bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of fluvial and glacial watershed dynamics on Holocene sediment accumulation in Cariboo Lake, Columbia Mountains, British Columbia, Canada
Authors: Cebulski A. , Desloges J.
Published: January 2024

Records of sedimentation collected from Cariboo Lake, situated in the northern Columbia Mountains, British Columbia, Canada, are analyzed to assess Holocene fluvial and glacial watershed dynamics. The aim of this study is to provide a proxy record of Holocene hydroclimate and glacier change from sediment archives at a higher temporal resolution compared to available records for the Interior Ranges of British Columbia. Deglacial and Holocene sediment accumulation is observed to reach a maximum thickness of 35 m in deep parts of the lake, using sub-bottom acoustic soundings. A transition from massive to well-stratified sediments is observed in the sub-bottom acoustic record during final phases of valley deglaciation in the region (~10.5–9 cal ka BP). Laminae couplets are interpreted to be deposited annually according to two 14C dates and a varve counting chronology. Two long cores, 2.9 and 3.8 m in length, were selected for analysis with estimated basal dates of 2 cal ka BP. Trends in downcore sediment characteristics were linked to environmental changes in the glaciated catchment headwaters at a temporal resolution of ~100 years. Upstream lake filtering of river floodplains and lakes prevented finding a higher temporal resolution linkage between the sediment characteristics and headwater fluvial and glacial activity. Despite some upstream filtering, the Cariboo River was found to be the primary source of sediment to the long core sites. Observed grain size and varve thickness from two long cores show above average trends, which are coincident with cooler temperatures and the primary glacier advances over the last 2 ka.
Semi-pelagic self-adjusting otter boards: effects on the catching performance of a demersal trawl
Authors: Eighani Morteza , Malta Tiago Veiga , Melli Valentina , O'Neill Finbarr G.
Published: January 2024

In this study, we investigate whether replacing conventional seabed-contacting otter boards with semi-pelagic self-adjusting otter (SAO) boards, which have the ability to maintain a given height above the seabed, affects the catch efficiency of a demersal fish trawl. Experimental fishing trials, using the alternate haul method, were conducted in the Kattegat and Skagerrak with three otter board configurations using conventional seabed-contacting otter boards; the SAO set to maintain a target height over the seabed of 1 m; and the SAO set to maintain a target height of 5 m. Replacing conventional otter boards with SAO resulted in a loss of catch efficiency for haddock ( Melanogrammus aeglefinus), whiting ( Merlangius merlangus), and plaice ( Hippoglossoides platessoides), while no significant difference was found for cod ( Gadus morhua), common dab ( Limanda limanda), and lemon sole ( Microstomus kitt). When comparing the SAO-1 m and SAO-5 m, it was observed that SAO-5 m resulted in a loss of catch efficiency for haddock and plaice, a minimal reduction for cod, and no significant difference for whiting, common dab, and lemon sole.
Improving escape efficiency in selective devices with the use of a dark tunnel
Authors: Svantemann Mette Munkholm , Savina Esther , Krag Ludvig Ahm
Published: January 2024

Despite management efforts, like the implementation of escape panels and openings, unwanted catch remains a challenge in demersal trawl fisheries. Studies report that selectivity in escape panels and openings can be low. We explore the selective potential of a large escape opening placed at the aft of the trawl. We then examine if adding a dark tunnel behind the escape opening can increase the escape efficiency of fish by triggering a station-holding behaviour. Our results showed limited escapement through the large escape opening; however, significant for narrow length ranges of some species. Adding the dark tunnel significantly increased the escapement for all analysed species, with escapement up to 70% (40%–83%) and 63% (8%–93%) for roundfish and flatfish, respectively. As target species, a loss of crustaceans up to 85% (60%–96%) highlighted the importance of optimising the integration of the dark tunnel in demersal trawls. Providing the dark tunnel is integrated correctly, our results suggest that currently implemented escape panels and openings with low selective efficiency could be substantially improved by simple means like the dark tunnel.
Inflationary quantum spectrum of the quasi-isotropic Universe
Authors: Bortolotti Nicola , Montani Giovanni
Published: January 2024

We investigate the quantum dynamics of the quasi-isotropic inflationary solution. This is achieved by deriving the Lagrangian and Hamiltonian for both the FLRW background and the inhomogeneous correction, via an expansion of the Einstein–Hilbert action up to second order in the perturbation amplitudes. Then we implement a semiclassical WKB scenario for which the inhomogeneous component of the Universe is treated as a “small” quantum subsystem, evolving on the classical isotropic background. Starting from the Wheeler–DeWitt equation, we recover a Schrödinger dynamics for the perturbations, in which the time dependence of the wave function emerges thanks to the classicality of the background, and we solve it for an inflationary phase. The main result of this paper is to show that, while the scalar component of the power spectrum has the standard scale invariant profile, the tensor one results to be not constrained by the inflationary expansion, apart from an overall normalization factor which guarantees a small tensor-to-scalar ratio. This means that the spatial distribution of the quasi-isotropic correction to the metric remains preserved, with the consequence that some information about the pre-inflationary Universe survives to the de Sitter expansion.
Disassembling blood clots and recovering blood oxygen function with strong magnetic field for severe COVID-19 patients
Authors: Tao R.
Published: January 2024

Blood clotting caused by COVID-19 has made this disease much more severe than other respiratory diseases. An alarming number of COVID-19 patients developed blood clots that trigger heart attack, stroke, and other disasters. Currently, blood thinner medicines are the only treatment. While blood thinners lower the blood’s ability to clot, they cannot disassemble existing blood clots. Many patients were not helped by them. Here we report our finding: Strong magnetic field can disassemble blood clots safely and effectively. This is attributed to the magnetic property of red cells and their unique disk shape. Hence, we have proposed a new treatment for patients with thrombosis: applying a strong magnetic field along the patients’ arm or leg. When the blood clots come to the magnetic field, they are disassembled safely; red cells recover their oxygen function; the blood viscosity along the flow direction is reduced, turbulence in blood circulation is suppressed, and the incidence of heart attack and stroke can be prevented. With thrombosis occurring in COVID-19 patients, the magnetic treatment will resolve this urgent issue and greatly help the patients to recover.
Theoretical study of physical properties of nanolaminated borides MAlB (M=Cr, Mo, W)
Authors: Wei Lei , Wei Chun , Yu Jing , Zhang Lei
Published: January 2024

In this study, we have conducted a thorough investigation into the influence of the atomic radius of transition metals on the structural, electronic, and optical properties of nanolaminated borides MAlB ([Formula: see text], Mo, W) using first principles calculation. The validity and dependability of our calculation parameters are confirmed and compared with other available data sets. The calculated elastic constants reveal stronger resistance to deformation along the c direction as compared to the a- and b-directions. The mechanical properties of these borides increased in tandem with the atomic radius of transition metal. The chemical bonding within the borides is a mix of metallic and covalent bonds. Interestingly, there is a decrease in the boride metallicity concurrent with an increase in the atomic radius of the transition metal. Optical property analysis shows promise for these borides as absorbent materials. Furthermore, there is a correlation between the increase in the atomic nucleus of the transition metal and the increase in the maximum absorption coefficient.
Multiparty Computation: To Secure Privacy, Do the Math
Authors: Smart Nigel , Baron Joshua W. , Saravanan Sanjay , Brandt Jordan , Mashatan Atefeh
Published: January 2024

Multiparty Computation is based on complex math, and over the past decade, MPC has been harnessed as one of the most powerful tools available for the protection of sensitive data. MPC now serves as the basis for protocols that let a set of parties interact and compute on a pool of private inputs without revealing any of the data contained within those inputs. In the end, only the results are revealed. The implications of this can often prove profound.
Open Set Dandelion Network for IoT Intrusion Detection
Authors: Wu Jiashu , Dai Hao , Kent Kenneth B. , Yen Jerome , Xu Chengzhong , Wang Yang
Published: January 2024

As Internet of Things devices become widely used in the real-world, it is crucial to protect them from malicious intrusions. However, the data scarcity of IoT limits the applicability of traditional intrusion detection methods, which are highly data-dependent. To address this, in this article, we propose the Open-Set Dandelion Network (OSDN) based on unsupervised heterogeneous domain adaptation in an open-set manner. The OSDN model performs intrusion knowledge transfer from the knowledge-rich source network intrusion domain to facilitate more accurate intrusion detection for the data-scarce target IoT intrusion domain. Under the open-set setting, it can also detect newly-emerged target domain intrusions that are not observed in the source domain. To achieve this, the OSDN model forms the source domain into a dandelion-like feature space in which each intrusion category is compactly grouped and different intrusion categories are separated, i.e., simultaneously emphasising inter-category separability and intra-category compactness. The dandelion-based target membership mechanism then forms the target dandelion. Then, the dandelion angular separation mechanism achieves better inter-category separability, and the dandelion embedding alignment mechanism further aligns both dandelions in a finer manner. To promote intra-category compactness, the discriminating sampled dandelion mechanism is used. Assisted by the intrusion classifier trained using both known and generated unknown intrusion knowledge, a semantic dandelion correction mechanism emphasises easily-confused categories and guides better inter-category separability. Holistically, these mechanisms form the OSDN model that effectively performs intrusion knowledge transfer to benefit IoT intrusion detection. Comprehensive experiments on several intrusion datasets verify the effectiveness of the OSDN model, outperforming three state-of-the-art baseline methods by 16.9%. The contribution of each OSDN constituting component, the stability and the efficiency of the OSDN model are also verified.
Digital 3D Reconstruction of Ancient Chinese Great Wild Goose Pagoda by TLS Point Cloud Hierarchical Registration
Authors: Lin Xiaohu , Xue Bei , Wang Xiqi
Published: January 2024

Digital reconstruction of ancient buildings is very challenging due to its architectural complexity and structural delicacy. Therefore, how to apply new Earth Observation (EO) technology to digitally reconstruct the complete and real model of ancient buildings without damage has become an urgent issue. This article proposes a multi-scan point cloud hierarchical registration method for 3D reconstruction of the ancient Chinese Great Wild Goose Pagoda based on Terrestrial Laser Scanner (TLS) data. First, a multi-scan point cloud hierarchical registration method is elaborately designed for 3D reconstruction. Then, the outline feature of the ancient Chinese Great Wild Goose Pagoda is automatically extracted by point cloud slicing. Finally, fine modeling is carried out according to the outline feature extracted from the reconstructed point cloud, and after that block combination and texture mapping are conducted for 3D digitalization and documentation. The experiments indicate that the Root Mean Square Error (RMSE) of multi-scan hierarchical registration of the translation and rotation are less than 3
cm
and 0.862
∘
, respectively, and the complete and real model of the Great Wild Goose Pagoda is obtained by fine modeling and texture mapping, which provides an important reference for 3D digital protection of ancient buildings.
Evaluating User Experience in the Context of Cultural Heritage Dissemination Using Extended Reality: A Case Study of the Dacian Bronze Matrix with Hollow Design
Authors: Neamțu Călin , Comes Radu , Popovici Dorin-Mircea , Băutu Elena , Liliana Mateescu-Suciu , Syrotnik Adrien , Popovici Matei-Ioan
Published: January 2024

Cultural institutions are increasingly prioritizing the utilization of diverse mixed reality technologies to enrich the visitor experience during their physical exhibitions. These institutions are actively integrating virtual assets to enhance interactivity and facilitate immersive storytelling experiences. The use of extended reality technologies in cultural heritage dissemination has become a common solution to improve the perception on cultural heritage of their visitors. The objective of the proposed research is to conduct a comparative analysis of three distinct extended reality applications used in cultural heritage experiences. The proposed workflow integrates advanced 3D scanning technology and additive manufacturing techniques to produce tangible replicas which are further enhanced using extended reality technologies, such as augmented reality, desktop virtual reality, and immersive virtual reality. To evaluate the developed extended reality applications, we have conducted various System Usability Scale tools to assess applications’ usability while also trying to identify the most appropriate application that can be integrated within the museum exhibition. From a utility point of view, we found no notable differences in the user perceptions between proposed solutions, whereas from a usability and satisfaction point of view, the most preferred solution was the augmented reality one. The workflow is presented in sufficient detail to ensure the replication of the results.
Potential Modulation and Control of Redox Reactions at Bipolar Electrodes Using an Ion-Selective Membrane
Authors: Mutalib Nurul Asyikeen Ab , Hsueh An-Ju , Deng Yi , Suzuki Miho , Wu Chia-Chien , Shirato Yusuke , Suzuki Hiroaki
Published: January 2024

Potential difference at a bipolar electrode (BPE)/solution interface was controlled by forming a polymeric Na ion-selective membrane (ISM) on one part of the BPE. Using the difference between the potentials at the solution/cathodic pole and solution/anodic pole interfaces along with a predetermined driving voltage, the potential differences at the cathodic/anodic pole interface were independently regulated. For open bipolar systems, distinct changes in the intensity of electrochemiluminescence (ECL) were observed by varying the location of the ISM and/or the concentrations of the primary ions determining the potential of the ISM. Folded BPE structures with ISMs at one or both ends of the BPEs were more effective in changing the potential differences at the cathodic/anodic pole interface over a wider range. Furthermore, the potential control was efficient and changes in the ECL intensity were more significant in closed bipolar systems. The device was used for measuring analyte concentration by optimizing the size of the cathodic pole employed for detection and adjusting the driving voltage. We believe that the technique can be a starting point to achieve bipolar electrochemical devices with better controllabilities than those of previous bipolar electrochemical systems and similar reliabilities as those of three-electrode systems.
Review—Electrochemical Immunosensors for Depression Markers Detection: Development in Recent Years
Authors: Guo Min , Chen Yan , Mo Xiaohui , Wei Hong , Li Yuanyuan , Jia Yanjun , Hu Fangdi , Du Yongling
Published: January 2024

Depression is one of the most severe mental disorders, and facing the challengeable lack of objective diagnosis, as well as early screening and predicting treatment responses. Consequently, developing sensitive, efficient, convenient, accurate, and real-time detection technology for depression markers earns more attention. Electrochemical immunosensor, as a promising method for analyzing disease markers, selectively binds the target antigen with antibodies (Abs), converting the biological signal of the antigen-antibody recognition reaction into an electrical signal related to the concentration of the target analyte. This method has thrived in recent years in areas such as point-of-care (POC) diagnosis. This article systematically reviews the construction of electrochemical immunosensors for the detection of biomarkers of depression over the past 6 years (2016–2022), including the classification of these sensors, commonly used electrode modification materials, and signal optimization strategies. Finally, the challenges and future development of electrochemical immunosensors in clinical applications are prospected.
Local Reaction Environment Deviations within Gas Diffusion Electrode Pores for CO2 Electrolysis
Authors: Butt Esaar N. , Padding Johan T. , Hartkamp Remco
Published: January 2024

The local conditions inside a gas diffusion electrode (GDE) pore, especially in the electrical double layer (EDL) region, influence the charge transfer reactions and the selectivity of desired CO2ER products. Most GDE computational models ignore the EDL or are limited in their applicability at high potentials. In this work, we present a continuum model to describe the local environment inside a catalytic pore at varying potentials, electrolyte concentrations and pore diameters. The systems studied in this work are based on an Ag catalyst in contact with KHCO3 solution. Our study shows that steric effects dominate the local environment at high cathodic potentials (≪−25 mV vs pzc at the OHP), leading to a radial drop of CO2 concentration. We also observe a drop in pH value within 1 nm of the reaction plane due to electrostatic repulsion and attraction of OH− and H+ ions, respectively. We studied the influence of pore radii (1–10 nm) on electric field and concentrations. Pores with a radius smaller than 5 nm show a higher mean potential, which lowers the mean CO2 concentration. Pores with a favourable local environment can be designed by regulating the ratio between the pore radius and Debye length.
Development of an m6A‐Related lncRNAs Signature Predicts Tumor Stemness and Prognosis for Low‐Grade Glioma Patients
Authors: Xu Dahua , Li Peihu , Zhang Chunrui , Shen Yutong , Cai Jiale , Wei Qingchen , Cao Meng , Xu Zhizhou , Wu Deng , Wang Hong , Bi Xiaoman , Wang Bo , Li Kongning
Published: January 2024

Background. Growing evidence has revealed that m6A modification of long noncoding RNAs (lncRNAs) dynamically controls tumor stemness and tumorigenesis‐related processes. However, the prognostic significance of m6A‐related lncRNAs and their associations with stemness in low‐grade glioma (LGG) remain to be clarified. Methods. A multicenter transcriptome analysis of lncRNA expression in 1,247 LGG samples was performed in this study. The stemness landscape of LGG tumors was presented and associations with clinical features were revealed. The m6A‐related lncRNAs were identified between stemness groups and were further prioritized via least absolute shrinkage and selection operator Cox regression analysis. A risk score model based on m6A‐related lncRNAs was constructed and validated in external LGG datasets. Results. Based on the expression of LINC02984, PFKP‐DT, and CRNDE, a risk model and nomogram were constructed; they successfully predicted the survival of patients and were extended to external datasets. Significant correlations were observed between the risk score and tumor stemness. Moreover, patients in different risk groups exhibited distinct tumor immune microenvironments and immune signatures. We finally provided several potential compounds suitable for specific risk groups, which may aid in LGG treatment. Conclusions. This novel signature presents noteworthy value in the prediction of prognosis and stemness status for LGG patients and will foster future research on the development of clinical regimens.
The Effects of Switch Therapy in Osteoporosis Treatment after Romosozumab after Comparing with Prior Treatment
Authors: Horikawa Akira , Kasukawa Yuji , Hongo Michio , Sano Akihisa , Miyakoshi Naohisa
Published: January 2024

Rationale. Although romosozumab is one of the most effective treatments for osteoporosis by increasing bone mineral density in the lumbar spine and femur and recommended for denosumab as switch therapy, these effects regarding its prior treatment have not yet been evaluated clearly. This study focused on the effects of switch therapy from romosozumab to denosumab in regard to prior treatment of osteoporosis including bone mineral density and bone turnover marker and other related factors. Patient Concerns. 15 osteoporotic patients were assigned to the naïve group, 15 were assigned to the teriparatide group, and 10 were assigned to the bisphosphonate group. Interventions. Patients who were treated as outpatients for osteoporosis with romosozumab for 1 year and switched to denosumab between 2020 and 2022 at our hospital were examined. Our hospital registry included 40 osteoporotic patients who were over 65 years of age with bone mineral density (bone mineral density): T score <−2.5 standard deviations (SDs) and fracture assessment tool (FRAX) score >20%. Outcomes. The naïve group had the highest increase in LS BMD among these three groups during switch therapy from romosozumab to denosumab, while there were no significant differences about adverse drug events and serum Ca concentration among them. There was no incidence of fracture. Conclusion. These findings indicate that the effects of osteoporotic treatment of switch therapy from romosozumab to denosumab were likely to affect prior treatment of osteoporosis.
MAPK and PI3K/Akt Signalling Pathways Potentially Modulate the Enhancing Effect of Black Tea Extracts on Endo180 Expression and Collagen Internalisation
Authors: Seo Sang Gwon , Jo Min Je , Park Hyung Gook , Jin Mu Hyun , Cho Ho Song
Published: January 2024

As the skin ages, collagen denatures into fragments that accumulate in the dermal matrix. Endo180 allows these fragments to reenter cells and be used for collagen recombination. While several studies have reported on the efficacy of green tea on skin health, studies on black tea have been limited. The aim of this study was to reveal the effects of black tea on skin health and the associated mechanisms. We estimated collagen internalisation using fluorescence-labelled gelatin and measured Endo180 expression following treatment with black tea extract (BTE). BTE at a concentration of 10 ug/ml increased Endo180 mRNA and protein expression by 1.67-fold p=0.006 and 1.46-fold p=0.010, respectively. In addition, collagen internalisation was increased by 1.29-fold p=0.001 in human skin fibroblasts compared with the untreated control group. These effects were reversed by five inhibitors of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathways to the same levels as those of the untreated control group. These results suggest that BTE enhances collagen internalisation and upregulates Endo180 expression via the MAPK and PI3K/Akt signalling pathways in HDFs and that black tea could be used as a functional food for improving skin health.
Feasibility Study of a Novel Modal Decomposition Method for Low‐Frequency Structure with Nonproportionally Distributed Rate‐Independent Linear Damping
Authors: Liu Wei , Ni Yi-Qing , Ao Wai Kei
Published: January 2024

Compared with conventional linear viscous damping (LVD), rate‐independent linear damping (RILD) mitigates floor response acceleration in low‐frequency structures more effectively without compromising the control performance of displacement responses during long‐period or low‐frequency earthquakes. Although theoretical and experimental attempts have been made to overcome the noncausality of RILD devices and realize RILD using passive or semiactive devices, only a few studies have highlighted the impulse‐response precursor and modal analysis method of multistory structures incorporated into RILD devices. This study investigated the impulse‐response precursor of a noncausal RILD system and proposed a novel modal decomposition method for the structures equipped with nonproportionally distributed RILD devices. Additionally, real‐time hybrid simulation was conducted to validate the effectiveness of the proposed modal analysis method and the feasibility of realizing ideal RILD using mechanical devices. This study is the first to demonstrate the differences between RILD and LVD devices in terms of controlling the modal responses of low‐frequency structures and how RILD can lower the floor response acceleration more effectively compared to LVD.
Supplementary Table S32 from Influence of Half-life and Smoking/Nonsmoking Ratio on Biomarker Consistency between Waves 1 and 2 of the Population Assessment of Tobacco and Health Study
Authors: Ashley David L. , Zhu Wanzhe , Bhandari Deepak , Wang Lanqing , Feng Jun , Wang Yuesong , Meng Lei , Xia Baoyun , Jarrett Jeffery M. , Chang Cindy M. , Kimmel Heather L. , Blount Benjamin C.
Published: January 2024

Supplementary Table S32 shows the results of weighted multiple linear regression analysis of log-transformed urinary N‐acetyl‐S‐(benzyl)‐L‐cysteine (BzMA) with study covariates
Abstract A001: Discovery of imidazo [4,5-c]pyridin-2-ones as selective inhibitors of DNA-dependent protein kinase and effective radiosensitizers
Authors: Hay Michael P. , Hong Cho R. , Liew Lydia P. , Dickson Benjamin D. , Wong Way W. , O'Brien-Gortner Sophia F. , Airey Rebecca , Jaiswal Jagdish , Wilson William R. , Jamieson Stephen M.
Published: January 2024

Inhibition of the repair of radiation-induced DNA double strand breaks (DSB) offers the potential to sensitize tumors to radiation therapy. The dominant role of non-homologous end-joining in the repair of radiation-induced DSBs indicates that DNA-dependent protein kinase (DNA-PK) is an excellent target for the development of radiosensitizers. We report the discovery of a new chemical class of kinase inhibitor based on the imidazo[4,5-c]pyridin-2-one scaffold. The class was developed by scaffold-hopping from the pan phosphoinositide 3-kinsase (PI3K) and PI3K-like kinase (PIKK) inhibitor dactolisib. Iterative development culminated in the identification of SN39536 as a low nM DNA-PK inhibitor with excellent selectivity. Further modification led to the discovery of the more potent and more selective SN40905. Both SN39536 and SN40905 were effective inhibitors of DNA-PK kinase activity in a biochemical assay with substantial selectivity for DNA-PK across the PIKK and PI3K families. Both compounds selectively inhibited growth of HAP1 PRKDC wild-type cells when combined with radiation, but not the corresponding PRKDC-/- cells. SN39536 and SN40905 were effective radiosensitizers of colorectal carcinoma (HCT116), non-small cell lung cancer (H460, H1299, and A549), pancreatic (BxPC-3, PANC-1, and MiaPaCa-2) and head and neck squamous cell carcinoma (FaDu and UT-SCC-74B) cells determined using a clonogenic survival endpoint. Both SN39536 and SN40905 displayed high oral bioavailability. When administered PO at a range of non-toxic doses, both SN39536 and SN40905 provided significant additional tumor cell killing of HCT116, UT-SCC-74B, and BxPC-3 tumor xenografts in combination with a single (13 Gy) radiation treatment determined by ex vivo clonogenic survival assays. SN39536 also provided substantial tumor growth inhibition of HCT116 tumor xenografts in combination with RAD (10 Gy). SN39536 and SN40905 represent a new, potent, and selective class of DNA-PK inhibitors with significant potential as radiosensitizers for the treatment of human cancers.

Citation Format: Michael P. Hay, Cho R. Hong, Lydia P. Liew, Benjamin D. Dickson, Way W. Wong, Sophia F. O'Brien-Gortner, Rebecca Airey, Jagdish Jaiswal, William R. Wilson, Stephen M. Jamieson. Discovery of imidazo [4,5-c]pyridin-2-ones as selective inhibitors of DNA-dependent protein kinase and effective radiosensitizers [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 A001.
Abstract A025: FANCI regulates Fanconi anemia pathway and counteracts the effects of DNA damaging chemotherapy in prostate cancer
Authors: Kaljunen Heidi , Taavitsainen Sinja , Kaarijärvi Roosa , Takala Eerika , Paakinaho Ville , Nykter Matti , Bova G. Steven , Ketola Kirsi
Published: January 2024

Prostate cancer is one of the leading causes of death among men worldwide and thus research on the genetic factors enabling the formation of treatment resistant cancer cells is crucial for improving patient outcomes. Here, we report a cell-line specific dependence on FANCI and related signaling pathways to counteract effects of DNA damaging chemotherapy in prostate cancer. Our results reveal that FANCI depletion results in significant downregulation of Fanconi anemia (FA) pathway members in prostate cancer cells indicating that FANCI is an important regulator of FA pathway. Furthermore, we found that FANCI silencing reduces proliferation in p53-expressing prostate cancer cells. This extends the evidence that inactivation of FANCI may convert cancer cells from a resistant to an eradicable state under the stress of DNA-damaging chemotherapy. Our results also indicate that high expression of FA pathway genes correlates with poorer survival in prostate cancer patients. Moreover, genomic alterations of FA pathway members are prevalent in prostate adenocarcinoma patients; mutation and copy number information for the FA pathway genes in seven patient cohorts (N = 1732 total tumor samples) reveals that 1025 (59.2%) tumor samples have an alteration in at least one of the FA pathway genes, suggesting that genomic alteration of the pathway is a prominent feature in patients with the disease.

Citation Format: Heidi Kaljunen, Sinja Taavitsainen, Roosa Kaarijärvi, Eerika Takala, Ville Paakinaho, Matti Nykter, G. Steven Bova, Kirsi Ketola. FANCI regulates Fanconi anemia pathway and counteracts the effects of DNA damaging chemotherapy in prostate cancer [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 A025.
Abstract B011: CDK9-55 guides the anaphase-promoting complex/cyclosome (APC/C) in choosing the DNA repair pathway by affecting the UFL1 ubiquitination
Authors: Alfano Luigi
Published: January 2024

DNA double-strand breaks (DSBs) contribute to genome instability, a key feature of cancer. DSBs are mainly repaired by homologous recombination (HR) and non-homologous end-joining (NHEJ). We investigated the role of an isoform of the multifunctional cyclin-dependent kinase 9, CDK9-55, in DNA repair, by generating CDK9-55-knockout HeLa clones (through CRISPR-Cas9), which showed potential HR dysfunction. A phosphoproteomic screening in these clones treated with camptothecin (CPT) revealed that CDC23 (cell division cycle 23), a component of the E3-ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome), is a new substrate of CDK9-55, with S588 being its putative phosphorylation site. Mutated non-phosphorylatable CDC23(S588A) affected the repair pathway choice by impairing HR and favoring error prone NHEJ. Moreover, CDC23(S588A) promoted the ubiquitination of UFL1, a recently identified HR player. Overall, CDK9-55 could guide APC/C in choosing the correct DNA repair pathway, possibly by regulating UFL1 stability. This CDK9 role should be considered when designing CDK-inhibitor-based cancer therapies.

Citation Format: Luigi Alfano. CDK9-55 guides the anaphase-promoting complex/cyclosome (APC/C) in choosing the DNA repair pathway by affecting the UFL1 ubiquitination [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 B011.
Abstract B033: Direct and sensitive in-situ detection of DNA breaks by STRIDE and its potential as a new biomarker
Authors: Solarczyk Kamil , Patterson Brian
Published: January 2024

DNA damage is usually detected using indirect methods which require active signaling and triggered DNA repair mechanisms. These methods, although relatively sensitive, are prone to false (positive or negative) results. Methods for direct DNA damage detection, on the other hand, suffer from low sensitivity or require DNA isolation, what can result in misleading artefactual readouts of the analysis. Here we present a method called STRIDE (SensiTive Recognition of Individual DNA Ends), which allows for specific, very sensitive in-situ detection of DNA breaks. This fluorescence-based method, in its two variants (dSTRIDE and sSTRIDE), allows selective labelling of double-or single-strand breaks, respectively. STRIDE enables highly sensitive and specific detection and quantification of single and double-strand DNA breaks in cultured cells and FFPE human tissues, both PBMCs as well as solid tumors. STRIDE is superior to classic methods used to measure DNA damage, as it combines a direct detection that is independent of DNA repair mechanisms with an unprecedented sensitivity. With its versatility it can be used in any type of biological material, including liquid biopsies as well as different types of tumors. STRIDE has the potential to become a very useful biomarker reporting about the efficiency of therapies based on DNA damage induction, such as DNA repair inhibitors or radiotherapy.

Citation Format: Kamil Solarczyk, Brian Patterson. Direct and sensitive in-situ detection of DNA breaks by STRIDE and its potential as a new biomarker [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 B033.
Abstract IA017: Drugging the DNA damage response (DDR) in the Clinic: Going beyond the approved PARP inhibitors
Authors: Yap Timothy A.
Published: January 2024

Genomic instability is a key hallmark of cancer that arises owing to defects in the DNA damage response (DDR) and/or increased replication stress. These alterations promote the clonal evolution of cancer cells via the accumulation of driver aberrations, including gene copy-number changes, rearrangements, and mutations; however, these same defects also create vulnerabilities that are relatively specific to cancer cells, which could potentially be exploited to increase the therapeutic index of anticancer treatments and thereby improve patient outcomes. The discovery that BRCA-mutant cancer cells are exquisitely sensitive to inhibition of poly(ADP-ribose) polymerase has ushered in a new era of research on biomarker-driven synthetic lethal treatment strategies for different cancers. The therapeutic landscape of antitumor agents targeting the DDR has rapidly expanded to include inhibitors of other key mediators of DNA repair and replication, such as ATR, ATM, CHK1, WEE1, PKMYT1 and PARG. Efforts to optimize these therapies are ongoing across a range of cancers, involving the development of predictive biomarker assays of response (beyond BRCA mutations), assessment of the mechanisms underlying intrinsic and acquired resistance, and evaluation of rational combinations to improve patient outcomes and widen the application of DDR agents.

Citation Format: Timothy A. Yap. Drugging the DNA damage response (DDR) in the Clinic: Going beyond the approved PARP inhibitors [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 IA017.
Abstract PR006: Elucidating the effect of PARP inhibitors on MMEJ-mediated DNA repair
Authors: Ortega Raquel , Arnoult Nausica , Bitler Benjamin G
Published: January 2024

First-line maintenance treatment for homologous recombination (HR)-deficient (HRD, e.g., BRCA1/2 mutations) cancers includes poly ADP-ribose inhibitors (PARPi, e.g., olaparib, niraparib). PARPi are lethal through multiple mechanisms, including PARP trapping and PARP activity inhibition, which both destabilize the replication fork machinery in the absence of BRCA1/2. However, only 50% of HRD tumors respond to PARPi treatment due to intrinsic resistance and of those that respond, most tumors eventually relapse due to acquired drug resistance. Because MMEJ is essential in HRD-cancers, it has emerged as a promising target to combat PARPi resistance, with POLQ inhibitors currently in clinical trials. Thus, understanding the interplay between MMEJ and PARP inhibitors is critical. While PARP1 is proposed to promote MMEJ, PARP regulates numerous aspects of DSB repair, and therefore its overall impact on MMEJ levels remains unclear. For instance, the effect of PARP inhibition on DSB end-resection, a critical step of MMEJ, remains controversial. Utilizing a DNA repair reporter, we assessed MMEJ levels following treatment with various PARP inhibitors, including those with minimal PARP trapping activity. Remarkably, we find that PARP inhibition systematically leads to elevated MMEJ levels in a POLQ-dependent fashion. Furthermore, PARP inhibition also induces higher MMEJ levels in cells treated with NHEJ inhibitors as well as in HR-deficient cells, including an HRD ovarian cancer cell line (PEO1, BRCA2mut). Therefore, this MMEJ upregulation cannot be simply attributed to a PARPi-mediated suppression of NHEJ or HR activity. Taken together, our data suggests that the overall effect of PARP inhibitors may lead to upregulation, rather than suppression, of MMEJ activity. We are currently assessing the contribution of PARP1 and PARP2 in MMEJ regulation and are testing whether PARPi also increase MMEJ levels at sites of replication induced DSBs. We hypothesize that PARPi could upregulate MMEJ through modulating DSB end-resection. This insight bears significant implications for the development of combination therapies of MMEJ and PARP inhibitors in treating HRD cancers.

Citation Format: Raquel Ortega, Nausica Arnoult, Benjamin G Bitler. Elucidating the effect of PARP inhibitors on MMEJ-mediated DNA 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 PR006.
LAND SUITABILITY ASSESSMENT FOR PATCHOULI (Pogostemon cablin) DEVELOPMENT AND ESSENTIAL OIL PRODUCTION
Authors: Setiawan Adi
Published: January 2024

The conformity of abiotic factors in the growing environment of crops determines the successful result of crop production. This study aims to assess and evaluate land suitability for plant growth and result of patchouli development in Dilem wilis, Bendungan Distric, Trenggalek Regency. The study was initiated with the survey and continued by utilizing analysis method to adjust the data with the criteria according to the classification of land suitability clashing and crops cultivation as indicator for assessing land suitability. The research was conducted on 3 locations from May to July 2017 for land suitability and from July to November 2017 for patchouli crops cultivation experiment. The result indicated from the three sampling Locations, specifically Location 1 presented the land suitability of N class, conforming that this Location was not suitable with the limiting factor of low K2O content of 0.08 me / 100 g. Meanwhile, both Location 2 and Location 3 presented similar land suitability class of S3s, tc, f, n conforming as less appropriate. The results of this study also depicted the influence of land suitability classes on plant growth; however, the difference in land classes (in this case S3 compared to N) did not demonstrate a correlation for oil yield and patchouli alcohol, where the element Potassium becomes a limiting factor.
CHARACTERIZATION OF RHIZOBACTERIA ISOLATES FROM SOIL AND NODULES
Authors: Widawati Sri , SULIASIH SULIASIH , Susilowati Dwi Ningsih , Muramatsu Yuki , Sudiana I Made
Published: January 2024

The plant growth promoting rhizobacteria (PGPR) is a group of bacteria capable of colonizing plants roots, thereby developing a system and improving plants growth and yield. The objectives of the study is to characterize the PGPR activities of several bacterial isolates {in-vitro screening), to examine their activities in stimulating soybean growth (in-vivo screening), and to identify the bacterial species. These were isolated from nodules and soil samples collected from Mount Pancar in Bogor, West Java Province as well as from Bangkirai Hill and Wain River in East Kalimantan, Indonesia. The in-vitro PGPR activity characterization includes the N-fixing ability, ACC-deaminase, indole acetic acid (IAA) production, cellulolytic activity, P-solubilization, Phosphomonoesterase (PME-ase), and nifH-gene detection. The in-vivo PGPR activity with the greenhouse assay was conducted on soybean plant {Glycine max L.). All bacterial isolates were identified using molecular methods based on nucleotide sequence generated from 16S rRNA gene. Three isolates of soil and nodule bacteria with 7 characteristics of PGPR (N2 fixation, ACC-deaminase, cellulolytic activity, IAA production, solubilization index, P available, and PMEase activity) were successfully identified. These isolates were B045 {Klebsiella variicola InaCC B827), B116 (Klebsiella sp. InaCC B833), and B210 {Mangrovibacterplantisponsorlaa.CC B841). The greenhouse assay showed that the plant height, plant dry weight and number of flowers in soybean seedlings significantly increased with Bradyrhispbium sp. strain 4167, then with Klebsiella sp. InaCC B833 and Mangrovibacterplantisponsor InaCC B841. These bacterial isolates which were characterized and screened in-vitro for PGPR potentials and their representative isolates which were identified by 16S rRNA sequence analysis are key factors for selecting PGPR isolates to be commercialized later as bio-stimulant.
REPRODUCTIVE BIOLOGY OF THE FRESHWATER CLAM POKEA (Batissa violacea var. celebensis, VON MARTEN 1897) (Bivalvia: Corbiculidae) IN THE POHARA RIVER, SOUTHEAST SULAWESI, INDONESIA
Authors: Bahtiar Bahtiar , Anadi La , Nurgayah Wa , Hamzah Muhaimin , Hernawan Udhi Eko
Published: January 2024

The freshwater clam, locally known as Pokea, (Batissa violaceaÂ varÂ celebensis, von Martens 1897; Bivalvia: Corbulidae) is a popular and widely consumed food in Kendari, Southeast Sulawesi. Despite its popularity, basic information required for conservation managenment, such as reproductive biology, is lacking. This study aims to examine the reproductive biology of the clam obtained from the Pohara River, Kendari. Pokea samples were collected monthly from February 2012 to January 2013. We recorded parameters of reproductive biology, including sex ratio, stage of gonadal maturity, gonadosomatic index (GSI), fecundity, and size of the first mature gonad from each sample. Data were analysed using chi-square test andÂ linear regression in the package Sigma Plot v.6.0. Pokea population in the Pohara River was male-biased. The population spawns throughout the year and the peak spawning season was August-September. Mature gonad was found at small shell size (indicating early sexual maturity). Food availability might have influenced the gonadal development in Pokea. This baseline information is very relevant for conservation practices of Pokea population in the Pohara River.
Hospital Variation in Skilled Nursing Facility Use After Coronary Artery Bypass Graft Surgery
Authors: Stewart James W. , Hou Hechuan , Hawkins Robert B. , Pagani Francis D. , Sterling Madeline R. , Likosky Donald S. , Thompson Michael P.
Published: January 2024

Background

Over 20% of patients are discharged to a skilled nursing facility (SNF) after coronary artery bypass graft surgery, but little is known about specific drivers for postdischarge SNF use. The purpose of this study was to evaluate hospital variation in SNF use and its association with postoperative outcomes after coronary artery bypass graft.

Methods and Results

A retrospective study design utilizing Medicare Provider Analysis and Review files was used to evaluate SNF use among 70 509 beneficiaries undergoing coronary artery bypass graft, with or without valve procedures, between 2016 and 2018. A total of 17 328 (24.6%) were discharged to a SNF, ranging from 0% to 88% across 871 hospitals. Multilevel logistic regression models identified significant patient‐level predictors of discharge to SNF including increasing age, comorbidities, female sex, Black race, dual eligibility, and postoperative complications. After adjusting for patient and hospital factors, 15.6% of the variation in hospital SNF use was attributed to the discharging hospital. Compared with the lower quartile of hospital SNF use, hospitals in the top quartile of SNF use had lower risk‐adjusted 1‐year mortality (12.5% versus 8.6%,
P
<0.001) and readmission (59.9% versus 49.8%,
P
<0.001) rates for patients discharged to a SNF.

Conclusions

There is high variability in SNF use among hospitals that is only partially explained by patient characteristics. Hospitals with higher SNF utilization had lower risk‐adjusted 1‐year mortality and readmission rates for patients discharged to a SNF. More work is needed to better understand underlying provider and hospital‐level factors contributing to SNF use variability.