bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza a virus antiparallel helical nucleocapsid-like pseudo-atomic structure
Authors: Chenavier Florian , Zarkadas Eleftherios , Freslon Lily-Lorette , Stelfox Alice J , Schoehn Guy , Ruigrok Rob W H , Ballandras-Colas Allison , Crépin Thibaut 
Published: December 2024

Abstract
Influenza A viruses are responsible for human seasonal epidemics and severe animal pandemics with a risk of zoonotic transmission to humans. The viral segmented RNA genome is encapsidated by nucleoproteins (NP) and attached to the heterotrimeric polymerase, forming the viral ribonucleoproteins (vRNPs). Flexible helical vRNPs are central for viral transcription and replication. In this study, we present an advanced biological tool, the antiparallel helical RNP-like complex, assembled from recombinant N-terminally truncated NP and short synthetic RNA. The 3.0 Å cryo-electron microscopy structure details for the first time the whole RNA pathway across NP as well as NP-NP interactions that drive the antiparallel helical assembly accommodating major and minor grooves. Our findings show that the surface of the protein can harbour several conformations of the RNA, confirming that the number of nucleobases that binds to NP is not fixed, but ranges probably between 20 and 24. Taking all together, our data provide details to further understand the genome encapsidation and explain the inherent flexibility of influenza A virus vRNPs.
Lig3-dependent rescue of mouse viability and DNA double-strand break repair by catalytically inactive Lig4
Authors: Medina-Suárez David , Han Li , O’Reilly Sandra , Liu Jiali , Wei Chao , Brenière Manon , Goff Noah J , Chen Chen , Modesti Mauro , Meek Katheryn , Harrington Bonnie , Yu Kefei 
Published: December 2024

Abstract
Recent studies have revealed a structural role for DNA ligase 4 (Lig4) in the maintenance of a repair complex during non-homologous end joining (NHEJ) of DNA double-strand breaks. In cultured cell lines, catalytically inactive Lig4 can partially alleviate the severe DNA repair phenotypes observed in cells lacking Lig4. To study the structural role of Lig4 in vivo, a mouse strain harboring a point mutation to Lig4’s catalytic site was generated. In contrast to the ablation of Lig4, catalytically inactive Lig4 mice are born alive. These mice display marked growth retardation and have clear deficits in lymphocyte development. We considered that the milder phenotype results from inactive Lig4 help to recruit another ligase to the repair complex. We next generated a mouse strain deficient for nuclear Lig3. Nuclear Lig3-deficient mice are moderately smaller and have elevated incidences of cerebral ventricle dilation but otherwise appear normal. Strikingly, in experiments crossing these two strains, mice lacking nuclear Lig3 and expressing inactive Lig4 were not obtained. Timed mating revealed that fetuses harboring both mutations underwent resorption, establishing an embryonic lethal genetic interaction. These data suggest that Lig3 is recruited to NHEJ complexes to facilitate end joining in the presence (but not activity) of Lig4.
A novel nuclear RNA HSD52 scaffolding NONO/SFPQ complex modulates DNA damage repair to facilitate temozolomide resistance
Authors: Sun Nan , Chen Qun , Chen Hao , Sun Penggang , Liu Yuxiang , Song Dan , Yu Daohan , Wang Pandeng , Song Yu , Qin Jie , Tian Kaifu , Zhong Junzhe , Ma Wenbin , Xuan Hanwen , Qian Da , Yuan Ye , Chen Tongzheng , Wang Xin , Jiang Chuanlu , Cai Jinquan , Meng Xiangqi 
Published: December 2024

Abstract

Background
Temozolomide (TMZ) is used in the treatment of glioblastoma (GBM). However, the primary obstacle remains the emergence of TMZ chemotherapy resistance. Non-POU domain-containing octamer-binding protein (NONO) and splicing factor proline/glutamine rich (SFPQ) are multifunctional nuclear proteins involved in genome stability and gene regulation. However, the specific role of NONO and SFPQ in TMZ resistance of GBM remains to be explored.

Methods
RNA-binding protein immunoprecipitation-microarray and RNA microarray of TMZ-resistant and parental cells were performed for the gain of HSD52. The effects of HSD52 on TMZ resistance were investigated through in vitro assays, intracranial xenograft, and GBM organoid models. The underlying mechanisms were explored by DNA methylation chip, RNA immunoprecipitation, RNA pull-down assays, among others. GBM clinical samples were rolled in to investigate the clinical significance of HSD52.

Results
We identified a novel noncoding RNA, HSD52, that was highly expressed in TMZ-resistant GBM and facilitated the interaction between NONO and SFPQ. H3 ubiquitination attenuation and reduced DNA methyltransferase 1 (DNMT1) recruitment increased HSD52 transcription via DNA hypo-methylation. HSD52 formed an RNA duplex with UFM1 specific ligase 1 (UFL1) mRNA, thereby promoting NONO/SFPQ complex binding to UFL1 mRNA and enhancing its stability, and then contributed to TMZ resistance through activating the ataxia telangiectasia mutated signaling pathway. In vivo xenograft and GBM organoid models showed significant repression in tumor growth after HSD52 knockout with TMZ treatment. In GBM clinical samples, HSD52 was responsible for the malignant progression and TMZ resistance.

Conclusions
Our results revealed that HSD52 could serve as a promising therapeutic target to overcome TMZ resistance, improving the clinical efficacy of TMZ chemotherapy in GBM.
Phase II trial of blood–brain barrier permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma
Authors: Dmello Crismita , Brenner Andrew , Piccioni David , Wen Patrick Y , Drappatz Jan , Mrugala Maciej , Lewis Lionel D , Schiff David , Fadul Camilo E , Chamberlain Marc , Kesari Santosh , Ahluwalia Manmeet , Ghosh Debora , Sonabend Adam M , Kumthekar Priya 
Published: December 2024

Abstract

Background
This study is a phase II clinical trial to evaluate the efficacy, safety, and tolerability of the blood–brain barrier (BBB) permeable peptide-paclitaxel conjugate ANG1005 in patients with recurrent high-grade glioma (HGG) (NCT01967810).

Methods
Seventy-three patients were enrolled in 3 separate arms-recurrent glioblastoma (GBM) (Arm 1), bevacizumab refractory GBM (Arm 2), and grade 3 anaplastic gliomas (AGs) (Arm 3). The study was started in October 2013, and the data were locked on September 29, 2017. Safety was evaluated for all three arms (n = 73), and the primary endpoint for Arms 1 and 3 was objective response rate (ORR), and Arm 2 primary endpoint was progression-free survival rate at 3 months (PFS3).

Results
Overall, the safety of ANG1005 was found to be consistent with a taxane toxicity profile. Otherwise, the primary efficacy endpoints of ORR and PFS were not met. The most common adverse events (AEs) were hematologic (32.9%), alopecia (31.5%), and fatigue (30.1%). The median PFS was 1.4 months (95% CI: 1.4, 2.1) and similar across all the treatment arms. The median overall survival was 13.4 months (95% CI: 3.4, 14.6) in Arm 1, 5.8 months (95% CI: 1.9, 9.7) in Arm 2, and 18.2 months (95% CI: 10.7, 35.3) in Arm 3.

Conclusion
A dose of 600 mg/m2 was determined to be safe in this study. However, the primary efficacy endpoint was not met in the NCT01967810-ANG1005 trial, and no further studies are planned in the glioma setting with this compound.
Atomically precise silver-based bimetallic clusters for electrocatalytic urea synthesis
Authors: Chen Hong , Liu Lin , Ma Xiao-Hong , Zheng Su-Jun , Dong Xiao-Yu , Huang Ren-Wu , Wang Zhao-Yang , Cai Jinmeng , Zang Shuang-Quan 
Published: December 2024

ABSTRACT
Electrocatalytic urea synthesis from CO2 and nitrate holds immense promise as a sustainable strategy, but its complicated synthesis steps and controversial C–N coupling mechanism restrict the design of efficient catalysts. Atomically precise metal cluster materials are ideal model catalysts for investigating the C–N coupling issues. Here we synthesize two atomically precise bimetallic clusters, Ag14Pd(PTFE)6(TPP)8 and Ag13Au5(PTFE)10(DPPP)4, both with icosahedral cores and similar ligands. We demonstrate that both clusters have good performance for electrocatalytic urea synthesis, with the production rates at the maximum Faradaic efficiency of 143.3 and 82.3 mg h−1 gcat−1, respectively. Bimetallic structures can induce charge polarization at the active sites of metal clusters, thereby influencing the selectivity. In mechanistic investigations, we propose that *NOH and *COOH are the rate-limiting steps for the reduction of nitrate and CO2, respectively, and that the key intermediates formed thereafter can significantly affect the C–N coupling process. This approach offers a deep understanding into C–N coupling through the utilization of atomically precise metal clusters.
Concentration and mergers: evidence from Italian labor markets
Authors: Passerini Filippo 
Published: December 2024

Abstract
This article investigates the effects of labor market concentration on employment, job security, and wages. By constructing a flow-based index, I find that concentration is generally low across markets but varies across industries. Then, I use a Two-Stage Least Squares (TSLS) strategy based on the different exposures of industries to horizontal mergers. I find that mergers increase concentration, which in turn reduces wages by −0.14 and −0.07 and hires by −0.77 and −0.68%age points. I also find that (1) concentration does not affect the likelihood of a permanent hire but increases the probability that, when a temporary worker is renewed, the contract is again temporary; (2) men are affected by concentration only through wages, while women are less affected but also through job security; (3) estimates magnitude increases in concentration levels.
Safety and quality of life with maintenance olaparib plus bevacizumab in older patients with ovarian cancer: subgroup analysis of PAOLA‑1/ENGOT-ov25
Authors: Montégut Coline , Falandry Claire , Cinieri Saverio , Cropet Claire , Montane Laure , Rousseau Frédérique , Joly Florence , Moubarak Malak , Mosconi Anna M , Guerra-Alía Eva M , Schauer Christian , Fujiwara Hiroyuki , Vergote Ignace , Parma Gabriella , Lindahl Gabriel , Anota Amélie , Canzler Ulrich , Marmé Frederik , Pujade-Lauraine Eric , Ray-Coquard Isabelle , Sabatier Renaud 
Published: December 2024

Abstract

Background
In PAOLA-1/ENGOT-ov25, the addition of olaparib to bevacizumab maintenance improved overall survival in patients with newly diagnosed advanced ovarian cancer. We describe the safety profile and quality of life (QoL) of this combination in older patients in PAOLA-1.

Methods
Safety (CTCAE v4.03) and QoL (EORTC QoL Questionnaires Core 30 and Ovarian 28) data were collected. We compared safety by age (≥70 vs &lt;70 years) in the olaparib-containing arm. QoL by treatment arm was assessed in older patients. Geriatric features, including Geriatric Vulnerability Score (GVS), were also gathered.

Results
Of 806 patients randomized, 142 were ≥70 years old (olaparib-containing arm: n = 104; placebo arm: n = 38). Older patients treated with olaparib exhibited a similar safety profile to younger patients, except for higher rates of all grades of lymphopenia and grade ≥3 hypertension (31.7% vs 21.6%, P =.032 and 26.9% vs 16.7%, P =.019, respectively). No hematological malignancy was reported. Two years after randomization, mean Global Health Status and cognitive functioning seemed better with olaparib than bevacizumab alone (adjusted mean difference: +4.47 points [95% CI, −0.49 to 9.42] and +4.82 [−0.57 to 10.21], respectively), and other QoL items were similar between arms. In the olaparib-containing arm, older patients with baseline GVS ≥ 1 (n = 48) exhibited increased toxicity and poorer QoL than those with GVS of 0 (n = 34).

Conclusion
Among older patients in PAOLA-1, olaparib plus bevacizumab had a manageable safety profile and no adverse impact on QoL. Additional data are required to confirm these results in more vulnerable patients.
(ClinicalTrials.gov Identifier: NCT02477644).
Feeding selectivity and niche characteristics in Southern Ocean salps
Authors: Fender Christian K , Décima Moira , Gutiérrez-Rodríguez Andres , Selph Karen E , Safi Karl A , Stukel Michael R 
Published: December 2024

Abstract
Salps are a group of pelagic tunicates with widespread distribution and the potential to strongly impact ecosystem dynamics through their rapid reproduction, carbon export and filtration rates. Like most filter feeders, they are considered to be nonselective in their feeding, although recent reports of differences in the proportions of prey types in salp diets compared to their availability have challenged this paradigm. We investigate the potential for selective feeding and its impacts on salp niche breadth and overlap using scanning electron microscopy of the gut contents of 58 salps from the Southwest Pacific east of New Zealand representing seven species: Salpa thompsoni, Thetys vagina, Thalia democratica, Salpa fusiformis, Ihlea magalhanica, Soestia zonaria and Pegea confoederata. We then compare their diet to water column plankton communities via FlowCam and flow cytometry. While most prey types were consumed without preference as expected, dinoflagellates were positively selected across five of the seven salp species regardless of water column prey compositions. Large, spinous diatoms and submicron particles were consistently negatively selected. These selectivities resulted in high niche breadths that still fell short of true generalists, highlighting that selectivity is a spectrum rather than a dichotomy.
Kiwifruit spatiotemporal multiomics networks uncover key tissue-specific regulatory processes throughout the life cycle
Authors: Zeng Zhebin , Li Yawei , Zhu Man , Wang Xiaoyao , Wang Yan , Li Ang , Chen Xiaoya , Han Qianrong , Nieuwenhuizen Niels J , Ampomah-Dwamena Charles , Deng Xiuxin , Cheng Yunjiang , Xu Qiang , Xiao Cui , Zhang Fan , Atkinson Ross G , Zeng Yunliu 
Published: December 2024

Abstract
Kiwifruit (Actinidia chinensis), a recently commercialized horticultural crop, is rich in various nutrient compounds. However, the regulatory networks controlling the dynamic changes in key metabolites among different tissues remain largely unknown. Here, high-resolution spatiotemporal datasets obtained by ultraperformance liquid chromatography-tandem mass spectrometry methodology and RNA-seq were employed to investigate the dynamic changes in the metabolic and transcriptional landscape of major kiwifruit tissues across different developmental stages, including from fruit skin, outer pericarp, inner pericarp, and fruit core. Kiwifruit spatiotemporal regulatory networks (KSRN) were constructed by integrating the 1,243 identified metabolites and co-expressed genes into 10 different clusters and 11 modules based on their biological functions. These networks allowed the generation of a global map for the major metabolic and transcriptional changes occurring throughout the life cycle of different kiwifruit tissues and discovery of the underlying regulatory networks. KSRN predictions confirmed previously established regulatory networks, including the spatiotemporal accumulation of anthocyanin and ascorbic acid (AsA). More importantly, the networks led to the functional characterization of three transcription factors: an A. chinensis ethylene response factor 1, which negatively controls sugar accumulation and ethylene production by perceiving the ripening signal, a basic-leucine zipper 60 (AcbZIP60) transcription factor, which is involved in the biosynthesis of AsA as part of the L-galactose pathway, and a transcription factor related to apetala 2.4 (RAP2.4), which directly activates the expression of the kiwi fruit aroma terpene synthase gene AcTPS1b. Our findings provide insights into spatiotemporal changes in kiwifruit metabolism and generate a valuable resource for the study of metabolic regulatory processes in kiwifruit as well as other fruits.
Designed to breathe: synthetic biology applications in plant hypoxia
Authors: Lavilla-Puerta Mikel , Giuntoli Beatrice 
Published: December 2024

Abstract
Over the past years, plant hypoxia research has produced a considerable number of new resources to monitor low oxygen responses in model species, mainly Arabidopsis thaliana. Climate change urges the development of effective genetic strategies aimed at improving plant resilience during flooding events. This need pushes forward the search for optimized tools that can reveal the actual oxygen available to plant cells, in different organs or under various conditions, and elucidate the mechanisms underlying plant hypoxic responses, complementing the existing transcriptomics, proteomics, and metabolic analysis methods. Oxygen-responsive reporters, dyes, and nanoprobes are under continuous development, as well as novel synthetic strategies that make precision control of plant hypoxic responses realistic. In this review, we summarize the recent progress made in the definition of tools for oxygen response monitoring in plants, either adapted from bacterial and animal research or peculiar to plants. Moreover, we highlight how adoption of a synthetic biology perspective has enabled the design of novel genetic circuits for the control of oxygen-dependent responses in plants. Finally, we discuss the current limitations and challenges toward the implementation of synbio solutions in the plant low-oxygen biology field.
The role of emotional and cultural intelligences on police leaders’ perceptions of reform
Authors: White David R , Schafer Joseph A 
Published: December 2024

Abstract
Police leaders’ support for policing reform is an important consideration because this population serves in some ways as gatekeepers of their respective organizations, setting organizational priorities and operationalizing change. Using survey data from 731 US police leaders who attended the FBI National Academy program in 2023, we evaluate the salience of emotional intelligence and cultural intelligence as key leadership contexts. Specifically, this study examines whether emotional and cultural intelligence relates to participants’ support for civilian oversight boards, and the belief that de-escalation and implicit bias training have a positive impact on policing. Controlling for other factors, the results indicate that emotional and cultural intelligence are significantly related to reform attitudes. Notably, we control for participants’ perceptions that systemic racism poses a problem in criminal justice and find that views of systemic racism also remain significant with most outcomes. Implications for police leadership training and policing reform are discussed.
The pattern of anti-IL-6 versus non-anti-IL-6 biologic disease modifying anti-rheumatic drugs use in patients with rheumatoid arthritis in Wales, UK: a real-world study using electronic health records
Authors: Cooksey Roxanne , Kennedy Jonathan , Rahman Muhammad , Brophy Sinead , Choy Ernest 
Published: December 2024

Abstract

Objective
Investigating factors associated with drug initiation and discontinuation in patients treated with anti-IL-6 biologic DMARDs (bDMARDs) (tocilizumab or sarilumab) vs non-anti-IL-6 (anti-TNF, B or T cell therapies) bDMARDs for RA.

Methods
A retrospective cohort study of patients with the diagnosis of RA in the Secure Anonymised Information Linkage Databank, comprising primary and secondary care and specialist rheumatology clinic records for &gt;90% of the population in Wales, UK. Patients initiated on first bDMARD treatment, discontinuation and clinical outcomes including infection and hospitalisation were analysed using Cox regression analysis.

Results
Of patients identified with RA in their primary care records, 95.7% (4691/4922) received conventional synthetic DMARDs (csDMARDs). More than one-third (36.2%) were treated with bDMARDs (1784/4922). Of these biologic-naïve patients, 6.5% (116) were treated with anti-IL-6 bDMARDs; this treatment was associated with a previous history of infection [difference 8.8% (95% CI 1.1, 17.8)] and kidney disease [14.3% (95% CI 8.0, 22.5)]. Treatment discontinuation was significantly higher in the non-anti-IL-6 bDMARD-treated patients (23.1%) compared with the anti-IL-6 bDMARD-treated individuals (18.1%) [difference 9.4% (95% CI 1.1, 15.7)]. For those discontinuing a first line of treatment, 385 patients (23%) and 21 patients (18%) switched to an alternative bDMARD from the non-anti-IL-6 and anti-IL-6 groups, respectively.

Conclusion
Comorbidities, history of infection and kidney disease were associated with choosing anti-IL-6 bDMARDs in biologic-naïve RA patients in Wales. Anti-IL-6 bDMARD-treated biologic-naïve patients were more likely to continue treatment than non-IL-6 bDMARD-treated patients.
Microchannel plate response to solar energetic particles and consequences for solar-wind measurements on ESA’s Vigil mission
Authors: Parent P-Y , Verscharen D , Nicolaou G , Owen C J 
Published: December 2024

ABSTRACT
Space weather forecasting aims at predicting the impacts of the Sun, interplanetary space, and the planetary environment on biological and technological systems. To monitor space weather, the European Space Agency is developing the Vigil mission. Vigil will carry the Plasma Analyser (PLA) instrument. We investigate the expected impact of Solar Energetic Particles (SEPs) on PLA. We analyse previous measurements from Solar Orbiter’s Solar Wind Analyser (SWA) Electron Analyser System (EAS) that, like PLA, uses a microchannel plate (MCP) as its detector. Using a fitting algorithm, we extract the number of erroneous counts created by the interaction between SEPs and the MCP. Using SEP flux measurements from Solar Orbiter’s Energetic Particle Detector (EPD) and multilinear regression, we establish a linear relationship between the number of erroneous counts and SEP fluxes. We define an SEP index, characterizing the impact of SEP events on EAS measurements. We then simulate PLA measurements during SEP events characterized by their SEP index. We show that moderate SEP events cause significant discrepancies in PLA plasma moment estimations under common solar-wind conditions. Based on our results, we propose a correction method for erroneous counts created by SEPs in instruments such as EAS and PLA.
A multifunctional photothermal electrospun PLGA/MoS2@Pd nanofiber membrane for diabetic wound healing
Authors: Chen Zhengrong , Mo Quansheng , Mo Dandan , Pei Xiaomin , Liang Anru , Cai Jinhong , Zhou Bo , Zheng Li , Li Hongmian , Yin Feiying , Zhao Jinmin 
Published: December 2024

Abstract
Injury caused by excess reactive oxygen species (ROS) may lead to susceptibility to bacterial infection and sustained inflammatory response, which are the major factors impeding diabetic wound healing. By utilizing optimal anti-inflammatory, antioxidant and antibacterial biomaterials for multifunctional wound dressings is critical in clinical applications. In this study, a novel electrospun PLGA/MoS2@Pd nanofiber membrane was synthesized by encapsulating antioxidant and near-infrared (NIR) responsive MOS2@Pd nanozymes in PLGA nanofibers to form a multifunctional dressing for diabetic wound repair. With excellent biocompatibility and hemostatic ability, this novel PLGA/MoS2@Pd nanofiber membrane can effectively reduce oxidative stress damage and intracellular inflammatory factors expression in fibroblasts by scavenging ROS. Additionally, the PLGA/MoS2@Pd nanofiber membrane exhibited favorable NIR-mediated photothermal antibacterial activity in vitro, with inhibition rates of 97.14% and 97.07% against Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli), respectively. In a diabetic rat wound infection model, NIR-assisted PLGA/MoS2@Pd nanofiber membrane effectively inhibited bacterial growth in the wound, reduced infection-induced inflammatory response, and promoted tissue epithelialization and collagen deposition, resulting in a wound healing rate of up to 98.5% on Day 14. This study highlighted the construction of a multifunctional nanofiber membrane platform and demonstrated its promising potential as a clinical dressing for diabetic wounds.