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The Fly-CURE is a genetics-focused multi-institutional Course-Based Undergraduate Research Experience (CURE) that provides undergraduate students with hands-on research experiences within a course. Through the Fly-CURE, undergraduate students at diverse types of higher education institutions across the United States map and characterize novel mutants isolated from a genetic screen in "Drosophila melanogaster." To date, more than 20 mutants have been studied across 20 institutions, and our scientific data have led to eleven publications with more than 500 students as authors. To evaluate the impact of the Fly-CURE experience on students, we developed and validated assessment tools to identify students' perceived research self-efficacy, sense of belonging in science, and intent to pursue additional research opportunities. Our data, collected over three academic years and involving 14 institutions and 480 students, show gains in these metrics after completion of the Fly-CURE across all student subgroups analyzed, including comparisons of gender, academic status, racial and ethnic groups, and parents' educational background. Importantly, our data also show differential gains in the areas of self-efficacy and interest in seeking additional research opportunities between Fly-CURE students with and without prior research experience, illustrating the positive impact of research exposure (dosage) on student outcomes. Altogether, our data indicate that the Fly-CURE experience has a significant impact on students' efficacy with research methods, sense of belonging to the scientific research community, and interest in pursuing additional research experiences.

This study aimed to assess the level of preparedness of alternatively licensed teachers who completed the Idaho CTE "InSpIRE" Educate program. A survey was distributed to 67 program completers, and the data were analyzed using statistical tools. The research found that participants believed "InSpIRE" provided adequate training to meet the Idaho requirements for new CTE teachers, indicating a perception of preparedness and self-efficacy. Higher self-efficacy was associated with participation in the program. However, the study also revealed room for improvement in the training, aligning with previous research that emphasized the unique needs of CTE teachers. Further research was recommended to compare the support provided by alternative CTE programs to traditional certification programs, particularly in rural settings where lower self-efficacy may be observed. Other recommendations included conducting personal interviews with "InSpIRE" completers, making improvements to the program based on participant feedback, and exploring the impact of pedagogical theory in training.

Abstract Behavioral variant frontotemporal dementia (bvFTD) is characterized by profound and early deficits in social cognition (SC) and executive functions (EF). To date it remains unclear whether deficits of the respective cognitive domains are based on the degeneration of distinct brain regions. In 103 patients with a diagnosis of bvFTD (possible/probable/definite: N = 40/58/5) from the frontotemporal lobar degeneration (FTLD) consortium Germany cohort (age 62.5±9.4 years, gender 38 female/65 male) we applied multimodal structural imaging, i.e. voxel-based morphometry, cortical thickness (CTH) and networks of structural covariance via source based morphometry. We cross-sectionally investigated associations with performance in a modified Reading the Mind in the Eyes Test (RMET; reflective of theory of mind - ToM) and five different tests reflective of EF (i.e. Hamasch-Five-Point Test, semantic and phonemic Fluency, Trail Making Test, Stroop interference). Finally, we investigated the conjunction of RMET correlates with functional networks commonly associated with SC respectively ToM and EF as extracted meta-analytically within the Neurosynth database. RMET performance was mainly associated with gray matter volume (GMV) and CTH within temporal and insular cortical regions and less within the prefrontal cortex (PFC), whereas EF performance was mainly associated with prefrontal regions (GMV and CTH). Overlap of RMET and EF associations was primarily located within the insula, adjacent subcortical structures (i.e. putamen) and the dorsolateral PFC (dlPFC). These patterns were more pronounced after adjustment for the respective other cognitive domain. Corroborative results were obtained in analyses of structural covariance networks. Overlap of RMET with meta-analytically extracted functional networks commonly associated with SC, ToM and EF was again primarily located within the temporal and insular region and the dlPFC. In addition, on a meta-analytical level, strong associations were found for temporal cortical RMET correlates with SC and ToM in particular. These data indicate a temporo-frontal dissociation of bvFTD related disturbances of ToM and EF, with atrophy of the anterior temporal lobe being critically involved in ToM deficits. The consistent overlap within the insular cortex may be attributable to the multimodal and integrative role of this region in socioemotional and cognitive processing.

Abstract Dendritic cells (DCs) are crucial for initiating protective immune responses and have also been implicated in the generation and regulation of Foxp3+ regulatory T cells (Treg cells). Here, we show that in the lamina propria of the small intestine, the alternative NF-κB family member RelB is necessary for the differentiation of cryptopatch and isolated lymphoid follicle-associated DCs (CIA-DCs). Moreover, single-cell RNA sequencing reveals a RelB-dependent signature in migratory DCs in mesenteric lymph nodes favoring DC-Treg cell interaction including elevated expression and release of the chemokine CCL22 from RelB-deficient conventional DCs (cDCs). In line with the key role of CCL22 to facilitate DC-Treg cell interaction, RelB-deficient DCs have a selective advantage to interact with Treg cells in an antigen-specific manner. In addition, DC-specific RelB knockout animals show increased total Foxp3+ Treg cell numbers irrespective of inflammatory status. Consequently, DC-specific RelB knockout animals fail to mount protective Th2-dominated immune responses in the intestine after infection with Heligmosomoides polygyrus bakeri. Thus, RelB expression in cDCs acts as a rheostat to establish a tolerogenic set point that is maintained even during strong type 2 immune conditions and thereby is a key regulator of intestinal homeostasis.

Residual fragments can remain after kidney stone extraction which may necessitate another intervention. A new approach needs to be developedis needed to lower the risk of disease severe side effects caused by these fragments. Magnetic nanoparticles can be applied due to their properties of being able to bind to residual fragments and to be extracted by an external magnetic field. Fractals and magnetic nanoparticles have been synthesized and characterized thoroughly. The small nanoparticles bind covalently to the kidney stones and a magnetic extraction of calcium oxalate fractals with magnetic nanoparticles is possible. The aggregation of nanoscale iron oxide nanoparticles can be induced with the addition of salt which improves the extraction process. The separation is validated by simulation and experimentally in a porcine kidney as well as in artificial kidney models. This proof-of-concept study successfullyis the fundament for a new waydemonstrated of extracting kidney stones extraction and including their fractals and might pave the way for new procedures in urology.

Abstract While large language models learn sound statistical representations of the language and information therein, ontologies are symbolic knowledge representations that can complement the former ideally. Research at this critical intersection relies on datasets that intertwine ontologies and text corpora to enable training and comprehensive benchmarking of neurosymbolic models. We present the MaterioMiner dataset and the linked materials mechanics ontology where ontological concepts from the mechanics of materials domain are associated with textual entities within the literature corpus. Another distinctive feature of the dataset is its eminently fine-grained annotation. Specifically, 179 distinct classes are manually annotated by three raters within four publications, amounting to 2191 entities that were annotated and curated. Conceptual work is presented for the symbolic representation of causal composition-process-microstructure-property relationships. We explore the annotation consistency between the three raters and perform fine-tuning of pre-trained language models to showcase the feasibility of training named entity recognition models. Reusing the dataset can foster training and benchmarking of materials language models, automated ontology construction, and knowledge graph generation from textual data.

Abstract Bees are often exposed to pesticides affecting physiological functions and molecular mechanisms. Studies showed a potential link between altered expression of energy metabolism related transcripts and increased homing flight time of foragers exposed to pesticides. In this study, we investigated the effects of thiamethoxam and pyraclostrobin on longevity, flight behavior, and expression of transcripts involved in endocrine regulation (hbg-3, buffy, vitellogenin) and energy metabolism (cox5a, cox5b, cox17) using radio frequency identification (RFID) technology and quantitative polymerase chain reaction. Parallel, a laboratory study was conducted investigating whether pesticide exposure alone without the influence of flight activity caused similar expression patterns as in the RFID experiment. No significant effect on survival, homing flight duration, or return rate of exposed bees was detected. The overall time foragers spent outside the hive was significantly reduced post-exposure. Irrespective of the treatment group, a correlation was observed between cox5a, cox5b, cox17 and hbg-3 expression and prolonged homing flight duration. Our results suggest that flight behavior can impact gene expression and exposure to pesticides adversely affects the expression of genes that are important for maintaining optimal flight capacity. Our laboratory-based experiment showed significantly altered expression levels of cox5a, cox6c, and cox17. However, further work is needed to identify transcriptional profiles responsible for prolonged homing flight duration.

Abstract People with diabetes have an increased cardiovascular risk and a poorer outcome after myocardial infarction (MI). However, the exact underlying mechanisms are still unclear, as is the question of which non-invasive measures could be used to predict the altered risk for the patient at early stages of the disease and adapt personalized treatment. Here, we used a holistic magnetic resonance approach to monitor longitudinally not only the main target heart, but also liver, peripheral/skeletal muscle, bone marrow, and hematopoiesis during disease development and subsequent MI. In prediabetic mice, we found a strong accumulation of lipids in all organs which preceded even a significant whole-body weight gain. Intramyocellular lipids (IMCLs) were most sensitive to reveal in vivo very early alterations in tissue properties during the prediabetic state. Subsequent induction of MI led to a persistent impairment of contractile function in septal/posterior segments of prediabetic hearts which correlated with their lipid load prior MI. At the same time, prediabetic cardiomyocytes exhibited sarcomere function at its limit resulting in overload and lower compensatory contractility of the healthy myocardium after MI. In summary, we identified IMCLs as very early marker in murine prediabetes and together with the cardiac lipid load as predictive for the functional outcome after MI.

Abstract Adolescence poses significant challenges for emotion regulation (ER) and is thus a critical phase in the emergence of various mental disorders, specifically internalising disorders such as anxiety and depression. Affective control, defined as the application of cognitive control in affective contexts, is crucial for effective ER. However, the relationship between ER and affective control is unclear. This study examined the predictive role of ER strategies and difficulties in affective control, measured as the congruency effect and error rate on an Emotional Stroop task (EST), in a sample of adolescents and young adults (aged 14–21, M = 17.28, 22% male). It was hypothesised that participants with internalising disorders would show higher congruency effects and error rates on the EST than healthy controls after a psychosocial stress induction, indicating lower affective control. Surprisingly, our findings revealed no significant differences in these measures between the groups. However, higher depression scores were associated with increased EST errors. While ER strategies and difficulties did not predict affective control, exploratory analyses unveiled associations between depression scores and ER strategy repertoire, perceived ER success and the ER strategy Acceptance. These findings underscore the importance of implicit ER facets, particularly perceived ER success and flexibility to change between applied strategies for adolescents and young adults with elevated depressive symptoms.

Introduction: Patients with long bone fractures often present to the emergency department (ED) with severe pain and are typically treated with opioid and non-opioid analgesics. Historical data reveals racial disparities in analgesic administration, with White patients more likely to receive analgesics. With the diversifying US population, health equity is increasingly crucial. In this study we aimed to evaluate the early administration of opioid and non-opioid analgesia among Black and White patients with long bone and femur fractures in EDs over different time frames using a substantial database. Methods: We retrospectively extracted Information from 57 US healthcare organizations within the TriNetX database, encompassing 95 million patients. The ED records from 2003–2023 were subjected to propensity score matching for age and gender. We focused on four cohorts: two comprising Black and White patients diagnosed with long bone fractures, and another two with Black and White patients diagnosed solely with femur fractures. We examined analgesic administration rates over 20 years (2003–2023) at five-year intervals (2003–2008; 2008–2013; 2013–2018; 2018–2023), and further analyzed the rates for the most recent two-year period (2021–2023). Results: Disparities in analgesic administration significantly diminished over the study period. For patients with long bone fractures (1,095,052), the opioid administration gap narrowed from 6.3% to 1.1%, while non-opioid administration disparities reduced from 4.4% to 0.3%. Similar trends were noted for femur fractures (265,181). By 2021–2023, no significant differences in analgesic administration were observed between racial groups. Conclusion: Over the past 20 years, the gap in early administration of opioid and non-opioid analgesics for Black and White patients presenting with long bone fractures or femur fractures has been disappearing.

Abstract Background Mining the vast pool of biomedical literature to extract accurate responses and relevant references is challenging due to the domain's interdisciplinary nature, specialized jargon, and continuous evolution. Early natural language processing (NLP) approaches often led to incorrect answers as they failed to comprehend the nuances of natural language. However, transformer models have significantly advanced the field by enabling the creation of large language models (LLMs), enhancing question-answering (QA) tasks. Despite these advances, current LLM-based solutions for specialized domains like biology and biomedicine still struggle to generate up-to-date responses while avoiding “hallucination” or generating plausible but factually incorrect responses. Results Our work focuses on enhancing prompts using a retrieval-augmented architecture to guide LLMs in generating meaningful responses for biomedical QA tasks. We evaluated two approaches: one relying on text embedding and vector similarity in a high-dimensional space, and our proposed method, which uses explicit signals in user queries to extract meaningful contexts. For robust evaluation, we tested these methods on 50 specific and challenging questions from diverse biomedical topics, comparing their performance against a baseline model, BM25. Retrieval performance of our method was significantly better than others, achieving a median Precision@10 of 0.95, which indicates the fraction of the top 10 retrieved chunks that are relevant. We used GPT-4, OpenAI's most advanced LLM to maximize the answer quality and manually accessed LLM-generated responses. Our method achieved a median answer quality score of 2.5, surpassing both the baseline model and the text embedding-based approach. We developed a QA bot, WeiseEule ( https://github.com/wasimaftab/WeiseEule-LocalHost ), which utilizes these methods for comparative analysis and also offers advanced features for review writing and identifying relevant articles for citation. Conclusions Our findings highlight the importance of prompt enhancement methods that utilize explicit signals in user queries over traditional text embedding-based approaches to improve LLM-generated responses for specialized queries in specialized domains such as biology and biomedicine. By providing users complete control over the information fed into the LLM, our approach addresses some of the major drawbacks of existing web-based chatbots and LLM-based QA systems, including hallucinations and the generation of irrelevant or outdated responses.

Abstract Triosephosphate isomerase deficiency (TPI Df) is a rare multisystem disorder with severe neuromuscular symptoms which arises exclusively from mutations within the TPI1 gene. Studies of TPI Df have been limited due to the absence of mammalian disease models and difficulties obtaining patient samples. Recently, we developed a novel murine model of TPI Df which models the most common disease-causing mutation in humans, TPI1 E105D . Using our model in the present study, the underlying pathogenesis of neuromuscular symptoms has been elucidated. This is the first report detailing studies of neuromuscular pathology within a murine model of TPI Df. We identified several contributors to neuromuscular symptoms, including neurodegeneration in the brain, alterations in neurotransmission at the neuromuscular junction, and reduced muscle fiber size. TPI Df mice also exhibited signs of cardiac pathology and displayed a deficit in vascular smooth muscle functionality. Together, these findings provide insight into pathogenesis of the neuromuscular symptoms in TPI Df and can guide the future development of therapeutics.

Abstract The basolateral amygdala (BLA) contains discrete neuronal circuits that integrate positive or negative emotional information and drive the appropriate innate and learned behaviors. Whether these circuits consist of genetically-identifiable and anatomically segregated neuron types, is poorly understood. Also, our understanding of the response patterns and behavioral spectra of genetically-identifiable BLA neurons is limited. Here, we classified 11 glutamatergic cell clusters in mouse BLA and found that several of them were anatomically segregated in lateral versus basal amygdala, and anterior versus posterior regions of the BLA. Two of these BLA subpopulations innately responded to valence-specific, whereas one responded to mixed - aversive and social - cues. Positive-valence BLA neurons promoted normal feeding, while mixed selectivity neurons promoted fear learning and social interactions. These findings enhance our understanding of cell type diversity and spatial organization of the BLA and the role of distinct BLA populations in representing valence-specific and mixed stimuli.

Different risk management activities, such as land-use planning, preparedness, and emergency response, utilize scenarios of earthquake events. A systematic selection of such scenarios should aim at finding those that are representative of a certain severity, which can be measured by consequences to the exposed assets. For this reason, defining a representative scenario as the most likely one leading to a loss with a specific return period, e.g., the 100-year loss, has been proposed. We adopt this definition and develop enhanced algorithms for determining such scenarios for multiple return periods. With this approach, we identify representative earthquake scenarios for the return periods of 50, 100, 500, and 1000 years in the Chilean communes of Valparaíso and Viña del Mar, based on a synthetic earthquake catalog of 20 000 scenarios on the subduction zone with a magnitude of Mw≥5.0. We separately consider the residential-building stock and the electrical-power network and identify and compare earthquake scenarios that are representative of these systems. Because the representative earthquake scenarios are defined in terms of the annual loss exceedance rates, they vary in function of the exposed system. The identified representative scenarios for the building stock have epicenters located not further than 30 km from the two communes, with magnitudes ranging between 6.0 and 7.0. The epicenter locations of the earthquake scenarios representative of the electrical-power network are more spread out but not further than 100 km away from the two communes, with magnitudes ranging between 7.0 and 9.0. For risk management activities, we recommend considering the identified scenarios together with historical events.

Abstract Retinitis pigmentosa (RP), an inherited retinal disease, affects 1,5 million people worldwide. The initial mutation-driven photoreceptor degeneration leads to chronic inflammation, characterized by Müller cell activation and upregulation of CD44. CD44 is a cell surface transmembrane glycoprotein and the primary receptor for hyaluronic acid. It is involved in many pathological processes, but little is known about CD44’s retinal functions. CD44 expression is also increased in Müller cells from our Pde6b STOP/STOP RP mouse model. To gain a more detailed understanding of CD44’s role in healthy and diseased retinas, we analyzed Cd44 −/− and Cd44 −/− Pde6b STOP/STOP mice, respectively. The loss of CD44 led to enhanced photoreceptor degeneration, reduced retinal function, and increased inflammatory response. To understand the underlying mechanism, we performed proteomic analysis on isolated Müller cells from Cd44 −/− and Cd44 −/− Pde6b STOP/STOP retinas and identified a significant downregulation of glutamate transporter 1 (SLC1A2). This downregulation was accompanied by higher glutamate levels, suggesting impaired glutamate homeostasis. These novel findings indicate that CD44 stimulates glutamate uptake via SLC1A2 in Müller cells, which in turn, supports photoreceptor survival and function.

Applied behavior analysis (ABA) focuses on providing socially significant treatments and practices. Recent advancements in ethically-minded research have encouraged practitioners to think beyond the technical skills required for implementing behavior-analytic practices and consider how these practices are delivered. Compassionate care in ABA has recently been conceptually defined and subsequently researched to explore ways to explicitly and systematically teach compassionate-care-based skills within the scope of ABA. Researchers have noted barriers specific to the time required to teach compassionate-care-based skills using behavior skills training (BST) especially when working to train groups in compassionate care skills. Further, these studies have focused primarily on using compassionate care towards interactions with caregivers as communication partners. This study operationalized the compassionate care-based skill of receiving feedback within a behavioral analytic lens and taught it to eight master's students enrolled in an ABA course. An experimental case study approach was used to evaluate the relative benefit of modified behavioral skills training (BST) versions, including conditions with and without rehearsal opportunities and individualized performance feedback. Results indicated that all participants demonstrated significant skill increases across multiple communication partners (i.e., client, caregiver, colleague) compared to baseline sessions, with conditions including opportunities for rehearsal and performance feedback resulting in higher skill acquisition for seven of the eight participants. Conditions that required the participants to generalize to novel scenarios and novel communication partners resulted in lower competencies; however, all participant skills across all communication partners remained higher than baseline measures. Limitations included practicing skills within role-play scenarios only, the application of compassionate care-based skills in a variety of cultures, and limits related to using an experimental case study as a methodological approach. Implications for future research and practitioner-based applications are discussed.