Individual Predisposition Research Articles

The Role of Pharmacogenetic Testing in Overcoming Pseudoresistance and Hyperprolactinemia in a Patient with Schizophrenia (Case Report)

Schizophrenia is a chronic mental disorder. It is treated with antipsychotics, which have a high risk of adverse drug reactions. Approximately 20-30% of patients with schizophrenia remain resistant to psychopharmacotherapy. Determining the individual predisposition to the response to antipsychotics and antipsychotic-induced adverse drug reactions development is possible using pharmacogenetic testing. Purpose is to present the role of pharmacogenetic testing in optimizing antipsychotic therapy. Materials and methods: The peripheral blood of patients was genotyping using real-time polymerase chain reaction. Results: This case report is about a 30- year-old female patient with paranoid schizophrenia, which had a long history of low effectiveness and poor tolerability of antipsychotics. The treatment was complicated by the pituitary microadenoma presence. According to the PGx results, the patient has a “poor transporter” phenotype, which also explains the high risk adverse drug reactions developing and therapeutic resistance while taking P- glycoprotein substrates antipsychotics. For the treatment, the antipsychotic brexpiprazole was selected, which did not have the P-glycoprotein substrate properties. It made possible to achieve paranoid schizophrenia remission and hyperprolactinemia correction. Conclusion: This case report demonstrates that wider implementation of pharmacogenetic testing into real clinical practice could help significantly improve the efficiency and safety of antipsychotic therapy.

A genome-wide association study identifies eight loci associated with intraductal papillary mucinous neoplasm progression toward malignancy.

Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer, but not all IPMNs progress to cancer. The objective of this study was to identify the germline genetic variants associated with IPMN clinical progression by conducting the first genome-wide association study (GWAS) and computing a polygenic hazard score (PHS) in 338 patients with IPMN. The study population was divided into two subsets, and a Cox analysis adjusted for sex, age, cyst size at diagnosis, and the top 10 principal components was performed. A PHS was calculated using the genotypes of common variants associated with IPMN progression identified. Eight loci with significant associations (p<5×10-8) were identified, and the most significant was 7q21.11-rs117620617 (hazard ratio, 16.35; 95% confidence interval, 6.93-38.60; p=1.80×10-10). All variants were associated with inflammatory processes, suggesting that alleles that predispose to an inflammatory prone phenotype may promote progression. The PHS indicated a statistically significant association (hazard ratio, 18.05; 95% confidence interval, 7.96-45.80; p=6.18×10-11) with IPMN progression among individuals who had the highest number of effect alleles (fourth quartile) compared with those who had the lowest number (first quartile). The current results study advance the understanding of individual predisposition to IPMN progression and underscore the potential use of genetics in the stratification of patients who have IPMN.

Combined Effect of Air Pollution and Genetic Risk on Incident Cardiovascular Diseases.

Whether genetic susceptibility to cardiovascular diseases (CVDs) enhances the vulnerability to adverse cardiovascular outcomes by air pollution is unknown. We assessed the combined effect of air pollution and genetic predispositions on CVD risk. From the UK Biobank cohort, we selected genetically unrelated White British participants without CVD. Levels of ambient particulate matter with a diameter of <2.5 μm (PM2.5) and <10 μm were estimated using land use regression models. An individual's genetic predisposition to CVDs was determined by polygenic risk scores for coronary artery disease, myocardial infarction, stroke, ischemic stroke, heart failure, and atrial fibrillation. We stratified mortality and CVD risk by PM2.5 exposure across high and low genetic risk groups. A total of 249 082 participants (aged 56.9±8.0 years, 46.8% men) were followed for a median of 10.8 years. The combined effect of PM2.5 exposure and the genetic predisposition of CVD demonstrated the highest risk of cardiovascular death in the high genetic risk group with the greatest PM2.5 exposure (adjusted hazard ratios ranging from 1.73 to 2.12 across the polygenic risk score of each CVD). The combination of higher exposure to ambient PM2.5 and high genetic risk was associated with higher incidence of all CVDs, although no significant interactions were observed between genetic risk and PM2.5 exposure on cardiovascular death or CVD events. A combination of greater PM2.5 exposure and higher genetic predisposition to particular CVDs was modestly associated with elevated risks of cardiovascular death and CVDs. Not only alleviating PM2.5 exposure in the general population but also implementing individualized preventive approach for those at high genetic risk might be beneficial.

Absolute Quantitative Targeted Monitoring of Potential Plasma Protein Biomarkers: A Pilot Study on Healthy Individuals.

The development of blood tests for the early detection of individual predisposition to socially significant diseases remains a pressing issue. In this pilot study, multiple reaction monitoring mass spectrometry (MRM-MS) with a BAK-270 assay was applied for protein concentrations analysis in blood plasma from 21 healthy volunteers of the European cohort. The levels of 138 plasma proteins were reliably and precisely quantified in no less than 50% of samples. The quantified proteins included 66 FDA-approved markers of cardiovascular diseases (CVD), and other potential biomarkers of pathologies such as cancer, diabetes mellitus, and Alzheimer's disease. The analysis of individual variations of the plasma proteins revealed significant differences between the male (11) and female (10) groups. In total, fifteen proteins had a significantly different concentration in plasma; this included four proteins that exhibited changes greater than ±1.5-fold, three proteins (RBP4, APCS, and TTR) with higher levels in males, and one (SHBG) elevated in females. The obtained results demonstrated considerable agreement with the data collected from 20 samples of a North American cohort, which were analyzed with the similar MRM assay. The most significant differences between the cohorts of the two continents were observed in the level of 42 plasma proteins (including 24 FDA markers), of which 17 proteins showed a ≥1.5-fold change, and included proteins increased in North Americans (APOB, CRTAC1, C1QB, C1QC, C9, CRP, HP, IGHG1, IGKV4-1, SERPING1, RBP4, and AZGP1), as well as those elevated in Europeans (APOF, CD5L, HBG2, SELPLG, and TNA). The results suggest a different contribution of specific (patho)physiological pathways (e.g., immune system and blood coagulation) to the development of socially significant diseases in Europeans and North Americans, and they should be taken into account when refining diagnostic panels.

Beyond dislike counts: How YouTube users react to the visibility of social cues

This study investigates the impact of YouTube’s 2021 policy, which hides dislike counts and limits a form of negative social feedback. It examines how this change affects social media herding behavior—the tendency of users to align with the majority opinion. We adopted a mixed-method approach, incorporating an online experiment that simulates the YouTube interface and an Interrupted Time Series analysis of real-world user reactions, to assess how the policy affects user engagement. Specifically, we looked at how the absence of one-sided digital cues, combined with content characteristics and individual user predispositions, influences user behavior. Our findings suggest that YouTube’s initiative to boost platform positivity had limited success: user responses were more influenced by their ideological leanings than by visible digital cues; Hiding dislikes reduced commenting frequencies and inadvertently increased negative expression. These results highlight the stronger role of ideological beliefs over social cues in shaping engagement, challenging the presumed impact of audience conformity and the negativity bias on social media dynamics.

Activity-based mindfulness: large-scale assessment of an online program on perceived stress and mindfulness.

Mindfulness has emerged as key construct in mental health over past decades. While current mindfulness-based interventions (MBIs) are usually rooted in Asian contemplative traditions, mindfulness practices can equally be found in other knowledge systems, including integrative medicine systems such as anthroposophic medicine (AM). The Activity-Based Stress Release (ABSR) program incorporates the latter as part of an 8-week-long online intervention combining mindfulness exercises, behavioral self-observation, and mindful movement practices derived from this integrative medicine frame. The program could offer additional means for cultivating mindfulness, thereby addressing the necessity for diverse approaches in conjunction with individual differences, diverse clinical demands, or restricted capacities to perform certain mindfulness practices. Using an observational repeated-measures design, the current study aimed to assess a large-scale online implementation of this program in terms of its feasibility, assessing perceived stress and mindfulness. Individuals who enrolled in any of the 37 ABSR program iterations carried out during 2023 and agreed to participate in the study completed online surveys including validated stress and mindfulness scales at the beginning, middle, end, and follow up of the intervention. Linear-mixed models were used for data analysis. A total of 830 individuals took part in the study, of which 53.5% filled in at least 2 surveys. In line with our expectation, mindfulness scores increased significantly over the course of the intervention, while stress scores decreased significantly in this timeframe. We further found differential effects of self-practice frequency and duration on the outcomes. This study provides a first indication of stress reduction in conjunction with the online implementation of this novel MBI. The work further suggests that this AM-based intervention indeed targets mindfulness, as do other MBIs, and that it is adaptable to an online format. However, given the observational single-arm design, controlled studies will be necessary to confirm these results. Nonetheless, the study adds a novel contribution to existent MBIs, which is significant in view of the need for diverse approaches to meet the heterogeneity of individual predispositions and clinical requirements. It remains to established by forthcoming research for which groups of individuals or clinical features this approach could be especially beneficial or less suitable.

Obesity Nephropathy: A Current Overview

The obesity pandemic is a public health problem that is evolving at high speed with both functional and vital outcomes. Recently, many studies have shown that obesity is a driver of chronic kidney disease onset and progression. The mechanisms underlying this fact are multiple including inflammation, oxidative stress, insuline resistance and hemodynamic change with inappropriate RAAS and SNS activation; occuring on a particularly genetic basis of individual predisposition. In this field, Obesity-related glomerulopathy is characterized by glomerulomegaly with localized and segmental glomerulosclerosis lesions. Main symptoms are non specific, dominated by microproteinuria, rarely nephrotic syndrome and a slowed decline in glomerular filtration rate. As for treatment, it starts essentially with lifestyle interventions targeting a meaningful and sustainable weight loss, accompanied by antiobesity medications (AOMS) including RAAS blockers, SGLT2inhibitors and since very recently, long-acting glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) which were shown to be effective in managing weight loss in non-chronic kidney disease (CKD) patients. Preliminary results of more definitive studies in CKD patients are currently being finalized. Bariatric surgery could reduce the risk of mortality in obese CKD patients; it is recommended for patients with severe morbid obesity, poor tolerance to AOMS, particularly GLP RA, or those whose long-term medication costs represent a barrier to sustainable results. In this review, we summarize epidemiological data on obesity nephropathy, its pathophysiological mechanisms, clinical features and perspectives on its treatment.

Virtual Reality Pursuit: Using Individual Predispositions towards VR to Understand Perceptions of a Virtualized Workplace Team Experience

Virtual Reality Pursuit: Using Individual Predispositions towards VR to Understand Perceptions of a Virtualized Workplace Team Experience

Integrating genomics as clinical biomarkers in pediatric pulmonology.

Respiratory diseases often result from complex interactions between an individual's genetic predisposition and their exposure to various environmental and other risk factors. Here we will briefly review how various types of "omics", particularly epigenomics and transcriptomics, hold promise for translation into clinical biomarkers in pediatric pulmonary medicine, using asthma and cystic fibrosis as examples.

THE INFLUENCE OF DRUG ADDICTION ON CRIMINAL BEHAVIOR

The relationship between drug addiction and criminal behavior constitutes a complex interplay, as substance abuse impacts a wide spectrum of criminal activities. Building on foundational knowledge and guided by theoretical frameworks, multiple contributing factors influencing this interaction have been investigated. Socio-economic conditions, individual predispositions, and the availability of illicit substances are among the key factors in this context. By examining such factors, we aim to achieve a broader understanding of how substance abuse can trigger various criminal activities. Law enforcement strategies, treatment approaches, and their broader societal consequences are integral components of this study. Additionally, the examination of ethical considerations and human rights concerns that may arise is of importance. This study emphasizes the need for a comprehensive and multidimensional approach to address the challenges posed by addiction and its relationship with criminality, with a focus on societal consequences and the potential for positive change. This can provide valuable insights into this issue, contributing to a deeper understanding and, among other things, its impact on the Western Balkans.

Investigation of genetic polymorphisms in genes encoding growth factors and dental pulp calcification in orthodontic patients

Background and objectivesPulp calcification is associated with many factors and triggers, including individual genetic predisposition and orthodontic forces. This study aimed to investigate whether genetic polymorphisms in epidermal growth factor (EGF), epidermal growth factor receptor (EGFR1), transforming growth factor-beta 1 (TGFβ1), and transforming growth factor-beta receptor 2 (TGFβR2) are associated with a risk of dental pulp calcifications in orthodontic patients. Materials and methodsDigital orthopantomography (OPG) and genomic DNA from 132 patients were analyzed in this cross-sectional study. Pulp calcification was observed in the maxillary and mandibular first molars. Genomic DNA extracted from saliva cells was used to genotype eight genetic polymorphisms using real-time polymerase chain reaction: EGF (rs2237051 and rs4444903), EGFR (rs2227983 and rs763317), TGFβ1 (rs1800469 and rs4803455), and TGFβR2 (rs3087465 and rs764522). The association between pulp calcification and genetic polymorphisms was analyzed using allelic and genotypic distributions, and haplotype frequencies (P < 0.05). ResultsThe prevalence of pulp calcification was 42.4 % in 490 molars. Genotypic analysis and allelic distribution showed no statistically significant association between the evaluated growth factors and molar calcification (P > 0.05). No haplotype combinations showed a statistically significant difference (P > 0.05). ConclusionThe genetic polymorphisms investigated were not associated with dental pulp calcification in orthodontic patients. Further studies should investigate other polymorphisms in genes encoding growth factors.

Dynamics in the heritability of leadership role occupancy: Evidence from a three-wave twin sample

Studies show that genetics matter in who becomes a leader. However, we know little about the dynamic properties of the heritability of leadership emergence or how genetics might interact with environmental conditions to shape leadership emergence. We track leadership role occupancy at three time points among a cohort of 1,079 Danish twin pairs over ten years. Our results suggest that genetics matter less when the cohort is young and increase over time as the cohort grows older. We argue that labor market entry costs coupled with free access to education constrain the effect of genetics in the cohort during early adulthood, suggesting differing effects of the environment on genetic expression as the cohort ages. Sorting based on individual predisposition towards leadership likely strengthens as the cohort grows older and gains labor market experience. This result implies that we should not view the effect of genes on leadership role occupancy as static and that environmental experiences could disproportionately affect critical early leadership advancement. Our study reinforces calls to consider dynamic properties such as gene x environment interactions to advance our broader understanding of leadership’s biology.

Literature as a Remedy for the (De)sensitization of the Contemporary Child. Attempt of Practical Approach Using the Theme of War

The text is theoretical in its nature and deals with the subject of the influence of literature on the child in early school age in terms of affecting the sensitivity of the recipient. The author considers the phenomenon of (de)sensitization as a process that would help the modern child to accept taboo phenomena on the example of the subject of war. The article refers to the theory of the Highly Sensitive Child and the “bitter-sweet” impact of art, recalling the works of Elaine Aron and Susan Cain. It was emphasized that the child’s hypersensitivity to certain images or sounds is related not only to natural stages of development, but also, or perhaps mainly, to individual predispositions to sensitivity to stimuli. The considerations included in the article also refer to war-themed texts for children published in Poland. The researcher provides a list of reading materials that may be interesting for contemporary child readers, but are not part of the school canon. The text is supplemented by a practical example of working with Liliana Bardijewska’s work entitled Karim’s Cat and Pictures with the use of a board game as a form of work with text at the level of grades I–III of primary school.

Risk assessment with gene expression markers in sepsis development

Infection is a commonplace, usually self-limiting, condition but can lead to sepsis, a severe life-threatening dysregulated host response. We investigate the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. Whole-blood RNA sequencing analysis was performed on preoperative samples from 267 patients. These patients developed postoperative infection with (n= 77) or without (n= 49) sepsis, developed non-infectious systemic inflammatory response (n= 31), or had an uncomplicated postoperative course (n= 110). Machine learning classification models built on preoperative transcriptomic signatures predict postoperative outcomes including sepsis with an area under the curve of up to 0.910 (mean 0.855) and sensitivity/specificity up to 0.767/0.804 (mean 0.746/0.769). Our models, confirmed by quantitative reverse-transcription PCR (RT-qPCR), potentially offer a risk prediction tool for the development of postoperative sepsis with implications for patient management. They identify an individual predisposition to developing sepsis that warrants further exploration to better understand the underlying pathophysiology.

Everyday Conversations About Economic Inequality: A Research Agenda

ABSTRACTHigh and rising levels of economic inequality come at a tremendous cost to societies, yet the public is often hesitant to confront these inequalities. Prior research has attempted to explain this paradox, pointing to how it is driven by individuals' misperceptions of the extent of inequality, broader narratives that justify inequality, and distrust in government intervention and redistribution. These beliefs and attitudes are not simply a reflection of individual predispositions; they are also a product of societal debates. The limited scholarship on such debates has focused on elite discourse, examining how discussions about inequality unfold among people in positions of power in formalized contexts such as parliaments or the media. Most of this research has been conducted in the Global North. We know very little about how ordinary people talk about economic inequality, especially in the Global South. Everyday conversations about economic inequality deserve more scholarly attention because of their distinct form and extensive range, covering diverse voices and social situations. They reflect how societies struggle with economic inequality and how some groups are silenced, while others have their voices amplified. Finally, conversations may affect opinion formation differently than unidirectional exposure to information. This article reviews the literature and sets out a research agenda to comprehensively study how ordinary people talk about economic inequality in various contexts.

Informing or guiding? The influence of party politicisation of the European Union on public opinion formation

How do individual predispositions towards national politics influence public opinion formation on the EU? This article addresses this question by unveiling the moderating role of party politicisation of the EU. Through debate and competition, political parties can affect how individuals rely on their predispositions towards national politics to form their views on the EU. Using individual-level and country-year-level data from 25 EU countries, results reveal that citizens are less likely to rely on short-term utilitarian appreciations of the national economy or trust in national institutions as the degree of party politicisation of the EU increases. The way individuals activate predispositions that reflect hostility towards immigrants is not dependent on the levels of party politicisation of the EU. The findings highlight that party politicisation of the EU informs public opinion by creating an information-rich environment; however, it does not guide individuals to mobilise and activate their cultural predispositions towards immigration.

Sustainable Entrepreneurial Orientation (SEO), and Organizational Performance: A Gender-Moderated Perspective in Peru

Sustainable Entrepreneurial Orientation (SEO) is an emergent concept and a complex dynamic capability that could explain the behavioral predisposition of individuals and organizations to contribute to sustainable development. This study examined the impact of decision-makers' SEO on the organizational performance of their companies. In addition, the study evaluated the moderating role of gender in the relationship between SEO and performance. The approach of the study was explanatory and non-experimental. It used a PLS-SEM technique on a sample of 121 decision-makers of micro and small enterprises operating in different sectors in Peru, a highly entrepreneurial country in Latin America. After validating the SEO measurement from the individual perspective, the results showed that SEO does affect performance. However, the moderating role of gender on the SEO-performance relationship was not empirically validated. This study contributes to the literature on sustainable entrepreneurship by confirming that the phenomenon of SEO, typically assessed at the organizational level, is also an important antecedent of organizational performance when viewed from the individual perspective. Although the moderating effect of gender was not proven, this study provides insightful directions on the SEO-performance relationship. Thus, by validating the SEO instrument that considers its components from an individual perspective, the literature on this strategic orientation has been expanded.

‘Are you still watching?’ – A study on the predictors of the problematic practice of binge-watching

By implementing innovative ways of accessing the media, video-on-demand services have renewed the concept of watching television, leading to the growth and popularity of social behavior of content consumption in the form of marathons, known as binge-watching. There is an increase in literature discussions about potential adverse outcomes that can arise from the excess of these marathons. It is because the adversities of its excessive use can affect its users in the social, physical, and mental spheres. Given the relevance of this social problem, this research aims to understand the main determining predictors of the problematic practice of binge-watching. The research sample consisted of binge-watching practitioners (n=467). The linear and multivariate methods used Structural Equation Modeling by Partial Least Squares (SEM-PLS) and Necessary Condition Analysis (NCA). As a result, the study showed that the practice, associated with the psychological predisposition of individuals, can lead to the development of negative symptoms similar to addiction to various technologies, compromising the individual’s life both physically and psychologically. This phenomenon intensified during the COVID-19 pandemic when binge-watching was used for distractions, entertainment, and the management of negative sensations arising from the pandemic. Finally, this research contributes to the proposition of an original theoretical model on the problematic practice of binge-watching. It brings elements to reflect from the ESG point of view, as companies must commit to their social governance, thinking of strategies to optimize the obtaining profits, in the present study, subscriptions, without compromising the health of individuals.

Research on the Impact of Landscape Planning on Visual and Spatial Perception in Historical District Tourism: A Case Study of Laomendong

Exploring the impact of landscape planning on visual and spatial perception is particularly significant for historical district tourism. The existing literature offers limited insight into which historical landscapes most effectively influence tourists’ visual and spatial perceptions. Our study investigates this relationship within the cultural heritage context of Laomendong, a historical district in Nanjing, China. Utilizing the Stimulus–Organism–Response (SOR) theoretical framework, this research explored how the stylistic, symbolic, and spatial dimensions of historical landscapes influence tourists’ visual and spatial perceptions. Structural equation modeling (SEM) was used to test hypotheses concerning the relationships between historical landscapes, visual perception, spatial perception, and individual predispositions. The findings revealed that stylistic factors (material, color, and ornament), symbolic factors (landmark, relic, and sign), and spatial factors (openness, scale, and layout) significantly enhance visual perception and subsequently spatial perception. Visual perception plays a mediating role in the influence of historical landscapes on spatial perception. Individual predispositions, like sensation-seeking, intensify spatial perception, while destination familiarity surprisingly shows a negative effect, suggesting that over-familiarity might diminish the novelty and excitement of a spatial experience. These insights provide practical implications for the sustainable development of landscape planning in historical district tourism.

Identification of Pathogenic Pathways for Recurrence of Focal Segmental Glomerulosclerosis after Kidney Transplantation.

Primary focal segmental glomerulosclerosis (FSGS) is a disease of the podocytes and glomerulus, leading to nephrotic syndrome and progressive loss of renal function. One of the most serious aspects is its recurrence of disease in over 30% of patients following allogeneic kidney transplantation, leading to early graft loss. This research investigates the individual genetic predispositions and differences in the immune responses leading to recurrence of FSGS after transplantation. We performed exome sequencing on six patients with recurrent FSGS to identify variants in fifty-one genes and found significant variations in the alpha-2-macroglobulin (A2M). Immunoblotting was used to investigate effects of specific gene variants at the protein level. Further expression analysis identified A2M, exophilin 5 (EXPH5) and plectin (PLEC) as specific proteins linked to podocytes, endothelial cells, and the glomerulus. Subsequent protein array screening revealed the presence of non-HLA-specific antibodies, including TRIM21, after transplantation. Using Metascape for pathway and process enrichment analysis, we focused on the IL-17 signaling and chemotaxis pathways. ELISA measurements showed significantly elevated IL-17 levels in patients with recurrent FSGS (32.30 ± 9.12 pg/mL) compared to individuals with other glomerular diseases (23.16 ± 2.49 pg/mL; p < 0.01) and healthy subjects (22.28 ± 0.94 pg/mL; p < 0.01), with no significant difference in plasma CCL2/MCP-1 levels between groups. This study explores the molecular dynamics underlying recurrence of FSGS after transplantation, offering insights into potential biomarkers and therapeutic targets for the future development of individualized treatments for transplant patients.