bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maize functional requirements drive the selection of rhizobacteria under long‐term fertilization practices
Authors: Zhang Liyu , Yuan Liang , Wen Yanchen , Zhang Meiling , Huang Shuyu , Wang Shiyu , Zhao Yuanzheng , Hao Xiangxiang , Li Lujun , Gao Qiang , Wang Yin , Zhang Shuiqing , Huang Shaomin , Liu Kailou , Yu Xichu , Li Dongchu , Xu Jiukai , Zhao Bingqiang , Zhang Lu , Zhang Huimin , Zhou Wei , Ai Chao 
Published: March 2024

Summary

Rhizosphere microbiomes are pivotal for crop fitness, but the principles underlying microbial assembly during root–soil interactions across soils with different nutrient statuses remain elusive.

We examined the microbiomes in the rhizosphere and bulk soils of maize plants grown under six long‐term (≥ 29 yr) fertilization experiments in three soil types across middle temperate to subtropical zones.

The assembly of rhizosphere microbial communities was primarily driven by deterministic processes. Plant selection interacted with soil types and fertilization regimes to shape the structure and function of rhizosphere microbiomes. Predictive functional profiling showed that, to adapt to nutrient‐deficient conditions, maize recruited more rhizobacteria involved in nutrient availability from bulk soil, although these functions were performed by different species. Metagenomic analyses confirmed that the number of significantly enriched Kyoto Encyclopedia of Genes and Genomes Orthology functional categories in the rhizosphere microbial community was significantly higher without fertilization than with fertilization. Notably, some key genes involved in carbon, nitrogen, and phosphorus cycling and purine metabolism were dominantly enriched in the rhizosphere soil without fertilizer input.

In conclusion, our results show that maize selects microbes at the root–soil interface based on microbial functional traits beneficial to its own performance, rather than selecting particular species.
Connectivity Constraints Ensuring Continuous Electrodes in Topology Optimization of Electroactive Polymer
Authors: Hård Daniel , Wallin Mathias , Ristinmaa Matti 
Published: March 2024

Abstract
Electroactive polymers (EAPs) deform when subject to an electric field, which is generated by two or more electrodes. To ensure proper function of the EAP, these electrodes are connected to a source and they are therefore required to be continuous such that no isolated islands exist. Increasing an EAP’s performance using topology optimization while ensuring electrode connectivity is the goal of this work. A topology optimization formulation is introduced where electrode connectivity is ensured using the virtual temperature method. Numerical experiments demonstrate that this is an efficient method to guarantee connectivity.
Flip the switch: the role of FleQ in modulating the transition between the free-living and sessile mode of growth in
Pseudomonas aeruginosa
Authors: Oladosu Victoria I. , Park Soyoung , Sauer Karin 
Published: March 2024

ABSTRACT

Pseudomonas aeruginosa
is a Gram-negative, opportunistic pathogen causing chronic infections that are associated with the sessile/biofilm mode of growth rather than the free-living/planktonic mode of growth. The transcriptional regulator FleQ contributes to both modes of growth by functioning both as an activator and repressor and inversely regulating flagella genes associated with the planktonic mode of growth and genes contributing to the biofilm mode of growth. Here, we review findings that enhance our understanding of the molecular mechanism by which FleQ enables the transition between the two modes of growth. We also explore recent advances in the mechanism of action of FleQ to both activate and repress gene expression from a single promoter. Emphasis will be on the role of sigma factors, cyclic di-GMP, and the transcriptional regulator AmrZ in inversely regulating flagella and biofilm-associated genes and converting FleQ from a repressor to an activator.
Structure-guided mutagenesis of Henipavirus receptor-binding proteins reveals molecular determinants of receptor usage and antibody-binding epitopes
Authors: Oguntuyo Kasopefoluwa Y. , Haas Griffin D. , Azarm Kristopher D. , Stevens Christian S. , Brambilla Luca , Kowdle Shreyas S. , Avanzato Victoria A. , Pryce Rhys , Freiberg Alexander N. , Bowden Thomas A. , Lee Benhur 
Published: March 2024

ABSTRACT

Nipah virus (NiV) is a highly lethal, zoonotic Henipavirus (HNV) that causes respiratory and neurological signs and symptoms in humans. Similar to other paramyxoviruses, HNVs mediate entry into host cells through the concerted actions of two surface glycoproteins: a receptor-binding protein (RBP) that mediates attachment and a fusion glycoprotein (F) that triggers fusion in an RBP-dependent manner. NiV uses ephrin-B2 (EFNB2) and ephrin-B3 (EFNB3) as entry receptors. Ghana virus (GhV), a novel HNV identified in a Ghanaian bat, uses EFNB2 but not EFNB3. In this study, we employ a structure-informed approach to identify receptor-interfacing residues and systematically introduce GhV-RBP residues into a NiV-RBP backbone to uncover the molecular determinants of EFNB3 usage. We reveal two regions that severely impair EFNB3 binding by NiV-RBP and EFNB3-mediated entry by NiV pseudotyped viral particles. Further analyses uncovered two-point mutations (
NiV
N557S
GhV
and
NiV
Y581T
GhV
) pivotal for this phenotype. Moreover, we identify NiV interaction with Y120 of EFNB3 as important for the usage of this receptor. Beyond these EFNB3-related findings, we reveal two domains that restrict GhV binding of EFNB2, confirm the HNV-head as an immunodominant target for polyclonal and monoclonal antibodies, and describe putative epitopes for GhV- and NiV-specific monoclonal antibodies. Cumulatively, the work presented here generates useful reagents and tools that shed insight to residues important for NiV usage of EFNB3, reveal regions critical for GhV binding of EFNB2, and describe putative HNV antibody-binding epitopes.

IMPORTANCE
Hendra virus and Nipah virus (NiV) are lethal, zoonotic Henipaviruses (HNVs) that cause respiratory and neurological clinical features in humans. Since their initial outbreaks in the 1990s, several novel HNVs have been discovered worldwide, including Ghana virus. Additionally, there is serological evidence of zoonotic transmission, lending way to concerns about future outbreaks. HNV infection of cells is mediated by the receptor-binding protein (RBP) and the Fusion protein (F). The work presented here identifies NiV RBP amino acids important for the usage of ephrin-B3 (EFNB3), a receptor highly expressed in neurons and predicted to be important for neurological clinical features caused by NiV. This study also characterizes epitopes recognized by antibodies against divergent HNV RBPs. Together, this sheds insight to amino acids critical for HNV receptor usage and antibody binding, which is valuable for future studies investigating determinants of viral pathogenesis and developing antibody therapies.
Complete genome sequence of
Methanosphaera
sp. ISO3-F5, a rumen methylotrophic methanogen
Authors: Palevich Nikola , Jeyanathan Jeyamalar , Reilly Kerri , Palevich Faith P. , Maclean Paul H. , Li Dong , Altermann Eric , Kelly William J. , Leahy Sinead C. , Attwood Graeme T. , Ronimus Ron S. , Henderson Gemma , Janssen Peter H. 
Published: March 2024

ABSTRACT

Methanosphaera
spp. are methylotrophic methanogenic archaea and members of the order Methanobacteriales with few cultured representatives.
Methanosphaera
sp. ISO3-F5 was isolated from sheep rumen contents in New Zealand. Here, we report its complete genome, consisting of a large chromosome and a megaplasmid (GenBank accession numbers
CP118753
and
CP118754
, respectively).
Geriatric screening and comprehensive geriatric assessment during initial oncology appointments
Authors: Madureira Tânia , Magalhães Joana , Vilas Pedro , Campôa Elsa , Luz Paulo , Coutinho Filipe 
Published: March 2024

IntroductionGeriatric oncology underscores the significance of assessing functional age in guiding medical decisions, endeavouring to delineate practical and efficacious methodologies for evaluating functionality, adapting therapeutic regimens and attenuating the risks of treatment-related deterioration.Objectives and MethodsIn this prospective study, we aimed to delineate the characteristics of older patients presenting for their initial oncology appointment by using geriatric screening (G8 score) and comprehensive geriatric assessment (CGA), while also assessing the feasibility of these evaluations. Secondary objectives included comparing the initial Eastern Cooperative Oncology Group (ECOG) performance status and any deviations from standard therapeutic strategies against the identified frailty in geriatric assessment.ResultsMost patients exhibited a G8 score ≤14 and underwent comprehensive geriatric assessment. While oncologists typically perceive patients’ general conditions, CGA enables a systematic assessment, providing a comprehensive characterisation of elderly patients to inform therapeutic decisions and address identified fragilities. The CGA highlighted vulnerabilities across all primary domains. Notably, even among patients with ECOG scores of 0 and 1, the application of G8 score and CGA revealed numerous fragilities. Consistent with existing literature, these scales offered additional insights beyond ECOG evaluation alone, suggesting their potential to guide therapeutic adaptations for this demographic.ConclusionOngoing research and continuous evaluation are imperative to refine and broaden the implementation of geriatric-focused interventions.
Abstract A036: Female spouse caregivers of patients with glioblastoma want better education and communication from health care professionals regarding what to expect during the disease progression
Authors: Coman Diana L. , Chard Megan P. , Lutz Barbara J. , Minns Laurie A. 
Published: March 2024

Abstract
The purpose of this study was to understand the challenges and unmet needs of primary spousal caregivers of patients with glioblastoma multiforme (GBM) through a qualitative analysis of letters written by current and former caregivers. GBM is a devastating and terminal cancer that results in memory loss, cognitive declines, personality changes, neuropsychiatric symptoms, and physical impairments that greatly affect quality of life of both the patient with GBM and their primary caregiver, who is often a spouse or partner. Open-ended letters (n=101) written by self-identified female spouse caregivers were analyzed using reflexive thematic analysis (IRB #22-0103). The six phases of reflexive thematic analysis involved 1) data familiarization, 2) systematic data coding, 3) generation of initial themes, 4) development and reviewing themes, 5) refinement and re-naming of themes and 6) writing the report to provide insight into caregiver’s experience. Seven distinct themes were identified from the letters. Three of the themes related to the patient experiences: 1) medical details of the disease trajectory (87%), 2) interactions of the patient/caregiver dyad with health care workers (67%), and 3) the changing patient condition over time (98%). Four themes focused on the caregiver experience: 1) caregiver challenges (80%), 2) caregiver responses (77%), 3) caregiver coping strategies (85%), and description of tangible needs that would help other caregivers in the future (91%). When mapped to the four phases of the caregiving trajectory: acute disease phase, living with disease progression, end of life phase, and the bereavement phase, caregivers needed better communication and support in every phase. The highest caregiver needs were for better education about GBM from health care professionals regarding what to expect and better communication with health care providers about disease progression, treatment options, and anticipated patient, caregiver, and family needs (65%). Caregivers indicated they wanted to be listened to and included in medical decision-making. These findings on the primary caregivers’ experiences provide opportunities to guide more timely and tailored interventions to provide support and improve care for patient/caregiver dyads to help mitigate the burden of this progressive disease and improve quality of life for caregivers and their patients with GBM.
Citation Format: Diana L. Coman, Megan P. Chard, Barbara J. Lutz, Laurie A. Minns. Female spouse caregivers of patients with glioblastoma want better education and communication from health care professionals regarding what to expect during the disease progression [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A036.
Abstract A046: Exogenous CD200 suppressing T cells is CD200R1 independent
Authors: Xiong Zhengming , Olin Micheal R. 
Published: March 2024

Abstract
As one of immune checkpoint blockade, CD200 is widely considered to exert immunosuppressive and inflammatory suppressive functions through receptors on its immune cell membrane (1,2,3). Unlike the widespread use of anti-PD-1, few successful studies have been reported in the use of anti-CD200/CD200R in anti-tumor immunotherapy researches. This makes it necessary to re-understand the mechanism of action and biological effects of CD200 protein. We studied antigen-presenting cells and T cells in an environment where CD200R1 knockout macrophages and wild-type macrophages interact with antigen-specific T cells, respectively, and in vitro in human PBMCs using synthetic CD200 membrane segments. Changes in immune function and gene expression in signaling pathways is also involved. The experimental results show that comparing with inactivated human PBMC, CD200-Fc fusion protein significantly inhibited the division of human PBMC cells activated by ConA (Fig 1). Further experiments showed that the recombinant CD200 extracellular domain has a positive inhibitory effect on IL6, TNF and IL17A produced from PBMCs activated by PMA + ionomycin but has no effect on the production of IFNr. The recombinant CD200 extracellular domain itself can induce a large amount of IL6. (Fig.2). In view of the close relationship between IFNr and antigen-TCR function, we speculate that CD200 protein has no direct relationship with immunosuppression of antigen-specific T cells. To this end, we performed the following experiments. When CD200 plus gp100 antigen polypeptide acted on only CD200R1 knock out macrophages, cocultured gp100 antigen-specific CD3 T cells produced significantly less IFNr and TNF than only gp100 antigen polypeptide stimulation (IFNr 227.8pg/ml vs 803.2 pg/ml, p &lt;0.01); TNF 3984pg/ml vs 5187pg/ml, p &lt;0.0001). Moreover, when using CD200 plus gp100 antigen polypeptide as stimuli of the APC, IFNr and TNF production during T cells cocultured with the APCs are not significant different between the macrophage groups with and without CD200R1 gene (IFNr 161.8pg/ml vs 227.8 pg/ml p&gt; 0.05; TNF 3715pg/ml vs 3984pg/ml, p&gt; 0.05). This indicates that CD200R1 is not required for the immunosuppressive function of CD200 in relation with antigen. Secondly, IFNr produced by T cells induced by gp100 on CD200R1 knockout macrophages was significantly higher than that of wild-type macrophages (IFNr 803.2pg/ml vs 329.3pg/ml, p&lt;0.01), which indicates that inactivated CD200R1 itself has positively regulated the activity of the antigen-TCR system. (Fig.4) In short, exogenous CD200 induces immunosuppression of antigen-specific T cells through a CD200R1-independent mechanism.
Citation Format: Zhengming Xiong, Micheal R. Olin. Exogenous CD200 suppressing T cells is CD200R1 independent [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A046.
Abstract A051: Treatment outcome of leptomeningeal metastasis from breast cancer
Authors: Kim Suzy , Lee Choong-won 
Published: March 2024

Abstract
Purpose: Leptomeningeal metastasis (LM) is well-known for its dismal prognosis. Despite various treatment approaches, there has been minimal improvement in survival, and the optimal treatment for leptomeningeal metastasis remains uncertain. Our study aimed to report treatment outcomes using different modalities for LM and to identify prognostic factors. Materials and Methods: We analyzed 111 breast cancer patients with LM, who were treated at Seoul National University and Seoul Metropolitan Government Seoul National University Boramae Medical Center between January 2010 and December 2022. The median follow-up period was 4.4 months (range, 0.2 – 125.4 months). Results: The median age was 48 years, with the majority having a Karnofsky performance status below 60 (n = 100, 90.1%). Among the 111 patients, intrathecal chemotherapy was the most commonly used treatment modality (n = 89, 80.2%), followed by radiotherapy (n = 74, 66.7%), and systemic chemotherapy (n = 56, 50.5%). The median freedom from progression was 3.4 months. In multivariate analysis, patients who underwent more than 2 treatment modalities experienced significantly longer progression-free interval (1.8 months vs. 7.4 months, HR = 0.20, p = 0.038). Additionally, patients who underwent excision of the primary breast tumor displayed a tendency for longer progression-free interval (3.1 months vs. 3.4 months, HR = 0.33, p = 0.084). Patients with systemic inflammation index greater than 500 × 103/mm3 at the time of the diagnosis of LM exhibited shorter progression-free interval (3.5 months vs. 2.9 months, HR = 2.88, p = 0.056). There was no difference of progression-free interval according to treatment modalities. Conclusions: The freedom from progression of LM originating from breast cancer was found to be poor, exhibiting less than 4 months. A multimodal approach upon LM and high systemic inflammation index at the time of the diagnosis of LM demonstrated significant difference in prognosis. Further research is warranted to elucidate the clinical implications and develop optimized treatment strategie
Citation Format: Suzy Kim, Choong-won Lee. Treatment outcome of leptomeningeal metastasis from breast cancer [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A051.
Abstract B046: Irradiation of patient-derived high-grade gliomas reduces 5-ALA-induced fluorescence utility during re-resection
Authors: Minhas Paras S. , Durairaj Aarooran , McReynolds Melanie , Andreasson Katrin I. , Jung YooJin , Rabinowitz Joshua 
Published: March 2024

Abstract
High grade gliomas HGGs are among the most aggressive primary brain tumors, yielding a median survival time of less than 2 years and a 5-year survival of 2.5%. There has been little in the way of treatments and novel approaches are needed to combat HGG’s poor prognosis. Recent studies have established that HGG cells exhibit metabolic reprogramming to adapt to diverse metabolic gradients within heterogenous tumor microenvironments. Using an unbiased metabolomics approach, we investigated metabolic changes both pre- and post-ionizing radiation across several patient-derived cell lines. Acute dosages of ionizing radiation resulted in significant changes in the synthesis of aminolevulinic acid (ALA), which is known to be converted into the fluorescent metabolite protoporphyrin IX (PpIX) in the porphyrin synthesis pathway. PpIX has been utilized by surgeons in fluorescence-guided tumor resection for clearer visualization of tumor boundaries in recent years. Fractionation of radiation therapy also resulted in dose-dependent changes in the pathway concerning heme synthesis within these cells, especially presenting decreased levels of ALA dehydratase (ALAD) and increased levels of ferrochelatase. As ALAD promotes PpIX accumulation and ferrochelatase catalyzes its conversion to heme, this indicates a decreased favorability for the accumulation of PpIX in the reprogrammed metabolism of HGG cells following radiation. Consequently, we propose that PpIX fluorescence is not a reliable visual aide in surgical re-resection of HGGs post-radiation therapy.
Citation Format: Paras S. Minhas, Aarooran Durairaj, Melanie McReynolds, Katrin I. Andreasson, YooJin Jung, Joshua Rabinowitz. Irradiation of patient-derived high-grade gliomas reduces 5-ALA-induced fluorescence utility during re-resection [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr B046.
Abstract B051: DNA damage signaling activates GTP synthesis to promote glioblastoma treatment resistance
Authors: Scott Andrew J. , O'Brien Alexandra , Zhou Weihua , Xu Jie , Palavalasa Sravya , Kothari Ayesha U. , Wilder-Romans Kari , Zhang Li , Andren Anthony C. , Chandrasekaran Sriram , Heth Jason , Umemura Yoshie , Qi Nathan , Lawrence Theodore S. , Al-Holou Wajd N. , Lyssiotis Costas A. , Wahl Daniel R 
Published: March 2024

Abstract
Glioblastoma (GBM) is the most common type of invasive brain tumor in adults and is uniformly fatal due to inherent resistance to radiation therapy (RT) and chemotherapy. Our group and others have found that metabolites can regulate DNA repair and therapy resistance in brain tumors, but little is known about how DNA damage regulates metabolic pathway activity in cancer. Here we show that following treatment with RT, GBMs increase rates of de novo guanylate synthesis in vitro and in orthotopic patient-derived xenograft models via signaling through the DNA repair protein DNA-PK. To determine if disrupting this regulation can augment GBM treatment efficacy, we combined an FDA-approved inhibitor of purine synthesis (mycophenolate mofetil, MMF) with chemoradiation in a variety of mouse models of GBM. Critically, targeting GTP synthesis improved the efficacy of both RT alone and chemoradiation in multiple patient-derived and syngeneic intracranial models. Our translational studies have shown that mycophenolic acid, the active metabolite of MMF, penetrates the blood-brain barrier at concentrations sufficient to inhibit GTP synthesis in GBMs of human patients. The phase 1 arms of our study, which are ongoing, are testing the safety and efficacy of combining MMF with standard of care chemoradiation for patients with primary and recurrent GBM.
Citation Format: Andrew J. Scott, Alexandra O'Brien, Weihua Zhou, Jie Xu, Sravya Palavalasa, Ayesha U. Kothari, Kari Wilder-Romans, Li Zhang, Anthony C. Andren, Sriram Chandrasekaran, Jason Heth, Yoshie Umemura, Nathan Qi, Theodore S. Lawrence, Wajd N. Al-Holou, Costas A. Lyssiotis, Daniel R Wahl. DNA damage signaling activates GTP synthesis to promote glioblastoma treatment resistance [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr B051.