bluuebunny/crossref_metadata_2025 huggingface dataset:
94 Incorporating Health Equity, Diversity and Inclusion Professional Development During Community Advisory Board Meetings
Authors: Sotto-Santiago Sylk , Claxton Gina , Hudson Brenda , Delp Lynsey , Moe Sharon , Wiehe Sarah
Published: April 2024

OBJECTIVES/GOALS: Incorporating health equity, diversity, and inclusion (HEDI) development during community advisory board meetings is essential for ensuring that perspectives of all community members are considered, that health research is centered on the experiences of historically marginalized groups, and organizational strategies align with the community. METHODS/STUDY POPULATION: All IN for Health is a public engagement program that promotes health and research literacy, seeking to increase the public’s understanding of the role and value of research in improving health. It is guided by an active CAB providing advice on strategic directions, feedback to all efforts, contributing ideas, priorities, and most importantly, accountability. In 2023, ALL IN for Health started to incorporate HEDI professional development during staff team meetings and most recently, into our quarterly CAB meetings. Initially, the CAB was asked to provide feedback about talks and potential presentations related to health-research, sponsored, and shared by All IN for Health. During this exercise, board members were asked to provide HEDI topics of interest. Their responses informed a plan for team and board members. RESULTS/ANTICIPATED RESULTS: Some of the topics suggested by board members include: understanding health equity in relation to research studies and protocols, and topics specific to health research such as: health care access for rural areas and vulnerable populations, culture-based attitudes and beliefs and how they impact decisions related to health care, being aware of limitations certain communities have and what they may not have access to. The initiative was positively received and unanimously adopted. We hope to introduce the HEDI integration model for CABs at this conference. (Conceptual Model attached). DISCUSSION/SIGNIFICANCE: It is important to learn and grow alongside our community members. Such practice is bound to sustain partnerships that promote health equity, and exemplify meaningful community engagement, bidirectional learning, and a shared leadership model. By consistently incorporating and prioritizing HEDI, HAB can contribute to more equitable initiatives.
96 Unlocking the Potential of Simalikalactone D as an Anticancer Agent in Ethnically Diverse Breast Cancer Populations
Authors: Sanchez-Alvarez Annelis O. , Vivas-Mejia Pablo E. , Ospina Claudia
Published: April 2024

OBJECTIVES/GOALS: This project focuses on investigating the potential of Simalikalactone D (SKD) as an anticancer agent, exploring the mechanisms underlying SKD’s induction of cell death, and assessing the impact of SKD on diverse breast cancer cell lines. Also, it Investigates the compound’s mechanisms of action beyond caspase 3-dependent pathways. METHODS/STUDY POPULATION: Three breast cancer cell lines were used: SKBR3, MDA-MB-231, and MDA-MB-468. Two triple-negative breast cancer cell lines are included to address cancer disparities across diverse ethnic backgrounds. Viability assays were conducted to determine half-maximal inhibitory concentrations (IC50). Caspase 3 activity assay was performed to evaluate apoptosis as a possible cell death pathway. Wound healing and colony formation assays are used to assess cell migration and clonogenic capacity. Proteomic analysis and phosphoarray analysis are planned for a deeper understanding of SKD’s anticancer properties, as well as testing for caspase 3 independent pathways. RESULTS/ANTICIPATED RESULTS: SKD demonstrated substantial cytotoxicity against all three breast cancer cell lines. IC50 values for SKBR3, MDA-MB-231, and MDA-MB-468 were 60.0 nM, 65.0 nM, and 116 nM, respectively. SKD induces cell death via caspase 3-independent pathways. Further experiments are needed to confirm and elucidate the molecular pathways being impacted. SKD inhibited cancer cell migration and clonogenic potential, suggesting it can reduce tumor growth and metastatic tendencies. DISCUSSION/SIGNIFICANCE: The study highlights SKD’s cytotoxicity across diverse breast cancer cell lines. It underscores the mechanism of action, a caspase 3 independent pathway. These findings hold promise for the development of innovative anticancer treatments and emphasize the importance of exploring varied cellular responses to mitigate global cancer disparities.
97 BUILD EXITO: a successful collaborative training program for STEM undergraduates to improve workforce diversity
Authors: Wolf De’Sha , Keller Thomas , Honore Matt , Dixon Shandee , Morris Cynthia
Published: April 2024

OBJECTIVES/GOALS: To truly improve health equity and accessibility, we must develop a diverse and inclusive workforce. The BUILD EXITO program developed as a collaboration between a network of undergraduate programs and a CTSA hub and now has become a sustainable resource that will outlive NIH funding. We will disseminate our successful model. METHODS/STUDY POPULATION: The BUILD EXITO program has completed 10 years of NIH funding, a partnership between OCTRI and Portland State University (PSU), to create a new model of research training for underrepresented and disadvantaged students. This model provides an opportunity to learn about clinical and translational research academic careers; participate in a research enhancement and professional development curriculum;have a long-term authentic research experience; and receive enhanced mentorship. BUILD EXITO includes PSU, and local and 3 US Pacific territory 2-year colleges. We have developed a sustainable plan that includes these core elements after NIH support for the program ends. We have tracked long-term student outcomes for entry into graduate programs and the research workforce. RESULTS/ANTICIPATED RESULTS: We will describe the experimental model and the network of university and community colleges in BUILD EXITO, including PSU, U of Alaska, and colleges in US territories of Guam, Northern Mariana Islands, and American Samoa. All these universities and colleges have high proportions of underrepresented and disadvantaged students. We will present data on characteristics of the >600 students who have participated in BUILD EXITO to demonstrate the diversity of the cohort. We will also describe 4-year degree completion, engagement in the research workforce, and entry into graduate or professional programs. We will show how this has positively affected faculty inclusion of students in research, institutional policies at the 2-year and 4-year programs, and how this model has become sustainable. DISCUSSION/SIGNIFICANCE: The BUILD EXITO program developed as a collaboration of the CTSA hub at OHSU and a highly diverse undergraduate programs. We have developed a successful model for training a diverse research workforce and will disseminate this sustainable model.
99 Using LGBTQ+ Community Expertise to Co-Develop Inclusive Sexual Orientation and Gender Identity (SOGI) Screening for Research Studies
Authors: Poger Jennifer , Kraschnewski Jennifer , Luquis Raffy , Moodie Paula , Thomas Gelise , Abrams Schrodel Jess , Poger Jennifer M. , Moodie Paula , Thomas Gelise , Luquis Raffy , Kraschnewski Jennifer L.
Published: April 2024

OBJECTIVES/GOALS: To promote diverse research engagement and address health disparities by creating an inclusive tool to collect sexual orientation and gender identity (SOGI) data from potential participants #_msoanchor_1 METHODS/STUDY POPULATION: The Penn State Community Health Equity & Engagement in Research (CHEER) team, part of our Clinical and Translational Science Institute (CTSI), developed inclusive screening guidance to collect SOGI data from potential research participants to fill an identified gap in the literature. Guidance was developed through an iterative feedback process, leveraging expertise from local, regional, and national organizations, healthcare systems, and leaders throughout Clinical & Translational Science Award hubs. By eliciting expert feedback, CHEER co-developed a comprehensive SOGI data collection form, filling an important gap of inclusivity in the consenting process. Training of this new tool was delivered to CHEER’s far-reaching listserv researchers (internal and external) and community partners. RESULTS/ANTICIPATED RESULTS: Feedback collected from our LGBTQ+ expert partners resulted in a total of five inclusive SOGI screening questions; two ‘Gender Identity’ questions, one ‘Sexual Orientation’ question, and two ‘Sex’ questions, with “prefer not to answer” and “another option not listed” provided. The goal of this effort is to equip research teams with a tool that integrates SOGI characteristics that may be particularly important to determine study eligibility respective to a person’s identity or orientation. Additionally, collecting SOGI data in an inclusive way may increase trust worthiness in research from potential research participants, particularly among the LGBTQ+ community, who have been underrepresented yet experience several inequities and disparities across multiple health outcomes. DISCUSSION/SIGNIFICANCE: CHEER’s goal is to reduce health disparities in underrepresented populations, including the LGBTQ+ community, by promoting inclusivity and engagement in research. Developing a community-driven screening that addresses the unique needs of the LGBTQ+ community successfully bridges a gap in equity across all research participants.
101 Participation of Racial and Ethnic Minorities in Decentralized Trials: The ACTIV-6 Experience
Authors: Rohde Maximilian , Jayaweera Dushyantha , Carrasquillo Olveen , Stewart Thomas
Published: April 2024

OBJECTIVES/GOALS: Racial and ethnic minority populations have been historically underrepresented in clinical trials, which limits the external validity of study findings. We analyze data from the ACTIV-6 trial to assess whether inclusion efforts were effective in increasing participation from minority groups. METHODS/STUDY POPULATION: ACTIV-6 is a decentralized randomized placebo-controlled platform trial investigating repurposed drugs for the treatment of mild to moderate COVID-19. Study participants could either self-refer online or be recruited through a study site. Two inclusion efforts were introduced to increase participation from racial or ethnic minority populations: targeted advertising and outreach, and strategic selection of study sites that serve diverse populations. We assessed the effectiveness of these interventions by analyzing enrollment trends over time. We also assessed whether participants from racial or ethnic minority populations experienced higher loss to follow-up. RESULTS/ANTICIPATED RESULTS: At the start of the trial, enrollment of non-Hispanic White participants outpaced enrollment from racial or ethnic minority populations. At 4 months, only 108 participants (20.5%) were from racial or ethnic minority populations, but greatly increased by 28 months to 3,544 participants (46.4%), nearly half of all participants. This increase was predominantly due to recruitment through study sites rather than self-referral. In particular, certain sites recruited large numbers of minority participants. We also observed that participants from racial or ethnic minority populations were more likely to drop out of the study before receiving the study drug (3% vs 1%). DISCUSSION/SIGNIFICANCE: Our results suggest that strategic site selection is an effective strategy for recruiting a study population that represents racial and ethnic populations. The benefits of targeted advertising and outreach were less clear. Retention efforts remain important to reduce loss to follow-up.
New material of the zosterophyllopsid Gosslingia from the Lower Devonian of Guizhou, southwestern China
Authors: Wang Yiling , Liu Lu , Huang Pu , Qin Min , Xue Jinzhuang
Published: April 2024

The zosterophyllopsids had a widespread distribution and constituted a dominant component in many plant assemblages during the Early Devonian. Although a large number of zosterophyllopsids have been documented, knowledge about the paleogeographic distribution of different genera/species remains to be expanded by further fossil evidence. In this article, new material assigned to the genus Gosslingia Heard, 1927 and designated as Gosslingia cf. G. breconensis Heard, 1927 is described from a new locality of the Lower Devonian of Guizhou Province, China. The Guizhou material shows main axes that are pseudomonopodially branched, pseudomonopodial lateral branching systems, subaxillary tubercle branches, circinate apices, elliptical xylem strand, exarch maturation of xylem, and G-type tracheids, and exhibits considerable similarities with the type and only species of Gosslingia, Gosslingia breconensis. Our finding represents the first report of Gosslingia in the South China Block and the most convincing occurrence of this genus outside of Wales, UK. Gosslingia adds to the diversity of genera shared among the Early Devonian floras of South China, western Europe, and North America, along with Distichophytum Mägdefrau, Estinnophyton Fairon-Demaret, Zosterophyllum Penhallow, and others, and indicates that the dispersal of early vascular plants among different paleocontinents was more common than previously appreciated.
The Extrajudicial Voice
Authors: Mallory Conall , Tyrrell Hélène
Published: April 2024

Judges communicate outside of the courtroom on a regular basis. They give speeches at universities and to societies; appear before select committees; write for a range of publications; and engage in both media and outreach activities. Existing literature has charted the value and perils of such extrajudicial communication. This paper contributes an explanation of what motivates judges towards such communication, and what shapes their discourse. The work draws on 13 semi-structured interviews with senior serving and recently retired judges, along with an extensive range of examples of judicial speech beyond the bench. It argues that extrajudicial communication is shaped by a shared conception amongst the judicial community of what is appropriate. This conception of propriety is principally motivated by a communal pursuit of sustaining public confidence in the judicial office. The conception also informs the limits of appropriate discourse and establishes the ramifications for breach.
APPROXIMATION OF IRRATIONAL NUMBERS BY PAIRS OF INTEGERS FROM A LARGE SET
Authors: DUBICKAS ARTŪRAS
Published: April 2024

We show that there is a set
$S \subseteq {\mathbb N}$
with lower density arbitrarily close to
$1$
such that, for each sufficiently large real number
$\alpha $
, the inequality
$|m\alpha -n| \geq 1$
holds for every pair
$(m,n) \in S^2$
. On the other hand, if
$S \subseteq {\mathbb N}$
has density
$1$
, then, for each irrational
$\alpha>0$
and any positive
$\varepsilon $
, there exist
$m,n \in S$
for which
$|m\alpha -n|<\varepsilon $
.
Corals Reveal Interdecadal Variation of Tropical Cyclones Modulated by Pacific Decadal Oscillation
Authors: Han Yansong , Jiang Wei , Jiang Leilei , Yong Yangyang , Yang Kai , Gu Tingwu , Guo Ning , Yu Kefu
Published: April 2024

Tropical cyclones (TCs) lead to huge economic losses and casualties in coastal regions, but multi‐decadal variation of TC remains poorly understood due to the limited length of observational records and low‐resolution reconstructions. Porites corals provide continuous and monthly resolved records that allow for the determination of weather‐timescale (weekly to monthly) extreme events, including TC, to overcome the above limitations. Here we synthesize five coral Δδ18O records from the South China Sea (SCS) and develop a coral TC frequency index, in good agreement with post‐1980 instrumental records and sediment‐based TC reconstructions over the past century. Our results indicate that TC frequency in the SCS exhibits pronounced decadal variations, with active TCs corresponding to the negative phase of the Pacific Decadal Oscillation. Our findings here provide novel evidence for past TC changes in the SCS and a constraint for predicting future TC changes.
Orthogonal analysis of mitochondrial function in Parkinson’s disease patients
Authors: Barnhoorn Sander , Milanese Chiara , Li Tracy , Dons Lieke , Ghazvini Mehrnaz , Sette Martina , Farina Stefania , Sproviero Daisy , Payan-Gomez Cesar , Mastroberardino Pier G.
Published: April 2024

The etiopathology of Parkinson’s disease has been associated with mitochondrial defects at genetic, laboratory, epidemiological, and clinical levels. These converging lines of evidence suggest that mitochondrial defects are systemic and causative factors in the pathophysiology of PD, rather than being mere correlates. Understanding mitochondrial biology in PD at a granular level is therefore crucial from both basic science and translational perspectives. In a recent study, we investigated mitochondrial alterations in fibroblasts obtained from PD patients assessing mitochondrial function in relation to clinical measures. Our findings demonstrated that the magnitude of mitochondrial alterations parallels disease severity. In this study, we extend these investigations to blood cells and dopamine neurons derived from induced pluripotent stem cells reprogrammed from PD patients. To overcome the inherent metabolic heterogeneity of blood cells, we focused our analyses on metabolically homogeneous, accessible, and expandable erythroblasts. Our results confirm the presence of mitochondrial anomalies in erythroblasts and induced dopamine neurons. Consistent with our previous findings in fibroblasts, we observed that mitochondrial alterations are reversible, as evidenced by enhanced mitochondrial respiration when PD erythroblasts were cultured in a galactose medium that restricts glycolysis. This observation indicates that suppression of mitochondrial respiration may constitute a protective, adaptive response in PD pathogenesis. Notably, this effect was not observed in induced dopamine neurons, suggesting their distinct bioenergetic behavior. In summary, we provide additional evidence for the involvement of mitochondria in the disease process by demonstrating mitochondrial abnormalities in additional cell types relevant to PD. These findings contribute to our understanding of PD pathophysiology and may have implications for the development of novel biomarkers and therapeutic strategies.
Eph-ephrin signaling couples endothelial cell sorting and arterial specification
Authors: Stewen Jonas , Kruse Kai , Godoi-Filip Anca T. , Zenia  , Jeong Hyun-Woo , Adams Susanne , Berkenfeld Frank , Stehling Martin , Red-Horse Kristy , Adams Ralf H. , Pitulescu Mara E.
Published: April 2024

Cell segregation allows the compartmentalization of cells with similar fates during morphogenesis, which can be enhanced by cell fate plasticity in response to local molecular and biomechanical cues. Endothelial tip cells in the growing retina, which lead vessel sprouts, give rise to arterial endothelial cells and thereby mediate arterial growth. Here, we have combined cell type-specific and inducible mouse genetics, flow experiments in vitro, single-cell RNA sequencing and biochemistry to show that the balance between ephrin-B2 and its receptor EphB4 is critical for arterial specification, cell sorting and arteriovenous patterning. At the molecular level, elevated ephrin-B2 function after loss of EphB4 enhances signaling responses by the Notch pathway, VEGF and the transcription factor Dach1, which is influenced by endothelial shear stress. Our findings reveal how Eph-ephrin interactions integrate cell segregation and arteriovenous specification in the vasculature, which has potential relevance for human vascular malformations caused byEPHB4mutations.
Shaping active matter from crystalline solids to active turbulence
Authors: Yang Qianhong , Jiang Maoqiang , Picano Francesco , Zhu Lailai
Published: April 2024

Active matter drives its constituent agents to move autonomously by harnessing free energy, leading to diverse emergent states with relevance to both biological processes and inanimate functionalities. Achieving maximum reconfigurability of active materials with minimal control remains a desirable yet challenging goal. Here, we employ large-scale, agent-resolved simulations to demonstrate that modulating the activity of a wet phoretic medium alone can govern its solid-liquid-gas phase transitions and, subsequently, laminar-turbulent transitions in fluid phases, thereby shaping its emergent pattern. These two progressively emerging transitions, hitherto unreported, bring us closer to perceiving the parallels between active matter and traditional matter. Our work reproduces and reconciles seemingly conflicting experimental observations on chemically active systems, presenting a unified landscape of phoretic collective dynamics. These findings enhance the understanding of long-range, many-body interactions among phoretic agents, offer new insights into their non-equilibrium collective behaviors, and provide potential guidelines for designing reconfigurable materials.
Mesenchymal glioma stem cells trigger vasectasia—distinct neovascularization process stimulated by extracellular vesicles carrying EGFR
Authors: Spinelli Cristiana , Adnani Lata , Meehan Brian , Montermini Laura , Huang Sidong , Kim Minjun , Nishimura Tamiko , Croul Sidney E. , Nakano Ichiro , Riazalhosseini Yasser , Rak Janusz
Published: April 2024

Targeting neovascularization in glioblastoma (GBM) is hampered by poor understanding of the underlying mechanisms and unclear linkages to tumour molecular landscapes. Here we report that different molecular subtypes of human glioma stem cells (GSC) trigger distinct endothelial responses involving either angiogenic or circumferential vascular growth (vasectasia). The latter process is selectively triggered by mesenchymal (but not proneural) GSCs and is mediated by a subset of extracellular vesicles (EVs) able to transfer EGFR/EGFRvIII transcript to endothelial cells. Inhibition of the expression and phosphorylation of EGFR in endothelial cells, either pharmacologically (Dacomitinib) or genetically (gene editing), abolishes their EV responses in vitro and disrupts vasectasia in vivo. Therapeutic inhibition of EGFR markedly extends anticancer effects of VEGF blockade in mice, coupled with abrogation of vasectasia and prolonged survival. Thus, vasectasia driven by intercellular transfer of oncogenic EGFR may represent a new therapeutic target in a subset of GBMs.
Age-progressive interplay of HSP-proteostasis, ECM-cell junctions and biomechanics ensures C. elegans astroglial architecture
Authors: Coraggio Francesca , Bhushan Mahak , Roumeliotis Spyridon , Caroti Francesca , Bevilacqua Carlo , Prevedel Robert , Rapti Georgia
Published: April 2024

Tissue integrity is sensitive to temperature, tension, age, and is sustained throughout life by adaptive cell-autonomous or extrinsic mechanisms. Safeguarding the remarkably-complex architectures of neurons and glia ensures age-dependent integrity of functional circuits. Here, we report mechanisms sustaining the integrity of C. elegans CEPsh astrocyte-like glia. We combine large-scale genetics with manipulation of genes, cells, and their environment, quantitative imaging of cellular/ subcellular features, tissue material properties and extracellular matrix (ECM). We identify mutants with age-progressive, environment-dependent defects in glial architecture, consequent disruption of neuronal architecture, and abnormal aging. Functional loss of epithelial Hsp70/Hsc70-cochaperone BAG2 causes ECM disruption, altered tissue biomechanics, and hypersensitivity of glia to environmental temperature and mechanics. Glial-cell junctions ensure epithelia-ECM-CEPsh glia association. Modifying glial junctions or ECM mechanics safeguards glial integrity against disrupted BAG2-proteostasis. Overall, we present a finely-regulated interplay of proteostasis-ECM and cell junctions with conserved components that ensures age-progressive robustness of glial architecture.
Global spatiotemporal synchronizing structures of spontaneous neural activities in different cell types
Authors: Shi Liang , Fu Xiaoxi , Gui Shen , Wan Tong , Zhuo Junjie , Lu Jinling , Li Pengcheng
Published: April 2024

Increasing evidence has revealed the large-scale nonstationary synchronizations as traveling waves in spontaneous neural activity. However, the interplay of various cell types in fine-tuning these spatiotemporal patters remains unclear. Here, we performed comprehensive exploration of spatiotemporal synchronizing structures across different cell types, states (awake, anesthesia, motion) and developmental axis in male mice. We found traveling waves in glutamatergic neurons exhibited greater variety than those in GABAergic neurons. Moreover, the synchronizing structures of GABAergic neurons converged toward those of glutamatergic neurons during development, but the evolution of waves exhibited varying timelines for different sub-type interneurons. Functional connectivity arises from both standing and traveling waves, and negative connections can be elucidated by the spatial propagation of waves. In addition, some traveling waves were correlated with the spatial distribution of gene expression. Our findings offer further insights into the neural underpinnings of traveling waves, functional connectivity, and resting-state networks, with cell-type specificity and developmental perspectives.
Cold-induced FOXO1 nuclear transport aids cold survival and tissue storage
Authors: Zhang Xiaomei , Ge Lihao , Jin Guanghui , Liu Yasong , Yu Qingfen , Chen Weizhao , Chen Liang , Dong Tao , Miyagishima Kiyoharu J. , Shen Juan , Yang Jinghong , Lv Guo , Xu Yan , Yang Qing , Ye Linsen , Yi Shuhong , Li Hua , Zhang Qi , Chen Guihua , Liu Wei , Yang Yang , Li Wei , Ou Jingxing
Published: April 2024

Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1. Our conclusions are supported by cold survival experiments with human cell models and zebrafish larvae. Promoting FOXO1 nuclear entry by the Exportin-1 inhibitor KPT-330 enhances cold tolerance in pre-diabetic obese mice, and greatly prolongs the shelf-life of human and mouse pancreatic tissues and islets. Transplantation of mouse islets cold-stored for 14 days reestablishes normoglycemia in diabetic mice. Our findings uncover a regulatory network and potential therapeutic targets to boost spontaneous cold adaptation.
Dopamine control of social novelty preference is constrained by an interpeduncular-tegmentum circuit
Authors: Molas Susanna , Freels Timothy G. , Zhao-Shea Rubing , Lee Timothy , Gimenez-Gomez Pablo , Barbini Melanie , Martin Gilles E. , Tapper Andrew R.
Published: April 2024

Animals are inherently motivated to explore social novelty cues over familiar ones, resulting in a novelty preference (NP), although the behavioral and circuit bases underlying NP are unclear. Combining calcium and neurotransmitter sensors with fiber photometry and optogenetics in mice, we find that mesolimbic dopamine (DA) neurotransmission is strongly and predominantly activated by social novelty controlling bout length of interaction during NP, a response significantly reduced by familiarity. In contrast, interpeduncular nucleus (IPN) GABAergic neurons that project to the lateral dorsal tegmentum (LDTg) were inhibited by social novelty but activated during terminations with familiar social stimuli. Inhibition of this pathway during NP increased interaction and bout length with familiar social stimuli, while activation reduced interaction and bout length with novel social stimuli via decreasing DA neurotransmission. These data indicate interest towards novel social stimuli is encoded by mesolimbic DA which is dynamically regulated by an IPN→LDTg circuit to control NP.
A distal enhancer guides the negative selection of toxic glycoalkaloids during tomato domestication
Authors: Bai Feng , Shu Peng , Deng Heng , Wu Yi , Chen Yao , Wu Mengbo , Ma Tao , Zhang Yang , Pirrello Julien , Li Zhengguo , Hong Yiguo , Bouzayen Mondher , Liu Mingchun
Published: April 2024

Steroidal glycoalkaloids (SGAs) are major plant defense metabolites against pests, while they are considered poisonous in food. The genetic basis that guides negative selection of SGAs production during tomato domestication remains poorly understood. Here, we identify a distal enhancer, GAME Enhancer 1 (GE1), as the key regulator of SGAs metabolism in tomato. GE1 recruits MYC2-GAME9 transcriptional complex to regulate the expression of GAME cluster genes via the formation of chromatin loops located in the neighboring DNA region. A naturally occurring GE176 allelic variant is found to be more active in stimulating GAME expression. We show that the weaker GE1 allele has been the main driver for selecting reduced SGAs levels during tomato domestication. Unravelling the “TFs-Enhancer-Promoter” regulatory mechanism operating in SGAs metabolism opens unprecedented prospects for SGAs manipulation in Solanaceae via precision breeding strategies.
Up-bottom assessments of nutrient supply and gaseous pollutant from Chinese wheat straw field management
Authors: Li Dongxue , Gu Jun , Chen Xiaoqin , Wang Yiliu , Lu Dianjun , Yokamo Solomon , Wang Huoyan , Hou Peng
Published: April 2024

To achieve resource efficiency, and carbon neutrality, it is vital to evaluate nutrient supply and gaseous pollutant emissions associated with field management of bio-straw resources. Previous straw yield estimates have typically relied on a constant grain-to-straw yield ratio without accounting for grain yield levels in a given region. Addressing this high-resolution data gap, our study introduces a novel empirical model for quantifying grain-to-straw yield, which has been used to gauge wheat straw field management practices at the city level during 2011–2015. Utilizing both statistical review and GIS-based methods, average nitrogen (N), phosphorus (P), and potassium (K) supplies from straw field management stood at 1510, 1229, and 61700 tons, respectively. Average emissions of PM2.5, SO2, NOx, NH3, CH4, and CO2 due to straw burning were 367, 41, 160, 18, 165, and 70,644 tons, respectively. We also reported uncertainty from Monte Carlo model as the 5th-95th percentiles of estimated nutrient supply and gaseous pollutant. These insights will provide foundational support for the sustainable and environmentally friendly management of wheat straw in China.
Spatiotemporal dynamics of cholera epidemics in Ethiopia: 2015–2021
Authors: Moore Sandra , Worku Demlie Yeshambel , Muluneh Dereje , Dunoyer Jessica , Hussen Mukemil , Wossen Mesfin , Edosa Moti , Sudre Bertrand
Published: April 2024

Since the onset of the seventh cholera pandemic, Ethiopia has been affected by recurrent epidemics. However, the epidemiology of cholera in this country remains poorly understood. This study aimed to describe cholera outbreak characteristics in Ethiopia from 2015 to 2021. During this period, Ethiopia experienced four epidemic waves. The first wave involved nationwide outbreaks during the second half of 2016 followed by outbreaks predominantly affecting Somali Region in 2017. The second wave primarily affected Tigray and Afar Regions. During the third wave, multiple smaller-scale outbreaks occurred during 2019. The fourth wave was limited to Bale Zone (Oromia Region) in 2021. Overall, a north to south shift was observed over the course of the study period. Major cholera transmission factors included limited access to safe water and sanitation facilities. Severe weather events (drought and flooding) appear to aggravate cholera diffusion. Cholera transmission between Ethiopia and nearby countries (Kenya and Somalia), likely plays a major role in regional cholera dynamics. Overall, this study provides the first understanding of recent spatiotemporal cholera dynamics in Ethiopia to inform cholera control and elimination strategies.
Comparison of analysis methods to classify cholera hotspots in Ethiopia from 2015 to 2021
Authors: Demlie Yeshambel Worku , Moore Sandra , Dunoyer Jessica , Muluneh Dereje , Hussen Mukemil , Wossen Mesfin , Edosa Moti , Sudre Bertrand
Published: April 2024

Cholera continues to represent a major public health concern in Ethiopia. The country has developed a Multi-sectoral National Cholera Elimination Plan in 2022, which targets prevention and control interventions in cholera hotspots. Multiple methods to classify cholera hotspots have been used in several countries. Since 2014, a classification method developed by United Nations Children's Fund has been applied to guide water, sanitation and hygiene interventions throughout Sub-Saharan Africa based on three outbreak parameters: frequency, duration and standardized attack rate. In 2019, the Global Task Force on Cholera Control (GTFCC) proposed a method based on two parameters: average annual cholera incidence and persistence. In 2023, an updated GTFCC method for multisectoral interventions considers three epidemiological indicators (cumulative incidence, cumulative mortality and persistence,) and a cholera-case confirmation indicator. The current study aimed to classify cholera hotspots in Ethiopia at the woreda level (equivalent to district level) applying the three methods and comparing the results to optimize the hotspot targeting strategy. From 2015 to 2021, cholera hotspots were located along major routes between Addis Ababa and woredas adjacent to the Kenya and Somalia borders, throughout Tigray Region, around Lake Tana, and in Afar Region. The multi-method comparison enables decision makers to prioritize interventions according to a sub-classification of the highest-priority areas.
AttGRU-HMSI: enhancing heart disease diagnosis using hybrid deep learning approach
Authors: Rao G. Madhukar , Ramesh Dharavath , Sharma Vandana , Sinha Anurag , Hassan Md. Mehedi , Gandomi Amir H.
Published: April 2024

Heart disease is a major global cause of mortality and a major public health problem for a large number of individuals. A major issue raised by regular clinical data analysis is the recognition of cardiovascular illnesses, including heart attacks and coronary artery disease, even though early identification of heart disease can save many lives. Accurate forecasting and decision assistance may be achieved in an effective manner with machine learning (ML). Big Data, or the vast amounts of data generated by the health sector, may assist models used to make diagnostic choices by revealing hidden information or intricate patterns. This paper uses a hybrid deep learning algorithm to describe a large data analysis and visualization approach for heart disease detection. The proposed approach is intended for use with big data systems, such as Apache Hadoop. An extensive medical data collection is first subjected to an improved k-means clustering (IKC) method to remove outliers, and the remaining class distribution is then balanced using the synthetic minority over-sampling technique (SMOTE). The next step is to forecast the disease using a bio-inspired hybrid mutation-based swarm intelligence (HMSI) with an attention-based gated recurrent unit network (AttGRU) model after recursive feature elimination (RFE) has determined which features are most important. In our implementation, we compare four machine learning algorithms: SAE + ANN (sparse autoencoder + artificial neural network), LR (logistic regression), KNN (K-nearest neighbour), and naïve Bayes. The experiment results indicate that a 95.42% accuracy rate for the hybrid model's suggested heart disease prediction is attained, which effectively outperforms and overcomes the prescribed research gap in mentioned related work.
Cross-domain information fusion and personalized recommendation in artificial intelligence recommendation system based on mathematical matrix decomposition
Authors: Meng Xiaoyan
Published: April 2024

Given the challenges of inter-domain information fusion and data sparsity in collaborative filtering algorithms, this paper proposes a cross-domain information fusion matrix decomposition algorithm to enhance the accuracy of personalized recommendations in artificial intelligence recommendation systems. The study begins by collecting Douban movie rating data and social network information. To ensure data integrity, Levenshtein distance detection is employed to remove duplicate scores, while natural language processing technology is utilized to extract keywords and topic information from social texts. Additionally, graph convolutional networks are utilized to convert user relationships into feature vectors, and a unique thermal coding method is used to convert discrete user and movie information into binary matrices. To prevent overfitting, the Ridge regularization method is introduced to gradually optimize potential feature vectors. Weighted average and feature connection techniques are then applied to integrate features from different fields. Moreover, the paper combines the item-based collaborative filtering algorithm with merged user characteristics to generate personalized recommendation lists.In the experimental stage, the paper conducts cross-domain information fusion optimization on four mainstream mathematical matrix decomposition algorithms: alternating least squares method, non-negative matrix decomposition, singular value decomposition, and latent factor model (LFM). It compares these algorithms with the non-fused approach. The results indicate a significant improvement in score accuracy, with mean absolute error and root mean squared error reduced by 12.8% and 13.2% respectively across the four algorithms. Additionally, when k = 10, the average F1 score reaches 0.97, and the ranking accuracy coverage of the LFM algorithm increases by 54.2%. Overall, the mathematical matrix decomposition algorithm combined with cross-domain information fusion demonstrates clear advantages in accuracy, prediction performance, recommendation diversity, and ranking quality, and improves the accuracy and diversity of the recommendation system. By effectively addressing collaborative filtering challenges through the integration of diverse techniques, it significantly surpasses traditional models in recommendation accuracy and variety.
Amino acid-specific isotopes reveal changing five-dimensional niche segregation in Pacific seabirds over 50 years
Authors: van Oordt Francis , Cuba Antonio , Choy Emily S. , Elliott John E. , Elliott Kyle H.
Published: April 2024

Hutchison’s niche theory suggests that coexisting competing species occupy non-overlapping hypervolumes, which are theoretical spaces encompassing more than three dimensions, within an n-dimensional space. The analysis of multiple stable isotopes can be used to test these ideas where each isotope can be considered a dimension of niche space. These hypervolumes may change over time in response to variation in behaviour or habitat, within or among species, consequently changing the niche space itself. Here, we use isotopic values of carbon and nitrogen of ten amino acids, as well as sulphur isotopic values, to produce multi-isotope models to examine niche segregation among an assemblage of five coexisting seabird species (ancient murrelet Synthliboramphus antiquus, double-crested cormorant Phalacrocorax auritus, Leach’s storm-petrel Oceanodrama leucorhoa, rhinoceros auklet Cerorhinca monocerata, pelagic cormorant Phalacrocorax pelagicus) that inhabit coastal British Columbia. When only one or two isotope dimensions were considered, the five species overlapped considerably, but segregation increased in more dimensions, but often in complex ways. Thus, each of the five species occupied their own isotopic hypervolume (niche), but that became apparent only when factoring the increased information from sulphur and amino acid specific isotope values, rather than just relying on proxies of δ15N and δ13C alone. For cormorants, there was reduction of niche size for both species consistent with a decline in their dominant prey, Pacific herring Clupea pallasii, from 1970 to 2006. Consistent with niche theory, cormorant species showed segregation across time, with the double-crested demonstrating a marked change in diet in response to prey shifts in a higher dimensional space. In brief, incorporating multiple isotopes (sulfur, PC1 of δ15N [baselines], PC2 of δ15N [trophic position], PC1 and PC2 of δ13C) metrics allowed us to infer changes and differences in food web topology that were not apparent from classic carbon–nitrogen biplots.
A framework for design optimization across multiple concepts
Authors: Kenny Angus , Ray Tapabrata , Singh Hemant
Published: April 2024

In engineering design, there often exist multiple conceptual solutions to a given problem. Concept design and selection is the first phase of the design process that is estimated to affect up to 70% of the life cycle cost of a product. Currently, optimization methods are rarely used in this phase, since standard optimization methods inherently assume a fixed (given) concept; and undertaking a full-fledged optimization for each possible concept is untenable. In this paper, we aim to address this gap by developing a framework that searches for optimum solutions efficiently across multiple concepts, where each concept may be defined using a different number, or type, of variables (continuous, binary, discrete, categorical etc.). The proposed approach makes progressive data-driven decisions regarding which concept(s) and corresponding solution(s) should be evaluated over the course of search, so as to minimize the computational budget spent on less promising concepts, as well as ensuring that the search does not prematurely converge to a non-optimal concept. This is achieved through the use of a tree-structured Parzen estimator (TPE) based sampler in addition to Gaussian process (GP), and random forest (RF) regressors. Aside from extending the use of GP and RF to search across multiple concepts, this study highlights the previously unexplored benefits of TPE for design optimization. The performance of the approach is demonstrated using diverse case studies, including design of a cantilever beam, coronary stents, and lattice structures using a limited computational budget. We believe this contribution fills an important gap and capitalizes on the developments in the machine learning domain to support designers involved in concept-based design.
Deep learning hybridization for improved malware detection in smart Internet of Things
Authors: Almazroi Abdulwahab Ali , Ayub Nasir
Published: April 2024

The rapid expansion of AI-enabled Internet of Things (IoT) devices presents significant security challenges, impacting both privacy and organizational resources. The dynamic increase in big data generated by IoT devices poses a persistent problem, particularly in making decisions based on the continuously growing data. To address this challenge in a dynamic environment, this study introduces a specialized BERT-based Feed Forward Neural Network Framework (BEFNet) designed for IoT scenarios. In this evaluation, a novel framework with distinct modules is employed for a thorough analysis of 8 datasets, each representing a different type of malware. BEFSONet is optimized using the Spotted Hyena Optimizer (SO), highlighting its adaptability to diverse shapes of malware data. Thorough exploratory analyses and comparative evaluations underscore BEFSONet’s exceptional performance metrics, achieving 97.99% accuracy, 97.96 Matthews Correlation Coefficient, 97% F1-Score, 98.37% Area under the ROC Curve(AUC-ROC), and 95.89 Cohen’s Kappa. This research positions BEFSONet as a robust defense mechanism in the era of IoT security, offering an effective solution to evolving challenges in dynamic decision-making environments.
Hepatic extracellular ATP/adenosine dynamics in zebrafish models of alcoholic and metabolic steatotic liver disease
Authors: Tokumaru Tomoko , Apolinario Magdeline E. Carrasco , Shimizu Nobuyuki , Umeda Ryohei , Honda Koichi , Shikano Kenshiro , Teranishi Hitoshi , Hikida Takatoshi , Hanada Toshikatsu , Ohta Keisuke , Li Yulong , Murakami Kazunari , Hanada Reiko
Published: April 2024

Steatotic liver disease (SLD) is a burgeoning health problem predominantly associated with excessive alcohol consumption, which causes alcohol-related liver disease (ALD), and high caloric intake, which results in metabolic dysfunction-associated SLD (MASLD). The pathogenesis of ALD and MASLD, which can progress from steatohepatitis to more severe conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma, is complicated by several factors. Recently, extracellular ATP and adenosine (Ado), as damage-associated molecular patterns, were reported to promote inflammation and liver fibrosis, contributing to SLD pathogenesis. Here, we explored the in vivo dynamics of hepatic extracellular ATP and Ado during the progression of steatohepatitis using a genetically encoded GPCR-activation-based sensor (GRAB) in zebrafish models. We established hepatocyte-specific GRABATP and GRABAdo in zebrafish and investigated the changes in in vivo hepatic extracellular ATP and Ado levels under ALD or MASLD conditions. Disease-specific changes in hepatocyte extracellular ATP and Ado levels were observed, clearly indicating a correlation between hepatocyte extracellular ATP/Ado dynamics and disease progression. Furthermore, clodronate, a vesicular nucleotide transporter inhibitor, alleviated the MASLD phenotype by reducing the hepatic extracellular ATP and Ado content. These findings provide deep insights into extracellular ATP/Ado dynamics in disease progression, suggesting therapeutic potential for ALD and MASLD.
Mosaic crack mapping of footings by convolutional neural networks
Authors: Buatik Apichat , Thansirichaisree Phromphat , Kalpiyapun Phisutwat , Khademi Navid , Pasityothin Ittipon , Poovarodom Nakhorn
Published: April 2024

Cracks are the primary indicator informing the structural health of concrete structures. Frequent inspection is essential for maintenance, and automatic crack inspection offers a significant advantage, given its efficiency and accuracy. Previously, image-based crack detection systems have been utilized for individual images, yet these systems are not effective for large inspection areas. This paper thereby proposes an image-based crack detection system using a Deep Convolution Neural Network (DCNN) to identify cracks in mosaic images composed from UAV photos of concrete footings. UAV images are transformed into 3D footing models, from which the composite images are created. The CNN model is trained on 224 $$\times$$
×
224 pixel patches, and training samples are augmented by various image transformation techniques. The proposed method is applied to localize cracks on composite images through the sliding window technique. The proposed VGG16 CNN detection system, with 95% detection accuracy, indicates superior performance to feature-based detection systems.