bluuebunny/crossref_metadata_2025 huggingface dataset:
A Role for Leucine-Rich α2-Glycoprotein in Leukocyte Trafficking and Mucosal Inflammation in Inflammatory Bowel Disease
Authors: Mishima Takashi , Fujimoto Minoru , Urushima Hayato , Funajima Eiji , Suzuki Yuji , Ohkawara Tomoharu , Murata Okinori , Serada Satoshi , Naka Tetsuji
Published: January 2025

Background

Leucine-rich α2-glycoprotein (LRG) has been identified as a disease activity marker that reflects pathology of inflammatory diseases including inflammatory bowel disease (IBD). Whereas LRG was reported to modulate transforming growth factor beta-1 (TGF-β) signaling, the role of LRG in inflammatory diseases has not been fully clarified. Here we investigated the role of LRG in IBD.

Methods

First, we investigated the difference of pathologies between wild-type (WT) mice and LRG-deficient (LRG−/−) mice in dextran sodium sulfate (DSS)-induced experimental colitis. Next, we analyzed the role of LRG in colonic inflammation by using in vitro assay.

Results

Prompt LRG upregulation was detected on the colonic epithelial cells on day 1 post 3% DSS treatment. Body weight loss after DSS treatment was significantly less severe in LRG−/− mice than in WT mice. Histological examination disclosed that leukocyte infiltration in colonic tissue was attenuated in LRG−/− mice compared with WT mice on day 3. Interestingly, the expression of endoglin, one of adhesion molecules in vascular endothelial cells, was markedly elevated in WT mice on day 1 post-DSS treatment, but was not in LRG−/− mice. Anti-TGF-β antibody treatment in mice with DSS colitis revealed that TGF-β is critical for endoglin upregulation in endothelial cells. Importantly, recombinant LRG when added to the culture media enhanced TGF-β1-induced endoglin expression in endothelial cells and increased adherence of monocytes to endothelial cells.

Conclusions

Our data suggest that LRG accelerates the progression of colonic inflammation at least in part by enhancing leukocyte trafficking through the upregulation of TGF-β1-induced endoglin expression in vascular endothelial cells.
More or the same? Radical, disruptive, discontinuous, and breakthrough innovation
Authors: Verhoeven Dennis , Kovacs Adrian , Marullo Cristina , Di Minin Alberto , Van Looy Bart
Published: January 2025

This paper addresses the conceptual ambiguity in the literature on exceptional innovations, labeled “radical,” “disruptive,” “breakthrough,” or “discontinuous.” A bibliometric analysis of 4407 articles shows that different labels are used by papers with shared theoretical foundations and thematic orientation. An in-depth analysis of 60 seminal contributions shows that definitions are (I) not always provided, (II) inconsistent within labels, and (III) not distinctive across labels. This complicates the exploration of the literature and the comparison of results. Definitions, when provided, agree on the existence of two underlying dimensions—novelty and impact—but disagree on how the labels relate to these dimensions. To advance conceptual clarity, we propose a typology of innovation trajectories that treats novelty and impact as distinct concepts and clarifies how and when novelty relates to impact.
It’s about time: moving away from statistical analysis of ecotoxicity data
Authors: Jager Tjalling
Published: January 2025

Environmental risk assessment (ERA) of chemicals relies on single-species laboratory testing to establish the toxic properties of a compound. However, ERA is not concerned with toxicity under laboratory conditions: it needs to assess the impacts of the compound in the real world. Data-driven statistical analyses (e.g., hypothesis testing and interpolation) are the common approaches for analyzing toxicity data, but such approaches are the wrong tool for the job at hand. Environmental risk assessment does not need a statistical description of the effects in the toxicity test (at the end of the standardized test duration); it needs to extrapolate from the laboratory test to longer and time-varying exposure. Such extrapolation requires mechanistic process models, providing a simplified representation of the mechanisms underlying toxicity. Any useful model for the toxicity process should explicitly consider both dose (e.g., exposure concentration) and time. In the history of effects analysis for ERA, the factor of time does not get as much attention as the dose, hence the common use of the term “dose-response analysis.” However, this is a historical oversight: time is a crucial factor for understanding toxicity and thereby essential for meaningful extrapolation from laboratory to field. Mechanistic models for ecotoxicity, considering both dose and time, have been around for quite some time and are classified as toxicokinetic-toxicodynamic (TKTD) models. Toxicokinetic-toxicodynamic models are starting to find their way into pesticide ERA in Europe next to the classical statistical approaches. In this opinion paper, I argue that it is about time to leave statistical analysis of toxicity data behind us. Statistics remains important for ERA effects assessment, but its role lies in the definition of appropriate “error models,” explaining the deviations between model output and observations, which is essential for parameter estimation, uncertainty quantification, and error propagation. The “process model,” essential for extrapolation, firmly belongs to TKTD modeling.
Using space technology approach to improve quality in emergency departments in India: a quality improvement program
Authors: Kumar Saravana , Vikneswaran G , Suryavamshi Jitendra , Kumar Srinath , Shaik Manzoor , Reshma GK , Suresh MR , Sigamani Alben , Shanmuganandan VC , Thomas Alexander , Venkatesh AN , Subhan Imron , Rajadurai M , Kailasam Sateesh Kumar , Nivetha B , Shameem KU , Sangtam TSarangpi
Published: January 2025

Introduction

Human errors are a leading cause of disability and death among hospitalized patients. Globally, various strategies have been employed to reduce errors and to improve the quality of patient care. One such novel effort never attempted before is the Health-QUEST (Quality Upgradation Enabled by Space Technology) initiative which aims at translating the best quality and safety practices of the Indian Space Research Organization (ISRO) into the realm of emergency care. The objective of this quality improvement initiative was to understand the performance of ED across India using key performance indicators (KPI) specified in HQ (Health Quest) document, adoptability of HQ based practices in hospitals and their effect on KPI.

Methods

A pre- and post-intervention study design was used where each hospital served as its own control. Preintervention phase captured the time-based key performance indicators based on their existing practice, followed by implementation and training on QUEST recommendations and the post intervention phase assessed any improvement in the KPIs.

Data was collected in real-time using REDCap mobile application by scanning the patient wrist bands. The time based KPIs include Door to triage time, Door to doctor time, Door to needle time, Door to pain assessment time, Door to ordering of investigation time, Time from ordering to first review of investigation, Door to discharge/disposition time.

Results

Seventeen hospitals were invited to participate in this quality improvement initiative, with 14 hospitals completing pilot training for real time data collection. Among them, 10 hospitals participated in the pre and post intervention data collection contributing to 10,332 patients (5296 patients during the pre-intervention and 5036 during the post intervention phase). All the hospitals had a median triage time of less than 5 minutes. Nine out of the ten hospitals recorded a baseline median discharge time of around 2 hours.

The most significant reductions in time (mean difference between pre- and post-intervention) were observed in triage time (11 minutes, p < 0.05), door-to-pain assessment time (23 minutes, p < 0.05), time from ordering to first review of investigation (26 hours, p < 0.05), and disposition time (1 hour and 30 minutes, p < 0.05)

Conclusion

This study evaluated real-time, time-based KPIs in patient management across emergency departments in India. The Health-QUEST program proved to be a straightforward and effective model, achieving significant improvements in multiple time-based KPIs across participating EDs.
Population structure varies among 4 western North American bumble bee species
Authors: Sakulich Elizabeth M , Koch Jonathan B Uhuad , Strange James P
Published: January 2025

Bumble bees (Hymenoptera: Apidae, Bombus Latreille, 1802) are critical pollinators—providing the necessary ecological services for food and crop production. In western North America, species-rich bumble bee communities inhabit mountain ranges. However, as climate change increases temperatures, montane populations are restricted to higher elevations, and their ability to disperse and maintain genetic diversity decreases as suitable habitat connecting populations decreases. This genetic isolation could lead to the extirpation of local pollinator populations and a loss of genetic diversity for pollinator species. We analyzed the genetic diversity of 4 broadly sympatric species of bumble bees with differing elevational niches—Bombus flavifrons, B. melanopygus, B. mixtus, and B. sylvicola—across the Rocky and Cascade Mountains of western North America to assess range-wide population genetic structure. We used microsatellite markers to assess genetic differentiation among populations (FST) and performed Bayesian clustering analyses to identify genetic groups within each study species. Further, we investigated if observed genetic differentiation within study species was better explained by isolation by distance (IBD) or isolation by resistance (IBR) by incorporating habitat suitability models (HSMs) into population structure analyses. Although we expected range-wide genetic differentiation for species with more narrow niche requirements, we found evidence of this differentiation for all 4 study species, with western populations experiencing significant genetic structure relative to inland populations. Additionally, IBR predicted genetic structure better than IBD for B. flavifrons and B. mixtus. Our results suggest that considering habitat connectivity across the geographic range of montane bumble bee species is important for understanding their population structures.
Oral switch antibiotic therapy in uncomplicated Enterococcus faecalis bloodstream infection
Authors: Al Mansi Sarah , Pokalsky Margaret , Turnley Katherine , Freeman Andrew , Bookstaver P Brandon , Kohn Joseph , Winders Hana R , Withers Sarah , Al-Hasan Majdi N
Published: January 2025

Background

The role of oral switch antibiotic therapy in uncomplicated Enterococcus faecalis bloodstream infection (BSI) remains unclear. This retrospective cohort study examines the effectiveness of oral switch compared with standard intravenous antibiotic therapy in uncomplicated E. faecalis BSI.

Methods

Adults with first episodes of uncomplicated monomicrobial E. faecalis BSI were admitted to 10 Prisma Health hospitals in South Carolina from January 2021 to June 2023 were included. Deaths within 7 days were excluded to mitigate immortal time bias. Multivariate Cox proportional hazards regression examined the risk of treatment failure (all-cause mortality or recurrence) within 90 days after adjustment for the propensity of transitioning to oral switch therapy.

Results

Of 476 screened patients, 131 with uncomplicated E. faecalis BSI were included in the analysis. The median age was 70 years, 84 (64%) were men, and 46 (35%) had a urinary source of infection. Eighty-seven patients (66%) received standard intravenous therapy and 44 (34%) were transitioned to oral switch therapy. Aminopenicillins were the most commonly used antibiotics for oral switch therapy (33/44; 75%). There was no increased risk of treatment failure with oral switch therapy compared with standard intravenous therapy (hazard ratio 0.77, 95% CIs 0.23–2.57, P = 0.67). Hospital length of stay (HLOS) was 7 and 11 days in the oral switch and standard intravenous groups, respectively (P < 0.001).

Conclusions

Transitioning patients with uncomplicated E. faecalis BSI from intravenous to oral switch antibiotic therapy appears to be a promising strategy with shorter HLOS and no significant increase in the risk of treatment failure.
Antibiotic resistance in the Middle East and Southern Asia: a systematic review and meta-analysis
Authors: Mathu Rachel , Diago-Navarro Elizabeth , Lynch Emily , Degail Marie-Amélie , Ousley Janet , Kanapathipillai Rupa , Michel Justine , Gastellu-Etchegorry Marc , Malou Nada
Published: January 2025

Introduction

Despite global surveillance efforts, antibiotic resistance (ABR) is difficult to address in low- and middle-income countries (LMICs). In the absence of country-wide ABR surveillance data, peer-reviewed literature is the next most significant source of publicly available ABR data. Médecins Sans Frontières conducted this review in hopes of using the pooled findings to inform treatment choices in the studied countries where sufficient local ABR data are unavailable.

Methods

A systematic literature review reporting ABR rates for six infection sites in nine countries in the Middle East and Southern Asia was conducted. PubMed was used to identify literature published between January 2012 and August 2022. A meta-analysis of the included studies (n = 694) was conducted, of which 224 are reviewed in this paper. The JBI critical appraisal tool was used to evaluate risk of bias for included studies.

Results

This paper focuses on sepsis, burns and wound infections, specifically, with the largest number of papers describing data from Iran, Türkiye and Pakistan. High (>30%) resistance to recommended first-line antibiotics was found. Gram-negative resistance to ceftriaxone, aminoglycosides and carbapenems was high in burn-related infections; colistin resistance among Klebsiella pneumoniae isolates in Pakistan was alarmingly high (81%).

Conclusions

High-quality data on ABR in LMIC settings remain difficult to obtain. While peer-reviewed literature is a source of publicly available ABR data, it is of inconsistent quality; the field also lacks agreed reporting standards, limiting the capacity to pool findings. Nonetheless, high resistance to first-line antibiotics underscores the need for improved localized surveillance and stewardship.
A meta-analysis of genome-wide association studies to identify candidate genes associated with feed efficiency traits in pigs
Authors: Silva Maria Rita Gonçalves da , Veroneze Renata , Marques Daniele B D , Silva Delvan A da , Machado Inaê I , Brito Luiz F , Lopes Paulo S
Published: January 2025

Pig production is an agricultural sector of great economic and social relevance to Brazil and global markets. Feed efficiency traits directly influence the sustainability of pig production due to the economic impact of feed costs on the production system and the environmental footprint of the industry. Therefore, breeding for improved feed efficiency has been a target of worldwide pig breeding programs. Genome-wide association studies (GWAS) enable the assessment of the genetic background of complex traits, which contributes to a better understanding of the biological mechanisms regulating their phenotypic expression. In this context, the primary objective of this study was to identify and validate genomic regions and candidate genes associated with feed conversion ratio (FCR) and residual feed intake (RFI) in pigs based on a comprehensive systematic review and meta-analysis of GWAS. The METAL software was used to implement the meta-analysis and the Bonferroni multiple testing correction considering a significance threshold 0.05. The significant single nucleotide polymorphisms (SNPs) in the meta-analysis were used to identify candidate genes, followed by a functional genomic enrichment analysis. The systematic review identified 13 studies, of which 7 evaluated FCR, 3 evaluated RFI, and 3 studies investigated both traits, with 160 and 96 SNPs identified for FCR and RFI, respectively. After the meta-analysis, 145 markers were significantly associated with FCR and 90 with RFI. The gene annotation process resulted in 105 and 114 genes for FCR and RFI, respectively. The enrichment analysis for FCR resulted in 16 significant gene ontology (GO) terms, while 6 terms were identified for RFI. The main GO terms were actin cytoskeleton (GO_BP:0030036), membrane (GO_CC:0016020), integral components of the peroxisomal membrane (GO_CC:0005779), and carbohydrate-binding (GO_MF:0030246). The main candidate genes identified were MED18, PHACTR4, ABCC2, TRHDE, FRS2, FAR2 and FIS1 for FCR, and ADGRL2, ASGR1, ASGR2, and MAN2B1 for RFI. These findings contribute to a better understanding of the genetic mechanisms associated with feed efficiency traits in pigs, providing a foundation for future improvements in pig breeding programs.
A novel fractional order partial grey model for forecasting short-term traffic flow
Authors: Wang Qiong , Li Chenghang , Zhan Guoping , Zhu Wei
Published: January 2025

Short-term traffic flow forecasting is an integral part of intelligent transportation systems, and a key foundation for traffic departments and travelers to obtain reliable traffic information. This paper constructs a fractional order partial grey model with a sine function control matrix by combining a partial differential equation. The model is capable of predicting short-term traffic flow with spatiotemporal and oscillatory characteristics. In the new model, the introduction of a fractional order accumulation operator may help reduce random fluctuations in data and enhance the flexibility of the model. Moreover, the model dynamically adjusts its parameters using a sine function control matrix, allowing it to better adapt to data with different oscillation types, thereby improving the versatility of the model. Additionally, the characteristic curve method is used to provide the time response function of the model, and the particle swarm optimization algorithm is employed to optimize the model parameters. To demonstrate the validation of the new model, two different road segments from two different highways were selected as research objects. Compared with two other partial grey models and two other algorithm models, the new model has the highest accuracy in simulation and prediction. Furthermore, this new model is applied to the simulation and prediction of the short-term traffic flow, and the results show that the simulated and predicted data have great similarity with the real data trend, which exhibits good reliability and applicability in solving the short-time traffic flow prediction problem.
ODE-DSN: A surrogate model for dynamic stiffness in microscopic RVE problems under nonuniform time-step strain inputs
Authors: Xie Kai , Huo Yongqing , Li Zhongxin , Wu Zhilin
Published: January 2025

In multiscale finite-element methods, solving macroscopic problems typically requires addressing computationally expensive microscopic representative volume element (RVE) problems. To reduce this computational burden, a data-driven approach using artificial neural networks has been employed to pretrain the strain–stress relationship of the microscopic RVE, bypassing the need for full microscale calculations. Existing research has also explored the use of recurrent neural networks to handle history-dependent materials. Building on this approach, this paper introduces a novel ordinary differential equation-dynamic stiffness network model to capture the dynamic stiffness of time-dependent materials and compute stress. The stiffness-based framework enhances the model’s physical consistency and interpretability, while the ordinary differential equation neural network effectively manages nonuniform time sampling in strain inputs. Examples demonstrate that the model accurately learns material behavior with limited data (around 560 random strain–stress sequences) and effectively handles nonuniform time steps. This method addresses the challenge of handling strain inputs with nonuniform time steps while offering potential advantages in computational efficiency and resource utilization.
Understanding screenshot collection and sharing on messaging platforms: a privacy perspective
Authors: Ingber Alexis Shore
Published: January 2025

Individuals rely on messaging platforms to form and maintain intimate relationships, trusting shared information will remain within intended digital confines. However, the screenshot feature allows people to capture and store pieces of private conversations as a separate file on their device, rendering them shareable with third parties. While usage of this feature can be benign, this study focuses on its ability to breach privacy expectations within messaging platforms, termed within communication privacy management theory as privacy turbulence. This study recognizes the power of both interpersonal dynamics and platform affordances in constraining existing norms around screenshot collection and sharing others’ private messages. Experimental results (n = 302) suggest obscuring received messages upon use of the screenshot feature and stating an explicit privacy rule significantly reduce screenshot collection and sharing, respectively. Implications for communication theory and the future of messaging platform design will be discussed.
Bit by bit: colocation and the death of distance in software developer networks
Authors: Goldbeck Moritz
Published: January 2025

Digital work environments potentially facilitate remote collaboration, thereby decreasing geographic friction in knowledge work. I examine spatial collaboration of 190,637 software developers in the USA on the largest coding platform, GitHub. Using a gravity framework that accounts for cluster size, I find that colocated developers collaborate about nine times more frequently than non-colocated developers. This colocation effect is about two to four times smaller than in less digital settings in inventor or social networks. Increased distance beyond colocation has little impact on collaboration. Heterogeneity analyses demonstrate the colocation effect is smaller within large organizations, among experienced developers, and for sporadic interactions. Results suggest geographic proximity is less important for collaboration in digital knowledge work.
The political effects of (mis)perceived immigration
Authors: Barilari Francesco , Bellucci Davide , Conzo Pierluigi , Zotti Roberto
Published: January 2025

Several studies document that exposure to actual immigration affects political outcomes. This article examines, instead, the influence of expected immigration, using data from local elections in Italy. We develop an index of potential exposure to pre-electoral sea arrivals, which varies over time and space depending on immigrants’ nationality. We find that such potential exposure causes a decrease in turnout and an increase in protest votes, shifting valid votes toward extreme-right parties. Support for populist and anti-immigration parties increased in highly exposed municipalities, where voters believed that the new inflow of refugees would increase the local stock of immigrants. However, Twitter data show that these expectations do not reflect actual immigration trends; immigration salience rises mainly during the election period, while most arrivals occur months later. This suggests that, around elections, informal media can bias people’s expectations and, consequently, influence voting behavior.
Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2
Authors: Qiao Peiwen , Yue Can , Peng Weiyu , Liu Kefang , Huo Shuting , Zhang Di , Chai Yan , Qi Jianxun , Sun Zeyu , Gao George F , Wu Guizhen , Liu Jun
Published: January 2025

As one of the earliest identified susceptible animals for the SARS-CoV-2, cats are also the vulnerable hosts for feline coronaviruses, ie feline enteric coronavirus (FECV). Here, to understand the cross-presentation of coronavirus-derived peptides by cat major histocompatibility complex molecule feline leucocyte antigen (FLA) class I, unpredictable natural peptide motifs presented by FLA-K*00701 and FLA-E*00301 were identified through peptide elution and further confirmed by the structural determination of the 2 FLA class I molecules. Based on these precise motifs of FLA class I peptides, the atlas of cross-presenting peptides from different coronaviruses in cats were sketched with 3 hotspots in C-terminal half of ORF1ab protein. The possibility of cross-presentation is further supported by the similar conformation of the corresponding peptides KP-CoV-9 (RSFIEDLLF) and KM-FECV-9 (RSAVEDLLF) from the 2 coronaviruses presented by FLA-K*00701. Our findings provide insights into the understanding of the cross-presentation of peptides from SARS-CoV-2 and feline coronaviruses FECV and the development of universal vaccine for coronaviruses.
Plasmacytoid dendritic cell sensing of African swine fever virus–infected macrophages results in STING-dependent robust interferon-α production
Authors: Sánchez-Carvajal José María , Godel Aurélie , Husson Nolwen , Summerfield Artur , García-Nicolás Obdulio
Published: January 2025

While several African swine fever virus (ASFV)–encoded proteins potently interfere with the cGAS-STING (cyclic GMP-AMP synthetase–stimulator of interferon genes) pathway at different levels to suppress interferon (IFN) type I production in infected macrophages, systemic IFN-α is induced during the early stages of AFSV infection in pigs. The present study elucidates a mechanism by which such responses can be triggered, at least in vitro. We demonstrate that infection of monocyte-derived macrophages (MDMs) by ASFV genotype 2 strains is highly efficient but immunologically silent with respect to IFN type I, IFN-stimulated gene induction, and tumor necrosis factor production. Additionally, ASFV does not directly activate plasmacytoid dendritic cells (pDCs). However, coculturing pDCs with ASFV-infected MDMs results in a strong pDC response characterized by high levels of IFN-α and tumor necrosis factor. IFN type I, in turn, promoted interleukin-1 receptor antagonist production by macrophages. Similar to the sensing of infected cells by other viruses, pDC activation required integrin-mediated cognate interactions with ASFV-infected MDMs to form an interferogenic synapse. Inhibitor studies indicated that the activation of pDCs requires the STING pathway and the formation of gap junctions. While IL-4–polarized macrophages showed increased susceptibility, IFN-γ–polarized ASFV-infected macrophages induced higher pDC activation. Pretreatment of pDCs with IFN-β and IFN-γ also enhanced IFN-α production in response to ASFV-infected macrophages, highlighting the influence of the immunological microenvironment. These findings suggest that the IFN-α detected during ASFV infection in pigs may be a result of pDC sensing ASFV-infected macrophages.
Impact of obesity on the CCR6-CCL20 axis in epidermal γδ T cells and IL-17A production in murine wound healing and psoriasis
Authors: Lawler William , Castellanos Tanya , Engel Emma , Alvizo Cristian R , Kasler Antolette , Bshara-Corson Savannah , Jameson Julie M
Published: January 2025

Obesity is associated with comorbidities including type 2 diabetes, chronic nonhealing wounds, and psoriasis. Normally, skin homeostasis and repair is regulated through the production of cytokines and growth factors derived from skin-resident cells including epidermal γδ T cells. However, epidermal γδ T cells exhibit reduced proliferation and defective growth factor and cytokine production during obesity and type 2 diabetes. One of the genes modulated in epidermal γδ T cells during obesity and type 2 diabetes is CCR6, which is the receptor for CCL20. CCL20 is elevated in the skin during obesity and type 2 diabetes. Here, we identify a subset of murine epidermal γδ T cells that express CCR6 upon activation, both in vitro and in vivo. We show that CCL20 stimulates epidermal γδ T cells to produce interleukin (IL)-17, indicating that CCR6 regulates the IL-17 axis in epidermal γδ T cells. In murine models of wound repair and psoriasis, these epidermal γδ T cells upregulate CCR6 and produce IL-17, with obesity amplifying this response during wound repair but having less effect during psoriasis. These findings have novel implications for the regulation of a specific population of IL-17–producing epidermal γδ T cells during skin damage and inflammation.
Genetic evidence for the suppressive role of zebrafish vhl targeting mavs in antiviral innate immunity during RNA virus infection
Authors: Sun Xueyi , Liu Wen , Zhu Chunchun , Wang Zixuan , Deng Hongyan , Liao Qian , Xiao Wuhan , Liu Xing
Published: January 2025

The von Hippel-Lindau (VHL) tumor suppressor gene VHL is a classic tumor suppressor that has been identified in family members with clear cell renal cell carcinomas, central nervous system and retinal hemangioblastomas, phaeochromocytomas, and pancreatic neuroendocrine tumors. The well-defined function of VHL is to mediate proteasomal degradation of hydroxylated hypoxia-inducible factor α proteins, resulting in the downregulation of hypoxia-responsive gene expression. Previously, we reported that VHL inhibits antiviral signaling by targeting mitochondrial antiviral signaling protein (MAVS) for proteasomal degradation. However, due to the lack of a viable animal model, the physiological role and underlying mechanism of VHL in antiviral immunity remains to be elucidated. In this study, we found that heterozygous vhl-deficient zebrafish have normal neutrophils and no gross phenotypic alterations. However, upon spring viremia of carp virus or grass carp reovirus infection, antiviral gene expression is induced in vhl+/− zebrafish compared with wild-type zebrafish. In addition, spring viremia of carp virus replication is suppressed in vhl+/− zebrafish, owing to the enhancement of antiviral ability. Furthermore, by crossing with mavs−/− zebrafish line, we observed that disruption of mavs in vhl+/− zebrafish abrogates the viral resistance exhibited in vhl+/− zebrafish. Thus, we reveal that heterozygous vhl deficiency enhances the antiviral ability of zebrafish against RNA virus infection, and we provide genetic evidence to support that zebrafish mavs serves as a mediator for the suppressive role of vhl in antiviral innate immunity.
Self-absorption effect in soft X-ray emission spectra utilized for bandgap evaluation of semiconductors
Authors: Terauchi Masami , Sato Yohei K
Published: January 2025

The self-absorption effects observed in the background intensity just above the Si L-emission spectra of Si and β-Si3N4, and the C K-emission spectra of diamond and graphite were examined. Based on comparisons with reported results, the energy positions of absorption edges – representing the bottom of conduction bands (CBs) – were assigned. The self-absorption profiles in the background intensities were consistent with previously reported data. The simultaneous observation of valence band and CB edges allowed the determination of a bandgap energy of 1.1 eV for Si, which agrees with the indirect bandgap energy of Si. For β-Si3N4, the bandgap energy was evaluated as 5.1 eV. For diamond, the edge positions were matched with reported values, and the bandgap energy was calculated to be 5.0 eV, slightly smaller than the optical gap of 5.5 eV. These observations suggest that both edges can be expected for semiconductors in principle. On the other hand, C K-emission spectrum of graphite, a semimetal also showed an edge structure, which was assigned to the self-absorption edge due to the transitions from 1s to σ* antibonding state of sp2 bonding.
Calothrixin B by docking JAK2 is a potential therapeutic inhibitor for pancreatic ductal adenocarcinoma
Authors: Wang Yang , Esa Sayed S , Yu Rongji , Ibrahim Sherif Abdelaziz , Li Yixin , Sheng Zhi , Wu Jinzheng , Jiang Hao , Di Xiaotang , Wen Doudou , Liu Sheng , Zhang Shubing
Published: January 2025

Objectives

Pancreatic cancer, a highly invasive and prognostically unfavorable malignant tumor, consistently exhibits resistance to conventional chemotherapy, leading to substantial side effects and diminished patient quality of life. This highlights the critical need for the discovery of novel, effective, and safe chemotherapy drugs. This study aimed to explore bioactive compounds, particularly natural products, as an alternative for JAK2 protein inhibitor in cancer treatment.

Methods

Molecular docking, molecular dynamics, and Western blot experiments were conducted to verify the binding of Calothrixin B to JAK2 and its inhibitory effect on the JAK2-STAT3 signaling axis.

Key findings

Recognizing the significant impact of JAK-STAT3 signaling pathway in pancreatic cancer, we screened the Zinc database to discover potential JAK2 inhibitors, and identified the small molecule Calothrixin B as a promising drug. Molecular simulations revealed stable interactions and the formation of hydrogen bonds between Calothrixin B and specific amino acids (Asp 994, Leu 855, and Arg 980) after a 100 ns simulation. Furthermore, we show that Calothrixin B inhibited the activity of the JAK2-STAT3 signaling pathway, arrested pancreatic cancer cells in the G1 phase, induced apoptosis, and significantly inhibited cell migration. Moreover, in vivo on a subcutaneous tumor model in nude mice confirmed that Calothrixin B effectively inhibited tumor growth in nude mice. In addition, the combination of Carlothrixin B and gemcitabine had a better inhibitory effect on pancreatic cancer cells.

Conclusion

These findings introduce new avenues for Calothrixin B as promising therapy for pancreatic cancer.
Reductions in mesophyll conductance under drought stress are influenced by increases in cell wall chelator-soluble pectin content and denser microfibril alignment in cotton
Authors: Sun Dongsheng , Lei Zhangying , Carriquí Marc , Zhang Yujie , Liu Tianyang , Wang Shengnan , Song Kunhao , Zhu Lan , Zhang Wangfeng , Zhang Yali
Published: January 2025

Plants commonly undergo leaf morphoanatomy and composition modifications to cope with drought stress, and these tend to reduce mesophyll conductance to CO2 diffusion (gm), a key limitation to photosynthesis. The cell wall appears to play a crucial role in this reduction, yet the specific effect of cell wall component on gm and the underlying regulatory mechanisms of cell wall thickness (Tcw) variation are not well understood. In this study, we subjected cotton plants to varying levels of water deficit to investigate the impact of leaf cell wall component and the arrangement patterns of microfibrils within cell walls on Tcw and leaf gas exchange. Drought stress resulted in a significant thickening of cell walls and a decrease in gm. Concurrently, drought stress increased the content of chelator-soluble pectin and cellulose while reducing hemicellulose content. The alignment of cellulose microfibrils became more parallel and their diameter increased under drought conditions, suggesting a decrease in cell wall effective porosity which coincides with the observed reduction in gm. This research demonstrates that reduced gm typically observed under drought stress is related not only to thickened cell walls, but also to ultra-anatomical and compositional variations. Specifically, increases in cellulose content, diameter, and a highly aligned arrangement of cellulose microfibrils collectively contributed to an increase in Tcw, which, together with increases in chelator-soluble pectin content, resulted in an increased cell wall resistance to CO2 diffusion.
The luminous, slow-rising orphan afterglow AT2019pim as a candidate moderately relativistic outflow
Authors: Perley Daniel A , Ho Anna Y Q , Fausnaugh Michael , Lamb Gavin P , Kasliwal Mansi M , Ahumada Tomas , Anand Shreya , Andreoni Igor , Bellm Eric , Bhalerao Varun , Bolin Bryce , Brink Thomas G , Burns Eric , Cenko S Bradley , Corsi Alessandra , Filippenko Alexei V , Frederiks Dmitry , Goldstein Adam , Hamburg Rachel , Jayaraman Rahul , Jonker Peter G , Kool Erik C , Kulkarni Shrinivas R , Kumar Harsh , Laher Russ , Levan Andrew , Lysenko Alexandra , Perley Richard A , Ricker George R , Riddle Reed , Ridnaia Anna , Rusholme Ben , Smith Roger , Svinkin Dmitry , Ulanov Mikhail , Vanderspek Roland , Waratkar Gaurav , Yao Yuhan
Published: January 2025

Classical gamma-ray bursts (GRBs) have two distinct emission episodes: prompt emission from ultrarelativistic ejecta and afterglow from shocked circumstellar material. While both components are extremely luminous in known GRBs, a variety of scenarios predict the existence of luminous afterglow emission with little or no associated high-energy prompt emission. We present AT 2019pim, the first spectroscopically confirmed afterglow with no observed high-energy emission to be identified. Serendipitously discovered during follow-up observations of a gravitational-wave trigger and located in a contemporaneous TESS sector, it is hallmarked by a fast-rising ($t \approx 2$ h), luminous ($M_{\rm UV,peak} \approx -24.4$ mag) optical transient with accompanying luminous X-ray and radio emission. No gamma-ray emission consistent with the time and location of the transient was detected by Fermi-GBM or by Konus, placing constraining limits on an accompanying GRB. We investigate several independent observational aspects of the afterglow in the context of constraints on relativistic motion and find all of them are consistent with an initial Lorentz factor of $\Gamma _0 \approx$ 10–30 for the on-axis material, significantly lower than in any well-observed GRB and consistent with the theoretically predicted ‘dirty fireball’ scenario in which the high-energy prompt emission is stifled by pair production. However, we cannot rule out a structured jet model in which only the line-of-sight material was ejected at low-$\Gamma$, off-axis from a classical high-$\Gamma$ jet core, and an on-axis GRB with below-average gamma-ray efficiency also remains a possibility. This event represents a milestone in orphan afterglow searches, demonstrating that luminous optical afterglows lacking detected GRB counterparts can be identified and spectroscopically confirmed in real time.
Inferring the ionizing photon contributions of high-redshift galaxies to reionization with JWST NIRCam photometry
Authors: Choustikov Nicholas , Stiskalek Richard , Saxena Aayush , Katz Harley , Devriendt Julien , Slyz Adrianne
Published: January 2025

JWST observations are providing unprecedented constraints on the history of reionization owing to the ability to detect faint galaxies at $z\gg 6$. Modelling this history requires understanding both the ionizing photon production rate ($\xi _{\rm ion}$) and the fraction of those photons that escape into the intergalactic medium ($f_{\rm esc}$). Observational estimates of these quantities generally rely on spectroscopy for which large samples with well-defined selection functions remain limited. To overcome this challenge, we present and release a novel implicit likelihood inference pipeline, PHOTONIOn, trained on mock photometry to predict the escaped ionizing luminosity of individual galaxies ($\dot{N}_{\rm ion}$) based on photometric magnitudes and redshifts. We show that PHOTONIOn is able to reliably infer $\dot{N}_{\rm ion}$ from photometry. This is in contrast to traditional spectral energy distribution-fitting approaches which rely on $f_{\rm esc}$ prescriptions that often overpredict $\dot{N}_{\rm ion}$ for Lyman Continuum (LyC)-dim galaxies, even when given access to spectroscopic data. We have deployed PHOTONIOn on a sample of 4559 high-redshift galaxies from the JWST Advanced Deep Extragalactic Survey (JADES), finding gentle redshift evolutions of $\log _{10}(\dot{N}_{\rm ion}) = (0.08\pm 0.01)z + (51.60\pm 0.06)$ and $\log _{10}(f_{\rm esc}\xi _{\rm ion}) = (0.07\pm 0.01)z + (24.12\pm 0.07)$. Late-time values for the ionizing photon production rate density are consistent with both theoretical models and observations. Finally, we measure the evolution of the intergalactic medium ionized fraction to find that observed populations of star-forming galaxies are capable of driving reionization in this field to completion by $z\sim 5.3$ without the need for active galactic nucleus or other exotic sources, consistent with other studies of the same field. The 20 per cent of UV-brightest galaxies ($M_{\rm UV}\lt -18.5$) reionize roughly 35 per cent of the survey volume, demonstrating that UV faint LyC emitters are crucial for reionization.
Age-dating early quiescent galaxies: high star formation efficiency, but consistent with direct, higher-redshift observations
Authors: Turner Crispin , Tacchella Sandro , D’Eugenio Francesco , Carniani Stefano , Curti Mirko , Glazebrook Karl , Johnson Benjamin D , Lim Seunghwan , Looser Tobias , Maiolino Roberto , Nanayakkara Themiya , Wan Jenny
Published: January 2025

We present a detailed analysis of JWST/NIRSpec and NIRCam observations of ZF-UDS-7329, a massive, quiescent galaxy at redshift $z=3.2$, which has been put forward to challenge cosmology and galaxy formation physics. We study on the impact of different star formation history (SFH) priors, stellar libraries, metallicity, and initial mass function assumptions. Our results show that ZF-UDS-7329, with a formed stellar mass of $M_{\star } \approx 10^{11.4}~{\rm M}_\odot $ (surviving mass $M_{\star \mathrm{,surv}} \approx 10^{11.2}~{\rm M}_\odot $) and a specific star formation rate of $\mathrm{sSFR} \approx 0.03~{\rm Gyr} ^{-1}$, formed efficiently in the first billion years of the Universe. In agreement with previous work, we find that the spectrum is consistent with mass-weighted stellar ages of $1.3{\!-\!}1.8$ Gyr, depending on the SFH prior used. A physically motivated rising SFH prior makes the formation history of ZF-UDS-7329 compatible with stellar mass and star formation rate estimates of $z\gt 6$ galaxies. Using NIRCam imaging, we identify a colour gradient indicative of an old, quiescent bulge and a younger disc component, as expected from a complex formation history. The inferred SFH is consistent a high stellar fraction of $f_{\star }=M_{\star }/(f_b \cdot M_{\rm h}) \approx 100{{\ \rm per\ cent}}$ at $z=7{\!-\!}12$, implying an extremely high integrated star formation efficiency. However, when considering cosmic variance and possible mergers as expected in overdense environments – as traced by ZF-UDS-7329 – the stellar fractions could be reduced to $f_{\star } \approx 50{{\ \rm per\ cent}}$, which is more consistent with galaxy formation models and the stellar-to-halo mass relation at lower redshifts. We conclude that ZF-UDS-7329 forms extremely efficient in the early universe, but does not necessitate unseen galaxies at higher redshifts since the inferred SFR of ancestors are consistent with those seen in $z\gt 6$ galaxies.
Stellar population and metal production in AGN discs
Authors: Fryer Chris L , Huang Jiamu , Ali-Dib Mohamad , Andrews Amaya , Xu Zhenghao , Lin Douglas N C
Published: January 2025

As gravitational wave detections increase the number of observed compact binaries (consisting of neutron stars or blacks), we begin to probe the different conditions producing these binaries. Most studies of compact remnant formation focus either on stellar collapse from the evolution of field binary stars in gas-free environments or on the formation of stars in clusters where dynamical interactions capture the compact objects, forming binaries. But a third scenario exists. In this paper, we study the fate of massive stars formed, accrete gas, and evolve in the dense discs surrounding supermassive black holes. We calculate the explosions produced and compact objects formed by the collapse of these massive stars. Nucleosynthetic yields may provide an ideal, directly observable, diagnostic of the formation and fate of these stars in active galactic nuclei. We present a first study of the explosive yields from these stars, comparing these yields with the observed nucleosynthetic signatures in the discs around supermassive stars with quasars. We show that, even though these stars tend to form black holes, their rapid rotation leads to discs that can eject a considerable amount of iron during the collapse of the star. The nucleosynthetic yields from these stars can produce constraints on the number of systems formed in this manner, but further work is needed to exploit variations from the initial models presented in this paper.
Orbital stability of hierarchical three- and four-body systems with inclination: results for Kepler-1625, 1708, and HD 23079
Authors: Patel Shaan D , Quarles Billy , Cuntz Manfred
Published: January 2025

As the number of potential exomoon candidates grows, there is a heightened motivation of pursing orbital stability analyses. In this work, we provide an in-depth investigation into four-body systems, consisting of a star, planet, moon, and submoon by using the N-body simulator rebound.. Particularly, we focus on the system of Kepler-1625, where evidence of a possible exomoon has been obtained. We investigate the three-body star–planet–moon system for the proposed exomoon parameters allowing us to identify stable regions associated with most of the space parameters. Thereafter, we consider a four-body system including a potential submoon. We find that there are both stable and unstable regions, as expected, as well as resonance patterns that are further explored using numerical and analytical methods including secular perturbation theory. We are able to identify these resonances as secular in nature. In addition, we investigate three-body versions of two other systems, Kepler-1708 and HD 23079, while also studying a four-body version of HD 23079. Our work may serve as a generalized framework for exploring other planet–moon cases in the future while noting that the current four-body study may be an incentive for studying further exomoon and submoon systems.
Modeling Biases from Low-Pass Genome Sequencing to Enable Accurate Population Genetic Inferences
Authors: Fonseca Emanuel M , Tran Linh N , Mendoza Hannah , Gutenkunst Ryan N
Published: January 2025

Low-pass genome sequencing is cost-effective and enables analysis of large cohorts. However, it introduces biases by reducing heterozygous genotypes and low-frequency alleles, impacting subsequent analyses such as model-based demographic history inference. Several approaches exist for inferring an unbiased allele frequency spectrum (AFS) from low-pass data, but they can introduce spurious noise into the AFS. Rather than correcting the AFS, here, we developed an approach that incorporates low-pass biases into the demographic modeling and directly analyzes the AFS from low-pass data. Our probabilistic model captures biases from the Genome Analysis Toolkit multisample calling pipeline, and we implemented it in the population genomic inference software dadi. We evaluated the model using simulated low-pass datasets and found that it alleviated low-pass biases in inferred demographic parameters. We further validated the model by downsampling 1000 Genomes Project data, demonstrating its effectiveness on real data. Our model is widely applicable and substantially improves model-based inferences from low-pass population genomic data.