anxiety, and stress. Results: The findings indicated a prevalence of smartphone addiction among medical students at 21.7%, with rates of 22.9% among males and 21.1% among females. Females exhibited significantly higher scores on the SAS-SV scale compared to males (p = 0.032). Univariate logistic regression analysis revealed significant associations between smartphone addiction and spending over 4 h daily on smartphones (OR = 2.39; p < 0.001), poor sleep quality (OR = 1.65; p = 0,005), as well as elevated levels of stress (OR = 1.75; p = 0.003), anxiety (OR = 2.04; p < 0.001), and depression (OR = 2.29; p < 0.001). Multivariate regression analysis identified spending more than 4 h daily on smartphones (OR = 2.39; p < 0.001) and increased levels of depression (OR = 2.51; p < 0.001) as independent significant factors associated with smartphone addiction. Conclusion: This study sheds light on the prevalence of smartphone addiction among medical students, with spending excessive time on smartphones and higher levels of depression standing out as significant factors. Future research should delve into the underlying mechanisms and causal relationships between smartphone addiction and these psychosocial factors. Understanding these connections will aid in developing effective interventions and strategies to tackle this growing public health concern.

Telemedicine in the Era of a Pandemic: Usefulness of a Novel Three-Lead ECG.

The 12-lead electrocardiogram (ECG) is a first-line diagnostic tool for patients with cardiac symptoms. As observed during the COVID-19 pandemic, the ECG is essential to the initial patient evaluation. The novel KardioPal three-lead-based ECG reconstructive technology provides a potential alternative to a standard ECG, reducing the response time and cost of treatment and improving patient comfort. Our study aimed to evaluate the diagnostic accuracy of a reconstructed 12-lead ECG obtained by the KardioPal technology, comparing it with the standard 12-lead ECG, and to assess the feasibility and time required to obtain a reconstructed ECG in a real-life scenario. A prospective, nonrandomized, single-center, adjudicator-blinded trial was conducted on 102 patients during the COVID-19 pandemic at the Dedinje Cardiovascular Institute in Belgrade. The KardioPal system demonstrated a high feasibility rate (99%), with high specificity (96.3%), sensitivity (95.8%), and diagnostic accuracy (96.1%) for obtaining clinically relevant matching of reconstructed 12-lead compared to the standard 12-lead ECG recording. This novel technology provided a significant reduction in ECG acquisition time and the need for personnel and space for obtaining ECG recordings, thereby reducing the risk of viral transmission and the burden on an already overwhelmed healthcare system such as the one experienced during the COVID-19 pandemic.

Predictors of Non-Adherence to Medications in Hypertensive Patients.

Background: Elevated blood pressure (BP) is one of the leading causes for developing major cardiovascular events and still represents a major public health challenge worldwide. We aimed to provide data on predictors of poor adherence to medication in hypertensive patients in Serbia. Methods: Observational, analytical study was undertaken at a group of 388 patients who refilled their medications in the Pharmacy Institution, "Apoteka Kragujevac", Kragujevac, Serbia between Jan and Mar 2019. Afterward, we conducted a case-control study to evaluate the influence of the variables associated with the adherence. We used a self-developed questionnaire and SF-36 to assess the influence of the quality of life on medication adherence. Results: Results revealed four independent predictors of non-adherence: increased number of medications, living in a city, forgetfulness of the dosing regimen and low energy. The odds of non-adherence were the highest among the participants living in the city and the low energy was the only factor inversely associated with the level of non-adherence. Conclusion: Many factors were associated with the non-adherence to medication. Further studies are needed to find the most appropriate protocol to promote adherence. The four risk factors (increased number of medications, living in a city, forgetfulness of the dosing regimen and low energy) are associated with non-adherence in adult hypertensive patients.

Eurasian consumers' food safety beliefs and trust issues in the age of COVID-19: evidence from an online survey in 15 countries.

BACKGROUND: This investigation provides an important insight into Eurasian consumers' food safety beliefs and trust issues influenced by the COVID-19 pandemic. An online survey was conducted in 15 European and Asian countries involving more than 4000 consumers. RESULTS: It has confirmed that different socioeconomic characteristics, cultural aspects and education levels shape food safety perceptions within Eurasian countries. The COVID-19 pandemic influenced their beliefs and trust in food safety, which is relatively low on average. However, it is significantly higher for European consumers (especially European Union ones) compared to their Asian counterparts. Both Asian and European respondents agreed that food fraud and climate changes represent a food safety issue. However, European consumers were less concerned regarding the food safety of genetically modified foods and meat and dairy analogs/hybrids. Asian consumers were, to a greater extent, worried about the risk of getting COVID-19 from food, restaurants, food retail establishments and home food deliveries. CONCLUSION: Eurasian consumers have put their greatest extent of trust, when food safety assurance is concerned, into food scientists and food producers holding a food safety certificate. Broadly, they are uncertain to what extent their federal governments and food inspectors are competent, able and efficient in ensuring food safety. Higher education of Eurasian consumers was followed by increased food safety confidence in all parts of the food chain. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Consumer attitudes and perceptions towards chilled ready-to-eat foods: a multi-national study.

Understanding consumers' behavior and their handling of high-risk foods at home is essential for reducing the number of foodborne illnesses. This study shows the results of a cross-national analysis of consumers' perception from nine countries, and the identification of customers' clusters and its characteristics in order to understand customers' behavior, and to build safe chilled ready-to-eat (RTE) foods prevention strategies. The cluster analysis resulted in two clusters: (1) "Precautious consumers" characterized by the orientation towards pre-packed RTE foods, with consumers mainly coming from Bosnia and Herzegovina, India, Poland, Portugal, Spain, and Turkey. Their attitudes and self-reported practices may be categorized as less risky in terms of food-borne illnesses connected with the consumption of RTE foods; (2) "Unconcerned consumers" preferred cutting and slicing RTE foods freshly at the point of purchase, usually sold at the delicatessen department in a supermarket or at open markets. Those consumers mostly came from Croatia, Serbia and Slovenia and their attitudes and self-reported practices were riskier. These results allow a better understating of what characterizes consumers of RTE foods in different countries.

Degradation of tartrazine by Oxone® in the presence of cobalt based catalyst supported on pillared montmorillonite - Efficient technology even in extreme conditions.

The catalytic degradation of hazardous organic contaminants in industrial wastewater is a promising technology. Reactions of tartrazine, the synthetic yellow azo dye, with Oxone® in the presence of catalyst in strong acidic condition (pH 2), were detected by using UV-Vis spectroscopy. In order to extend the applicability profile of Co-supported Al-pillared montmorillonite catalyst an investigation of Oxone® induced reactions were performed in extreme acidic environment. The products of the reactions were identified by liquid chromatography-mass spectrometry (LC-MS). Along with the catalytic decomposition of tartrazine induced by radical attack (confirmed as unique reaction path under neutral and alkaline conditions), the formation of tartrazine derivatives by reaction of nucleophilic addition was also detected. The presence of derivatives under acidic conditions slowed down the hydrolysis of tartrazine diazo bond in comparison to the reactions in neutral environment. Nevertheless, the reaction in acidic conditions (pH 2) is faster than the one conducted in alkaline conditions (pH 11). Theoretical calculations were used to complete and clarify the mechanisms of tartrazine derivatization and degradation, as well as to predict the UV-Vis spectra of compounds which could serve as predictors of certain reaction phases. ECOSAR program, used to estimate toxicological profile of compounds to aquatic animals, indicated an increase in the harmfulness of the compounds identified by LC-MS as degradation products from the reaction conducted for 240min. It could be concluded that an intensification of the process parameters (higher concentration of Oxone®, higher catalyst loading, increased reaction time, etc.) is needed in order to obtain only biodegradable products.

Chronic stress targets mitochondrial respiratory efficiency in the skeletal muscle of C57BL/6 mice.

Episodes of chronic stress can result in psychic disorders like post-traumatic stress disorder, but also promote the development of metabolic syndrome and type 2 diabetes. We hypothesize that muscle, as main regulator of whole-body energy expenditure, is a central target of acute and adaptive molecular effects of stress in this context. Here, we investigate the immediate effect of a stress period on energy metabolism in Musculus gastrocnemius in our established C57BL/6 chronic variable stress (Cvs) mouse model. Cvs decreased lean body mass despite increased energy intake, reduced circadian energy expenditure (EE), and substrate utilization. Cvs altered the proteome of metabolic components but not of the oxidative phosphorylation system (OXPHOS), or other mitochondrial structural components. Functionally, Cvs impaired the electron transport chain (ETC) capacity of complex I and complex II, and reduces respiratory capacity of the ETC from complex I to ATP synthase. Complex I-OXPHOS correlated to diurnal EE and complex II-maximal uncoupled respiration correlated to diurnal and reduced nocturnal EE. Bioenergetics assessment revealed higher optimal thermodynamic efficiencies (ƞ-opt) of mitochondria via complex II after Cvs. Interestingly, transcriptome and methylome were unaffected by Cvs, thus excluding major contributions to supposed metabolic adaptation processes. In summary, the preclinical Cvs model shows that metabolic pressure by Cvs is initially compensated by adaptation of mitochondria function associated with high thermodynamic efficiency and decreased EE to manage the energy balance. This counter-regulation of mitochondrial complex II may be the driving force to longitudinal metabolic changes of muscle physiological adaptation as the basis of stress memory.

Changes in Attitudes toward COVID-19 Vaccination and Vaccine Uptake during Pandemic.

The epidemic control approach was based on non-pharmacological measures in the first year of the COVID-19 pandemic, followed by vaccine uptake in the second year. Vaccine uptake depends on the individual attitude toward vaccination. The aim was to assess the changes in attitudes regarding COVID-19 vaccine protection during the pandemic and to determine the vaccination uptake concerning these attitudes. A panel study on COVID-19 vaccine attitudes and vaccination against COVID-19 was conducted in Belgrade, Serbia. The first survey was carried out in May−June 2020, and the second survey was organized in August−September 2021. During the baseline testing performed in 2020, 64.4% of respondents believed that the future vaccine against COVID-19 could protect against the COVID-19 disease, while 9.7% thought that it could not, and 25.9% were unsure. One year later, in the second survey, the percentage of participants with positive attitudes was slightly lower (64.7% vs. 62.5%). However, negative attitudes turned positive in 34% of cases, and 28.9% became unsure about vaccine protection (p < 0.001). Out of the 390 participants included in the study, 79.7% were vaccinated against COVID-19 until follow-up. There is a statistically significant difference in vaccination uptake compared to the baseline attitude about the protection of the COVID-19 vaccine. The main finding of our study is that the majority of participants who were vaccine hesitant during the baseline testing changed their opinion during the follow-up period. Additionally, the baseline attitude about the protection of the COVID-19 vaccine has been shown to be a potential determinant of vaccination uptake.

Genetic analysis and allele-specific expression of SMAD7 3'UTR variants in human colorectal cancer reveal a novel somatic variant exhibiting allelic imbalance.

BACKGROUND: Considering the impact of SMAD7 deregulation in colorectal cancer (CRC) progression and the significance of single nucleotide variant (SNV)-mediated disruptions of microRNA (miRNA)-dependent regulation for cancer susceptibility, our study aimed to analyze genetic variation in the SMAD7 3' untranslated region ( 3'UTR) in CRC, measure differences in allelic mRNA expression, and evaluate its interference with miRNA-mediated post-transcriptional regulation. PATIENTS AND METHODS: This study included 80 patients with different CRC stages and six human colon cancer cell lines of various histological origins. SMAD7 3'UTR was analyzed by direct sequencing, followed by the relative quantification of differential allelic expression of detected variants by allele-specific qRT-PCR. In silico tools were employed for predictions of regulatory consequences of detected variants. RESULTS: A total of four different SNVs in one cell line and nine patients were found, among which were a novel somatic point variant and three already known germline variants (rs16950113, rs1050799536, and rs1043778717). All evaluated SNVs exhibited variable extents of allelic imbalance in expression. In silico analysis predicted significant effects of SNVs on miRNA binding efficiency, with each SNV disrupting existing and creating new target sites for one or more miRNAs. CONCLUSION: Imbalance observed in the expression of SNV alleles altering miRNA binding suggests that all investigated SNVs are potential contributing factors impacting SMAD7 expression regulation in CRC that further studies should investigate.