Exercise-Induced Proteomic Profile Changes in Patients with Advanced Heart Failure.

BACKGROUND/OBJECTIVES: The pathophysiological background of the processes activated by physical activity in patients with heart failure (HF) is not fully understood. Proteomic studies can help to preliminarily identify new protein markers for unknown or poorly defined physiological processes. We aimed to analyse the changes in the plasma proteomic profile of HF patients after a cardiopulmonary exercise test (CPET) to define pathways involved in the response to exercise. METHODS: The study prospectively enrolled 20 male patients with advanced HF (aged 53.3 ± 8.3 years). Blood samples were taken from the patients before and immediately after the CPET to obtain plasma proteomic profiles. Two-sample t-tests (paired or non-paired) were performed with and without false discovery rate (FDR) correction for multiple testing. Enrichment analysis was performed to associate biological processes and pathways with the study results. RESULTS: A total of 968 plasma proteins were identified, of which 722 underwent further statistical analysis. Of these, 236 proteins showed differential expression when comparing all plasma samples collected before and after CPT (p < 0.05), and for 86 of these the difference remained statistically significant after FDR correction. Proteins whose expression changed after exercise are mostly involved in immune response and inflammatory processes, coagulation, cell adhesion, regulation of cellular response to stimulus and regulation of programmed cell death. There were no differences in resting proteomics according to HF etiology (ischemic vs. non-ischemic). CONCLUSIONS: Changes in the proteomic profile revealed a complexity of exercise-induced processes in patients with HF, suggesting that few major physiological pathways are involved. Further studies focusing on specific pathways are needed.

Daily life in the Open Biologist's second job, as a Data Curator.

Background: Data reusability is the driving force of the research data life cycle. However, implementing strategies to generate reusable data from the data creation to the sharing stages is still a significant challenge. Even when datasets supporting a study are publicly shared, the outputs are often incomplete and/or not reusable. The FAIR (Findable, Accessible, Interoperable, Reusable) principles were published as a general guidance to promote data reusability in research, but the practical implementation of FAIR principles in research groups is still falling behind. In biology, the lack of standard practices for a large diversity of data types, data storage and preservation issues, and the lack of familiarity among researchers are some of the main impeding factors to achieve FAIR data. Past literature describes biological curation from the perspective of data resources that aggregate data, often from publications. Methods: Our team works alongside data-generating, experimental researchers so our perspective aligns with publication authors rather than aggregators. We detail the processes for organizing datasets for publication, showcasing practical examples from data curation to data sharing. We also recommend strategies, tools and web resources to maximize data reusability, while maintaining research productivity. Conclusion: We propose a simple approach to address research data management challenges for experimentalists, designed to promote FAIR data sharing. This strategy not only simplifies data management, but also enhances data visibility, recognition and impact, ultimately benefiting the entire scientific community.

Researchers should openly share data associated with their publications unless there is a valid reason not to. Additionally, datasets have to be described with enough detail to ensure that they are reproducible and reusable by others. Since most research institutions offer limited professional support in this area, the responsibility for data sharing largely falls to researchers themselves. However, many research groups still struggle to follow data reusability principles in practice. In this work, we describe our data curation (data organization and management) efforts working directly with the researchers who create the data. We show the steps we took to organize, standardize, and share several datasets in biological sciences, pointing out the main challenges we faced. Finally, we suggest simple and practical data management actions, as well as tools that experimentalists can integrate into their daily work, to make sharing data easier and more effective.

Prevalence of Obesity among Polish Primary Care Population Considered Healthy.

Obesity is a complex disease with numerous health complications, influenced by factors such as genetics, lifestyle, mental health, societal impact, economic status, comorbidities, and treatments. This multicenter study included adults aged ≥35 years referred to a CVD prevention program, where sociodemographic data, anthropometric examinations, laboratory tests, and HLPCQ responses were collected. The study analyzed 1044 patients with a mean age of 47.9 years. Among them, 22.2% (232 patients) were diagnosed with obesity. These patients exhibited higher blood pressure, non-HDL cholesterol, triglycerides, and glucose levels (all p < 0.001). A comparative analysis showed that obese patients had significantly lower scores in healthy dietary choices, dietary harm avoidance, daily routine, organized physical exercise, and overall HLPCQ scores. These results indicate that individuals considered healthy were actually living with obesity and its associated complications. Consequently, family physicians should proactively identify patients at risk of obesity using existing programs. The Polish healthcare system urgently needs systemic solutions, including effective health promotion and the creation of obesity prevention programs at an early stage of adult life. These measures are essential to address the growing obesity epidemic and improve public health outcomes.

Mental Health, and Eating Disorders in Patients After Roux-en-Y Gastric Bypass Surgery (RYGB).

<b>Introduction:</b> Obesity, as one of the main health problems worldwide, is associated with an increased risk of developing mental and eating disorders and negative eating habits. Bariatric surgery allows for rapid weight loss and alleviates the symptoms of concomitant diseases in obese patients.<b>Aim:</b> Pre- and postoperative estimation of mental disorders and eating behaviors in patients after Roux-en-Y Gastric Bypass (RYGB).<b>Material and methods:</b> Analysis of data from up to 5 years of follow-up including clinical examination and questionnaires.<b>Results:</b> Following parameters decreased after RYGB: anxiety and hyperactivity from 32.81% to 21.88%, mood disorders - 31.25% to 20.31%, substance abuse - 40.63% to 28.13%, emotional eating - 76.56% to 29.69%, binge eating - 50% to 6.25%, night eating - 87.5% to 20.31%. Postoperative rates of: negative eating habits, daily intake of calories and sweetened beverages, flatulence, constipation, and abdominal pain decreased, while the rate of food intolerance and emesis increased.<b>Conclusions:</b> In our patients, the occurrence of: mental and eating disorders, negative eating habits, daily calories, sweetened beverages, coffee intake decreased after weight loss (as a result of RYGB), but water, vegetables and fruit consumption increased. Lower rate of flatulence, constipation, and abdominal pain, but higher of food intolerance and emesis were also confirmed after RYGB.

Troponin T Assessment Allows for Identification of Mutation Carriers among Young Relatives of Patients with LMNA-Related Dilated Cardiomyopathy.

Background:LMNA-related dilated cardiomyopathy (LMNA-DCM) caused by mutations in the lamin A/C gene (LMNA) is one of the most common forms of hereditary DCM. Due to the high risk of mutation transmission to offspring and the high incidence of ventricular arrhythmia and sudden death even before the onset of heart failure symptoms, it is very important to identify LMNA-mutation carriers. However, many relatives of LMNA-DCM patients do not report to specialized centers for clinical or genetic screening. Therefore, an easily available tool to identify at-risk subjects is needed. Methods: We compared two cohorts of young, asymptomatic relatives of DCM patients who reported for screening: 29 LMNA mutation carriers and 43 individuals from the control group. Receiver operating characteristic (ROC) curves for potential indicators of mutation carriership status were analyzed. Results: PR interval, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hscTnT) serum levels were higher in the LMNA mutation carrier cohort. Neither group differed significantly with regard to creatinine concentration or left ventricular ejection fraction. The best mutation carriership discriminator was hscTnT level with an optimal cut-off value at 5.5 ng/L, for which sensitivity and specificity were 86% and 93%, respectively. The median hscTnT level was 11.0 ng/L in LMNA mutation carriers vs. <3.0 ng/L in the control group, p < 0.001. Conclusions: Wherever access to genetic testing is limited, LMNA mutation carriership status can be assessed reliably using the hscTnT assay. Among young symptomless relatives of LMNA-DCM patients, a hscTnT level >5.5 ng/L strongly suggests mutation carriers.

The impact of lifestyle, measured with the HLPCQ questionnaire on the prevalence of metabolic syndrome in Poland: a multicenter study.

Metabolic syndrome is one of the most common health problems for people around the world. The aim of our study was to assess the prevalence of metabolic syndrome among adults without prior diagnosis of cardiovascular disease, diabetes, and chronic kidney disease. We also plan to assess the influence of certain lifestyle components on prevalence of metabolic syndrome. The study involved cardiovascularly healthy patients undergoing lab tests, measurements, and the HLPCQ questionnaire (The Healthy Lifestyle and Personal Control Questionnaire). The data were used to diagnose metabolic syndrome. Out of 1044 patients from 10 primary care facilities, 23.3% met the metabolic syndrome criteria, showing a strong link with increased blood pressure, cholesterol, and fasting glucose. Lower scores in the Organized physical exercise subscale of the HLPCQ questionnaire were noted in those with metabolic syndrome. Comparing the subscale of HLPCQ questionnaire, the lower results in Organized physical exercise subscale were found among the participants with metabolic syndrome, both male and females. Metabolic syndrome, a significant risk factor for cardiovascular disease, should be screened for actively, even in apparently healthy populations. Results obtained in our study from analysis of HLPCQ show that screening for metabolic syndrome should be preceded by prevention based on regular physical activity and proper eating habits.

Acute pancreatitis associated with primary hyperparathyroidism during pregnancy.

Not required for Clinical Vignette.

Long-term cenobamate retention, efficacy, and safety: outcomes from Expanded Access Programme.

AIM OF THE STUDY: To evaluate the long-term retention rate, efficacy, and tolerability of adjunctive cenobamate (CNB) in patients with drug-resistant epilepsy within the Polish Expanded Access Programme (EAP). CLINICAL RATIONALE FOR THE STUDY: Long-term retention rate is a useful measure of effectiveness including efficacy, safety, and tolerability of antiseizure medications. MATERIAL AND METHODS: We conducted a multicentre retrospective analysis of consecutive patients with focal epilepsy treated with CNB in the EAP between January 2020 and May 2023. All patients who completed the open-label extension phases of the YKP3089C013 and YKP3089C017 trials were offered the opportunity to continue CNB treatment within the EAP. We analysed cenobamate retention, seizure outcomes, and adverse events. RESULTS: 38 patients (18 females; 47.3%) continued CNB treatment within the Expanded Access Programme for 41 months. The mean baseline age of patients was 39.3 years (range: 18-57). All patients were on polytherapy, with the most commonly used antiseizure medications being valproate, levetiracetam, and carbamazepine. Adjunctive CNB treatment resulted in a reduced mean seizure frequency from 8.1 seizures (range: 4-20) per month to 3 seizures (range: 0-8) per month. At the final follow-up, the median CNB dose was 200 mg/day (range: 50-350). Among the patients, 24 (63.1%) achieved ≥ 50% seizure reduction, and eight (21%) remained seizure-free for at least 12 months. One in three patients experienced adverse events, which resolved in half of the subjects. The most frequent adverse events were dizziness, somnolence, and headache. The retention rate after completing the open-label extension phase was 100%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Long-term effectiveness, including ≥ 50% seizure reduction and a 100% retention rate, was sustained over 41 months of CNB treatment within the Expanded Access Programme. No new safety issues were identified. These results provide support for the potential long-term clinical benefits of cenobamate.

Plasma Treatment of PDMS for Microcontact Printing (µCP) of Lectins Decreases Silicone Transfer and Increases the Adhesion of Bladder Cancer Cells.

The present study investigates silicone transfer occurring during microcontact printing (µCP) of lectins with polydimethylsiloxane (PDMS) stamps and its impact on the adhesion of cells. Static adhesion assays and single-cell force spectroscopy (SCFS) are used to compare adhesion of nonmalignant (HCV29) and cancer (HT1376) bladder cells, respectively, to high-affinity lectin layers (PHA-L and WGA, respectively) prepared by physical adsorption and µCP. The chemical composition of the µCP lectin patterns was monitored by time-of-flight secondary ion mass spectrometry (ToF-SIMS). We show that the amount of transferred silicone in the µCP process depends on the preprocessing of the PDMS stamps. It is revealed that silicone contamination within the patterned lectin layers inhibits the adhesion of bladder cells, and the work of adhesion is lower for µCP lectins than for drop-cast lectins. The binding capacity of microcontact printed lectins was larger when the PDMS stamps were treated with UV ozone plasma as compared to sonication in ethanol and deionized water. ToF-SIMS data show that ozone-based treatment of PDMS stamps used for µCP of lectin reduces the silicone contamination in the imprinting protocol regardless of stamp geometry (flat vs microstructured). The role of other possible contributors, such as the lectin conformation and organization of lectin layers, is also discussed.

Keep It Simple: Using README Files to Advance Standardization in Chronobiology.

Standardization plays a crucial role in ensuring the reliability, reproducibility, and interoperability of research data in the biomedical sciences. Metadata standards are one foundation for the FAIR (Findable, Accessible, Interoperable, and Reusable) principles of data management. They facilitate data discovery, understanding, and reuse. However, the adoption of metadata standards in biological research lags in practice. Barriers such as complexity, lack of incentives, technical challenges, resource constraints, and resistance to change hinder widespread adoption. In the field of chronobiology, standardization is essential but faces particular challenges due to the longitudinal nature of experimental data, diverse model organisms, and varied measurement techniques. To address these challenges, we propose an approach that emphasizes simplicity and practicality: the development of README templates tailored for particular data types and species. Through this opinion article, our intention is to initiate a dialogue and commence a community-driven standardization process by engaging potential contributors and collaborators.

Heart failure with reduced, mildly reduced, and preserved ejection fraction: outcomes and predictors of prognosis.

INTRODUCTION: Recently, a stratification of the heart failure (HF) phenotypes, which classifies HF into 3 subtypes based on ejection fraction, has been introduced. Before that, clinical trials and registries have been mainly devoted to HF with reduced ejection fraction (HFrEF). As a result, data on long­term survival trends for individual HF phenotypes are scarce. OBJECTIVES: The study aimed to evaluate survival according to the HF phenotype and to identify predictors of mortality. PATIENTS AND METHODS: Patients hospitalized for HF in our referral center between January 2014 and May 2019 were included in the analysis. HF phenotyping was based on EF: reduced (HFrEF with EF <40%), mildly reduced (HFmrEF with EF = 40%-49%), and preserved (HFpEF with EF ≥50%). RESULTS: Of 2601 patients included in the study, 1608 individuals (62%) presented with HFrEF, 331 patients with HFmrEF (13%), and 662 patients with HFpEF (25%). The median follow­up was 2.43 years (interquartile range, 1.56-3.49). The risk of death was 61% higher in HFrEF than in HFpEF (P <0.001), while in HFmrEF and HFpEF it was similar. Survival rates at 1 and 5 years in HFrEF, HFmrEF, and HFpEF were 81%, 84%, 84%, and 47%, 61%, and 59%, respectively. The HF phenotypes differed in most of the parameters that affect prognosis. Only the use of inotropes, which was linked to an increased risk of death, and the use of angiotensin­converting enzyme inhibitors, which reduced this risk, were independent of the HF phenotype. CONCLUSIONS: Survival in HFrEF is worse as compared with HFmrEF and HFpEF, where it is similar. The HF phenotypes differ in most of the parameters that affect survival.

Bladder Cancer Cells Interaction with Lectin-Coated Surfaces under Static and Flow Conditions.

Aberrant expression of glycans, i.e., oligosaccharide moiety covalently attached to proteins or lipids, is characteristic of various cancers, including urothelial ones. The binding of lectins to glycans is classified as molecular recognition, which makes lectins a strong tool for understanding their role in developing diseases. Here, we present a quantitative approach to tracing glycan-lectin interactions in cells, from the initial to the steady phase of adhesion. The cell adhesion was measured between urothelial cell lines (non-malignant HCV29 and carcinoma HT1376 and T24 cells) and lectin-coated surfaces. Depending on the timescale, single-cell force spectroscopy, and adhesion assays conducted in static and flow conditions were applied. The obtained results reveal that the adhesion of urothelial cells to two specific lectins, i.e., phytohemagglutinin-L and wheat germ agglutinin, was specific and selective. Thus, these lectins can be applied to selectively capture, identify, and differentiate between cancer types in a label-free manner. These results open up the possibility of designing lectin-based biosensors for diagnostic or prognostic purposes and developing strategies for drug delivery that could target cancer-associated glycans.

L-arginine and Its Derivatives Correlate with Exercise Capacity in Patients with Advanced Heart Failure.

Methylated arginine metabolites interrupt nitric oxide synthesis, which can result in endothelium dysfunction and inadequate vasodilation. Since little is known about the dynamics of arginine derivatives in patients with heart failure (HF) during physical exercise, we aimed to determine this as well as its impact on the patient outcomes. Fifty-one patients with HF (left ventricle ejection fraction-LVEF ≤ 35%, mean 21.7 ± 5.4%) underwent the cardiopulmonary exercise test (CPET). Plasma concentrations of L-arginine, citrulline, ornithine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were measured before and directly after CPET. All patients were followed for a mean of 23.5 ± 12.6 months. The combined endpoint was: any death, urgent heart transplantation, or urgent LVAD implantation. L-arginine concentrations increased significantly after CPET (p = 0.02), when ADMA (p = 0.01) and SDMA (p = 0.0005) decreased. The parameters of better exercise capacity were positively correlated with post-CPET concentration of L-arginine and inversely with post-CPET changes in ADMA, SDMA, and baseline and post-CPET SDMA concentrations. Baseline and post-CPET SDMA concentrations increased the risk of endpoint occurrence (HR 1.02, 95% CI 1.009-1.03, p = 0.04 and HR 1.02, 95% CI 1.01-1.03, p = 0.02, respectively). In conclusion, in patients with HF, extensive exercise is accompanied by changes in arginine derivatives that can reflect endothelium function. These observations may contribute to the explanation of the pathophysiology of exercise intolerance in HF.

Immunoexpression of Bmi-1, CK15, Bcl-2 in different types of basal cell carcinomas.

Introduction: Basal cell carcinoma (BCC) occurs in aggressive and non-aggressive forms. The expression of immunohistochemical markers varies in different types of BCC. Aim: Immunohistochemical analysis of selected proteins in BCCs. Material and methods: The immunohistochemical method was used to examine the immunoexpression of Bmi-1, CK15 and Bcl-2 in 56 cases of BCC divided into four groups. Results: Positive Bmi-1 staining 3-4+ level (nodular type) was seen in 91.3% of samples, 4+ (infiltrative) in 92.3%, 4+ (nodular/infiltrative) - 69.2%, 3+ - 30.8%, in BSC 3+ - 42.8%, and 28.6% each for 2+ and 4+. Low grade positivity (0-1+) in CK15 staining was present in 52.1% of nodular BCC, 46.2% - nodular/infiltrative, 92.3% - infiltrative, and 100% - BSC, but levels 2-3+ in nodular BCC in 47.8%, nodular/infiltrative BCC - 53.8%, infiltrative - 7.7%. Bcl-2 positivity (3-4+) was revealed in nodular BCC in 95.6%, (1-2+) in 100% of BSC, infiltrative and infiltrative/nodular BCC, but the lowest (0-1+) in 76.9% of nodular/infiltrative BCC, 71.4% of BSC, and in 38.4% of infiltrative BCC. Conclusions: Positive Bmi-1 staining was the highest in the aggressive infiltrative subtype of BCCs, whereas the lowest in basosquamous cell carcinomas (BSC). Infiltrative BCC was characterized by a lower level of CK15 expression than nodular BCC and nodular/infiltrative BCC. Differentiation of Bcl-2 expression depended on the type of tumour; the highest level was found in nodular BCC, low grade in nodular/infiltrative and infiltrative BCCs, and BSC.

SARS-CoV-2 RNA levels in Scotland's wastewater.

Nationwide, wastewater-based monitoring was newly established in Scotland to track the levels of SARS-CoV-2 viral RNA shed into the sewage network, during the COVID-19 pandemic. We present a curated, reference dataset produced by this national programme, from May 2020 to February 2022. Viral levels were analysed by RT-qPCR assays of the N1 gene, on RNA extracted from wastewater sampled at 162 locations. Locations were sampled up to four times per week, typically once or twice per week, and in response to local needs. We report sampling site locations with geographical coordinates, the total population in the catchment for each site, and the information necessary for data normalisation, such as the incoming wastewater flow values and ammonia concentration, when these were available. The methodology for viral quantification and data analysis is briefly described, with links to detailed protocols online. These wastewater data are contributing to estimates of disease prevalence and the viral reproduction number (R) in Scotland and in the UK.

Changes in nanomechanical properties of single neuroblastoma cells as a model for oxygen and glucose deprivation (OGD).

Although complex, the biological processes underlying ischemic stroke are better known than those related to biomechanical alterations of single cells. Mechanisms of biomechanical changes and their relations to the molecular processes are crucial for understanding the function and dysfunction of the brain. In our study, we applied atomic force microscopy (AFM) to quantify the alterations in biomechanical properties in neuroblastoma SH-SY5Y cells subjected to oxygen and glucose deprivation (OGD) and reoxygenation (RO). Obtained results reveal several characteristics. Cell viability remained at the same level, regardless of the OGD and RO conditions, but, in parallel, the metabolic activity of cells decreased with OGD duration. 24 h RO did not recover the metabolic activity fully. Cells subjected to OGD appeared softer than control cells. Cell softening was strongly present in cells after 1 h of OGD and with longer OGD duration, and in RO conditions, cells recovered their mechanical properties. Changes in the nanomechanical properties of cells were attributed to the remodelling of actin filaments, which was related to cofilin-based regulation and impaired metabolic activity of cells. The presented study shows the importance of nanomechanics in research on ischemic-related pathological processes such as stroke.