bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macroscale impact assessment of flood damage reduction from climate change adaptation policies
Authors: Jee Hee Won , Seo Seung Beom , Ko Kyeong‐Moon , Cho Jaepil , Chae Yeora 
Published: January 2024

AbstractAdaptation policies are being increasingly implemented to cope with the increased frequency of natural disasters due to climate change. However, it is crucial to quantitatively evaluate the mitigating effects of these policies, as this allows for their assessment and prioritization. Therefore, this study sought to develop a nonlinear flood damage function for each administrative region of South Korea to quantify the potential damage caused by extreme rainfall events. Afterward, a power function was nested to model the coefficient of the flood damage function with regional factors characterizing each region's flood mitigation capacity. Here, regional factors were selected based on their linkage to two potential adaptation policies: enhancing retention reservoir and pumping capacity and enhancing river dike construction. The proposed evaluation framework was tested in 15 administrative districts in South Korea and the flood damage reduction effects of the two policy scenarios were estimated. The enhancement of retention reservoir and pumping capacity showed a 6.7% reduction effect, whereas enhancing river dike construction showed a 29.2% reduction effect. The implementation of both policies yielded a 34.3% reduction effect. Despite the limitations of this study, our findings still provide a quantitative comparison of the long‐term effects of national climate change adaptation measures. Additionally, accumulating more damage records would allow for the development of damage functions at a finer scale.
Binucleate Rhizoctonia AG‐A causing black root rot of strawberry in Albania
Authors: Cara Magdalena , Merkuri Jordan , Salliu Alkida , Vojvodić Mira , Knežević Isidora , Grkinić Miljan , Bulajić Aleksandra 
Published: January 2024

AbstractStrawberry production in Albania is very important and growing rapidly, while data on strawberry diseases are lacking. In 2022, symptoms of leaf necrosis, root rot, and wilt were observed on strawberry plants of cultivars ‘Savana’, ‘Sabrina’, and ‘Fortuna’ in greenhouses near Vajkan, Fier, Albania. The disease incidence was estimated at 50%. Only isolates of Rhizoctonia spp. were obtained from symptomatic plants. The isolates formed fast‐growing, white colonies with binucleate, typically branching hyphae and no sclerotia, resembling Rhizoctonia AG‐A. BLAST analyses of the ITS rDNA of isolate RhizAl (accession number OR231136) revealed the highest nt homology of 99%–100% (100% query coverage) with binucleate Rhizoctonia AG‐A isolates, while the neighbour‐joining phylogenetic analyses confirmed the identification. The pathogenicity of the isolate RhizAl was demonstrated by inoculations of disease‐free strawberry daughter plants (cv. ‘Fortuna’) that developed mild wilting and leaf necrosis 45 days after inoculation while plants collapsed with root necrosis 60 days after inoculation. In this study, binucleate Rhizoctonia AG‐A was detected for the first time as a causal agent of black root rot of strawberries in Albania and in general, and studies on the general importance of Rhizoctonia spp. in different crops in Albania are needed.
Evidence that genetic drift not adaptation drives fast‐Z and large‐Z effects in Ficedula flycatchers
Authors: Chase Madeline A. , Vilcot Maurine , Mugal Carina F. 
Published: January 2024

AbstractThe sex chromosomes have been hypothesized to play a key role in driving adaptation and speciation across many taxa. The reason for this is thought to be the hemizygosity of the heteromorphic part of sex chromosomes in the heterogametic sex, which exposes recessive mutations to natural and sexual selection. The exposure of recessive beneficial mutations increases their rate of fixation on the sex chromosomes, which results in a faster rate of evolution. In addition, genetic incompatibilities between sex‐linked loci are exposed faster in the genomic background of hybrids of divergent lineages, which makes sex chromosomes contribute disproportionately to reproductive isolation. However, in birds, which show a Z/W sex determination system, the role of adaptation versus genetic drift as the driving force of the faster differentiation of the Z chromosome (fast‐Z effect) and the disproportionate role of the Z chromosome in reproductive isolation (large‐Z effect) are still debated. Here, we address this debate in the bird genus Ficedula flycatchers based on population‐level whole‐genome sequencing data of six species. Our analysis provides evidence for both faster lineage sorting and reduced gene flow on the Z chromosome than the autosomes. However, these patterns appear to be driven primarily by the increased role of genetic drift on the Z chromosome, rather than an increased rate of adaptive evolution. Genomic scans of selective sweeps and fixed differences in fact suggest a reduced action of positive selection on the Z chromosome.
Clinical outcomes and frequency of persistent infection among immunosuppressed patients treated with bebtelovimab for COVID‐19 infection at an ambulatory cancer center
Authors: Sanchez Eduardo , Krantz Elizabeth M , Yoke Leah , Gallaher Molly , Bhattacharyya Pooja , So Lisa , Escobar Zahra Kassamali , Tverdek Frank , Rosen Emily A , Quinn ZZ , Swetky Michelle , Walji Salma , Wilson Marie H. , McCreery Brittany , McCulloch Denise , Weixler Amelia , Roychoudhury Pavitra , Pergam Steven A , Liu Catherine 
Published: January 2024

AbstractBackgroundThere are limited data on clinical outcomes associated with the use of bebtelovimab for the treatment of coronavirus disease 2019 (COVID‐19) among cancer patients. We aimed to define the clinical characteristics and outcomes among patients receiving bebtelovimab as part of the COVID‐19 therapeutics program at our cancer center.MethodsThis is a retrospective cohort study of immunosuppressed adult patients who received bebtelovimab at Fred Hutchinson Cancer Center between March 2022, and November 2022. We reviewed medical records to capture the date of the first positive COVID‐19 test, clinical characteristics, outcomes, and follow‐up COVID‐19 testing for 60 days after the first positive. Persistent infection was defined as a positive test beyond day 30; these patients were reviewed beyond day 60.ResultsAmong 93 patients who received bebtelovimab, 64 (69%) had hematologic malignancy. Sixty‐nine (74%) patients received bebtelovimab within 2 days after diagnosis. Two (2%) patients were hospitalized, none required ICU care, and one patient died on day 52; although it is unknown if death was directly related to COVID‐19. Ten (11%) patients had persistent COVID‐19 infection; of these, four received additional COVID‐19 therapy with either nirmatrelvir/ritonavir or remdesivir, and five out of six patients with sequencing data available had spike protein mutations associated with bebtelovimab resistance.ConclusionA coordinated systems‐based approach led to prompt initiation of bebtelovimab within two days of testing positive in most patients. We observed few hospitalizations or deaths. Persistent infection was noted in 11% of patients with four requiring additional therapies, highlighting a need for novel strategies to manage immunosuppressed patients.
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Effects of organic fertilizers on plant growth and the rhizosphere microbiome
Authors: Yu Yitian , Zhang Qi , Kang Jian , Xu Nuohan , Zhang Zhenyan , Deng Yu , Gillings Michael , Lu Tao , Qian Haifeng 
Published: January 2024

ABSTRACT

Application of organic fertilizers is an important strategy for sustainable agriculture. The biological source of organic fertilizers determines their specific functional characteristics, but few studies have systematically examined these functions or assessed their health risk to soil ecology. To fill this gap, we analyzed 16S rRNA gene amplicon sequencing data from 637 soil samples amended with plant- and animal-derived organic fertilizers (hereafter plant fertilizers and animal fertilizers). Results showed that animal fertilizers increased the diversity of soil microbiome, while plant fertilizers maintained the stability of soil microbial community. Microcosm experiments verified that plant fertilizers were beneficial to plant root development and increased carbon cycle pathways, while animal fertilizers enriched nitrogen cycle pathways. Compared with animal fertilizers, plant fertilizers harbored a lower abundance of risk factors such as antibiotic resistance genes and viruses. Consequently, plant fertilizers might be more suitable for long-term application in agriculture. This work provides a guide for organic fertilizer selection from the perspective of soil microecology and promotes sustainable development of organic agriculture.

IMPORTANCE
This study provides valuable guidance for use of organic fertilizers in agricultural production from the perspective of the microbiome and ecological risk.
Biosynthetic mechanism of the yellow pigments in the marine bacterium
Pseudoalteromonas
sp. strain T1lg65
Authors: Ren Yixuan , Liu Ruoyu , Zheng Yifan , Wang Hang , Meng Qiu , Zhu Tingheng , Yin Jianhua , Cao Xueqiang , Yu Zhiliang 
Published: January 2024

ABSTRACT

The
Pseudoalteromonas
genus marine bacteria have attracted increasing interest because of their abilities to produce bioactive metabolites. The pigmented
Pseudoalteromonas
group encodes more secondary metabolite biosynthetic gene clusters (BGCs) than the non-pigmented group. Here, we report a yellow pigmented bacterium
Pseudoalteromonas
sp. strain T1lg65, which was isolated from a mangrove forest sediment. We showed that the yellow pigments of T1lg65 belong to the group of lipopeptide alterochromides. Further genetic analyses of the alterochromide BGC revealed that the yellow pigments are biosynthesized by aryl-polyene synthases and nonribosomal peptide synthases. Within the gene cluster,
altA
encodes a tyrosine ammonia acid lyase, which catalyzes synthesis of the precursor 4-hydroxycinnamic acid (4-HCA) from tyrosine in the alterochromide biosynthetic pathway. In addition,
altN
, encoding a putative flavin-dependent halogenase, was proven to be responsible for the bromination of alterochromides based on gene deletion, molecular docking, and site mutagenesis analyses. In summary, the biosynthetic pathway, precursor synthesis, and bromination mechanism of the lipopeptide alterochromides were studied in-depth. Our results expand the knowledge on biosynthesis of
Pseudoalteromonas
pigments and could promote the development of active pigments in the future.

IMPORTANCE

The marine bacteria
Pseudoalteromonas
spp. are important biological resources because they are producers of bioactive natural products, including antibiotics, pigments, enzymes, and antimicrobial peptides. One group of the microbial pigments, alterochromides, holds a great value for their novel lipopeptide structures and antimicrobial activities. Previous studies were limited to the structural characterization of alterochromides and genome mining for the alterochromide biosynthesis. This work focused on the biosynthetic mechanism for alterochromide production, especially revealing functions of two key genes within the gene cluster for the alterochromide biosynthesis. On the one hand, our study provides a target for metabolic engineering of the alterochromide biosynthesis; on the other hand, the 4-HCA synthase AltA and brominase AltN show potential in the biocatalyst industry.
Abstract A005: Enhanced DNA damage and disruption of repair by iodinated thymidine analogues with Tipiracil for clinical radiation sensitization
Authors: Grindrod Scott , Velana Alfredo , Rich Tyvin , Jung Mira , Pang Dalong , Dritschilo Anatoly 
Published: January 2024

Abstract
IUdR incorporation into cellular DNA enhances radiation induced DNA damage and impairs repair pathways. IUdR has been explored as a clinical radiation sensitizer in Phase I and II clinical trials of sarcomas and gliomas, showing clinical activity. A major barrier to acceptance of this therapy has been the poor pharmacokinetic (PK) profile of IUdR which has a blood plasma half-life of less than 10 minutes. Continuous IV infusion of IUdR has been used to achieve clinically relevant DNA incorporation into tumor cells, but technical limitations of delivery and acute toxicities in rapidly proliferating normal tissues presented barriers to advancing this approach. To improve the PK profile of IUdR, a prodrug strategy has been employed leading to the development of ropidoxuridine (IPdR), which improved the PK profile, demonstrated oral bioavailability of the active metabolite IUdR, showed less normal tissue toxicity, and provided tumor radiation sensitization. IPdR plus XRT has been tested in Phase 0 and Phase 1 clinical trials and a phase II trial is proposed for glioblastoma treatment. We report here a second approach to improve the PK profile of orally administered IUdR by combining these iodinated thymidine analogs with the metabolism inhibitor, Tipiracil (TPI) which inhibits thymidine phosphorylase, the primary enzyme responsible for irreversible IUdR degradation, and is currently used in the FDA approved combination drug Lonsurf. Oral co-administration of IUdR and TPI in rats dramatically improved the PK profile of IUdR, increasing the half-life of the compound to 1.5 hours and boosting the maximum plasma concentration by approximately 8-fold. We studied the effects of Tipiracil on the metabolism of IUdR by varying the molecular ratio of IUdR/TPI from 2:1 up to a ratio of 10:1 and discovered that the plasma concentration of IUdR plateaued between a ratio of 5:1 and 10:1. This new combination therapy of IUdR/TPI yields a PK profile of IUdR that is relevant to clinical treatment in combination with RT and offers to expand potential clinical radiation sensitizer applications.
Citation Format: Scott Grindrod, Alfredo Velana, Tyvin Rich, Mira Jung, Dalong Pang, Anatoly Dritschilo. Enhanced DNA damage and disruption of repair by iodinated thymidine analogues with Tipiracil for clinical radiation sensitization [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A005.
Abstract A007: Ser/Thr kinase BUB1 stabilizes DNAPKcs in response to radiation induced DNA double strand break repair
Authors: Sriramulu Sushmitha , Thoidingjam Shivani , Brown Stephen , Siddiqui Farzan , Movsas Benjamin , Green Michael , Speers Corey , Nyati Shyam 
Published: January 2024

Abstract
Ser/Thr kinase BUB1 is known to regulate chromosomal segregation during mitosis. However, its exact role in DNA damage repair in response to radiotherapy remained elusive. Here, we demonstrate that inhibition of BUB1 kinase activity (BAY1816032) or genomic depletion (CRISPR) lead to radiation sensitization in triple negative breast cancer and lung cancer cell lines and in TNBC tumor xenograft models. Mechanistic studies demonstrated reduced DNA-DSB repair (γ-H2AX foci assay), and effect on the NHEJ pathway by the bioluminescent DNA repair reporter (BLRR). Gene expression analysis show that BUB1 expression correlates tightly with key members of the NHEJ machinery including H2AX, ATM, 53BP1, DNAPKcs, Ku70, Ku80, Lig4 among others. Cycloheximide-chase experiments demonstrate that BUB1 ablation (pharmacological or genomic) stabilizes DNAPKcs after irradiation. The half-lives (t1/2) of total-DNAPK, phospho-DNAPK could not be estimated in BUB1 ablated cells post radiotherapy. Conversely, we observed BUB1 stabilization following radiotherapy alone while pre-treatment with BUB1i or DNAPKi caused robust degradation of BUB1 (significantly shorter t1/2). Nuclear and chromatin fractionation assays revealed an increase in the phospho- and total- DNAPK, ATM, and KAP1 in nuclear fractions and in chromatin enriched fractions in BUB1 inhibited or depleted cells. There was no significant change in the levels of Ku70 and Ku80 in the nuclear fractions or in the chromatin enriched fractions. This data indicates that BUB1 may be involved in the activation and recruitment of key NHEJ proteins (ATM, DNAPKcs) to DSBs. Further experiments are underway to determine how BUB1 stabilizes DNAPKcs and regulate chromatin loading of key NHEJ factors following radiation. Additionally, we demonstrate that BUB1 mediate apoptotic cell death of cancer cells post-radiation. Our findings suggest that BUB1 may serve as a novel molecular target for radiosensitization in various solid cancers including TNBC.
Citation Format: Sushmitha Sriramulu, Shivani Thoidingjam, Stephen Brown, Farzan Siddiqui, Benjamin Movsas, Michael Green, Corey Speers, Shyam Nyati. Ser/Thr kinase BUB1 stabilizes DNAPKcs in response to radiation induced DNA double strand break repair [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A007.
Abstract A009: DNA damage-induced senescence as a driver of glioblastoma recurrence
Authors: Burma Sandeep , Tomimatsu Nozomi , Cristofaro Luis , Kanji Suman , Jordan Benjamin , Mukherjee Bipasha 
Published: January 2024

Abstract
Glioblastomas (GBM) are treated with high doses of ionizing radiation (IR), yet these tumors inevitably recur, and the recurrent tumors are highly therapy resistant. An understanding of mechanisms driving GBM recurrence is critical for improving therapy. During GBM therapy, both the tumor and the normal brain tissue surrounding the tumor are treated with up to 60 Gy of IR. IR is a potent inducer of senescence, and senescent stromal cells can promote the growth of neighboring tumor cells by secreting proteases, cytokines and growth factors that create a senescence-associated secretory phenotype (SASP). We have shown previously that IR-induced senescence of astrocytes in the brain leads to the secretion of SASP factors that promote the growth and invasiveness of tumor cells in mouse models of GBM (Fletcher-Sananikone, et al, Cancer Research, 2021). Following up on this study, we irradiated a panel of GBM cell lines and found that a significant fraction of these cells senesced rapidly in a p21-dependent manner. Senescent glioma cells upregulated SASP genes in a NF-kB-dependent manner, prominently, the interleukin IL6, which is an activator of the JAK-STAT pathway. Conditioned media from senescent GBM cells activated the JAK-STAT pathway in non-senescent GBM cells and promoted tumor cell proliferation and radiation resistance. Interestingly, conditioned media from senescent GBM cells could also activate the NF-kB pathway and induce SASP in non-senescent cells. These results indicate that senescent GBM cells can activate pro-tumorigenic pathways in their non-senescent counterparts and SASP can spread from senescent to non-senescent cells. Bioinformatic analyses of the transcriptomic profiles of irradiated GBM cells and the TCGA database revealed that the inhibitor of apoptosis protein cIAP2 is a critical survival factor for senescent glioma cells. We find that targeting cIAP2 using Smac mimetics triggers apoptosis of senescent GBM cells with minimal toxicity towards normal brain cells like astrocytes. Upregulation of cIAP2 in irradiated tumor cells was also seen in multiple PDX models of GBM. Using these PDX lines, we demonstrate that adjuvant senolytic treatment can delay or even prevent recurrence in pre-clinical mouse models of GBM. In sum, our findings illustrate how senescence of both stromal and tumor cells promote GBM recurrence via different mechanisms and underscore the potential utility of adjuvant senolytic therapy for blunting GBM recurrence after radiotherapy.
Citation Format: Sandeep Burma, Nozomi Tomimatsu, Luis Cristofaro, Suman Kanji, Benjamin Jordan, Bipasha Mukherjee. DNA damage-induced senescence as a driver of glioblastoma recurrence [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A009.
Abstract A013: Selective HDAC6 inhibition by SP-2-225 enhances the innate anti-tumor immune response after radiation exposure
Authors: Grindrod Scott , Noonepalle Satish , Li Xingtang , Quiceno David , Jung Mira , Dritschilo Anatoly , Villagra Alejandro 
Published: January 2024

Abstract
Circulating tumor DNA fragments and other antigens resulting from radiation therapy cause activation of the STING pathway and initiate an inflammatory anti-tumor immune response. However, when pro-inflammatory immune cells interact with the tumor microenvironment, they are rapidly converted to their anti-inflammatory, pro-tumor state associated with wound healing. HDAC6 presents an important target due to its role in immune regulatory processes involved in antitumor immune responses. We have shown that SP-2-225, a selective inhibitor of HDAC6, regulates macrophages to recognize, phagocyte, and present antigens to the adaptive immune system. Treatment with SP-2-225 enhances the production of cancer-associated antigens and macrophage antigen cross-presentation to T cells. Through a non-cytotoxic mechanism, SP-2-225 significantly reduced the tumor volume in syngeneic SM1 melanoma and 4T1 breast models. Tumor analysis from treated animals showed a shift in the M1/M2 ratio of the infiltrating macrophages as compared to controls, demonstrating that SP-2-225 caused a pro-inflammatory, antitumor shift in the macrophage equilibrium present in the tumor microenvironment. The putative mechanism was identified through adoptive cell therapy where macrophages from naive animals were harvested and treated ex-vivo with SP-2-225. Reimplantation of these SP-2-225 ex-vivo treated macrophages resulted in reduced tumor volumes when compared to both vehicle and untreated macrophage animal cohorts. We propose that this selective inhibitor of HDAC6 offers potential in combination with radiation therapy for cancer.
Citation Format: Scott Grindrod, Satish Noonepalle, Xingtang Li, David Quiceno, Mira Jung, Anatoly Dritschilo, Alejandro Villagra. Selective HDAC6 inhibition by SP-2-225 enhances the innate anti-tumor immune response after radiation exposure [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr A013.