Distinct Sets Research Articles

Abstract PR015: Sepsis-induced inflammation alters natural killer cell-mediated surveillance of liver metastasis

Abstract A majority of pancreatic ductal adenocarcinoma (PDAC) patients who undergo surgery for primary tumor resection will develop lethal metastases, despite having no evidence of metastasis at the time of their initial diagnosis. Liver metastases constitute nearly half of recurrences detected within the first six months following PDAC resection. Several clinical and experimental studies provide evidence that perioperative inflammation, including infectious complications like sepsis, positively correlates with liver metastasis across several malignancies. Despite these observations, it is still unknown whether there is a causal link between perioperative inflammation and PDAC liver metastasis. To gain mechanistic insight into the regulation of PDAC liver metastasis in the context of perioperative inflammation, we established mouse models that combine experimental PDAC liver metastasis with either the cecal ligation and puncture (CLP) model of polymicrobial sepsis or the lipopolysaccharide (LPS) model of acute sterile endotoxemia. Mice challenged with CLP prior to seeding PDAC cells in the liver had increased metastatic burden at endpoint compared to sham laparotomy controls. In contrast, mice challenged with LPS prior to PDAC cell seeding had reduced metastatic burden at endpoint compared to PBS-injected controls. We hypothesized that these opposing pro- and anti-metastatic effects of CLP and LPS, respectively, were due to qualitatively distinct inflammatory responses elicited in the liver. Our profiling of the host response to either CLP or LPS revealed shared systemic changes, including activation of the acute-phase protein response. However, LPS-associated inflammation uniquely upregulated a distinct set of interferon-regulated genes in the liver important for modifying immune cell activity (i.e., Ccl2, Ccl5, Cxcl9, Cxcl10). Accordingly, immunostaining and flow cytometry of the liver revealed that LPS uniquely increased the abundance of activated natural killer (NK) cells and MPO+ myeloid cells. We utilized Tlr4 -/- mice, which lack the primary receptor for LPS, to determine that the anti-metastatic effect of LPS required a host-facilitated response downstream of TLR4-mediated signaling. Through a series of genetic models and short-term depletion experiments, we determined that NK cells restrict PDAC cell seeding and outgrowth in our experimental liver metastasis model, and that this protective effect is further enhanced by activation of type-I interferon signaling in the host. Our findings confirm prior work identifying NK cell-mediated surveillance of disseminated cancer cells as an important mechanism in protecting against liver metastasis and show sterile endotoxemia and its associated inflammation establish a protective ‘anti-metastatic niche’ marked by enhanced NK cell activity. Further insights into the establishment of this niche may reveal potential therapeutic strategies to reduce the incidence of liver metastasis among resected PDAC patients. Citation Format: Nicole Sivetz, Patrick J. Cunniff, Christopher R. Vakoc, Semir Beyaz, Mikala Egeblad. Sepsis-induced inflammation alters natural killer cell-mediated surveillance of liver metastasis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr PR015.

‘Stories have to be told or they die’: A Critique of the Essentialist Paradigms of Female Genital Mutilation and Religion in Nawal El Saadawi’s Woman at Point Zero (1977)

ABSTRACT This study offers a postcolonial feminist reading of Nawal El Saadawi’s novel Woman at Point Zero (1975), examining how the novel addresses essentialist and reductionist narratives of female genital mutilation (FGM), kinship structures and religion in the context of Egypt. The paper argues that through her protagonist, Firdaus, El Saadawi depicts FGM not only as a form of violence against women but also as a symptom of deeper structural oppression rooted in patriarchy, capitalism and the misrepresentation and misinterpretation of religion. The idea is to read the novel as a female Bildungsroman, drawing attention to the specific experiences of Firdaus within a particular historical and socio-cultural background. Drawing on the concepts of intersectionality, power and resistance, the paper examines how Firdaus’s story highlights the multifaceted and context-specific nature of these forces, demonstrating that they do not function autonomously but instead intersect and interrelate in intricate ways, culminating in a distinctive set of conditions that profoundly influence her desires, relationships, identity and experience.

Prediction of lateral lymph node metastasis with short diameter less than 8mm in papillary thyroid carcinoma based on radiomics.

The aim of this study was to establish an ensemble learning model based on clinicopathological parameter and ultrasound radomics for assessing the risk of lateral cervical lymph node with short diameter less than 8mm (small lymph nodes were used instead) metastasis in patients with papillary thyroid cancer (PTC), thereby guiding the selection of surgical methods. This retrospective analysis was conducted on 454 patients diagnosed with papillary thyroid carcinoma who underwent total thyroidectomy and lateral neck lymph node dissection or lymph node intraoperative frozen section biopsy at the First Hospital of China Medical University between January 2015 and April 2022. In a ratio of 8:2, 362(80%) patients were assigned to the training set and 92(20%) patients were assigned to the test set. Clinical pathological features and radomics features related to ultrasound imaging were extracted, followed by feature selection using recursive feature elimination (RFE). Based on distinct feature sets, we constructed ensemble learning models comprising random forest (RF), extreme gradient boosting (XGBoost), categorical boosting (CatBoost), gradient boosting decision tree (GBDT), and light gradient boosting machine (Lightgbm) to develop clinical models, radiomics models, and clinical-radiomic models. Through the comparison of performance metrics such as area under curve (AUC), accuracy (ACC), specificity (SPE), precision (PRE), recall rate, F1 score, mean squared error (MSE) etc., we identified the optimal model and visualized its results using shapley additive exPlanations (SHAP). In this study, a total of 454 patients were included, among whom 342 PTC patients had small lymph node metastasis in the lateral neck region, while 112 did not have any metastasis. A total of 1035 features were initially considered for inclusion in this study, which were then narrowed down to 10 clinical features, 8 radiomics features, and 17 combined clinical-omics features. Based on these three feature sets, a total of fifteen ensemble learning models were established. In the test set, RF model in the clinical model is outperforms other models (AUC = 0.72, F1 = 0.75, Jaccard = 0.60 and Recall = 0.84), while CatBoost model in the radiomics model is superior to other models (AUC = 0.91, BA = 0.83 and SPE = 0.76). Among the clinical-radiomic models, Catboost exhibits optimal performance (AUC = 0.93, ACC = 0.88, BA = 0.87, F1 = 0.91, SPE = 0.83, PRE = 0.88, Jaccard = 0.83 and Recall = 0.92). Using the SHAP algorithm to visualize the operation process of the clinical-omics CatBoost model, we found that clinical omics features such as central lymph node metastasis (CLNM), Origin_Shape_Sphericity (o_shap_sphericity), LoG-sigma3_first order_ Skewness (log-3_fo_skewness), wavelet-HH_first order_Skewness (w-HH_fo_skewness) and wavelet-HH_first order_Skewness (sqr_gldm_DNUN) had the greatest impact on predicting the presence of lateral cervical small lymph node metastasis in PTC patients. (1) In this study, among the ensemble learning models established based on clinicopathological features and radiomics features for predicting PTC lateral small lymph node metastasis, the clinical-radiomic CatBoost model has the best performance. (2) SHAP can visualize how the clinical and radiomics features affect the results and realize the interpretation of the model. (3) The combined CatBoost model can improve the diagnostic accuracy of suspicious lymph nodes with short diameter < 8mm that are difficult to obtain accurate puncture results. The combined application of radiomics features is more accurate and reasonable than the prediction of clinical data alone, which helps to accurately evaluate the surgical scope and provide support for individual clinical decision making.

Computational Identification of Milk Trait Regulation Through Transcription Factor Cooperation in Murciano-Granadina Goats

The Murciano-Granadina goat (MUG) is a renowned dairy breed, known for its adaptability and resilience, as well as for its exceptional milk traits characterized by high protein and fat content, along with low somatic cell counts. These traits are governed by complex biological processes, crucial in shaping phenotypic diversity. Thus, it is imperative to explore the factors regulating milk production and lactation for this breed. In this study, we investigated the genetic architecture of seven milk traits in MUGs, employing a two-step computational analysis to examine genotype–phenotype associations. Initially, a random forest algorithm identified the relative importance of each single-nucleotide polymorphism (SNP) in determining the traits of interest. The second step applied an information theory-based approach to exploring the complex genetic architecture of quantitative milk traits, focusing on epistatic interactions that may have been overlooked in the first step. These approaches allowed us to identify an almost distinct set of candidate genes for each trait. In contrast, by analyzing the promoter regions of these genes, we revealed common regulatory networks among the milk traits under study. These findings are crucial for understanding the molecular mechanisms underlying gene regulation, and they highlight the pivotal role of transcription factors (TFs) and their preferential interactions in the development of these traits. Notably, TFs such as DBP, HAND1E47, HOXA4, PPARA, and THAP1 were consistently identified for all traits, highlighting their important roles in immunity within the mammary gland and milk production during lactation.

START domains generate paralog-specific regulons from a single network architecture.

Functional divergence of transcription factors (TFs) has driven cellular and organismal complexity throughout evolution, but its mechanistic drivers remain poorly understood. Here we test for new mechanisms using CORONA (CNA) and PHABULOSA (PHB), two functionally diverged paralogs in the CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) family of TFs. We show that virtually all genes bound by PHB ( ~ 99%) are also bound by CNA, ruling out occupation of distinct sets of genes as a mechanism of functional divergence. Further, genes bound and regulated by both paralogs are almost always regulated in the same direction, ruling out opposite regulation of shared targets as a mechanistic driver. Functional divergence of CNA and PHB instead results from differential usage of shared binding sites, with hundreds of uniquely regulated genes emerging from a commonly bound genetic network. Regulation of a given gene by CNA or PHB is thus a function of whether a bound site is considered 'responsive' versus 'non-responsive' by each paralog. Discrimination between responsive and non-responsive sites is controlled, at least in part, by their lipid binding START domain. This suggests a model in which HD-ZIPIII TFs use information integrated by their START domain to generate paralog-specific transcriptional outcomes from a shared network architecture. Taken together, our study identifies a mechanism of HD-ZIPIII TF paralog divergence and proposes the ubiquitously distributed START evolutionary module as a driver of functional divergence.

Insecticide resistance and its intensity in urban Anopheles arabiensis in Kisumu City, Western Kenya: Implications for malaria control in urban areas.

The rise of insecticide resistance poses a growing challenge to the effectiveness of vector control tools, particularly in rural areas. However, the urban setting has received comparatively less focus despite its significance in attracting rural to urban migration. Unplanned urbanization, often overlooked, exacerbates insecticide resistance as Anopheles mosquitoes adapt to the polluted environments of rapidly expanding cities. This study aimed to assess the insecticide susceptibility status of malaria vectors and identify potential underlying mechanisms across three distinct ecological settings characterized by differing levels of urbanization in Kisumu County, Kenya. The study was conducted in 2022-2023 in Kisumu County, western Kenya. Field-derived An. gambiae (s.l.) larvae collected from a long stretch of urban-to-rural continuum were phenotyped as either resistant or susceptible to six different insecticides using the World Health Organization (WHO) susceptibility test. Polymerase chain reaction (PCR) techniques were used to identify the species of the An. gambiae complex and screened for mutations at voltage-gated sodium channels (Vgsc-1014F, Vgsc-1014S, Vgsc-1575Y) and acetylcholinesterase (Ace1) target site mutation 119S. Metabolic enzyme activities (non-specific β-esterases and monooxygenases) were evaluated in mosquitoes not exposed to insecticides using microplate assays. Additionally, during larval sampling, a retrospective questionnaire survey was conducted to determine pesticide usage by the local inhabitants. Anopheles arabiensis dominated in urban (96.2%) and peri-urban (96.8%) areas, while An. gambiae (s.s.) was abundant in rural settings (82.7%). Urban mosquito populations showed high resistance intensity to deltamethrin (Mortality rate: 85.2% at 10x) and suspected resistance to Pirimiphos-methyl and bendiocarb while peri-urban and rural populations exhibited moderate resistance intensity to deltamethrin (mortality rate >98% at 10x). Preexposure of mosquitoes to a synergist piperonyl butoxide (PBO) significantly increased mortality rates: from 40.7% to 88.5% in urban, 51.9% to 90.3% in peri-urban, and 55.4% to 87.6% in rural populations for deltamethrin, and from 41.4% to 78.8% in urban, 43.7% to 90.7% in peri-urban, and 35% to 84.2% in rural populations for permethrin. In contrast, 100% mortality to chlorfenapyr and clothianidin was observed in all the populations tested. The prevalence of L1014F mutation was notably higher in urban An. arabiensis (0.22) unlike the peri-urban (0.11) and rural (0.14) populations while the L1014S mutation was more prevalent in rural An. gambiae (0.93). Additionally, urban An. arabiensis exhibited elevated levels of mixed function oxidases (0.8/mg protein) and non-specific esterases (2.12/mg protein) compared to peri-urban (0.57/mg protein and 1.5/mg protein, respectively) and rural populations (0.6/mg protein and 1.8/mg protein, respectively). Pyrethroids, apart from their use in public health through LLINs, were being highly used for agricultural purposes across all ecological settings (urban 38%, peri-urban 36% and rural 37%) followed by amidine group, with organophosphates, neonicotinoids and carbamates being of secondary importance. These findings show high resistance of An. arabiensis to insecticides commonly used for vector control, linked with increased levels of detoxification enzymes. The observed intensity of resistance underscores the pressing issue of insecticide resistance in urban areas, potentially compromising the effectiveness of vector control measures, especially pyrethroid-treated LLINs. Given the species' unique behavior and ecology compared to An. gambiae, tailored vector control strategies are needed to address this concern in urban settings.

Prevention and Treatment of Neonatal Infections in Facility and Community Settings of Low- and Middle-Income Countries: A Descriptive Review

Introduction: We present a robust and up-to-date synthesis of evidence on the effectiveness of interventions to prevent and treat newborn infections in low- and middle-income countries (LMICs). Newborn infection prevention interventions included strategies to reduce antimicrobial resistance (AMR), prevention of healthcare-associated infections (HAIs), clean birth kits (CBKs), chlorhexidine cleansing, topical emollients, and probiotic and synbiotic supplementation. Interventions to treat suspected neonatal infections included prophylactic systemic antifungal agents and community-based antibiotic delivery for possible serious bacterial infections (PSBIs). Methods: A descriptive review combining different methodological approaches was conducted. To provide the most suitable recommendations for real-world implementation, our analyses considered the impact of these interventions within three distinct health settings: facility, mixed, and community. Results: In facility settings, the strongest evidence supported the implementation of multimodal stewardship interventions for AMR reduction and device-associated infection prevention bundles for HAI prevention. Emollients in preterm newborns reduced the risk of invasive infection compared to routine skin care. Probiotics in preterm newborns reduced neonatal mortality, invasive infection, and necrotizing enterocolitis (NEC) risks compared to standard care or placebo. There was insufficient evidence for synbiotics and prophylactic systemic antifungals in LMICs. In mixed settings, CBKs reduced neonatal mortality risk compared to standard care. In community settings, chlorhexidine umbilical cord cleansing reduced omphalitis risk compared to dry cord care. For the treatment of PSBIs, purely domiciliary-based antibiotic delivery reduced the risk of all-cause neonatal mortality when compared to the standard hospital referral. Conclusion: Strategies for preventing HAIs and reducing AMR in healthcare facilities should be multimodal, and strategy selection should consider the feasibility of integration within existing newborn care programs. Probiotics are effective for facility-based use in preterm newborns; however, the establishment of high-quality, cost-effective mass production of standardized formulations is needed. Chlorhexidine cord cleansing is effective in community settings to prevent omphalitis in contexts where unhygienic cord applications are prevalent. Community-based antibiotic delivery of simplified regimens for PSBIs is a safe alternative when hospital-based care in LMICs is not possible or is declined by parents. More randomized trial evidence is needed to establish the effectiveness of CBKs, emollients, synbiotics, and prophylactic systemic antifungals in LMICs.

Impostor phenomenon short scale (IPSS-3): a novel measure to capture impostor feelings in large-scale and longitudinal surveys

The Imposter Phenomenon (IP) is gaining increasing attention in academia, not only as an overall attractive research topic but also as a concern that especially affects members of minority groups. Nevertheless, there is little evidence for the occurrence and socio-structural correlates of the IP. Against the backdrop of a pressing need to contextualize the IP, this paper provides (1) an overview of the existing empirical evidence on the IP from a perspective that incorporates the role of social contexts, (2) highlights shortcomings in both existing theoretical approaches and methodological tools, (3) introduces the Impostor Phenomenon Short Scale (IPSS-3) as a novel, time-efficient and universally applicable IP measure, and (4) underscores that the IP, in fact, does not occur in a social vacuum but is closely intertwined with socio-structural characteristics. To this end, the paper draws on three distinct data sets gathered among German adolescents and adults for the development of the IPSS-3 (Study 1: n = 271), its validation (Study 2: n = 427), and to assess the IP’s socio-structural correlates (Study 3: n = 865). The findings demonstrate that the IPSS-3 represents the first time-efficient and universally applicable instrument suitable for capturing the IP in large-scale and longitudinal research designs, e.g., initiated in adolescence. Thus, the IPSS-3 can address key open questions related to age effects, the role of transitions in the life course, and systematic variations in IP intensity among different social groups.

Investigation of size-segregated particulate matter and carbonaceous components in Phnom Penh, Cambodia.

This study investigated the size-segregated carbonaceous components of particulate matter (PM), including ultrafine particles (UFP or PM0.1), across three distinct urban settings in Phnom Penh, Cambodia: an educational site (University of Health Sciences, UHS), an institutional site (Ministry of Environment, MoE), and a residential area near a landfill. A cascade impactor-type sampler equipped with an inertial filter was used to collect size-segregated particles down to UFPs. Carbonaceous species, including organic carbon (OC) and elemental carbon (EC), were analyzed using a thermal/optical carbon analyzer to determine their composition and ratios. The results indicated no significant differences in mass concentration between weekdays and weekends at all sites; however, PM profiles varied across the location. The UHS site displayed higher EC levels in UFP, with concentrations suggesting significant local vehicular emissions, underscored by a lower OC/EC ratio (2.39 ± 1.13) compared to other sites. In contrast, the landfill site exhibited higher OC components in finer particles, suggesting emissions from organic sources such as waste burning and cooking activities, evidenced by higher OC/EC ratios across all particle sizes (e.g., OC/EC ratio in UFP at 3.78 ± 0.98). The MoE site presented a balanced profile with moderate levels of both OC and EC, influenced by its proximity to natural dispersion factors like the Tonle Sap River. Additionally, air mass backward trajectory analysis integrated with hotspot data indicated transboundary influences, particularly from agricultural burning in surrounding provinces, including Vietnam. Therefore, both local and transboundary emissions influenced the PM levels in Phnom Penh city.

Emotion as Cause, Effect, Mediator, and Moderator in Marketing: An Integrative Review and Future Research Directions

ABSTRACTThe study aims to synthesize four decades of research on emotions in marketing by delving into the specifics of who, where, how, what and when. Using quantitative and qualitative methods, 453 articles from top marketing journals were analysed. The study first presents a descriptive account of publication and citation metrics and theoretical underpinning, resolving contestation around emotion function as cause, effect, mediator and moderator. Secondly, using science mapping, along with performance and content analysis landscape of emotion research is unravelled by identifying eight clusters. These clusters placed on development timelines provide a bird's eye view and are presented on a three‐level categorization: Theory, Characteristics and Context. Clusters 1 and 2 focus on theoretical underpinning of emotion interrelationship with cognition and construal. Clusters 3 and 4 emphasized unique characteristics of emotion as antecedents and outcomes to/of evaluations/behaviours. Clusters 5, 6, 7, and 8 emphasized distinct emotional settings—notably, cluster 5 accounts for emotion interaction across service encounters and elements of service interface. Cluster 6 emphasizes effectiveness, advantage and measurement of emotion in advertising. Cluster 7 highlights how emotions are profoundly shaped by and influence social interactions/behaviour, and Cluster 8 underscores emotion embedded in brands, products and life experiences. Finally, a diverse yet unified field of emotion research in marketing is advocated by reflecting on findings, identifying opportunities for cross‐pollination, highlighting cluster‐specific future research directions and developing an integrative framework. The framework, beyond decision‐making, synthesizes distinct ways emotion arises and permeates marketplace and accounts for alternate lenses to emotion functioning, promoting newer research.

Comparative transcriptomic analyses of thymocytes using 10x Genomics and Parse scRNA-seq technologies.

Single-cell RNA sequencing experiments commonly use 10xGenomics (10x) kits due to their high-throughput capacity and standardized protocols. Recently, Parse Biosciences (Parse) introduced an alternative technology that uses multiple in-situ barcoding rounds within standard 96-well plates. Parse enables the analysis of more cells from multiple samples in a single run without the need for additional reagents or specialized microfluidics equipment. To evaluate the performance of both platforms, we conducted a benchmark study using biological and technical replicates of mouse thymus as a complex immune tissue. We found that Parse detected nearly twice the number of genes compared to 10x, with each platform detecting a distinct set of genes. The comparison of multiplexed samples generated from 10xand Parse techniques showed 10xdata to have lower technical variability and more precise annotation of biological states in the thymus compared to Parse. Our results provide a comprehensive comparison of the suitability of both single-cell platforms for immunological studies.

PATH-65. MONITORING MENINGIOMA CELL CYCLE ACTIVITY THROUGH DREAM-MMB ACTIVITY SWITCHING

Abstract Meningiomas account for over 40% of all primary intracranial brain tumors, with approximately one-fifth of these tumors recurring. Our lab has previously used molecular techniques to identify three subgroups: MenG A, B, and C, which have been independently validated. Interestingly, only MenG C tumors harbor recurring patients, making it an aggressive subtype of meningioma. One hallmark of MenG C tumors is the overexpression of a distinct set of genes that harbor in their promoter the CDE-CHR DNA-binding element, used by a transcriptional complex that in dormant cells functions as a repressor (DREAM). Before phosphorylation, this complex functions as an activator (MBB) in cycling cells. Upon a phosphorylation-dependent switch, the dual-specificity tyrosine kinase DYRK1A phosphorylates S28 on LIN52, which itself is dimerized with LIN9 of the core complex. Phosphorylation shifts the complex to DREAM, while lack thereof allows the core complex to interact with MYBL2 (now MBB) and activate the same genes repressed in quiescent cells. We seek to quantify this switch activity using an in vivo luciferase sensor using NanoBiT technology. Our biosensor is based on a split nanoluciferase, where one half is fused to the LIN52/LIN9 dimer and the other is fused to MYBL2. When MYBL2 binds to the LIN52/LIN9 dimer, a functional nanoluciferase is formed, and its activity can be measured using a luciferase-specific substrate. As proof of principle, we have increased cell proliferation by increasing FBS concentration in cultured cells as well as by blocking S28 phosphorylation using the DYRK1A-specific inhibitor Harmine. We screened all possible combinations (alternating NanoBiT fragments) for the highest luciferase activity after stimulation. In the future, this biosensor can be used to monitor cell cycle activity in vitro as well as in vivo using low-cost Luciferase reporter assays to better understand the regulation of specific genes in MenG C tumors.

Comparisons of different electrical stimulation modalities for treating visceral pain in a rodent model of irritable bowel syndrome

The purpose of this study was to investigate the effects of different electrical stimulation methods (bilateral electroacupuncture (BEA), unilateral EA (UEA), transcutaneous electrical acustimulation (TEA, stimulation via surface electrodes placed at acupoints), and sacral nerve stimulation (SNS)) on visceral pain in a rodent model of irritable bowel syndrome (IBS). Ten-day-old male and female pups were treated with 0.2 ml of 0.5% acetic acid (AA) solution. Visceral sensitivity was assessed using an electromyogram (EMG) in response to graded colorectal distension. In the first experiment, bilateral EA at ST36 acupoint was performed with different parameters in male rats to determine the best stimulation parameters. In the second experiment, male rats were randomly assigned into the Sham, BEA, UEA, TEA, and SNS groups to determine the best stimulation method. Lastly, the AA-treated female rats were randomly assigned into the BEA and sham groups to investigate a potential treatment difference between the sexes. Two distinct sets of stimulation parameters were used: Set 1 (100 Hz, 0.5 ms pulse width, 0.1 s ON, 0.4 s OFF, 0.4–3.0 mA current) and Set 2 (25 Hz, 0.5 ms pulse width, 2 s ON, 3 s OFF, 0.4–3.0 mA current).Results (1) The parameter set of 100Hz was found to be most effective in reducing visceral pain. (2) Both acute UEA and TEA effectively relieved visceral pain, whereas acute SNS did not exhibit such an effect. (3) Acute BEA improved visceral pain in both male and female rats.Conclusions These findings suggest that transcutaneous ST36 stimulation is as effective as direct ST36 stimulation and unilateral ST36 stimulation is comparable to bilateral stimulation. Development of a novel therapy using unilateral transcutaneous ST36 stimulation is warranted.

SMEs in a Digital Era: The Role of Management

This article aims to explore the role of management in translating the external factors’ and internal barriers’ impacts on the level of adoption of digital technologies as a lever for change in business operations and processes in small- and medium-sized enterprises (SMEs). SMEs face a distinct set of challenges when adopting digital technologies, often lacking resources and knowledge. On the other hand, they have certain characteristics, such as simpler organisational structures and processes, that make them more flexible than larger firms in leveraging technologies into new business models. Data for this study are obtained from 989 SMEs in Bulgaria in the manufacturing and services sectors. A PLS–SEM analysis confirms eight hypotheses raised on the relationships between environmental factors and government support and internal factors (management support, organisational flexibility, and risk-tolerant culture) that impact digital business intensity. Environmental factors’ impact is stronger than government support, while internal barriers are found to have no statistically significant relationship. The research findings highlight the important role of management support in guiding digital transformation through supporting organisational flexibility and promoting a risk-tolerant culture.

Implementation of Distributed Machine Learning in Cloud Calculation: Evidence from Consumer Behavior Prediction

Abstract. In the field of machine learning, distributed machine learning (DML) has gained massive popularity in research and appeared in a wide range of applications including transportation, medicine, and business. Distributed machine learning showed huge potential in processing large amounts of data while keeping the data private. In this paper, a distributed implementation of a deep neural network (DNN) with a large dataset from a telecom company, aiming to predict consumer behavior based on usage data is carried out. Various datasets with distinct heterogeneity settings were applied to the network, simulating a real-world cloud application scenario. Comparisons between both the centralized model and the distributed models were made to analyze the impact on model performance with device heterogeneity and data heterogeneity. These result indicate that under certain circumstances, DML models showed better accuracy and lower loss compared to the centralized model. The paper provided some insights and made some assumptions on how the data and the parameters affect the model performance.

Children’s Diets and Planetary Health: A Study in Wroclaw, Poland, and Sydney, Australia

Meals served to children should not only satisfy hunger and taste preferences but also be nutritionally adequate. Nutrition in early childhood is critical, as children spend a significant portion of their day in kindergarten or preschool, making these settings key contributors to their overall dietary intake. With the rising prevalence of nutrition-related health conditions among children, early interventions are essential for developing and establishing lifelong healthy eating habits. This study assessed the nutritional value and quality of children’s diets in two distinct settings: kindergartens in Wroclaw, Poland, and preschools in Sydney, Australia, evaluating their alignment with the planetary health diet. The research analysed 10-day menu cycles from five kindergartens in Wroclaw and the contents of lunchboxes from five preschools in Sydney’s Upper North Shore area. A total of 100 menus were reviewed in Poland, while 100 children’s lunchboxes were assessed in Australia. Different analytical methods were employed: the Diet 6D software program for the Polish menus and the Food Consumption Score for the Australian lunchboxes. Both methods revealed dietary imbalances, such as excessive intake of protein, vitamin A, salt, and sugar, alongside deficiencies in calcium, vitamin C, and vitamin D. The study concluded that children’s diets should adhere to nutritional guidelines, meeting both Polish and Australian standards, and align with the principles of the planetary health diet. To achieve this, nutritional education is essential for kindergarten staff in Poland, while targeted educational interventions are needed for parents and children in both Poland and Australia, promoting health and environmental sustainability through better nutrition.

The dynamic relationship between enjoyment and anxiety in monologue communication tasks of Arab female EFL undergraduate students: an idiodynamic approach

Foreign language learners experience fluctuations in their levels of enjoyment and anxiety during communication tasks as they navigate communication challenges. These emotional surges can impact cognitive resources and speech-processing ability. However, there is scant empirical evidence on the associations between emotions at the personal level during foreign language learning (FLL) communication task performances. To address this gap, the present study utilized the idiodynamic approach to investigate the relationship between enjoyment and anxiety in monologue tasks performed by Arab Female undergraduate learners of English as a foreign language (EFL). Participants rated their emotions on a per-second basis after watching a video recording of their task performances and were interviewed about the reasons for fluctuations in their ratings. The study found that the negative relationship between anxiety and enjoyment varied from strong to moderate across 30 segments of speech per person. The emotions of anxiety and enjoyment were analyzed through triangulation of ratings, prompted recall interviews, and performance data. As a result of this investigation, four distinct sets of factors that affected these emotions were identified: Task execution (such as pre-task preparation and time constraints), task layout (including its structure and theme), cognitive-linguistic factors (such as transient disruptions in conceptualization and formulation speech processes), and performance measure (including assessment of one’s own linguistic proficiency).

Global Co-regulatory Cross Talk Between m6A and m5C RNA Methylation Systems Coordinate Cellular Responses and Brain Disease Pathways.

N6 adenosine and C5 cytosine modification of mRNAs, tRNAs and rRNAs are regulated by the behaviour of distinct sets of writer, reader and eraser effector proteins which are conventionally considered to function independently. Here, we provide evidence of global cross-regulatory and functional interaction between the m6A and m5C RNA methylation systems. We first show that m6A and m5C effector protein transcripts are subject to reciprocal base modification supporting the existence of co-regulatory post-transcriptional feedback loops. Using global mass spectrometry proteomic data generated after biological perturbation to identify proteins which change in abundance with effector proteins, we found novel co-regulatory cellular response relationships between m6A and m5C proteins such as between the m6A eraser, ALKBH5, and the m5C writer, NSUN4. Gene ontology analysis of co-regulated proteins indicated that m6A and m5C RNA cross-system control varies across cellular processes, e.g. proteasome and mitochondrial mechanisms, and post-translational modification processes such as SUMOylation and phosphorylation. We also uncovered novel relationships between effector protein networks including contributing to intellectual disability pathways. Finally, we provided in vitro confirmation of colocalisation between m6A-RNAs and the m5C reader protein, ALYREF, after synaptic NMDA activation. These findings have important implications for understanding control of RNA metabolism, cellular proteomic responses, and brain disease mechanisms.

Exploring vaccine hesitancy in digital public discourse: From tribal polarization to socio-economic disparities.

This study analyzed online public discourse on Twitter (later rebranded as X) during the COVID-19 pandemic to understand key factors associated with vaccine hesitancy by employing deep-learning techniques. Text classification analysis reveals a significant association between attitudes toward vaccination and the unique socio-economic characteristics of US states, such as education, race, income or voting behavior. However, our results indicate that attributing vaccine hesitancy solely to a single social factor is not appropriate. Furthermore, the topic modeling of online discourse identifies two distinct sets of justifications for vaccine hesitancy. The first set pertains to political concerns, including constitutional rights and conspiracy theories. The second pertains to medical concerns about vaccine safety and efficacy. However, vaccine-hesitant social media users pragmatically use broad categories of justification for their beliefs. This behavior may suggest that vaccine hesitancy is influenced by political beliefs, unconscious emotions, and gut-level instinct. Our findings have further implications for the critical role of trust in public institutions in shaping attitudes toward vaccination and the need for tailored communication strategies to restore faith in marginalized communities.

Large-scale gene expression data clustering through incremental ensemble approach

Abstract DNA microarray technology monitors gene activity in real-time in living organisms. It creates a large amount of data that helps scientists learn about how genes work. Clustering this data helps understand gene interactions and uncover important biological processes. However, the traditional clustering techniques have difficulties due to the enormous dimensionality of gene expression data and the intricacy of biological networks. Although ensemble clustering is a viable strategy, such high-dimensional data may not lend itself well to traditional approaches. This study introduces a novel technique for gene expression data clustering called incremental ensemble clustering for gene expression data (IECG). There are two steps in the IECG. A technique for grouping gene expression data into windows is presented in the first step, producing a tree of clusters. This procedure is carried out again for succeeding windows that have distinct feature sets. The base clusterings of two consecutive windows are ensembled using a new goal function to form a new clustering solution. By repeating this step-by-step method for further windows, reliable patterns that are beneficial for medical applications can be extracted. The results from both biological and non-biological data demonstrate that the proposed algorithm outperformed the state-of-the-art algorithms. Additionally, the running time of the proposed algorithm has been examined.