Additional Driver Research Articles

Exploring the Value drivers for Platform Based Business: Scaling, Organizing, Financing, Controlling & Leveraging Networks among Multiple Parties

Platform-based business models have become increasingly popular in recent years. These models allow businesses to connect with customers in new and innovative ways, and they can offer several advantages over traditional channels. However, there is still a lack of understanding of the key value drivers that contribute to the success of platform-based business models. This study addresses this gap in the literature by conducting a two-step qualitative-empirical analysis to identify the value drivers of platform-based business models. In the first step, a systematic literature analysis (SLA) is conducted to outline the research landscape holistically and to identify existing value drivers. In the second step, data is collected from 15 expert interviews from Pakistani online platform-based companies to identify additional value drivers. The results of the study identify four categories of value drivers: Organization and scaling: the category includes factors such as the platform ecosystem, architecture, user acquisition, and willingness to participate. Financial performance: this category includes factors such as retention, performance-promise, resources, and abilities. Control mechanisms: the category includes factors such as pricing, performance measures, and behavioral control. Environment: This category includes factors such as technology and competition. The study also provides an overview of a large number of value drivers that have not been previously identified in the literature. These results can help platform operators in their strategic planning and can provide them with concrete measures for the successful implementation of a platform.

Battery Thermal Runaway Preventive Time Delay Strategy Using Different Melting Point Phase Change Materials

<div>The production of alternative clean energy vehicles provides a sustainable solution for the transportation industry. An effective battery cooling system is required for the safe operation of electric vehicles throughout their lifetime. However, in the pursuit of this technological change, issues of battery overheating leading to thermal runaways (TRs) are seen as major concerns. For example, lithium (Li)-ion batteries of electric vehicles can lose thermal stability owing to electrochemical damage due to overheating of the core. In this study, we look at how a different melting point phase change material (PCM) can be used to delay the TR trigger point of a high-energy density lithium-iron phosphate (LiFePO<sub>4</sub>) chemistry 86 Amp-hour (Ah) battery. The battery is investigated under thermal abuse conditions by wrapping heater foil and operating it at 500-W constant heat conditions until the battery runs in an abuse scenario. A comparative time delay methodology is developed to understand the TR trigger points under a timescale factor for different ambient conditions such as 25°C, 35°C, and 45°C. In the present study, two different types of PCMs are selected, that is, paraffin wax which melts at 45°C and Organic Axiotherm (ATP-78) which melts at 78°C. Modeling results suggest that the TR trigger point and peak onset temperature are greatly influenced by the battery operating temperature. The concluded results indicate that by submerging the battery in PCM, the TR trigger point can be greatly delayed, providing additional time for the driver and passenger to evacuate the vehicle. However, the present findings also reflect that fire propagation cannot be completely extinguished due to the volatile hydrocarbon content in the PCM. Hence from this study, it is recommended that whenever using a PCM-equipped passive cooling strategy, thermal insulation should be provided at the wall of the PCM to delay the TR propagation from one battery to another at pack-level configuration.</div>

Fish body size influenced by multiple drivers

There is evidence that organisms have become smaller during the past periods of global warming. Global change has substantial effects on biodiversity, with body size reduction being the third most common response to global warming. Body size allometry in ectotherms needs to be explored further; the objectives of this study were to better understand the mechanisms regulating body size in fish by testing: 1) Bergmann's rule with temperature and elevation, 2) additional environmental drivers, 3) the role of isolation, 4) ecoevolutionary hypotheses comparing native and exotic species and 5) the role of migration propensity in comparing migratory and resident species. We analyzed an extensive dataset of Chilean fish composed of 75 198 records which included 25 species from 12 different families between latitudes −28.80 to −51.42 using linear mixed models to discern the best environmental variables contributing to body size changes, as well as incorporating factors related to dispersal capabilities, biogeographic isolation and levels of exotic/native interactions. Bergmann's rule is supported by changes in elevation, and our study shows that freshwater fish body size also increases with increasing environmental heterogeneity and productivity. In general, inland native fish tend to be smaller than coastal ones, supporting the island rule with evidence of gigantism or dwarfism in selected species. Ecological variables affecting fish body size do not differ between native and exotic fish unless other factors are considered, such as dispersal capacity (migrating vs resident fish) or mechanisms related to their isolation. Although temperature is not a direct driver of body size in Chilean fish, heterogeneity, productivity, geography, migratory ability and species origin may affect body size. A better understanding of the mechanisms driving body size in ectotherms will aid in determining management priorities in the face of global climate disruption.

Genomic and transcriptomic analyses of thyroid cancers identify DICER1 somatic mutations in adult follicular-patterned RAS-like tumors.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC). Several genomic and transcriptomic studies explored the molecular landscape of follicular cell-derived TCs, and BRAFV600E, RAS mutations, and gene fusions are well-established drivers. DICER1 mutations were described in specific sets of TC patients but represent a rare event in adult TC patients. Here, we report the molecular characterization of 30 retrospective follicular cell-derived thyroid tumors, comprising PTCs (90%) and poorly differentiated TCs (10%), collected at our Institute. We performed DNA whole-exome sequencing using patient-matched control for somatic mutation calling, and targeted RNA-seq for gene fusion detection. Transcriptional profiles established in the same cohort by microarray were investigated using three signaling-related gene signatures derived from The Cancer Genome Atlas (TCGA). The occurrence of BRAFV600E (44%), RAS mutations (13%), and gene fusions (13%) was confirmed in our cohort. In addition, in two patients lacking known drivers, mutations of the DICER1 gene (p.D1709N and p.D1810V) were identified. DICER1 mutations occur in two adult patients with follicular-pattern lesions, and in one of them a second concurrent DICER1 mutation (p.R459*) is also observed. Additional putative drivers include ROS1 gene (p.P2130A mutation), identified in a patient with a rare solid-trabecular subtype of PTC. Transcriptomics indicates that DICER1 tumors are RAS-like, whereas the ROS1-mutated tumor displays a borderline RAS-/BRAF-like subtype. We also provide an overview of DICER1 and ROS1 mutations in thyroid lesions by investigating the COSMIC database. Even though small, our series recapitulates the genetic background of PTC. Furthermore, we identified DICER1 mutations, one of which is previously unreported in thyroid lesions. For these less common alterations and for patients with unknown drivers, we provide signaling information applying TCGA-derived classification.

Beyond the role of climate and soil conditions: Living and dead trees matter for soil biodiversity in mountain forests

While forests’ contributions to people are intimately linked to their soil biodiversity, little is known about how forest soil biodiversity is structured and influenced by forest characteristics. Living and dead trees influence the quantity and the diversity of resources (e.g. litter content) and habitats (e.g. microclimate) available for soil organisms. In this study, we explored the effects of forest characteristics and their relative importance to regional climate and local soil conditions in explaining forest soil biodiversity.We characterised forest quantity (abundance of living and dead trees, and dominant tree leaves C/N), and diversity characteristics (tree sizes, deadwood and tree species diversities). We assessed the response of the diversity of 34 soil trophic groups to climate, soil properties and forest characteristics using environmental DNA metabarcoding data along 16 elevational gradients in the French Alps.Overall, we showed that climate and soil characteristics explained most of the diversity of soil trophic groups. For the diversity of some groups, however, forest characteristics were important drivers (e.g. ectomycorrhizal fungi). In general, forest diversity characteristics had a positive effect on the diversity of soil trophic groups, in agreement with the resource-heterogeneity hypothesis. We also found that the effects of forest characteristics can percolate to high trophic level groups or to groups that do not have a direct link with living or dead trees (e.g. fungivore mites).Forest characteristics can have complex indirect effects that branch out throughout the whole soil food web. Even if mountain forests span large climatic gradients, forest structure and composition can be additional key drivers of soil biodiversity. Thus forest management, by driving forest structure and composition, can have important effects on soil biodiversity in managed forests.

Clinical Characteristics, Response to Platinum-Based Chemotherapy and Poly (Adenosine Phosphate-Ribose) Polymerase Inhibitors in Advanced Lung Cancer Patients Harboring BRCA Mutations.

The oncogenic role and clinical relevance of BRCA mutations in NSCLC remain unclear. We aim to evaluate the characteristics and clinical outcomes of patients with NSCLC harboring BRCA mutations treated at Hadassah Medical Center (HMC). We retrospectively assessed all patients with advanced NSCLC who underwent next-generation sequencing (NGS) and were found to have pathogenic somatic BRCA mutations (p-BRCA). We compared clinical outcomes in NSCLC patients with wild-type BRCA (wt-BRCA) matched by age, stage, gender, smoking, PDL-1 and driver mutations. Between 2015 and 2022, we evaluated 598 patients with advanced NSCLC using NGS and found 26 patients with p-BRCA, of whom 17 (65.4%) were carriers of germline BRCA variants and represented 1% of all BRCA carriers HMC. The median age of diagnosis was 67 years old (40-78), 13 patients (50%) had a history of smoking and 9 patients (34.6%) had additional driver mutations (EGFR, ALK, BRAF, MET or ERBB2). Objective response rate and median progression-free survival (PFS) for first-line platinum-based chemotherapy in the p-BRCA group compared to wt-BRCA controls were 72.2% and 16 months (CI 95%, 5-22), compared to 47.4% and 7 months (CI 95%, 5-9), respectively, and HR for PFS was 0.41 (CI 95%, 0.17-0.97). Six patients in the p-BRCA group were treated with advanced-line poly (adenosine-phosphate-ribose) polymerase inhibitors (PARPi), with a durable response observed in four patients (66%). In this cohort, patients with NSCLC harboring p-BRCA exhibit high-sensitivity PARPi and a prolonged response to platinum, suggesting some oncogenic role for BRCA mutations in NSCLC. The results support further prospective trials of the treatment of NSCLC harboring p-BRCA with PARPi.

Microbial Community and Abundance of Selected Antimicrobial Resistance Genes in Poultry Litter from Conventional and Antibiotic-Free Farms.

In this study, a culture-independent approach was applied to compare the microbiome composition and the abundance of the antimicrobial resistance genes (ARGs) aadA2 for aminoglycosides, tet(A), tet(B), tet(K), and tet(M) for tetracyclines, and mcr-1 for colistin in broiler litter samples collected from conventional and antibiotic-free flocks located in Central Italy. A total of 13 flocks and 26 litter samples, collected at the beginning and at the end of each rearing cycle, were submitted to 16s rRNA sequence analysis and quantitative PCR for targeted ARGs. Firmicutes resulted in the dominant phylum in both groups of flocks, and within it, the Clostridia and Bacilli classes showed a similar distribution. Conversely, in antibiotic-free flocks, a higher frequency of Actinobacteria class and Clostridiaceae, Lactobacillaceae, Corynebacteriaceae families were reported, while in the conventional group, routinely treated with antibiotics for therapeutic purposes, the Bacteroidia class and the Enterobacteriaceae and Bacillaceae families were predominant. All investigated samples were found to be positive for at least one ARG, with the mean values of aadA2 and tet(A) the highest in conventional flocks by a significant margin. The results suggest that antibiotic use can influence the frequency of resistance determinants and the microbial community in poultry flocks, even though other environmental factors should also be investigated more deeply in order to identify additional drivers of antimicrobial resistance.

Embedding Technology Interface and Digital Payment Drivers in the Unified Theory of Acceptance and Use of Technology 2 Model: Transforming Behavioral Intention to Sustained Intention

Purpose: The present study was undertaken with the purpose of embedding Technology Interface drivers and Digital Payment drivers as additional drivers in the Unified Theory of Acceptance and Use of Technology (UTAUT2) to examine their influence on the Behavioral Intention of online shoppers. Technology Interface drivers include chatbots (CBs) and virtual try-on (VTO) technology. Further, this study also links Behavioral Intention with Sustained Intention to analyze whether it translates into repeated online buying. Research Methods: The study is based on a survey instrument using snowball sampling with data collected from 600 consumers from northern India. The study uses PLS-SEM for gauging the association of UTAUT2 drivers, Technology Interface drivers, and Digital Payment drivers with Behavioral Intention. Findings/Results: The results show a positive and significant association with Behavioral Intention of Technology Interface drivers and Digital Payment drivers as additional drivers to UTAUT2 drivers. UTAUT2 drivers had the highest impact (β: 0.465), followed by Digital Payment and Technology Interface drivers (β: 0.263 and β: 0.211). Further examination suggests a positive impact of Behavioral Intention on Sustained Intention (β: 0.868). The outcomes reflect that the model explained 69.5% of the variation in Behavioral Intention and 75.4% of the variation in Sustained Intention. Implications: The study suggests that Indian managers need to adopt DPM as a support service to make online shopping a worthwhile experience. Technology Interface drivers have a comparatively lower coefficient, indicating that in India, they are yet to reach the optimum level for consumers to adopt them fully. Efforts to transform Behavioral Intention into repeated online buying or Sustained Intention may go a long way in building a strong, committed community of online sellers to assist in enhancing customer experience.

Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease.

Background Coronary artery disease is a primary cause of death around the world, with both genetic and environmental risk factors. Although genome-wide association studies have linked >100 unique loci to its genetic basis, these only explain a fraction of disease heritability. Methods and Results To find additional gene drivers of coronary artery disease, we applied machine learning to quantitative evolutionary information on the impact of coding variants in whole exomes from the Myocardial Infarction Genetics Consortium. Using ensemble-based supervised learning, the Evolutionary Action-Machine Learning framework ranked each gene's ability to classify case and control samples and identified 79 significant associations. These were connected to known risk loci; enriched in cardiovascular processes like lipid metabolism, blood clotting, and inflammation; and enriched for cardiovascular phenotypes in knockout mouse models. Among them, INPP5F and MST1R are examples of potentially novel coronary artery disease risk genes that modulate immune signaling in response to cardiac stress. Conclusions We concluded that machine learning on the functional impact of coding variants, based on a massive amount of evolutionary information, has the power to suggest novel coronary artery disease risk genes for mechanistic and therapeutic discoveries in cardiovascular biology, and should also apply in other complex polygenic diseases.

Forests on the move: Tracking climate‐related treeline changes in mountains of the northeastern United States

AbstractAimAlpine treeline ecotones are influenced by environmental drivers and are anticipated to shift their locations in response to changing climate. Our goal was to determine the extent of recent climate‐induced treeline advance in the northeastern United States, and we hypothesized that treelines have advanced upslope in complex ways depending on treeline structure and environmental conditions.LocationWhite Mountain National Forest (New Hampshire) and Baxter State Park (Maine), USA.TaxonHigh‐elevation tree species—Abies balsamea, Picea mariana and Betula cordata.MethodsWe compared current and historical high‐resolution aerial imagery to quantify the advance of treelines over the last four decades, and link treeline changes to treeline form (demography) and environmental drivers. Spatial analyses of the aerial images were coupled with ground surveys of forest vegetation and topographical features to ground‐truth treeline classification and provide information on treeline demography and additional potential drivers of treeline locations. We used multiple linear regression models to examine the importance of both topographic and climatic variables on treeline advance.ResultsRegional treelines have significantly shifted upslope over the past several decades (on average by 3 m/decade). Gradual diffuse treelines (characterized by declining tree density) showed significantly greater upslope shifts (5 m/decade) compared to other treeline forms, suggesting that both climate warming and treeline demography are important correlates of treeline shifts. Topographical features (slope, aspect) as well as climate (accumulated growing degree days, AGDD) explained significant variation in the magnitude of treeline advance (R2 = 0.32).Main ConclusionsThe observed advance of treelines is consistent with the hypothesis that climate warming induces upslope treeline shifts. Overall, our findings suggest that gradual diffuse treelines at high elevations may be indicative of climate warming more than other alpine treeline ecotones and thus they can inform us about past and ongoing climatic changes.

Rapid increase in soil organic carbon and structural stability in a sandy loam soil following conversion from long-term arable to semi-natural grassland irrespective of initial soil conditions

Converting arable land to semi-natural grassland has the potential to restore soil structural stability (SSS) and increase soil organic carbon (SOC) storage. However, the effect of the initial soil C level and conditions on the changes following introduction of grassland is poorly understood. We quantified changes in SSS and SOC in topsoil from the Askov straw disposal and cover cropping experiment initiated in 1981 in Denmark before and after its conversion to semi-natural grassland in 2020. Due to different straw input and cover crop use in the arable phase, the grass was established on soils with different initial conditions (11.9–17.9 g C kg−1 oven-dry soil). Soils sampled in 2019 and 2021 from plots subjected to different treatments in the arable phase were analyzed for clay dispersibility measured on two macro-aggregate sizes (ClayDis 1–2 mm and ClayDis 8–16 mm), wet stability of aggregates (WSA) and SOC. Irrespective of initial soil conditions, introduction of semi-natural grassland resulted in a rapid increase in SOC, a decline in ClayDis 1–2 mm and no change in WSA. The relative change in ClayDis 1–2 mm was larger than the change in SOC, and the slope for the relationship between SOC and ClayDis 1–2 mm decreased after conversion to grassland. Based on these observations, we suggest that the additional driver in play was aggregate-binding and -bonding agents being persistent due to the absence of tillage following the conversion to grassland. Notably, changes in SOC and SSS were similar regardless of initial soil conditions, which may be related to a similar productivity in the semi-natural grassland and soil C saturation.

CYBERSECURITY ANALYSIS OF WEB-ORIENTED INDUSTRIAL IOT-SYSTEMS

In modern world cybersecurity ensuring is one of the most crucial issues, especially in the context of the dynamic development of web-oriented industrial Internet of Things (IoT) systems. The subject of research of the paper is cybersecurity ensuring of web-oriented industrial IoT systems. The purpose of the paper is to analyze existing methods of cybersecurity analysis, identify limitations, and formulate requirements for a new assessment concept, which includes ways to eliminate identified limitations. Tasks to be solved: analysis of existing methods, tools and technologies for the organization of web-oriented industrial IoT systems and the problems of ensuring their cyber security. Applied methods: source analysis, system analysis. Obtained results: The analysis of sources has shown that the problems of industrial IoT systems cybersecurity ensuring are relevant due to the use in one system of both the latest information technologies (IT) and traditional operational technologies (OT), such as industrial protocols, etc. In addition, the ever-increasing number and types of attacks aimed specifically at industrial IoT systems are additional drivers for the further development of the cybersecurity assessing and ensuring methods. A generalized concept of the cybersecurity assessing and ensuring process of web-oriented industrial IoT systems is proposed, which includes the stages of identification, analysis, security enhancement, detection and protection. Conclusions: The issue of the cybersecurity ensuring of the web-oriented industrial IoT systems is extremely relevant, and the existing analysis methods and ensuring means do not fully satisfy the existing requirements for such systems. That is why the development and implementation of the proposed concept of cybersecurity assessing and ensuring will allow to significantly influence the improvement of industrial IoT systems cybersecurity.

HGFAP-mediated GLI2 overexpression leads to early death and severe cerebellar malformations with rare tumor formation

The zinc-finger transcription factor GLI2 is frequently amplified in childhood medulloblastoma of the Sonic-hedgehog type (SHH-MB), with or without amplification of NMYC or deletion of TP53. Despite the aggressive tumor behavior, tumorigenesis is not well understood, and adequate mouse models are lacking. Therefore, we generated mice with a GLI2 overexpression under control of the hGFAP-promoter. These mice died within 150days. The majority only survived until postnatal day 40. They displayed severe cerebellar hypoplasia, cortical malformations, but no brain tumors, except for one out of 23 animals with an undifferentiated hindbrain lesion. Additional loss of p53 did not result in cerebellar tumors, but partially rescued the cerebellar phenotype induced by GLI2 overexpression. Similarly, the combination of GLI2 and NMYC was neither sufficient for the development of SHH-MB. We therefore assume that the development of childhood SHH-MB in mice is either occurring in cellular origins outside the hGFAP-positive lineage or needs additional genetic drivers.

Evolutionary histories of breast cancer and related clones

Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1–3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves.

Pathways from climate change to emotional wellbeing: A qualitative study of Kenyan smallholder farmers living with HIV.

Climate change is associated with adverse mental and emotional health outcomes. Social and economic factors are well-known drivers of mental health, yet comparatively few studies examine the social and economic pathways through which climate change affects mental health. There is additionally a lack of research on climate change and mental health in sub-Saharan Africa. This qualitative study aimed to identify potential social and economic pathways through which climate change impacts mental and emotional wellbeing, focusing on a vulnerable population of Kenyan smallholder farmers living with HIV. We conducted in-depth, semi-structured interviews with forty participants to explore their experience of climate change. We used a thematic analytical approach. We find that among our study population of Kenyan smallholder farmers living with HIV, climate change is significantly affecting mental and emotional wellbeing. Respondents universally report some level of climate impact on emotional health including high degrees of stress; fear and concern about the future; and sadness, worry, and anxiety from losing one's home, farm, occupation, or ability to support their family. Climate-related economic insecurity is a main driver of emotional distress. Widespread economic insecurity disrupts systems of communal and family support, which is an additional driver of worsening mental and emotional health. Our study finds that individual adaptive strategies used by farmers in the face of economic and social volatility can deepen economic insecurity and are likely insufficient to protect mental health. Finally, we find that agricultural policies can worsen economic insecurity and other mental health risk factors. Our proposed conceptual model of economic and social pathways relevant for mental health can inform future studies of vulnerable populations and inform health system and policy responses to protect health in a changing climate.

The effects of floods, droughts and elephants on riparian tree mortality in a semi-arid savanna

Riparian forests have declined around the world over the past century. This is mostly attributed to alteration of river flow regimes and abstraction of alluvial groundwater, although in Africa damage from elephants is often considered the primary cause. Large stands of riparian forest along the Limpopo River in Mapungubwe National Park (South Africa) were transformed to woodland between 1990 and 2005, and water stress resulting from reduced river flows and abstraction, an extreme flood and canopy infestation by climbing plants were identified as contributing causes. Recent recolonization of the area by elephant has created an additional potential driver of mortality. To determine if tree losses have continued and gain further insights into the causes - particularly the relative importance of water stress versus debarking by elephant - tagged trees were surveyed annually from 2011 to 2022. Rates of mortality were higher than in the previous decade for four of the five dominant tree species. Bank erosion from flooding remained a cause but accounted for far less mortality than in the past. For individuals not lost to floods, survival analysis indicated that low rainfall was the primary driver of mortality. Canopy infestation by climbers did not decrease survival, and while elephant damage was common for all species and most likely killed some individuals, it had far less effect than our measures of water availability. Isotopic analysis of xylem, soil, river and groundwater revealed few differences in source water use between species, and marginal contributions from the alluvial aquifer. All species relied on deep soil water, illustrating a key linkage between rainfall and survival under the current hydrological regime. Persistence of the remaining large trees at this site is highly unlikely, considering the altered flow regime of the river and likelihood that future climate change will exacerbate water stress. Given the degree of ecosystem change over the past four decades, future conservation should shift focus to the recruitment and establishment of other large tree species, particularly those tolerant of water stress and elephant browsing.

What influences parental decisions about antibiotic use with their children: A qualitative study in rural Australia.

Inappropriate use of antibiotics can promote bacterial resistance, which is a growing public health concern. As children are amongst the highest recipients of antibiotics, understanding the drivers of parental decisions towards their children's antibiotic use is imperative for the development of strategies to assist parents in making more informed decisions. This is particularly relevant to the decisions of parents living in resource-limited settings. This study explored the perspectives and practices of parents living in a rural setting about the use of antibiotics in their children. Three focus group interviews were conducted with 10 parents of children under 12yrs, living in rural and remote areas of the Northern Territory, Australia. A focus group guide was developed to facilitate discussions, which was informed by the Theory of Planned Behaviour. Transcripts were analysed abductively using thematic analysis. Four themes emerged explaining factors that contributed to parent decisions about their children's antibiotic use: 1) Parental knowledge, attitudes and decision making; 2) Perceptions of antimicrobial resistance; 3) Healthcare challenges; 4) Behaviours with antibiotics. While parents demonstrated accurate knowledge of the indications for antibiotic use, their decisions about the need for antibiotics were often driven by fear of serious illness. This fear was exacerbated by resource limitations associated with living in a resource-limited setting. Additional drivers of parental decision making included what parents have read or heard from both medical and non-medical networks, underscoring the importance of Social Norms in predicting behavioural intentions. Mothers living in remote areas experiencing reduced access to health services may make decisions about antibiotic use out of fear and based on the advice of their personal network when they perceive their child is vulnerable to a health threat. Findings from this study provide guidance for future research in the prediction of antibiotic use behaviours and for context-specific interventions.

GRM1 Gene Fusions as an Alternative Molecular Driver in Blue Nevi and Related Melanomas

Activating mutations in GNAQ, GNA11, CYSLTR2, and PLCB4 genes are regarded as the main oncogenic drivers of blue nevi (BN) and blue malignant melanocytic tumors. Here we report 4 cases of blue melanocytic neoplasms devoid of these mutations but harboring GRM1 gene fusions. In this short series, there was no gender predominance (sex ratio, 1). The mean age at diagnosis was 40 years (range, 12-72). Tumors were located on the face (n = 2), forearm (n = 1), and dorsum of the foot (n = 1). Clinically, a plaque-like pre-existing BN was found in 2 cases, including a deep location; another case presented as an Ota nevus. Two cases were diagnosed as melanoma ex-BN, one as an atypical BN, and one as a plaque-like BN. Microscopic examination revealed a dermal proliferation of dendritic melanocytes in a sclerotic stroma. A dermal cellular nodule with atypia and mitotic activity was observed in 3 cases. Genetic investigation by whole exome RNA sequencing revealed MYO10::GRM1 (n = 2) and ZEB2::GRM1 (n = 1) fusions. A GRM1 rearrangement was identified by fluorescence in situ hybridization in the remaining case. SF3B1 comutations were present in the 2 melanomas, and both had a MYO10::GRM1 fusion. Array comparative genomic hybridization was feasible for 3 cases and displayed multiple copy number alterations in the 2 melanomas and limited copy number alterations in the atypical BN, all genomic profiles compatible with those of classical blue lesions. GRM1 was overexpressed in all cases compared with a control group of blue lesions with other typical mutations. Both melanomas rapidly developed visceral metastases following diagnosis, with a fatal outcome in one case and tumor progression under palliative care in the other. These data suggest that GRM1 gene fusions could represent an additional rare oncogenic driver in the setting of BN, mutually exclusive of classical canonical mutations, especially in plaque-type or Ota subtypes.

210-OR: Long-Acting GIPR Agonism Enhances Body Weight Regulation of Multiple Weight-Reducing Agents in Diet-Induced Obese Mice

The development of multi-agonists targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) has resulted in significant clinical improvements in body weight management, however the contribution of GIPR agonism to this effect is incompletely understood. Using a diet induced obese (DIO) mouse model, GIPR agonism (LAGIPRA) alone has demonstrated little to no efficacy in weight management, whereas the addition of LAGIPRA to long acting GLP-1R agonism decreased food intake and increased energy expenditure resulting in greater weight loss compared with GLP-1R agonism alone suggesting a synergistic benefit. To determine whether GIPR agonism would provide similar synergistic improvements in energy metabolism with additional pharmacologic drivers of weight loss, we treated DIO mice with various weight reducing agents plus and minus LAGIPRA in metabolic chambers. Interestingly, addition of LAGIPRA enhanced weight loss, fat mass reduction, energy expenditure, and lipid oxidation whether combined with T3, FGF21, or long-acting glucagon (IUB288); consistent with earlier experiments, it had little effect on its own. Assessment of adipose tissue engagement in these and subsequent studies suggest GIPR agonism in this tissue may enhance lipolysis, potentially enabling greater energy expenditure via release of stored lipids. These findings suggest a unique role for GIPR agonism to regulate energy expenditure when combined with molecules that reduce body weight generating a greater negative caloric balance and enhancing body weight reduction. Disclosure W.Roell: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.O'farrell: None. A.Regmi: Employee; Eli Lilly and Company. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

172-LB: Traditional Risk Factors for Elevated A1C Persist among Youth with T1D Using CGM—Results from the 4T Study 1

Continuous glucose monitoring (CGM) use soon after T1D diagnosis in the 4T Study was associated with improved glycemic outcomes. We evaluated participant factors associated with elevated versus in target A1c for youth in the 4T Study. All youth from the 4T Study 1 (n=133) were evaluated. In this analysis, the 110 youth who had a final A1c between 6-13 months were included in a complete case analysis. These 110 youth were comparable to the 133 4T Study 1 youth by race/ethnicity, insurance, preferred language, and age. Group differences by non-ordered A1c categories were evaluated for categorical (race/ethnicity, insurance, gender, and language) and continuous (age and time from CGM start) variables via chi-square and ANOVA, respectively. A majority of youth in the 4T Study 1 met glycemic targets (65% with A1c ≤7% between 6-13 months post-diagnosis). Age, race/ethnicity, and insurance status were significantly associated with A1c categories (p=0.02 for all; Table). Higher A1c categories were more likely to include Hispanic youth and youth with public insurance. In the 4T Study 1, Hispanic youth and youth with public insurance had higher A1c categories despite similar CGM access and training. These findings suggest the need to address additional drivers of disparities in addition to CGM access. Approaches focused on health equity are required to improve glycemic outcomes in all youth newly diagnosed with T1D. Disclosure J. Kim: None. D. P. Zaharieva: Advisory Panel; Dexcom, Inc., Research Support; Hemsley Charitable Trust, International Society for Pediatric and Adolescent Diabetes, Insulet Corporation, Speaker's Bureau; American Diabetes Association, Ascensia Diabetes Care, Medtronic. F. K. Bishop: None. D. Scheinker: None. R. Johari: None. M. Desai: None. K. K. Hood: Consultant; Cecelia Health. D. M. Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. A. Addala: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K23DK13134201, R18DK122422)