bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance to the herbicide metribuzin conferred to Arabidopsis thaliana by targeted base editing of the chloroplast genome
Authors: Nakazato Issei , Yamori Wataru , Matsumura Hiroyoshi , Qu Yuchen , Okuno Miki , Tsutsumi Nobuhiro , Arimura Shin‐ichi 
Published: October 2024

SummaryThe chloroplast genome has considerable potential to enhance crop productivity, but it remains underutilized in breeding because it is difficult to modify. This study elucidates the potential of recently developed chloroplast‐targeted C‐to‐T base editors in facilitating the use of the chloroplast genome for crop breeding. The herbicide metribuzin interferes with photosynthesis by binding to the D1 protein of photosystem II, encoded by the chloroplast genome. Naturally occurring D1 mutants with V219I or A251V substitutions are known to have resistance to some herbicides including metribuzin. Here, using the base editors, we introduced these substitutions and showed that the A251V single mutation and the V219 & A251V double mutations conferred significant metribuzin resistance to Arabidopsis thaliana. The V219I & A251V double mutants exhibited increased metribuzin resistance and grew better than the A251V single mutants. Furthermore, the double mutants grew as well as wild‐type plants in the absence of metribuzin. The single and double mutants, which are a challenge to obtain through traditional mutagenesis and crossbreeding methods, can be relatively easily generated using C‐to‐T base editors. In view of the conservation of V219 and A251 across numerous species, C‐to‐T base editing can potentially confer metribuzin resistance to a wide range of crops. Compared to nuclear genes, chloroplast genes are also less likely to spread into wild populations. Our findings suggest that chloroplast‐targeting C‐to‐T base editors will find many roles in future crop breeding efforts.
Detection of novel pathogenic variants of Fusarium oxysporum f. sp. lactucae in California
Authors: Nayak Santosh , Richardson Kelley L. , Putman Alexander I. , LeBlanc Nicholas R. , Martin Frank N. , Li Ningxiao , McCreight James D. 
Published: October 2024

AbstractFusarium wilt, caused by the soilborne fungal pathogen Fusarium oxysporum f. sp. lactucae (FOL), is an economically important disease of lettuce (Lactuca sativa) throughout the world. Four pathogenic races of FOL are reported, though only race 1 is known to exist in the United States. Recently, Californian lettuce growers have expressed increasing concern about Fusarium wilt, as some race 1‐resistant cultivars have exhibited susceptibility, and some susceptible cultivars have displayed reduced disease severity. To determine whether such changes in disease patterns are responses to potentially novel variants, we collected infected plants from commercial fields in the Salinas Valley and Santa Maria regions, isolated the fungus, and conducted a series of pathogenicity tests using a set of FOL race differential cultivars over 2 years (2022 and 2023) in controlled conditions. Pathogenicity tests revealed two new FOL variants that elicited novel disease reaction patterns on the set of differential cultivars that have not been previously described. Isolates Fol621 and Fol621s were less aggressive on race 1‐susceptible Banchu Red Fire, designated Variant‐1. Isolate VSP‐0916 incited severe Fusarium wilt on race 1‐resistant Costa Rica No. 4, designated Variant‐2. Moreover, VSP‐0916 exhibited high aggressiveness and the ability to induce disease in other race 1‐resistant cultivars. This study is the first documentation, to our knowledge, of the occurrence of FOL‐inciting Fusarium wilt on race 1‐resistant lettuce in the United States. Our work provides valuable information critical for the development of Fusarium wilt management strategies, including broad‐spectrum resistance breeding efforts against multiple FOL races.
Transcriptome dynamics in developing leaves from C3 and C4Flaveria species
Authors: Billakurthi Kumari , Wrobel Thomas J. , Gowik Udo , Bräutigam Andrea , Weber Andreas P. M. , Westhoff Peter 
Published: October 2024

SUMMARYC4 species have evolved more than 60 times independently from C3 ancestors. This multiple and parallel evolution of the complex C4 trait suggests common underlying evolutionary mechanisms, which could be identified by comparative analysis of closely related C3 and C4 species. Efficient C4 function depends on a distinctive leaf anatomy that is characterised by enlarged, chloroplast‐rich bundle sheath cells and narrow vein spacing. To elucidate the molecular mechanisms that generate the Kranz anatomy, we analysed a developmental series of leaves from the C4 plant Flaveria bidentis and the closely related C3 species Flaveria robusta by comparing anatomies and transcriptomes. Vascular density measurements of all nine leaf developmental stages identified three leaf anatomical zones whose proportions vary with respect to the developmental stage. We then deconvoluted the transcriptome datasets using non‐negative matrix factorisation, which identified four distinct transcriptome patterns in the growing leaves of both species. By integrating the leaf anatomy and transcriptome data, we were able to correlate the different transcriptional profiles with different developmental zones in the leaves. These comparisons revealed an important role for auxin metabolism, in particular auxin homeostasis (conjugation and deconjugation), in establishing the high vein density typical of C4 species.
Competitive control of CsNCED1‐1 by CsLOB1 and CsbZIP40 triggers susceptibility to citrus canker
Authors: Long Qin , Zhang Lehuan , Zhu Tianxiang , Zhao Shuyang , Zou Changyu , Xu Lanzhen , He Yongrui , Chen Shanchun , Zou Xiuping 
Published: October 2024

SUMMARYPustule formation is pivotal for the development of the Xanthomonas citri subsp. citri (Xcc)‐induced citrus canker disease (CCD). Although our previous study demonstrated that the exogenous application of abscisic acid (ABA) facilitated pustule formation induced by Xcc, the precise mechanism remains elusive. The 9‐cis‐epoxycarotenoid dioxygenase (NCED) is a crucial enzyme in ABA biosynthesis. This study explored the role of citrus CsNCED1‐1 in CCD resistance through overexpression and RNA interference of CsNCED1‐1 in Wanjincheng orange (Citrus sinensis). Our findings indicated that CsNCED1‐1 negatively modulated CCD resistance by fostering ABA accumulation, concomitant with an increase in jasmonic acid (JA) and a decrease in salicylic acid (SA). Plants overexpressing CsNCED1‐1 displayed shortened leaves with smaller and denser stomata along with irregular and increased palisade cells. CsLOB1 is a known susceptibility gene for CCD, and CsbZIP40 positively influences resistance to this disease. We further confirmed that CsLOB1 promoted and CsbZIP40 suppressed the transcription of CsNCED1‐1 by directly binding to the CsNCED1‐1 promoter. Notably, CsbZIP40 and CsLOB1 showed a competitive relationship in the regulation of CsNCED1‐1 expression, with CsbZIP40 exhibiting greater competitiveness. Overall, our findings highlight that CsNCED1‐1 promotes susceptibility to citrus canker by disrupting JA‐ and SA‐mediated defense mechanisms and triggering the proliferation and remodeling of palisade cells, thereby facilitating pathogen colonization and pustule formation. This study offers novel insights into the regulatory mechanisms underlying citrus canker resistance and the role of CsNCED1‐1 in citrus.
GhGRF4/GhARF2‐GhGASA24 module regulates fiber cell wall thickness by modulating cellulose biosynthesis in upland cotton (Gossypium hirsutum)
Authors: Tian Zailong , Chen Baojun , Sun Yaru , Sun Gaofei , Gao Xu , Pan Zhaoe , Song Guoli , Du Xiongming , He Shoupu 
Published: October 2024

SUMMARYFiber elongation rate is an essential characteristic of cotton fiber in the textile industry, yet it has been largely overlooked in genetic studies. Gibberellins (GAs) and auxin (IAA) are recognized for their role in directing numerous developmental processes in plants by influencing cell differentiation and elongation. However, the degree to which GA–IAA interaction governs cellular elongation in cotton fiber cells remains to be fully understood. In this study, we identified a causal gene, Gibberellic Acid‐Stimulated in Arabidopsis 24 (GhGASA24), that appears to be responsible for fiber elongation rate via regulating fiber cell wall thickness. Subsequent experiments revealed that GhGASA24 influences cell wall formation by promoting the expression of GhCesA8 and GhCesA10. Our findings suggest that Auxin Response Factor 2 (GhARF2) regulates fiber elongation rate by directly binding to the AuxRE elements in GhGASA24 promoter. In addition, we identified Growth Regulation Factor 4 (GhGRF4) as a transcription factor that interacts with GhARF2 to form a heterodimer complex, which also transcriptionally activates GhGASA24. Intriguingly, GhGRF4 regulates GhARF2 expression by directly binding to its promoter, thereby acting as a cascade regulator to enhance the transcriptional levels of GhGASA24. We propose that the GhGRF4/GhARF2‐GhGASA24‐GhCesAs module may contribute to fiber cell wall thickness by modulating cellulose biosynthesis, and provide a theoretical basis for improvement of fiber quality.
Genome‐based discovery of pachysiphine synthases in Tabernaemontana elegans
Authors: Lezin Enzo , Durand Mickael , Birer Williams Caroline , Lopez Vazquez Ana Luisa , Perrot Thomas , Gautron Nicolas , Pétrignet Julien , Cuello Clément , Jansen Hans J. , Magot Florent , Szwarc Sarah , Le Pogam Pierre , Beniddir Mehdi A. , Koudounas Konstantinos , Oudin Audrey , St‐Pierre Benoit , Giglioli‐Guivarc'h Nathalie , Sun Chao , Papon Nicolas , Jensen Michael Krogh , Dirks Ron P. , O'Connor Sarah E. , Besseau Sébastien , Courdavault Vincent 
Published: October 2024

SUMMARYPlant‐specialized metabolism represents an inexhaustible source of active molecules, some of which have been used in human health for decades. Among these, monoterpene indole alkaloids (MIAs) include a wide range of valuable compounds with anticancer, antihypertensive, or neuroactive properties. This is particularly the case for the pachysiphine derivatives which show interesting antitumor and anti‐Alzheimer activities but accumulate at very low levels in several Tabernaemontana species. Unfortunately, genome data in Tabernaemontanaceae are lacking and knowledge on the biogenesis of pachysiphine‐related MIAs in planta remains scarce, limiting the prospects for the biotechnological supply of many pachysiphine‐derived biopharmaceuticals. Here, we report a raw version of the toad tree (Tabernaemontana elegans) genome sequence. These new genomic resources led to the identification and characterization of a couple of genes encoding cytochrome P450 with pachysiphine synthase activity. Our phylogenomic and docking analyses highlight the different evolutionary processes that have been recruited to epoxidize the pachysiphine precursor tabersonine at a specific position and in a dedicated orientation, thus enriching our understanding of the diversification and speciation of the MIA metabolism in plants. These gene discoveries also allowed us to engineer the synthesis of MIAs in yeast through the combinatorial association of metabolic enzymes resulting in the tailor‐made synthesis of non‐natural MIAs. Overall, this work represents a step forward for the future supply of pachysiphine‐derived drugs by microbial cell factories.
Clinical Efficacy of Hexue Tongbi Formula on Oxaliplatin-Induced Peripheral Neuropathy: A Randomized Controlled Study
Authors: Sun Lingling , Lv Yiying , Li Duo , Feng Jingyu , Chen Zhuangzhong , Lin Lizhu 
Published: October 2024

Aim: The aim of this study was to analyse the effiacy of HeXue Tongbi Formula in the treatment of oxaliplatin-induced perpheral neuropathy. Method: An open randomized, non-blind, controlled study was conducted at the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from September 2019 to December 2020. A total of 78 maligant tumor patients receiving oxaliplatin-containing chemotherapy were recruited, with half of them receiving HeXue Tongbi Formula for 4 cycles of 21 days. The study assessed the incidence and severity of perpheral neuropathy and the safety of HeXue Tongbi Formula. Result: After 4 cycles of treatment, the incidence of perpheral neuropathy in the treatment group was significantly lower than that in the control group (30.77% versus 84.62%, P < .05). The severity of perpheral neuropathy in the treatment group increased sligthly and stabilized from the third cycle, whlie it gradually increased in the control group. yhere were no severe adverse reactions to HeXue Tongbi Formula. Conclusion: HeXue Tongbi Formula demonstrated good preventive and therapeutic effects on oxaliplatin-induced perpheral neuropathy. Trial registration: This trial has been registered with the Chinese Clinical Trial Registry (ChiCTR2000032996).
Influence of Social Deprivation on Patient-Reported Outcomes in Foot and Ankle Patients
Authors: Wagers Kade , Ofori-Atta Blessing , Presson Angela , Nixon Devon 
Published: October 2024

Background: The impact of social health on patient-reported outcomes (PROs) is gaining increasing attention within the orthopaedic community. Few studies have explored any relationship between social deprivation levels and PROs in orthopaedic foot and ankle patients. Methods: We retrospectively identified patients who presented to an orthopaedic foot and ankle clinic for new evaluation. Patients completed PROs including PROMIS physical function (PF), PROMIS pain interference (PI), and the Foot and Ankle Ability Measure (FAAM). Social deprivation was measured using the Area Deprivation Index (ADI), a metric that incorporates various domains of poverty, education, housing, and employment. The ADI score quantifies the degree of social deprivation based on the 9-digit home zip code but is not a specific measure to an individual patient. Briefly, a lower ADI indicates less deprivation whereas a higher score denotes greater deprivation. Patient characteristics and outcomes were summarized and stratified by the nationally defined median ADI. Multivariable linear regression models assessed the relationships between PROs and continuous ADI controlling for demographics (age, sex, race/ethnicity, marital status, and employment status). Results: Our cohort consisted of 1565 patients with PRO and appropriate zip code data. Patients in the most-deprived median ADI split had more pain (median PROMIS-PI 62.7 vs 61.2, P = .001) and less function (median PROMIS-PF 37.1 vs 38.6, P = .021) compared with the least-deprived median ADI split. The clinical significance of these findings is unclear, though, given the minimal differences between groups for PROMIS measures. There was no relationship between ADI and FAAM scores. Conclusion: More socially deprived patients presented to the clinic with marginally less function and greater pain. Although statistically significant, the clinical significance of these relationships is unclear and merits further exploration. We plan to continue to study the connection between social deprivation and patient outcomes in specific clinical conditions as well as before/after surgical interventions. Level of Evidence: Level IV, retrospective cases series.
The high-grade B-cell lymphomas: double hit and more
Authors: Davies Andrew J. 
Published: October 2024

Abstract
Both the 2022 World Health Organization Classification of Hematolymphoid Tumors, 5th Edition and the International Consensus Classification of lymphoma have refined the way we now approach high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements moving the previous generation of classification a step forward. The unifying biology of MYC/BCL2 tumors has become clearer and their inferior prognosis confirmed compared with those with morphologic similar phenotypes but lacking the classifcation defining cytogenetic abnormalities. Fluorescent in situ hybridization testing has now become largely population based, and we have learned much from this. We can readily define molecular categories and apply these widely to clinical practice. Uncertainty has, however, been shed on the place of MYC/BCL6 translocations in defining a common disease group of double hit lymphoma due to biological heterogeneity. We have enhanced our knowledge of outcomes and the role of therapy intensification to overcome chemotherapy resistance in HGBL. For those patients failed by initial induction chemotherapy, immunotherapy approaches, including chimeric antigen receptor T-cell therapies, are improving outcomes. Novel inhibitors, targeting dysregulated oncogenic proteins, are being explored at pace. The rare, but difficult, diagnostic classification HGBL (not otherwise specified) remains a diagnosis of exclusion with limited data on an optimal clinical approach. The days of talking loosely of double- and triple-hit lymphoma are numbered as biology and outcomes may not be shared. This review synergizes the current data on biology, prognosis, and therapies in HGBL.
Enhancing cotton whitefly (Bemisia tabaci) detection and counting with a cost-effective deep learning approach on the Raspberry Pi
Authors: Feng Zhen , Wang Nan , Jin Ying , Cao Haijuan , Huang Xia , Wen Shuhan , Ding Mingquan 
Published: October 2024

Abstract
Background
The cotton whitefly (Bemisia tabaci) is a major global pest, causing significant crop damage through viral infestation and feeding. Traditional B. tabaci recognition relies on human eyes, which requires a large amount of work and high labor costs. The pests overlapping generations, high reproductive capacity, small size, and migratory behavior present challenges for the real-time monitoring and early warning systems. This study aims to develop an efficient, high-throughput automated system for detection of the cotton whiteflies. In this work, a novel tool for cotton whitefly fast identification and quantification was developed based on deep learning-based model. This approach enhances the effectiveness of B. tabaci control by facilitating earlier detection of its establishment in cotton, thereby allowing for a quicker implementation of management strategies.

Results
We compiled a dataset of 1200 annotated images of whiteflies on cotton leaves, augmented using techniques like flipping and rotation. We modified the YOLO v8s model by replacing the C2f module with the Swin-Transformer and introducing a P2 structure in the Head, achieving a precision of 0.87, mAP50 of 0.92, and F1 score of 0.88 through ablation studies. Additionally, we employed SAHI for image preprocessing and integrated the whitefly detection algorithm on a Raspberry Pi, and developed a GUI-based visual interface. Our preliminary analysis revealed a higher density of whiteflies on cotton leaves in the afternoon and the middle-top, middle, and middle-down plant sections.

Conclusion
Utilizing the enhanced YOLO v8s deep learning model, we have achieved precise detection and counting of whiteflies, enabling its application on hardware devices like the Raspberry Pi. This approach is highly suitable for research requiring accurate quantification of cotton whiteflies, including phenotypic analyses. Future work will focus on deploying such equipment in large fields to manage whitefly infestations.
A review on the promising antibacterial agents in bone cement–From past to current insights
Authors: Lin Hao , Gao Zhe , Shan Tao , Asilebieke Ayakuzi , Guo Rui , Kan Yu-chen , Li Chun , Xu Yang , Chu Jian-jun 
Published: October 2024

AbstractAntibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents to address these defects. In this review, we provide an overview and prospect of the new antibacterial agents that can be used or have the potential to be applied in bone cement, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides and enzymes. Additionally, we have conducted a preliminary assessment of the feasibility of bone cement containing N-halamine, which has demonstrated good antibacterial activities. The conclusion of this review is that the research and utilization of bone cement containing novel antibacterial agents contribute to addressing the limitations of ALBCs. Therefore, it is necessary to continue expanding the research and use of bone cement incorporating novel antibacterial agents. This review offers a novel perspectives for designing ABCs and treating bone infections.
Graphical abstract
Establishment of a value assessment framework for orphan medicinal products in China
Authors: Chen Handong , Xiang Yuliang , Tang Xian , Hu Ming 
Published: October 2024

Abstract
Background
This study aimed to establish a suitable value assessment framework for orphan medicinal products in China based on the multi-criteria decision analysis (MCDA) method.

Methods
First, a draft framework of the MCDA criteria was built based on a systematic literature evaluation and the EVIDEM framework tools. Second, stakeholder groups were formed and expert opinions were collected through the brainstorming and expert consultation methods. Third, from the perspective of stakeholders, the five-point weighting method and a two-step percentile distribution method were employed to weigh the quantitative criteria in the framework for orphan drug value evaluation. Meanwhile, from the public perspective, a survey was conducted on a sample of 71 people to obtain the scoring scale of the framework for orphan drugs through a two-step percentile distribution method. Finally, based on the synthetization and comparison of all evidence and methods, we developed the framework criteria and scoring scale for the orphan medicinal products.

Results
Combined with the stakeholder selection and suggestions in the stakeholder workshop, the framework criteria for the evaluation were constructed based on China’s national conditions, which included 11 quantitative and 8 qualitative criteria. The two-step percentile distribution method was selected as the weighting method.

Conclusions
MCDA is feasible for the value assessment of orphan drugs in China and can be used as a supplementary tool for drug access decisions in medical insurance. It is suggested to further improve the value assessment framework of orphan medicinal products, scientifically evaluate the MCDA framework weighting method, explore a framework system suitable for China’s national conditions.