bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated multi-omics investigation revealed the importance of phenylpropanoid metabolism in the defense response of Lilium regale Wilson to fusarium wilt
Authors: Deng Jie , Che Xiaoli , Gu Yue , Qu Yuan , Liu Diqiu 
Published: May 2024

Abstract
Lilies (genus Lilium) play a significant role in the global cut-flower industry, but they are highly susceptible to fusarium wilt caused by Fusarium oxysporum. However, Lilium regale, a wild lily species, exhibits remarkable resistance to F. oxysporum. To investigate the quantitative resistance of L. regale to fusarium wilt, a comprehensive multi-omics analysis was conducted. Upon inoculation with F. oxysporum, L. regale roots showed a significant accumulation of phenylpropane metabolites, including lignin precursors, flavonoids, and hydroxycinnamic acids. These findings were consistent with the upregulated expression of phenylpropanoid biosynthesis-related genes encoding various enzymes, as revealed by transcriptomics and proteomics analyses. Furthermore, metabolomics and proteomics data demonstrated differential activation of monoterpenoid and isoquinoline alkaloid biosynthesis. Colorimetry and high-performance liquid chromatography analyses revealed significantly higher levels of total flavonoids, lignin, ferulic acid, phlorizin, and quercetin contents in L. regale scales compared with susceptible lily ‘Siberia’ scales during F. oxysporum infection. These phenylpropanes exhibited inhibitory effects on F. oxysporum growth and suppressed the expression of pathogenicity-related genes. Transcriptional regulatory network analysis suggested that ethylene-responsive transcription factors (ERFs) may positively regulate phenylpropanoid biosynthesis. Therefore, LrERF4 was cloned and transiently overexpressed in the fusarium wilt-susceptible Oriental hybrid lily ‘Siberia’. The overexpression of LrERF4 resulted in increased levels of total flavonoids, lignin, ferulic acid, phlorizin, and quercetin, while the silencing of LrERF4 in L. regale through RNAi had the opposite effect. In conclusion, phenylpropanoid metabolism plays a crucial role in the defense response of L. regale against fusarium wilt, with LrERF4 acting as a positive regulator of phenylpropane biosynthesis.
Short-Term Use of Upadacitinib in Combination With Biologic Therapy for Inducing Clinical Remission in Patients With Active Inflammatory Bowel Disease
Authors: Yin Jianyi , El-Najjar Yassin , Cordova Noelle , Touma Mary-Joe , Nguyen Noelle , Boktor Moheb , Burstein Ezra , Fudman David I 
Published: May 2024

Lay Summary
We report that upadacitinib intended for short-term use in combination with biologic therapy appeared to be effective in inducing steroid-free clinical remission in patients with active inflammatory bowel disease, but a substantial proportion of patients required extended use.
A Mitochondrial Perspective on the Demands of Reproduction
Authors: Hood Wendy R 
Published: May 2024

Synopsis
The cost of supporting traits that increase mating opportunities and maximize the production of quality offspring is paid in energy. This currency of reproduction is enabled by bioenergetic adaptations that underlie the flexible changes in energy utilization that occur with reproduction. This review considers the traits that contribute to variation in the capacity of an organ to produce ATP. Further, it synthesizes findings from studies that have evaluated bioenergetic adaptations to the production of sexually selected traits and performance during reproduction and the role of change in mitochondrial respiratory performance in the tradeoff between reproduction and longevity. Cumulatively, these works provide evidence that in selecting for redder males, female finches will likely mate with a male with high mitochondrial respiratory performance and, potentially, a higher probability of mitonuclear compatibility. Females from diverse taxa allocate more to reproduction when the respiratory performance of mitochondria or density of the inner mitochondrial membrane in the liver or skeletal muscle is higher. Finally, reproduction does not appear to have persistent negative effects on mitochondrial respiratory performance, countering a role for mitochondria in the trade-off between reproduction and longevity. I close by noting that adaptations that improve mitochondrial respiratory performance appear vital for optimizing reproductive fitness.
Symbiotic bacteria and fungi proliferate in diapause and may enhance overwintering survival in a solitary bee
Authors: Christensen Shawn M , Srinivas Sriram N , McFrederick Quinn S , Danforth Bryan N , Buchmann Stephen L , Vannette Rachel L 
Published: May 2024

Abstract
Host–microbe interactions underlie the development and fitness of many macroorganisms, including bees. Whereas many social bees benefit from vertically transmitted gut bacteria, current data suggests that solitary bees, which comprise the vast majority of species diversity within bees, lack a highly specialized gut microbiome. Here, we examine the composition and abundance of bacteria and fungi throughout the complete life cycle of the ground-nesting solitary bee Anthophora bomboides standfordiana. In contrast to expectations, immature bee stages maintain a distinct core microbiome consisting of Actinobacterial genera (Streptomyces, Nocardiodes) and the fungus Moniliella spathulata. Dormant (diapausing) larval bees hosted the most abundant and distinctive bacteria and fungi, attaining 33 and 52 times their initial copy number, respectively. We tested two adaptive hypotheses regarding microbial functions for diapausing bees. First, using isolated bacteria and fungi, we found that Streptomyces from brood cells inhibited the growth of multiple pathogenic filamentous fungi, suggesting a role in pathogen protection during overwintering, when bees face high pathogen pressure. Second, sugar alcohol composition changed in tandem with major changes in fungal abundance, suggesting links with bee cold tolerance or overwintering biology. We find that A. bomboides hosts a conserved core microbiome that may provide key fitness advantages through larval development and diapause, which raises the question of how this microbiome is maintained and faithfully transmitted between generations. Our results suggest that focus on microbiomes of mature or active insect developmental stages may overlook stage-specific symbionts and microbial fitness contributions during host dormancy.
Strengthening the use of artificial intelligence within healthcare delivery organizations: balancing regulatory compliance and patient safety
Authors: Sendak Mark P , Liu Vincent X , Beecy Ashley , Vidal David E , Shaw Keo , Lifson Mark A , Tobey Danny , Valladares Alexandra , Loufek Brenna , Mogri Murtaza , Balu Suresh 
Published: May 2024

Abstract

Objectives
Surface the urgent dilemma that healthcare delivery organizations (HDOs) face navigating the US Food and Drug Administration (FDA) final guidance on the use of clinical decision support (CDS) software.

Materials and Methods
We use sepsis as a case study to highlight the patient safety and regulatory compliance tradeoffs that 6129 hospitals in the United States must navigate.

Results
Sepsis CDS remains in broad, routine use. There is no commercially available sepsis CDS system that is FDA cleared as a medical device. There is no public disclosure of an HDO turning off sepsis CDS due to regulatory compliance concerns. And there is no public disclosure of FDA enforcement action against an HDO for using sepsis CDS that is not cleared as a medical device.

Discussion and Conclusion
We present multiple policy interventions that would relieve the current tension to enable HDOs to utilize artificial intelligence to improve patient care while also addressing FDA concerns about product safety, efficacy, and equity.
Fatally impaired glucose digestion by propylene glycol in Aedes aegypti (Diptera: Culicidae) and co-formulation with terpenoids for enhancing attractive toxic sugar baits
Authors: Maes Gavin , Tintorri Giulia , Nelson Irvane E , Baker Kobi A , Seavey Corey E , Rehbein Michele M , White Gregory S , Faraji Ary , Willenberg Bradley J , Bibbs Christopher S 
Published: May 2024

Abstract
Propylene glycol (PG) demonstrates greater efficacy than other sugar polyols. However, the attributes it confers for toxicity and possible co-formulation with other ingredients are unknown. To evaluate this, α-glucosidase and glucose oxidase reactions were performed in Aedes aegypti (L.) (Diptera: Culicidae) to categorize if PG behaves similarly to prior studied sugar alcohols. A combination of no-choice and choice assays was used to determine effective ratios of PG and sucrose, competitiveness against a control of 10% sucrose, and whether mosquitoes recovered from PG consumption. The final trials included β-cyclodextrin encapsulated cinnamon leaf oil, clove stem oil, patchouli oil, garlic oil, cedarwood oil, and papaya seed oil formulated with 5% sucrose + 5% PG. PG functioned as a linear competitive inhibitor of α-glucosidase. The efficacy of PG was synergized by co-ingestion with equivalent ratios of sucrose. Unlike the high diuretic response to other sugar alcohols, PG resulted in diminished excretion regardless of being co-formulated with sucrose or terpenoids. PG is not especially competitive against unadulterated sugar meals but is likewise not clearly repellent. Although mosquitoes did not recover from ingestion of the glycol meals, there was no indication that mortality would continue to accumulate once the treatments were removed. Of the terpenoids tested, cinnamon and patchouli caused ~50% or less mortality; garlic, cedarwood, and clove caused 80-90% mortality; and papaya seed caused 100% mortality, exceeding all other test groups and the formulation blank. PG is a useful supporting ingredient in attractive toxic sugar bait formulations with flexibility in formulation.
GL-V9 synergizes with oxaliplatin of colorectal cancer via Wee1 degradation mediated by HSP90 inhibition
Authors: Chen Hongyu , Yang Fan , Zhao Qianying , Wang Hongzheng , Zhu Mengyuan , Li Hui , Ge Zheng , Zhang Shuai , Guo Qinglong , Hui Hui 
Published: May 2024

Abstract

Objectives
GL-V9 exhibited anti-tumour effects on various types of tumours. This study aimed to verify if GL-V9 synergized with oxaliplatin in suppressing colorectal cancer (CRC) and to explore the synergistic mechanism.

Methods
The synergy effect was tested by MTT assays and the mechanism was examined by comet assay, western blotting and immunohistochemistry (IHC). Xenograft model was constructed to substantiated the synergy effect and its mechanism in vivo.

Results
GL-V9 was verified to enhance the DNA damage effect of oxaliplatin, so as to synergistically suppress colon cancer cells in vitro and in vivo. In HCT-116 cells, GL-V9 accelerated the degradation of Wee1 and induced the abrogation of cell cycle arrest and mis-entry into mitosis, bypassing the DNA damage response caused by oxaliplatin. Our findings suggested that GL-V9 binding to HSP90 was responsible for the degradation of Wee1 and the vulnerability of colon cancer cells to oxaliplatin. Functionally, overexpression of either HSP90 or WEE1 annulled the synergistic effect of GL-V9 and oxaliplatin.

Conclusions
Collectively, our findings revealed that GL-V9 synergized with oxaliplatin to suppress CRC and displayed a promising strategy to improve the efficacy of oxaliplatin.
Lights, location, action: shade avoidance signalling over spatial scales
Authors: Gautrat Pierre , Matton Sanne E A , Oskam Lisa , Shetty Siddhant S , van der Velde Kyra J , Pierik Ronald 
Published: May 2024

Abstract
Plants growing in dense vegetation need to flexibly position their photosynthetic organs to ensure optimal light capture in a competitive environment. They do so through a suite of developmental responses referred to as the shade avoidance syndrome. Below ground, root development is also adjusted in response to above-ground neighbour proximity. Canopies are dynamic and complex environments with heterogeneous light cues in the far-red, red, blue, and UV spectrum, which can be perceived by photoreceptors in spatially separated plant tissues. Molecular regulation of plant architecture adjustment via PHYTOCHROME-INTERACTING FACTOR transcription factors and growth-related hormones such as auxin, gibberellic acid, brassinosteroids, and abscisic acid were historically studied without much attention to spatial or tissue-specific context. Recent developments and technologies have, however, sparked strong interest in spatially explicit understanding of shade avoidance regulation. Other environmental factors such as temperature and nutrient availability interact with the molecular shade avoidance regulation network, often depending on the spatial location of the signals, and the responding organs. Here, we review recent advances in how plants respond to heterogeneous light cues and integrate these with other environmental signals.
HCN as a probe of the inner disc in a candidate proto-brown dwarf
Authors: Riaz B , Thi W -F , Machida M N 
Published: May 2024

ABSTRACT
The detection of Keplerian rotation is rare among Class 0 protostellar systems. We have investigated the high-density tracer HCN as a probe of the inner disc in a Class 0 proto-brown dwarf candidate. Our ALMA high angular resolution observations show the peak in the HCN (3–2) line emission arises from a compact component near the proto-brown dwarf with a small bar-like structure and a deconvolved size of ∼50 au. Radiative transfer modelling indicates that this HCN feature is tracing the innermost, dense regions in the proto-brown dwarf where a small Keplerian disc is expected to be present. The limited velocity resolution of the observations, however, makes it difficult to confirm the rotational kinematics of this feature. A brightening in the HCN emission towards the core centre suggests that HCN can survive in the gas phase in the inner, dense regions of the proto-brown dwarf. In contrast, modelling of the HCO+ (3–2) line emission indicates that it originates from the outer pseudo-disc/envelope region and is centrally depleted. HCN line emission can reveal the small-scale structures and can be an efficient observational tool to study the inner disc properties in such faint compact objects where spatially resolving the disc is nearly impossible.
Speed, Spectrum, and Satisfaction: Assessment of an Infectious Diseases eConsult Program
Authors: Hofmann Justin , Coe Kelci , Young Jeremy D 
Published: May 2024

Abstract
This report examines the implementation and early functioning of a new infectious diseases (ID) eConsult program. We recorded the reasons for placing ID eConsults, time to eConsult completion, in-person clinic wait times, and referring provider satisfaction following implementation of our outpatient eConsult program. Our data suggest that this ambulatory eConsult program led to improved access to ID subspecialty care, both via eConsults directly, and by reducing clinic wait times for patients who required an in-person evaluation.
Estimating scenarios for survival time in patients with advanced melanoma receiving immunotherapy and targeted therapy
Authors: Smith-Uffen Megan , Park John , Parsonson Andrew , Kiely Belinda E , Vasista Anuradha 
Published: May 2024

Abstract

Background
We aim to provide survival scenario estimates for patients with advanced melanoma starting targeted therapies and immunotherapies.

Materials and Methods
We sought randomized trials of targeted therapies and immunotherapies for advanced melanoma and recorded the following percentiles (represented survival scenario) from each overall survival (OS) curve: 90th (worst-case), 75th (lower-typical), 50th (median), 25th (upper-typical), and 10th (best-case). We tested whether these scenarios can be estimated for each OS curve by multiplying its median by 4 multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case).

Results
We identified 15 trials with 8025 patients. For first-line combination targeted therapy treatment groups, the median (interquartile range, IQR) in months for each percentile was: 90th, 6.2 (6.0-6.5); 75th, 11.3 (11.3-11.4); and median, 24.4 (23.5-25.3). For the first-line combination immunotherapy treatment group, the percentiles in months were: 90th, 3.9 (2.8-4.5); 75th, 13.4 (10.1-15.4), median 73 (not applicable). In targeted therapy groups, simple multiples of the median OS were accurate for estimating the 90th percentile in 80%; 75th percentile in 40%; 25th percentile in 100%. In immunotherapy groups, these multiples were accurate at 0% for the 90th percentile, and 43% for the 75th percentile. The 90th percentile (worst-case scenario) was better estimated as 1/6× median OS, and the 75th percentile (lower-typical) as 1/3× median OS.

Conclusions
Simple multiples of the median OS are a useful framework to estimate scenarios for survival for patients receiving targeted therapies, not immunotherapy. Longer follow-up is required to estimate upper-typical and best-case scenarios.
Optimizing abemaciclib-induced diarrhea management in patients with breast cancer: a pragmatic 2-group study using a postbiotic microbiota stabilizer
Authors: De Sanctis Rita , Tiberio Paola , Jacobs Flavia , Gaudio Mariangela , Benvenuti Chiara , Giordano Laura , Torrisi Rosalba , Zambelli Alberto , Pozzi Chiara , Penna Giuseppe , Santoro Armando , Rescigno Maria 
Published: May 2024

Abstract

Background
Abemaciclib-induced diarrhea is a relevant concern in clinical practice. Postbiotics have emerged as a promising option for managing it.

Materials and Methods
We conducted a retrospective-prospective, 2-group, observational study to assess the impact of the postbiotic PostbiotiX-Restore, derived by Lactobacillus paracasei CNCM I-5220, on abemaciclib-induced diarrhea in patients with hormone receptor-positive HER2-negative breast cancer. The prospective population (Postbio group) received postbiotic during the first cycle of abemaciclib, while the retrospective one received standard care (Standard group). Diarrhea grading was defined according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events.

Results
During the first cycle, diarrhea occurred in 78.9% of patients in the Standard cohort and 97.1% in the Postbio one, with most cases being G1-G2. Severe (G3) diarrhea was significantly less frequent in the Postbio group (0%) compared to the Standard one (7.9%; P = .029). Over the entire study period, while the grading difference was not statistically significant, G3 events were less frequent in the Postbio population (5.9%) than the Standard one (15.4%). Moreover, Postbio patients required fewer dose reductions due to diarrhea compared to the Standard group (P = .002). Notably, in the Postbio population, G1 and G2 events had short median durations (3 and 1 days, respectively) and, for the 2 patients experiencing G3 events during the second abemaciclib cycle (off postbiotic), diarrhea lasted only 1 day.

Conclusions
Our study demonstrates the effect of PostbiotiX-Restore in mitigating abemaciclib-induced diarrhea, resulting in reduced severity, fewer dose reductions, and shorter duration. Further exploration and validation in larger cohorts are needed.
Foucault’s Emancipatory Contributions to Method, and Why We Still Need Ideology Critique
Authors: Wedeen Lisa 
Published: May 2024

Abstract
This chapter explores the merits and limitations of Foucauldian discourse analysis. It discusses how Michel Foucault’s view in particular is informed by his philosophical insights about modern power, resulting in a genealogical method that opens up emancipatory possibilities for politics. Foucault teaches us how to take language and issues of subjectivity seriously without miring analysis in unanswerable questions about individual intention. His method provides a way to chart historical changes without overstating causal claims. And by accounting for the embodied disciplinary workings of power, it trains our focus on observable mechanisms suitable for grounding empirical arguments. Attuned also to the limitations of Foucauldian discourse analysis, this chapter concludes by bringing to bear insights drawn from ideology critique as understood in cultural Marxism, as well as from feminist and queer approaches to affect theory. The chapter makes a case for understanding ideology not simply in terms of content but also of form, and it shows how to put the resulting conceptualization to practical use in ethnographic research. The overall orientation helps theorize how discourse operates as a material force, clarifying issues of political belief, the temporalities of political affect, the role of incoherence in politics, and how ambivalence matters.
Theory and Possibilities in Social Network Analysis
Authors: Heaney Michael T. 
Published: May 2024

Abstract
As social network analysis has grown in use over the past quarter century, it has become a staple in the disciplinary toolkit of political science. While political scientists have been at the forefront of innovating network methodologies, these developments have outstripped advances in political network theory. This chapter makes the case for greater attention to political network theory. It points to four promising areas for investigation. First, it advocates greater theorization of the strength of political ties that moves beyond the weak ties/strong ties dichotomy. Second, it identifies opportunities for theorizing types of ties to expand understandings of multiplex networks, such as by modeling their isomorphic structures. Third, it endorses the extension of multimodal models to incorporate the number of types of actors beyond the traditional bipartite structure. Fourth, it proposes blending theories of temporal network dynamics (e.g., preferential attachment, triadic closure, balance, homophily, reciprocity, decay) with extant theories of political time related to path dependence and sequences. Finally, it considers possibilities for traversing these areas of advance using an illustration from the study of political brokerage.