Low-level Stress Research Articles

Robust Decision Support System for Stress Prediction Using Ensemble Techniques

The prevalence of stress among students has become a significant concern, impacting academic performance and overall well-being. Low-level stress can be beneficial as it helps us maintain focus on our daily routines, enabling us to perform tasks efficiently. However, severe stress can lead to heart disease, diabetes, aches, pains, and numerous other serious health issues. To address this issue, this research presents a comprehensive Decision Support System (DSS) tailored for predicting student stress levels using ensemble techniques. The goal of this project is to develop an ensemble model method of voting to classify the student dataset. An ensemble model is a combination of individual machine-learning algorithms that enhance the accuracy of the model by taking different approaches to the problem and their summary output through base classifiers. Extensive experimentation and validation are conducted using real-world student data to assess the effectiveness of the proposed DSS. In this research, we employed an ensemble modeling voting approach to classify the student dataset. Ensemble models integrate individual machine learning algorithms to enhance accuracy by leveraging the combined output of the base classifiers. Gradient Boosting Classifier (GBC), Random Forest (RF), Bagging Classifier (BC), and Extra Trees Classifier (ETC) served as base learners to construct a voting ensemble model for student dataset classification. Our findings revealed that the voting classifier consisting of Support Vector Machine (SVM), Random Forest (RF), Extra Trees Classifier (ETC), and Bagging Classifier (BC) yielded the highest accuracy at 94.78%, while GBC achieved 84.39% accuracy, RF attained 94.26% accuracy, ETC achieved 94.02% accuracy, and BC obtained 93.65% accuracy. The ensemble modeling approach significantly outperformed individual machine learning algorithms, demonstrating superior accuracy by mitigating variance and classification errors. Implementing such a system not only enhances the student assessment process in the education sector but also fosters interdisciplinary research collaboration across diverse fields within the region.

Protective properties of milk-derived peptide QEPV in attenuating oxidative stress through AMPK/PPARα signaling pathways

Peptides derived from fermented milk have demonstrated diverse bioactivities. In this study, we investigated the protective effects of Gln-Glu-Pro-Val (QEPV) against hydrogen peroxide (H2O2) induced oxidative stress in RAW 264.7 cells and further evaluated its potential in Drosophila melanogaster (D. melanogaster). Pre-incubation with QEPV in vitro dose-dependently promoted cell viability, suppressed oxidative damage, and increased antioxidant enzyme activities in a low-level oxidative stress model. QEPV remarkably extended lifespan under the low-level oxidative stress, validating its practical applicability. These effects were attributed to the upregulation of 5′ adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPARα) signaling pathways, as revealed by label-free proteomic analysis. To confirm the roles of these two signaling pathways, antagonists of AMPK (Dorsomorphin) and PPARα (GW6471) were applied in vitro and in vivo. The protective effects of QEPV were reversed by both antagonists. Overall, QEPV exhibits protective properties by selectively upregulating the AMPK and PPARα signaling pathways, indicating its potential application as an antioxidant food ingredient.

Patterns of Health Behaviors and Trajectories of Stress among People with Disabilities in Korea.

As a health vulnerable group, people with disabilities require more health-promoting behavior than non-disabled people. We aimed to identify the types of health behavior of disabled people and to track the trajectories of stress by the type of health behaviors. Data came from the Panel Survey of Employment for the Disabled Second Wave by the Employment Development Institute (EDI) in Korea. We used dataset from the first 6 years of the 2nd wave of PSEDSW (2016-2021). The current study analyzed 3,991 subjects. The types of health behavior were identified through latent class analysis (LCA) and the trajectories of stress were estimated through multi-group latent growth modeling using Mplus 8.0. Two types of groups in health behaviors, smoking-drinking group (SD), nonsmoking-less drinking group (NLSD) were derived. Depending on the types of health behavior, the trajectories of stress appeared significantly different: the NLSD had significantly lower stress than the SD in the first year, and this low-level stress trajectory was maintained continuously for 6 years. Health behaviors could be suitable as a stress coping method for people with disabilities. This study suggests that it is necessary to make efforts to create an environment that supports people with disabilities to learn healthier ways to cope with stress.

Functional connectivity of the amygdala in relation to high stress and low mindfulness

BackgroundHigh psychological stress has been associated with several brain functional changes, including functional connectivity (FC) alterations in regions such as the prefrontal cortex and the amygdala. This study explored FC alterations associated with high perceived stress, and also investigated whether these neuroimaging features were correlated with low levels of mindfulness. MethodsThis study included 29 adults (12 males and 17 females; mean age: 27.6 ± 3.2) who complained of moderate or higher perceived stress and 31 adults (17 males and 14 females; mean age: 29.2 ± 7.2) who complained of low-level stress on the questionnaire scale. Seed-based resting-state FC analysis was conducted to compare between high and low stress groups. The dorsolateral prefrontal cortex (DLPFC), the ventromedial prefrontal cortex (VMPFC) and the amygdala were selected as seeds. ResultsHigh stress group showed weaker left amygdala-based FC in the left cerebellum crus II and the left orbitofrontal cortex compared with low stress group. High stress group had weaker FC between the left DLPFC and the left inferior parietal lobule. On the contrary, high stress group had stronger FC between the left VMPFC and the left caudate compared with low stress group. Weaker FC between the amygdala and the cerebellum crus II was correlated with lower level of awareness facet of mindfulness. ConclusionsThose with high perceived stress showed low levels of mindfulness and several FC alterations centered on the prefrontal cortex and amygdala. Our findings also suggest that weak amygdala-based FC alterations associated with high psychological stress are related to low-level awareness facet of mindfulness.

Physiological and communicative emotional disconcordance in children on the autism spectrum

BackgroundIndividuals on the autism spectrum commonly have differences from non-autistic people in expressing their emotions using communicative behaviors, such as facial expressions. However, it is not yet clear if this reduced expressivity stems from reduced physiological reactivity in emotional contexts or if individuals react internally, but do not show these reactions externally to others. We hypothesized that autism is characterized by a discordance between in-the-moment internal psychophysiological arousal and external communicative expressions of emotion.MethodsForty-one children on the autism spectrum and 39 non-autistic, typically developing (TD) children of two age groups (2–4 and 8–12 years) participated in a low-level stress task whilst wearing a wireless electrocardiogram. Children’s negative emotional expressions (facial, vocal, bodily) were coded following standardized protocols. Alexithymia traits were assessed using the Children’s Alexithymia Measure with school-aged children only. Data analyses involved ANOVAs, correlations, and sensitivity analyses.ResultsThere were no group differences in physiological arousal (heart rate) or in communicative expressions of stress to the stress task. For TD preschoolers, physiological arousal during the stress task was associated with vocal expressions and for TD school-aged children, they were associated with facial and bodily expressions. By contrast, for children on the autism spectrum, physiological arousal during the stress tasks was not associated with communicative expressions across age groups.ConclusionsOur findings suggest that children on the autism spectrum might experience emotional disconcordance, in that their physiological arousal does not align with their communicative expressions. Therefore, the internally experienced stress of children on the autism spectrum may be inadvertently missed by teachers and caregivers and, consequently, learning opportunities for teaching emotional communication and regulation may be also missed. Our results support the use of wearable biosensors to facilitate such interventions in children on the autism spectrum.

A novel development of wide voltage supply DC–DC converter for fuel stack application with PSO-ANFIS MPPT controller

The present power production companies are working on renewable energy systems because their features are more reliable for the local energy consumers, high continuity in the energy production, and less cost is required for maitainence. In this article, the proton exchange membrane fuel stack (PEMFS) renewable energy is utilized to supply energy to the automotive systems. Here, the PEMFS is selected because of its merits are high energy density, quick system response concerning the source operational temperature, and more suitable for electric vehicle application. However, the PEMFS supplied voltage is completely nonlinear which is solved by utilizing the modified particle swarm optimization with adaptive neuro-fuzzy inference system (MPSO with ANFIS) controller. This hybridization-based maximum power point tracking controller provides more accuracy, high power point identifying speed, best dynamic response at different fuel stack functioning temperature conditions, and easy maitainence. Here, the fuel stack generated current is very high which is optimized by introducing the new DC–DC converter. The advantages of this DC–DC converter are more voltage transformation ratio, low-level voltage stress appearing across the switches, and wide voltage gain. The overall system is investigated by utilizing the MATLAB/Simulink tool.

A new wide input voltage DC-DC converter for solar PV systems with hybrid MPPT controller

The present working conventional power generation systems utilization is reducing day by day because of their demerits are more functioning cost, high carbon dioxide emission, more complexity in handling, and required high installation area. So, the current power generation company focuses on Renewable Energy Sources (RES) which are wind, tidal, and solar. Here, the solar power network is utilized for supplying electricity to the electrical vehicle battery charging system. The Solar photovoltaic (PV) modules supply nonlinear power which is not useful for automotive systems. To maximize the supply power of the solar PV system, an Adaptive Step Genetic Algorithm Optimized (ASGAO) Radial Basis Functional Network (RBFN) is utilized for tracking the working point of the solar PV module thereby enhancing the operating efficiency of the overall system. The features of this proposed hybrid Maximum Power Point Tracking (MPPT) controller are quick system dynamic response, easy operation, quick convergence speed, more robustness, and high operating efficiency when equalized with the basic MPPT controllers. The major issue of solar PV modules is low supply voltage which is increased by introducing the wide input voltage DC-DC converter. The merits of this introduced converter are low-level voltage stress on diodes, good quality supply power, high voltage gain, plus low implementation cost. Here, the introduced converter along with the AGAO-RBFN controller is analyzed by selecting the MATLAB/Simulink environment. Also, the proposed converter is tested with the help of a programable DC source.

Unraveling the effect of phenolic extract derived from olive mill solid wastes on agro-physiological and biochemical traits of pomegranate and its associated rhizospheric soil properties

Agricultural waste management poses a significant challenge in circular economy strategies. Olive mill wastes (OMW) contain valuable biomolecules, especially phenolic compounds, with significant agricultural potential. Our study evaluate the effects of phenolic extract (PE) derived from olive mill solid wastes (OMSW) on pomegranate agro-physiological and biochemical responses, as well as soil-related attributes. Pomegranate plants were treated with PE at doses of 100 ppm and 200 ppm via foliar spray (L100 and L200) and soil application (S100 and S200). Results showed increased biomass with PE treatments, especially with soil application (S100 and S200). Proline and soluble sugar accumulation in leaves suggested plant adaptation to PE with low-level stress. Additionally, PE application reduced malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents. Higher doses of PE (S200) significantly improved net photosynthesis (Pn), transpiration rate (E), water use efficiency (WUEi), and photosynthetic efficiency (fv/fm and PIabs). Furthermore, PE treatments enhanced levels of chlorophylls, carotenoids, polyphenols, flavonoids, and antioxidant activity. Soil application of PE also increased soil enzyme activities and microbial population. Our findings suggest the beneficial impact of PE application on pomegranate agro-physiological responses, laying the groundwork for further research across various plant species and soil types to introduce nutrient-enriched PE as an eco-friendly biostimulant.

Potential categories of employment stress among rural college students and their relationship to employment psychology.

Psychological problems related to employment are among the most common psychological problems faced by rural college students. Employment stress is an important factor affecting the development of psychological health in employees; thus, reducing employment stress can improve the psychological state of employment. This study aimed to understand the potential profiles of employment stress among rural college students to determine the relationship between different profiles and employment psychology. This study was conducted in a higher education institution in Qingdao, Shandong Province, China between June and December 2023, and 249 rural college students participated. The Employment Stress Scale and Employment Psychology Scale were used to collect the data. Data were analyzed using latent profile analysis, independent sample t-tests, and binary logistic regression analysis. The results showed that rural university students were categorized into low-level (49.80%) and high-level (50.21%) employment stress groups. There was a statistically significant difference between the employment psychology of rural college students in the low- and high-level groups (p < 0.001). Juniors/seniors were more likely to be classified in the high-level group (OR = 0.477, p = 0.011). Intervention programs should be developed and implemented to address the characteristics of employment stress among rural college students with different profiles to promote the healthy development of their attitudes toward employment.

A Novel Hybrid MPPT Controller for PEMFC Fed High Step-Up Single Switch DC-DC Converter

At present, there are different types of Renewable Energy Resources (RESs) available in nature which are wind, tidal, fuel cell, and solar. The wind, tidal, and solar power systems give discontinuous power supply which is not suitable for the present automotive systems. Here, the Proton Exchange Membrane Fuel Stack (PEMFS) is used for supplying the power to the electrical vehicle systems. The features of fuel stack networks are very quick static response, plus low atmospheric pollution. Also, this type of power supply system consists of high flexibility and more reliability. However, the fuel stack drawback is a nonlinear power supply nature. As a result, the functioning point of the fuel stack varies from one position to another position on the V-I curve of the fuel stack. Here, the first objective of the work is the development of the Grey Wolf Optimization Technique (GWOT) involving a Fuzzy Logic Controller (FLC) for finding the Maximum Power Point (MPP) of the fuel stack. This hybrid GWOT-FLC controller stabilizes the source power under various operating temperature conditions of the fuel stack. However, the fuel stack supplies very little output voltage which is improved by introducing the Single Switch Universal Supply Voltage Boost Converter (SSUSVBC) in the second objective. The features of this proposed DC-DC converter are fewer voltage distortions of the fuel stack output voltage, high voltage conversion ratio, and low-level voltage stress on switches. The fuel stack integrated SSUSVBC is analyzed by selecting the MATLAB/Simulink window. Also, the proposed DC-DC converter is tested by utilizing the programmable DC source.

Oxidative replication stress induced by long-term exposure to hydroxyurea in root meristem cells of Vicia faba.

Low concentrations of hydroxyurea, an inhibitor of DNA replication, induced oxidative and replicative stress in root apical meristem (RAM) cells of Vicia faba. Plant cells are constantly exposed to low-level endogenous stress factors that can affect DNA replication and lead to DNA damage. Long-term treatments of Vicia faba root apical meristems (RAMs) with HU leads to the appearance of atypical cells with intranuclear asynchrony. This rare form of abnormality was manifested by a gradual condensation of chromatin, from interphase to mitosis (so-called IM cells). Moreover, HU-treated root cells revealed abnormal chromosome structure, persisting DNA replication, and elevated levels of intracellular hydrogen peroxide (H2O2) and superoxide anion (O2∙-). Immunocytochemical studies have shown an increased number of fluorescent foci of H3 histones acetylated at lysine 56 (H3K56Ac; canonically connected with the DNA replication process). We show that continuous 3-day exposure to low concentrations (0.75mM) of hydroxyurea (HU; an inhibitor of DNA replication) induces cellular response to reactive oxygen species and to DNA replication stress conditions.

Deoxygenation following coral spawning and low-level thermal stress trigger mass coral mortality at Coral Bay, Ningaloo Reef

Oxygen depletion is well recognized for its role in the degradation of tropical coral reefs. Extreme acute hypoxic events that lead to localized mass mortality and the formation of ‘dead zones’ (a region where few or no organisms can survive due to a lack of oxygen) are particularly concerning as they can result in wide-ranging losses of biodiversity, ecosystem productivity and functioning, economic prosperity, and wellbeing. In March of 2022, the annual coral spawning event at Bills Bay (Coral Bay, Ningaloo Reef, Western Australia) coincided with elevated seawater temperature, calm weather conditions and a flood tide resulting in coral spawn becoming trapped in Bills Bay. Immediately after, there was a mass fish kill, which is believed to have been caused by local eutrophication resulting in severe oxygen depletion. The impact the deoxygenation and thermal stress event had on benthic communities has not yet been quantified; hence, the principal aim of this study is to document the extent of change that occurred in the benthic communities before and after the 2022 coral spawning event over a spatial gradient from the nearshore to mid-reef. Percent coral cover in the Bay decreased from 55.62 ± 2.26% in 2016–2018 and 70.44 ± 5.24% in 2021 to 1.16 ± 0.51% in 2022. Over the same period, the percent cover of turf algae increased from 27.40 ± 2.00% in 2016–2018 and 24.66 ± 6.67% in 2021 to 78.80 ± 3.06% in 2022, indicating a dramatic phase shift occurred at Bills Bay. The abundance of healthy coral colonies recorded on replicated belt transects at nine sites declined from 3452 healthy individuals in 2018 to 153 individuals in 2022 and coral generic richness decreased by 84.61%, dropping from 26 genera in 2018 to 4 genera in 2022. Previously dominant genera such as Acropora,Montipora and Echinopora, were extirpated from survey sites. Isolated colonies of massive Porites spp. and encrusting Cyphastrea sp. survived the event and understanding the mechanisms underpinning their greater survivorship is an important area of future research. Long-term monitoring is recommended to track the community recovery process and improve our understanding of the longer-term implications of this acute mortality event on the ecological, socio-economic and cultural values of Ningaloo Reef.

Aesthetic Cellulose Filaments with Water-Triggered Switchable Internal Stress and Customizable Polarized Iridescence Toward Green Fashion Innovation.

Healthy, convenient, and aesthetic hair dyeing and styling are essential to fashion trends and personal-social interactions. Herein, we fabricate green, scalable, and aesthetic regenerated cellulose filaments (ACFs) with customizable iridescent colors, outstanding mechanical properties, and water-triggered moldability for convenient and fashionable artificial hairdressing. The fabrication of ACFs involves cellulose dissolution, cross-linking, wet-spinning, and nanostructured orientation. Notably, the cross-linking strategy endows the ACFs with significantly weakened internal stress, confirmed by monitoring the offset of the C-O-C group in the cellulose molecular chain with Raman imaging, which ensures a tailorable orientation of the nanostructure during wet stretching and tunable iridescent polarization colors. Interestingly, ACFs can be tailored for three-dimensional shaping through a facile water-triggered adjustable internal stress: temporary shaping with low-level internal stress in the wet state and permanent shaping with high-level internal stress in the dry state. The health, convenience, and green aesthetic filaments show great potential in personal wearables.

Factors Influencing Maternal Stress during Infant’s NICU Stay in a Tertiary Care Center, South Kerala, India: A Cross-sectional Study

Introduction: Recent advances in neonatal medicine have helped sick babies survive. However, the birth of a baby needing Neonatal Intensive Care Unit (NICU) stay may be a significant source of stress for mothers. Aim: To assess the maternal stress level perceived due to an infant’s NICU stay and the factors influencing this stress. Materials and Methods: The present cross-sectional study was conducted in the NICU of Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla, Kerala, India, between March 2021 and September 2021. The study included 74 mothers of infants requiring at least five days of NICU stay. The stress levels were recorded using the Parental Stressor Scale: NICU (PSS:NICU) questionnaire, which included 27 items under three stressor domains: Sights and Sounds (SS), Parental Role Alteration (PRA), and looks and behaviour of the baby. Data were statistically analysed using the Mann-Whitney U test and Kruskal-Wallis tests. Results: In the study group, 33 (45%) mothers experienced moderate stress, 18 (24%) experienced a high level, and the remaining 23 (31%) experienced only low-level stress. The overall maternal stress perceived in the study group was found to be at a moderate level with a mean of 3.36±0.67. Factors causing stress in mothers included prematurity, low birth weight, low 1st-minute Appearance, Pulse, Grimace, Activity and Respiration (Apgar) score, expressed breastfeeding, and previous experience with abortion. Conclusion: The present study found that mothers experienced moderate stress when their babies were admitted to the NICU. Significant stress was experienced by mothers when they were unable to perform their maternal duties.

The effects of multifactorial stress combination on rice and maize.

The complexity of environmental factors affecting crops in the field is gradually increasing due to climate change-associated weather events, such as droughts or floods combined with heat waves, coupled with the accumulation of different environmental and agricultural pollutants. The impact of multiple stress conditions on plants was recently termed "multifactorial stress combination" (MFSC) and defined as the occurrence of 3 or more stressors that impact plants simultaneously or sequentially. We recently reported that with the increased number and complexity of different MFSC stressors, the growth and survival of Arabidopsis (Arabidopsis thaliana) seedlings declines, even if the level of each individual stress is low enough to have no significant effect on plants. However, whether MFSC would impact commercial crop cultivars is largely unknown. Here, we reveal that a MFSC of 5 different low-level abiotic stresses (salinity, heat, the herbicide paraquat, phosphorus deficiency, and the heavy metal cadmium), applied in an increasing level of complexity, has a significant negative impact on the growth and biomass of a commercial rice (Oryza sativa) cultivar and a maize (Zea mays) hybrid. Proteomics, element content, and mixOmics analyses of MFSC in rice identified proteins that correlate with the impact of MFSC on rice seedlings, and analysis of 42 different rice genotypes subjected to MFSC revealed substantial genetic variability in responses to this unique state of stress combination. Taken together, our findings reveal that the impacts of MFSC on 2 different crop species are severe and that MFSC may substantially affect agricultural productivity.

Behaviour of hTERT in the tears of neophyte contact lens wearers during the sleep/wake cycle

PurposeTo investigate the behaviour of telomerase reverse transcriptase (hTERT) in the tears of healthy neophyte contact lenses-wearing individuals during the sleep/wake cycle. A subsequent aim was to investigate whether hTERT behaviour was associated with inflammatory mediators interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in tears. MethodsFlush tears were collected from 19 healthy, non-contact lens-wearing participants (11 males, 8 females, mean age 31.9 ± 5.7 years), before and during contact lens wear. Tears were collected at noon, before sleep and upon awakening and levels of hTERT, IL-6 and TNF-α, were determined using enzyme-linked immunosorbent assays (ELISA). ResultshTERT levels (median [interquartile range]) during contact lens wear were significantly higher before sleep (436.5 (263.9 – 697.7) ng/ml compared to the same time point without contact lenses (256.1 (0.0 – 590.9) ng/ml (p = 0.01). There was no difference between contact lens wear (851.3 [353.2 – 2109.9]) ng/ml, and no wear (1091.0 [492.3 – 3045.4]) ng/ml, upon awakening (p = 0.94). A significant increase was found upon awakening compared to before sleep, irrespective of the presence of a contact lens (p = 0.02). IL-6 and TNF-α levels in tears were below the limit of detection. ConclusionsThe study showed that hTERT increases after a contact lens is placed on the eye, but this change is small, compared to the impact of overnight eye closure. Taken together with the lack of responses of the inflammatory markers monitored at the same time points, this may suggest that hTERT can respond both to low-level stress stimuli acting on the ocular surface, and to situations where inflammation is a likely factor.

Modulation of the Oceanic Mesoscale Activity by the Mesoscale Thermal Feedback to the Atmosphere

Abstract Ocean mesoscale thermal feedback (TFB) is the influence of mesoscale sea surface temperature (SST) anomalies on the overlying atmosphere and its feedback to the ocean. Over the past few decades, TFB has been shown to affect the atmosphere by inducing low-level wind and surface stress anomalies and modulating ocean–atmosphere heat fluxes ubiquitously over the global oceans. These anomalies can alter the climate variability. However, it is not clear yet to what extent heat and momentum flux anomalies modulate the mesoscale ocean activity. Here, using coupled ocean–atmosphere mesoscale simulations over a realistic subtropical channel centered on the equator in which the TFB can be turned off by spatially smoothing the SST as seen by the atmosphere, we show that TFB can damp the mesoscale activity, with a more pronounced effect near the surface. This damping appears to be sensitive to the cutoff filter used: on average, the surface mesoscale activity is attenuated by 9% when smoothing the SST using an ∼1000-km cutoff but by only 2% when using an ∼350-km cutoff. We demonstrate that the mesoscale activity damping is primarily caused by a sink of available eddy potential energy that is controlled by the induced-anomalous heat fluxes, the surface stress anomalies having a negligible role. When TFB is neglected, the absence of sink of potential energy is partly compensated by a more negative eddy wind work. We illustrate that TFB filtering in a coupled model must be done carefully because it can also impact the large-scale meridional SST gradients and subsequently the mean large-scale wind stress curl and ocean dynamics.

Prediction of Chronic Stress and Protective Factors in Adults: Development of an Interpretable Prediction Model Based on XGBoost and SHAP Using National Cross-sectional DEGS1 Data.

Chronic stress is highly prevalent in the German population. It has known adverse effects on mental health, such as burnout and depression. Known long-term effects of chronic stress are cardiovascular disease, diabetes, and cancer. This study aims to derive an interpretable multiclass machine learning model for predicting chronic stress levels and factors protecting against chronic stress based on representative nationwide data from the German Health Interview and Examination Survey for Adults, which is part of the national health monitoring program. A data set from the German Health Interview and Examination Survey for Adults study including demographic, clinical, and laboratory data from 5801 participants was analyzed. A multiclass eXtreme Gradient Boosting (XGBoost) model was constructed to classify participants into 3 categories including low, middle, and high chronic stress levels. The model's performance was evaluated using the area under the receiver operating characteristic curve, precision, recall, specificity, and the F1-score. Additionally, SHapley Additive exPlanations was used to interpret the prediction XGBoost model and to identify factors protecting against chronic stress. The multiclass XGBoost model exhibited the macroaverage scores, with an area under the receiver operating characteristic curve of 81%, precision of 63%, recall of 52%, specificity of 78%, and F1-score of 54%. The most important features for low-level chronic stress were male gender, very good general health, high satisfaction with living space, and strong social support. This study presents a multiclass interpretable prediction model for chronic stress in adults in Germany. The explainable artificial intelligence technique SHapley Additive exPlanations identified relevant protective factors for chronic stress, which need to be considered when developing interventions to reduce chronic stress.

Mechanical Regulation of Oral Epithelial Barrier Function.

Epithelial cell function is modulated by mechanical forces imparted by the extracellular environment. The transmission of forces onto the cytoskeleton by modalities such as mechanical stress and matrix stiffness is necessary to address by the development of new experimental models that permit finely tuned cell mechanical challenges. Herein, we developed an epithelial tissue culture model, named the 3D Oral Epi-mucosa platform, to investigate the role mechanical cues in the epithelial barrier. In this platform, low-level mechanical stress (0.1 kPa) is applied to oral keratinocytes, which lie on 3D fibrous collagen (Col) gels whose stiffness is modulated by different concentrations or the addition of other factors such as fibronectin (FN). Our results show that cells lying on intermediate Col (3 mg/mL; stiffness = 30 Pa) demonstrated lower epithelial leakiness compared with soft Col (1.5 mg/mL; stiffness = 10 Pa) and stiff Col (6 mg/mL; stiffness = 120 Pa) gels, indicating that stiffness modulates barrier function. In addition, the presence of FN reversed the barrier integrity by inhibiting the interepithelial interaction via E-cadherin and Zonula occludens-1. Overall, the 3D Oral Epi-mucosa platform, as a new in vitro system, will be utilized to identify new mechanisms and develop future targets involved in mucosal diseases.

Abstract 3856: Evaluation of replication protein A inhibitor, NERx329 in combination with EGFR mutant targeted therapy

Abstract Lung cancer is the leading cause of cancer related deaths worldwide with the majority (~80%) of patients diagnosed with non-small lung cancer (NSCLC). Targeted therapies directed against tumor initiating growth factor receptors are effective treatment options for driver mutation positive NSCLC. Osimertinib is a third-generation EGFR-Tyrosine Kinase inhibitor (TKI) that has activity against EGFR exon 19, exon 21, and T790M mutations. Unfortunately, Osimertinib treated patients acquire resistance and median progression free survival is 18 months. Moreover, Osimertinib does not cure stage IV EGFR mutant NSCLC. The acquisition of secondary mutations leading to activation of bypass pathways, MET amplification, EMT, compensatory pathway activation and histological transformation to small cell phenotype are major causes of acquiring resistance to EGFR TKIs. Proliferating cancer cells regularly experience a low level of replication stress. Additionally, receptor tyrosine kinases such as EGFR are known to interact with DNA repair proteins and impact DNA damage repair following chemotherapy, radiation therapy, and EGFR TKI treatment. However, the role of DNA repair pathways in EGFR-TKI resistance is unknown and the interaction between EGFR pathway, DNA damage, and repair pathways has not been fully elucidated. At low-level replicative stress promotes genomic instability but at a high level through mitotic catastrophe it causes cell death. Replication protein A is a critical sensor of the DNA damage response detecting replication stress. The small molecule inhibitor of RPA, NERx 329, sequesters active RPA and induces replication catastrophe and cell death. Here we demonstrate that NERx329 in combination with Osimertinib enhanced Osimertinib mediated cell death. CCk-8 assays performed after 48h of NERx329 and Osimertinib combination treatment result in a robust decrease in IC50 compared to single agent therapy. Dissection of signaling pathways leading to this death-promoting effect of NERx329 showed a combination of bypass pathway marker (AXL) and compensatory pathway marker (STAT) inhibition in AXL-high expressing EGFR mutant lung cancer cells. Whereas inhibition of STAT pathway was responsible for the death-promoting effect of NERx329 in AXL-low expressing EGFR mutant lung cancer cells. AXL and STAT inhibition are associated with induced DNA damage and impaired DNA repair. From these data, we infer that DNA damage repair pathways could be involved in TKI resistance and NERx329 could be a promising drug candidate for combination targeted therapy. Citation Format: Reshma Bhowmick, John J. Turchi, Shadia I. Jalal. Evaluation of replication protein A inhibitor, NERx329 in combination with EGFR mutant targeted therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3856.