Individual Trajectories Research Articles

Healthcare trajectories of aging individuals during their last year of life: application of process mining methods to administrative health databases

ContextWorld is aging and the prevalence of chronic diseases is raising with age, increasing financial strain on organizations but also affecting patients’ quality of life until death. Research on healthcare trajectories has gained importance, as it can help anticipate patients’ needs and optimize service organization. In an overburdened system, it is essential to develop automated methods based on comprehensive and reliable and already available data to model and predict healthcare trajectories and future utilization. Process mining, a family of process management and data science techniques used to derive insights from the data generated by a process, can be a solid candidate to provide a useful tool to support decision-making.ObjectiveWe aimed to (1) identify the healthcare baseline trajectories during the last year of life, (2) identify the differences in trajectories according to medical condition, and (3) identify adequate settings to provide a useful output.MethodsWe applied process mining techniques on a retrospective longitudinal cohort of 21,255 individuals who died between April 1, 2014, and March 31, 2018, and were at least 66 years or older at death. We used 6 different administrative health databases (emergency visit, hospitalisation, homecare, medical consultation, death register and administrative), to model individuals’ healthcare trajectories during their last year of life.ResultsThree main trajectories of healthcare utilization were highlighted: (i) mainly accommodating a long-term care center; (ii) services provided by local community centers in combination with a high proportion of medical consultations and acute care (emergency and hospital); and (iii) combination of consultations, emergency visits and hospitalization with no other management by local community centers or LTCs. Stratifying according to the cause of death highlighted that LTC accommodation was preponderant for individuals who died of physical and cognitive frailty. Conversely, services offered by local community centers were more prevalent among individuals who died of a terminal illness. This difference is potentially related to the access to and use of palliative care at the end-of-life, especially home palliative care implementation.ConclusionDespite some limitations related to data and visual limitations, process mining seems to be a method that is both relevant and simple to implement. It provides a visual representation of the processes recorded in various health system databases and allows for the visualization of the different trajectories of healthcare utilization.

A Context-Aware Content Recommendation Engine for Personalized Learning using Hybrid Reinforcement Learning Technique

In the evolving landscape of e-learning, delivering personalized content that aligns with learners' needs and preferences is crucial. This study proposes a Context-Aware Content Recommendation Engine (CACRE) that utilizes a Hybrid Reinforcement Learning (HRL) technique to optimize personalized learning experiences. The engine incorporates learners' contextual data, such as learning pace, preferences, and performance, to deliver tailored recommendations. The proposed HRL model combines Deep Q-Learning for dynamic content selection and Policy Gradient Methods to adapt to individual learning trajectories. Experimental results demonstrate significant improvements in learner engagement, content relevance, and knowledge retention. This approach underscores the potential of context-aware recommendation systems to revolutionize personalized education by fostering adaptive and interactive learning environments.

Inpatient dialectical behavior therapy combined with trauma-focused therapy for PTSD and borderline personality disorder symptoms: study design of the naturalistic trauma therapy study

IntroductionChildhood traumatization can result in physical and mental health problems in adulthood, such as post-traumatic stress disorder (PTSD), which negatively influences quality of life and social functioning. Although evidence based trauma treatments benefit clients with PTSD after childhood abuse and comorbid personality disorders, they are less effective than in clients who were traumatized in adulthood, and drop-out is substantial. The current study aims to assess the effects of inpatient dialectical behavior therapy combined with prolonged exposure (DBT-PTSD) on severity of PTSD, dissociation, parasuicidal behavior and borderline personality disorder (BPD) in clients with severe PTSD and comorbid psychiatric disorders. Secondary outcomes are social functioning, quality of life, borderline and cluster C personality disorder symptoms as treatment predictors, treatment trajectories, clients’ experiences and health economic consequences.MethodsThe naturalistic, longitudinal Trauma Therapy Study is conducted from January 2019 until May 2025 in a mental healthcare center in the Netherlands. Clients with severe PTSD and comorbid conditions who are referred to inpatient DBT-PTSD are included into the study. Based on power analyses a total sample size of N=56 is needed. Measurements take place before the waiting list period, at pre- and posttreatment and at six- and twelve-months follow-up. Clients fill in a daily DBT-PTSD diary, which gives insight into individual symptom trajectories.ResultsStatistical analyses include two-sided paired samples t-tests, linear mixed model analyses and cost-effectiveness analyses. Qualitative interviews are conducted within two years posttreatment and analyzed using a phenomenological approach. We correct for chance capitalization by using a conservative α-level of.01. Multiple imputation is used to handle missing data.DiscussionResearch on the effects of integrated treatment programs for clients with severe PTSD and co-morbid conditions is scarce. This study extends current knowledge on the effects of inpatient DBT-PTSD on PTSD and BPD symptoms, clients’ social functioning and quality of life. In addition, it provides insight into individual symptom trajectories and experiences, inspiring future treatment improvements for clients with severe psychopathology.Trial registrationMedical Ethical Committee approval (NL669060018, RTPO1044/01.10.2018). Preregistration: Dutch registration database Centrale Commissie Mensgebonden Onderzoek and International Clinical Trials Registry Platform (NL-OMON46167/01.10.2018/https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON46167).

Increasing the Efficiency of Ensemble Molecular Dynamics Simulations with Termination of Unproductive Trajectories Identified at Runtime.

The application of molecular dynamics (MD) simulations to study increasingly larger and more complex systems is challenged by the required amounts of trajectory data needed to sample their conformational space appropriately. The analysis and interpretation phase of such massive data sets that have to be stored and fed to the various algorithms to reveal the dynamic behaviors of the systems and the underlying energetics in structural terms related to functional mechanisms are also a significant challenge. To develop computational means that can address these challenges, we are developing a software framework that can increase the efficiency of this process. We present one component of this framework that can reduce the size of the accumulating data set while maintaining the structural attributes, distribution, and relative probability ranking of the minima in the free energy map for the system. This framework component utilizes early termination of individual trajectories identified as unproductive in the sampling of conformational space. The criteria for termination are derived quantities such as collective variables (CVs) and secondary quantities calculated from the time series of CVs. They are computed and applied during the trajectory generation. The approach is illustrated with simulations of the FS peptide and evaluated from comparisons between the free energy surfaces calculated from ensembles of complete, unabridged simulations with those obtained from ensembles in which ∼5-50% of trajectories were terminated early. Our early termination approach can optimize computational efficiency while achieving a robust representation of conformational space.

Cognitive predictors of mental health trajectories are mediated by inferior frontal and occipital development during adolescence.

Laboratory studies show brain maturation involves synaptic pruning and cognitive development. Human studies suggest links between early cognitive performance and later mental health, but inconsistencies remain. It is unclear if specific brain regions mediate this relationship, and the molecular underpinnings are not well understood. Here, our longitudinal analyses in both the Adolescent Brain Cognitive Development and IMAGEN cohorts establish inverted U-shaped relationships between baseline executive function and subsequent symptom trajectories in the high-symptom individuals, whose externalizing (n = 963) or internalizing (n = 1762) symptoms exceed a clinical threshold at any point during the follow-up period, but not in the control group (n = 4291). Volumetric changes in the left lateral occipital cortex (LOC) mediated the relationship with externalizing symptoms (outwardly directed behaviors such as aggression), while changes in the right LOC and pars triangularis mediated the relationship with internalizing symptoms (inwardly directed emotional problems such as anxiety). Transcriptomic and genomic findings highlighted synaptic biology and particularly the gene ADCY1, which is implicated in synaptic pruning, as underlying both moderate executive function and its associated brain mediators. Notably, preadolescent cognitive performance predicts late-onset externalizing symptoms and remitting internalizing symptoms with high accuracies (area under the curve: 0.87 and 0.79). Our findings highlight the predictive value of cognitive performance for adolescent mental health trajectories, and indicate how this is mediated by specific brain regions, and underpinned by particular molecular pathways.

218. Attenuated PreFusion F Antibody Response to RSV Vaccines in Solid Organ Transplant Recipients

Abstract Background RSV causes serious morbidity in solid organ transplant recipients (SOTRs). Novel RSV vaccines are highly protective in the general population, yet immunogenicity among SOTRs is unknown. Demographic and Transplant Characteristics of SOTRs Reporting RSV Vaccination Methods Within a national, prospective cohort study SOTRs submitted whole blood samples at baseline and 2, 4, and 12 weeks post receipt of RSV vaccination (RSVPreF3 [GSK, AREXVY™] or RSVpreF [Pfizer, ABRYSVO™]) between October 2023-March 2024. Plasma prefusion F IgG and IgM (preF Ab) was tested using the Meso Scale Discovery platform and compared between baseline and 4 weeks to assess fold-change (FC); the proportion achieving high-titer Ab (IgG ≥high-titer reference plasma [BEI Resources]) at 4 weeks was also assessed. Ab measures were compared between GSK and Pfizer vaccinees. Change in Prefusion F IgG Titers following RSV Vaccination in SOTRs Blue dots represent Pfizer vaccine recipients and pink dots represent GSK vaccine recipients. Individual titer trajectories are connected by grey lines. High-titer response is denoted by the upper red horizontal line, corresponding to high-titer pooled control plasma. Results Among 27 participants (median [IQR] age 65-73 years, 44% female, 59% GSK and 30% Pfizer vaccinees [11% unspecified]), median [IQR] preF IgG rose from 76,252 [59,116-185,845] to 424,618 [153,503-1,905,705] AU/mL by 4 weeks (median [IQR] FC 5.54 [2.06-13.26]). Overall, 67% demonstrated IgG FC ≥4 at 4 weeks (69% GSK vs 50% Pfizer vaccinees) and 52% demonstrated high-titer Ab at 4 week (62% GSK vs 25% Pfizer vaccinees); clinical and transplant factors were similar between response groups. By 12 weeks, 56% showed high-titer Ab (62% GSK vs 38% Pfizer vaccinees) (Figure). Response patterns varied, including greater IgM change from baseline to 4 weeks in GSK vaccinees (IgM FC ≥4: 31% GSK vs 25% Pfizer) and more pronounced IgG peak-and-wane in GSK vaccinees (median FC from 4 to 12 weeks 1.01 GSK vs 0.49 Pfizer). No participants reported RSV infection during follow up. Prefusion F IgG Titers pre and post RSV Vaccination in SOTRs, by Vaccine Type Blue dots represent Pfizer vaccine recipients and pink dots represent GSK vaccine recipients. High-titer response is denoted by the upper red horizontal line, corresponding to high-titer pooled control plasma. Open circles represent ≥ 4-fold change in titer at 4 weeks. Conclusion RSV preF Ab responses are highly variable and often attenuated in SOTRs following RSV vaccination; 44% did not show high-titer Ab at 4 weeks. Response level and pattern vary by vaccine platform (i.e., adjuvanted versus unadjuvanted), which may imply different risk periods post vaccination and potential role for additional vaccine doses to improve immunoprotection. Prefusion F IgM Titers pre and post RSV Vaccination in SOTRs, by Vaccine Type Blue dots represent Pfizer vaccine recipients and pink dots represent GSK vaccine recipients. Open circles represent ≥ 4-fold change in titer at 4 weeks. Disclosures Andrew H. Karaba, MD PhD, Hologic: Advisor/Consultant William Werbel, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|IDSA: Advisor/Consultant|Novavax: Advisor/Consultant

Интегративная методика формирования лексической компетенции студентов направления «Лингвистика» на основе аудиовизуальных микромодулей: технологический и лингводидактический аспекты

The aim of this research is the theoretical justification and experimental verification of the effectiveness of an integrative methodology that combines the technological principles of designing audiovisual micro-modules and the linguodidactic mechanisms for the development of lexical competence in students of the "Linguistics" program (level B2) in a digital educational environment. The article presents the results of theoretical substantiation and experimental research, within which a three-phase learning model was developed and tested, based on the principles of neurodidactics and cognitive visualization, integrating technological and methodological aspects of the formation of lexical competence. A microlearning system has been implemented on the Moodle educational platform, including an optimized combination of micro-videos (40%), animated flashcards (35%), and interactive infographics (25%), which ensures the comprehensive development of all components of lexical competence. The scientific novelty of the research lies in the development of a theoretical and methodological justification for a three-phase microlearning model, based on the principles of neurodidactics and cognitive visualization for the formation of lexical competence. Significant correlation links between the parameters of the digital footprint and the effectiveness of learning lexical material have been identified and statistically confirmed (r = 0.82, p < 0.001), which creates a scientific basis for predicting individual educational trajectories. The effectiveness of the developed model has been experimentally proven, providing a significant increase in the rate of learning lexical material (by 37.4%, p < 0.01) and the sustainability of formed skills (an increase in material retention by 42.3%) compared to traditional teaching methods.

THE PERSONNEL DEVELOPMENT MANAGEMENT MECHANISM IN THE SYSTEM OF HUMAN RESOURCES POTENTIAL FORMING: LESSONS FOR THE MODERN ENTERPRISES ACCORDING TO FOREIGN EXPERIENCE

The elements of the mechanism of personnel development management in the system of personnel potential formation at modern enterprises are structured and grouped. It is determined that an important role in the human resource formation at the business entity is played by the personnel development strategy, which should combine such components as: establishing strategic guidelines for personnel characteristics, choosing directions for personnel development (training, advanced training, mentoring, coaching); forming the individual career trajectories of employees; developing the internal personnel training tools and choosing of external training tools; drawing up a budget for personnel development costs; fixing the measures for retaining talents, motivating them to be loyal to the enterprise goals. It is specified that the mechanism for managing the enterprise's personnel development should combine such elements as: goal, objectives, subjects, objects, tasks, functions, principles, and methods of professional development of employees. It has been established that the employee development mechanism functioning is influenced by the state of resource provision and the level of professionalism of the HR-management of the business entity. Analysis of personnel indicators of Ukrainian enterprises allowed us to conclude about high staff turnover, inability to form a high-quality employer brand, inability to maintain staff loyalty. It is proposed to borrow the foreign experience in forming human resources potential through mechanisms of recruitment, staff development and creation of such working conditions for them that will maintain a stable desire of the employee to remain part of the team and work to achieve the company's goals, conscientiously fulfilling their job duties. Approaches used in foreign practice of personnel development management are identified and the possibilities of their introduction into the activities of Ukrainian enterprises are established. It is substantiated that personnel development management should be one of the areas of strategic management of a modern enterprise.

Masked autoencoder for multiagent trajectories

Automatically labeling trajectories of multiple agents is key to behavioral analyses but usually requires a large amount of manual annotations. This also applies to the domain of team sport analyses. In this paper, we specifically show how pretraining transformer models improves the classification performance on tracking data from professional soccer. For this purpose, we propose a novel self-supervised masked autoencoder for multiagent trajectories to effectively learn from only a few labeled sequences. Our approach builds upon a factorized transformer architecture for multiagent trajectory data and employs a masking scheme on the level of individual agent trajectories. As a result, our model allows for a reconstruction of masked trajectory segments while being permutation equivariant with respect to the agent trajectories. In addition to experiments on soccer, we demonstrate the usefulness of the proposed pretraining approach on multiagent pose data from entomology. In contrast to related work, our approach is conceptually much simpler, does not require handcrafted features and naturally allows for permutation invariance in downstream tasks.

How public libraries reach out to adolescents: a study of adolescents’ perceptions of teen spaces1) in Korean public libraries

ABSTRACT Adolescence is a crucial period for developing abilities necessary for future success. This study focuses on Teen Spaces in public libraries as an environment where adolescents can develop diverse future visions tailored to their personalities. We aim to identify environmental planning factors that influence adolescents’ preference for Teen Spaces, to create dedicated spaces supporting healthy growth. A survey of 234 adolescents using public libraries was conducted to derive key environmental planning factors. Linear regression analysis revealed that “creativity support”, “amenity support”, and “learning support” significantly influenced adolescents’ preference for Teen Spaces. Interestingly, adolescents with prior experience of youth spaces were additionally influenced by “universal design support”, while those without experience were affected by “safety support”, “leisure support”, and “openness support”. The findings suggst that improving Teen Spaces in public libraries, considering these factors and the segmented characteristics of adolescents, can positively impact their growth and future development. This research contributes to ongoing efforts to create supportive environments for adolescents in public libraries, emphasizing the need for spaces that foster diverse future visions and support individual growth trajectories.

Individual-specific strategies inform category learning

Categorization is an essential task for sensory perception. Individuals learn category labels using a variety of strategies to ensure that sensory signals, such as sounds or images, can be assigned to proper categories. Categories are often learned on the basis of extreme examples, and the boundary between categories can differ among individuals. The trajectories for learning also differ among individuals, as different individuals rely on different strategies, such as repeating or alternating choices. However, little is understood about the relationship between individual learning trajectories and learned categorization. To study this relationship, we trained mice to categorize auditory stimuli into two categories using a two-alternative forced choice task. Because the mice took several weeks to learn the task, we were able to quantify the time course of individual strategies and how they relate to how mice categorize stimuli around the categorization boundary. Different mice exhibited different trajectories while learning the task. Mice displayed preferences for a specific category, manifested by a choice bias in their responses, but this bias drifted with learning. We found that this drift in choice bias correlated with variability in the category boundary for sounds with ambiguous category membership. Next, we asked how stimulus-independent, individual-specific strategies informed learning. We found that the tendency to repeat choices, which is a form of perseveration, contributed to long-term learning. These results indicate that long-term trends in individual strategies during category learning affect learned category boundaries.

P1058 Trajectories of response in patients with moderately-to-severely active Crohn’s disease treated with mirikizumab based on biofailed status: Post hoc results from the VIVID-1 study

Abstract Background Mirikizumab, an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile1. We explored the trajectory of response to treatment in patients with moderate-to-severely active Crohn’s disease (CD), in patients treated with mirikizumab based on biofailed status at study baseline. Methods Biofailed was defined as patients with demonstrated intolerance, inadequate response, or loss of response to an approved biologic therapy for CD (BF, N=275) and Not Biofailed (NBF, N=297) patients described previously1 were assessed via Growth Mixture Model to identify distinct clusters based on individual patient response trajectories. Change from baseline in Crohn’s Disease Activity Index total score was used in the Growth Mixture Model to identify trajectories. Modified baseline observation carried forward imputation used. Results There were four clusters identified for both the BF and NBF groups. Mirikizumab trajectory groups by baseline biofailed status: Super Responder (BF/NBF: 18.9%/17.8%), Responder (BF/NBF: 19.3%/25.3%), Delayed Responder (BF/NBF, 29.8%/29.3%), and Non/Incomplete Responder (BF/NBF, 32.0%/27.6%) (Figure 1). The overall response rate across responder groups for BF patients was 68.0% and for NBF patients was 72.4%. Conclusion Mirikizumab clinical response groups (Super Responder, Responder, Delayed Responder, and Non/Incomplete Responder) were similar for BF and NBF patients suggesting mirikizumab works consistently for BF and NBF patients, and prior biofailed status is not associated with the speed or magnitude of a MIRI-triggered clinical response.

P1071 Trajectories of response in patients with moderately-to-severely active ulcerative colitis treated with mirikizumab: Results from the LUCENT-1 study

Abstract Background Mirikizumab, an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile1. We explored the trajectory of response to mirikizumab treatment in patients with moderate-to-severely active ulcerative colitis. Methods Mirikizumab patients described previously1 were assessed via Growth Mixture Model (GMM) to identify distinct clusters based on individual patient response trajectories. The sum of stool frequency and rectal bleeding modified Mayo subscores was used in the GMM to identify trajectories. Week 12 clinical endpoints were assessed by trajectory group. Modified baseline observation carried forward imputation was used. Results Trajectory groups were identified as Super Responder (N=223; 25.7%), Responder (N=409; 47.1%), and Delayed or Non/Incomplete Responder (N=236; 27.2%) (Figure 1). At week 12, a different proportion of patients achieved efficacy endpoints by Super Responder, Responder, and Delayed or Non/Incomplete Responder trajectory groups, respectively: symptomatic remission: 70%/58%/0%; bowel urgency improvement: 72%/51%/22%; clinical response: 95%/75%/14%; clinical remission: 36%/32%/0% (Figure 2). Conclusion Three response trajectory groups were identified for mirikizumab treatment of ulcerative colitis: Super Responder, Responder, and Delayed or Non/Incomplete Responder. At week 12 of treatment, the proportion of patients achieving efficacy endpoints in general was greatest in Super Responders followed by Responders and then Delayed or Non/Incomplete Responders, with an overall response rate of 72.8%. Efficacy was similarly robust across both the Super Responder and Responder groups.

P0833 Trajectories of response in patients with moderately-to-severely active Crohn’s disease treated with mirikizumab or ustekinumab: Post hoc results from the VIVID-1 study

Abstract Background Mirikizumab (MIRI), an anti-IL-23p19 antibody, demonstrated robust efficacy in improving clinical and endoscopic endpoints with an acceptable safety profile1. In patients with moderate-to-severely active Crohn’s disease (CD), we explored the trajectory of response to MIRI or ustekinumab (USTE), an anti-IL-23p19p40 active comparator. Methods MIRI (N=572) and USTE (N=285) patients described previously1 were assessed via Growth Mixture Model to identify distinct clusters based on individual patient response trajectories. The Growth Mixture Model was first fit with MIRI only patient data with standardized beta link function to accommodate the non-Gaussian outcomes. Then the model was run with USTE only patient data based on the model parameter settings from the MIRI model to allow comparison. Change from baseline in Crohn’s Disease Activity Index (CDAI) total score was used in the Growth Mixture Model to identify trajectories. Week 52 clinical endpoints were assessed by trajectory group for MIRI and USTE. Modified baseline observation carried forward imputation used. Results There were four response trajectory clusters identified for MIRI, which were then compared to USTE: Super Responder (MIRI/USTE: 18.4%/10.9%), Responder (MIRI/USTE: 22.4%/13.0%), Delayed Responder (MIRI/USTE, 29.5%/31.2%), and Non/Incomplete Responder (MIRI/USTE, 29.7%/44.9%) (Figure 1). The proportion of Super Responders plus Responders was greater for MIRI vs USTE (40.7% vs 23.9%) and the proportion of Non/Incomplete Responders less (29.7% vs 44.9%). The proportion of patients achieving Week 52 clinical, endoscopic, and histologic endpoints was generally greatest for Super Responders followed by Responders and then Delayed Responders (Table 1). The proportion of patients achieving these endpoints for Super Responders + Responders was generally greater for MIRI vs USTE, in particular histologic response (70% vs 60%) and remission (36% vs 22%). Conclusion The overall response rate was 70.3% for MIRI and 55.1% for USTE. For the 4 MIRI symptom response trajectory groups – Super Responder, Responder, Delayed Responder, and Non/Incomplete Responder – the proportion of Super Responders plus Responders was greater for MIRI vs USTE and the proportion of Non/Incomplete Responders was less for MIRI vs USTE, while the proportion of patients achieving clinical endpoints for MIRI was generally numerically greater than USTE for Super Responders plus Responders.

P0597 Clinical and biochemical correlates of infliximab pharmacokinetics in adult patients with Inflammatory Bowel Disease

Abstract Background Antibodies against tumor necrosis factor-alpha (TNF-α) such as infliximab (IFX) are important in the treatment of patients with inflammatory bowel disease (IBD), but many patients lose drug response over time or do not respond at all. Loss-of-response and non-response can at least be partially attributed to suboptimal dosing due to individual differences in pharmacokinetics (PK)1. In this real-world study, we aimed to identify clinical, biochemical and endoscopic variables influencing IFX PK in patients with IBD. Methods Patients diagnosed with IBD aged ≥18 years who were treated with IFX were included based on available IFX trough levels from a hospital-based pharmacy registry. Information on endoscopic, clinical, and biochemical parameters was collected. Univariable and multivariable linear mixed-effects models were used to model associations between individual IFX trough level trajectories and identified factors to examine their relative contributions to IFX PK. In addition, a systematic literature study on IFX PK in adults with IBD and other immune-mediated inflammatory diseases was performed to better contextualize the obtained findings. Results A total of 200 patients were included (Crohn’s disease [CD] (n=163) and ulcerative colitis [UC] (n=37)) with 452 IFX trough levels available for analysis (Figure 1). Patients with antibodies (ATI) to IFX (unstandardized β=4.35, p<0.001) and those treated with longer dosing intervals (β=-1.89, p=<0.001) exhibited lower trough levels (Figure 2). Higher levels of aspartate aminotransferase (AST) (β=0.04, p=0.027), hemoglobin (β=0.76, p=0.022) and albumin (β=0.15, p=0.029) were positively associated with IFX trough levels. Among clinical factors, Simple Clinical Colitis Activity Index (SCCAI) scores in patients with UC, both as continuous (β=3.31, p=0.03) and as categorical variable (β=13.25, p=0.033), were positively associated with higher IFX trough levels. The presence of endoscopic inflammation, regardless of its severity, was also positively correlated with IFX trough levels (β=2.60, p=0.045). Conclusion This data demonstrates a role of AST, albumin, hemoglobin, SCCAI, and endoscopic inflammation as covariates potentially relevant to IFX PK in IBD. Findings of albumin, endoscopic inflammation, dosage interval and ATI were supported by our systematic review confirming them as previously identified covariates. AST, hemoglobin, and SCCAI were newly identified covariates. These covariates could optimize treatment strategies and should therefore be considered for integration in population-PK/PD models and PK dashboards in order to make patient-specific prediction models for IFX treatment.

Biomimetic artificial cilia with three-dimensional motion driven by magnetic fields

Abstract Inspired by natural cilia, we developed magnetically actuated artificial cilia capable of controlled three-dimensional motion. The key innovation lies in concentrating hard magnetic particles at the tip of a silicon pillar, enabling asymmetric effective and recovery strokes under a constant rotational magnetic field. By magnetizing the pillar at 45° to the ground, we achieved complex three-dimensional movements that closely mimic biological ciliary motion. Our developed simulation system reproduced individual pillar trajectories in static conditions, showing consistency with experimental results in the range without snapping, a phenomenon characterized by the sudden release of twist-induced stress. Furthermore, we demonstrated metachronal wave-like motion in pillar arrays. These arrays exhibited both transport capabilities, successfully moving a 10 mg object, and locomotion functions. The combination of precise motion control, predictive modeling, and demonstrated functionality suggests promising applications in microfluidic manipulation and biomedical devices.

Polarity sorting of actin filaments by motor-driven cargo transport.

During the active transport of cellular cargo, forces generated by cargo-associated molecular motors propel the cargo along cytoskeletal tracks. However, the forces impact not only the cargo, but also the underlying cytoskeletal filaments. To better understand the interplay between cargo transport and the organization of cytoskeletal filaments, we employ coarse-grained computer simulations to study actin filaments interacting with cargo-anchored myosin motors in a confined domain. We show that cargo transport can lead to the segregation of filaments into domains of preferred filament polarity separated by clusters of aggregated cargoes. The formation of polarity-sorted filament domains is enhanced by larger numbers of cargoes, more motors per cargo, and longer filaments. Analysis of individual trajectories reveals dynamic and heterogeneous behavior, including locally stable aggregates of cargoes that undergo rapid coalescence into larger clusters when sufficiently close. Our results provide insight into the impact of motor-driven organelle transport on actin filaments, which is relevant both in cells and in synthetic environments.

Through Their Eyes: Defining 'good life' in dementia for health economics and outcomes research.

Despite progress in involving people living with dementia in health research, disparities remain, particularly in the field of health economics and outcomes research, where excessive reliance on proxy reports from care partners or healthcare professionals persists even when people are capable of self-reporting, leading to inequitable inclusion. This study aimed to understand the concept of a 'good life' from the perspectives of people living with dementia and examine how well current preference-based outcome measures used in health economics and outcomes research capture these perspectives. Twenty-three community-dwelling people with mild to moderate dementia in Ireland participated in in-depth interviews (September 2022-February 2023). Data were analysed using an adapted Colaizzi's seven-step phenomenological method, followed by mapping identified themes against ten commonly used preference-based outcome measures in dementia research. Results show that participants perceive a 'good life' through independence, social connections, engagement with life, adaptation to changing abilities. As dementia progresses, perceptions shift from striving for independence and active life engagement to accepting assistance and increased social support. This transition reflects a journey of adaptation, where participants redefine their sense of a 'good life' with evolving challenges and capabilities. The mapping analysis reveal that current preference-based outcome measures vary considerably in their coverage of these themes (33-83%), with none fully capturing the dynamic and evolving nature of a 'good life' as described by participants. These findings expose disparities between lived experiences and current measurement frameworks in health economics and outcomes research in dementia, calling for developing flexible and adaptive approaches to quality of life assessment in progressive conditions-approaches that not only reflect quality of life as defined by those living with the condition but also accommodate its dynamic and evolving nature throughout individual disease trajectories.

The study of applicants' preferences in the context of the modern labor market and the education system desynchronization

Subject. The article considers the effectiveness of interaction between universities and applicants. Objectives. The aim is to investigate applicants’ preferences of in the context of desynchronization of the modern labor market and the education market. Methods. As part of the study, we conducted 46 personal interviews and interviewed 1,562 respondents, using an online questionnaire (51.9% from Moscow, 22.2% from the Moscow Oblast, 21.8% from Russian regions, 2.8% from CIS countries, 1.3% from other countries). Results. The study of applicants' preferences when choosing a university is an integral part of analyzing the effectiveness of educational institutions and training areas. The factors that influence the choice of a university by an applicant are correlated with the current and projected in the near future requirements of the labor market. Based on the study of current educational practices and preferences of applicants, we formulated recommendations aimed at transforming educational processes in universities, increasing the effectiveness of educational services promotion programs during the admission campaign. Conclusions. The emergence of programs or individual faculties using the model of free education with the application of an individual educational trajectory is an effective tool for detaching from competitors and, in the future, will help such universities move from the category of universities of mass professions to the category of regional level universities or research universities.

Development of Career Centers of Russian Universities: Challenges and Opportunities

Placement training of students for employment is a serious challenge for modern Russian universities. University graduates are faced with solving the problem of employment in the face of continuous transformation of the labor market. As a result, the issue of training highly professional specialists capable of adapting to the dynamically changing requirements of employers and willing to build a successful career throughout their lives is on the agenda. As the university practice of career centers shows, the job search assistance and employment support is usually carried out within its framework. Meanwhile, the issue of training students for career development should become a key one in the philosophy of university education. In modern conditions, universities are designed to prepare a student who is potentially capable of acting independently to develop his career to meet the challenges of the labor market and his own vision of an individual educational trajectory and professional interests. Thus, university training programs for specialists in a context of ever-changing technologies in the professional sphere need to be adjusted accordingly. It assumes restructuring the system of relations between all the subjects of the educational process, when it is necessary to take into account the importance of readiness for employability and building a career of a university graduate and his life self-determination. Despite the importance of the employability problem and career development readiness to achieve the sustainable development of the Russian economy, this topic has been little studied by domestic scientists. At the same time, Russia's higher education development agenda began to see the problem of graduate employment as a special one especially during the pandemic. In particular, the topic on developing career centers of universities has gained momentum in the large-scale program of the Ministry of Science and Higher Education of the Russian Federation on the development of Russian universities Priority-2030. Thus, this study will be useful to the stakeholders of systemic changes in processes related to building employment conditions for students and graduates. Also, this study can contribute to analytical basis development for the expansion of career centers of Russian universities.