bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complementing Drawability Assessment of Deep-Drawn Components With Surrogate-Based Global Sensitivity Analysis
Authors: Lehrer Tobias , Kaps Arne , Lepenies Ingolf , Raponi Elena , Wagner Marcus , Duddeck Fabian 
Published: March 2024

Abstract
In the early-stage development of sheet metal parts, key design properties of new structures must be specified. As these decisions are made under significant uncertainty regarding drawing configuration changes, they sometimes result in the development of new parts that, at a later design stage, will not be drawable. As a result, there is a need to increase the certainty of experience-driven drawing configuration decisions. Complementing this process with a global sensitivity analysis (GSA) can provide insight into the impact of various changes in drawing configurations on drawability, unveiling cost-effective strategies to ensure the drawability of new parts. However, when quantitative global sensitivity approaches, such as Sobol's method, are utilized, the computational requirements for obtaining Sobol indices can become prohibitive even for small application problems. To circumvent computational limitations, we evaluate the applicability of different surrogate models engaged in computing global design variable sensitivities for the drawability assessment of a deep-drawn component. Here, we show in an exemplary application problem, that both a standard Gaussian process regression (GPR) model and an ensemble model can provide commendable results at a fraction of the computational cost. We compare our surrogate models to existing approaches in the field. Furthermore, by comparing drawability measures we show that the error introduced by the surrogate models is of the same order of magnitude as that from the choice of drawability measure. In consequence, our surrogate models can improve the cost-effective development of a component in the early design phase.
Ultrasonic Guided Wave Scattering Spectra by Hybrid Global–Local Modeling for Nondestructive Evaluation in Composites With Varying Defect Features
Authors: Zhang Mingyue , Galvis Luis Waldo Escalona , Spada Antonino , Capriotti Margherita 
Published: March 2024

Abstract
The nondestructive characterization and monitoring of defects in composite structures by ultrasonic guided waves are hindered by the complexity of the interaction. Efficient computational modeling of propagating ultrasonic guided waves in waveguides with discontinuities is necessary to properly tune inspections and correctly interpret the scattering behavior. This paper studies the influence of different defect types in composite plates on ultrasonic guided wave scattering. Employing a hybrid global–local method, the energy spectra of transmitted and reflected waves in defected composite plates are numerically analyzed over a broad frequency range. Through parametric analyses of defect dimensions and locations, the resulting trends of the effect of specific defect features on the scattering behavior, as well as the importance of observing scattering on a broad frequency range, are accurately computed and highlighted. The presented findings indicate the potential for effective defect characterization and monitoring.
The complete genome sequence of a new fowl adenovirus (Fadv-4) strain from a recent outbreak in a chicken farm in Iran
Authors: khabiri Aliakbar , Ghalyanchilangeroudi Arash , Kim Doan Phuong Thi , Pakbaz Mohammadreza , Pakbaten Bahareh , Hemmatzadeh Farhid 
Published: March 2024

ABSTRACT

The whole genomic sequence of fowl adenovirus C (FAdV-4) strain FAdV-4/Pasouk, isolated from chickens with hepatitis-hydropericardium syndrome (HHS) from an outbreak in Iran, has been deposited in GenBank under accession number
ON652872
. Notably, this FAdV-4 isolate exhibited significant genetic similarities to contemporary isolates originating from China, indicating a shared ancestry.
Reduction of malaria case incidence following the introduction of clothianidin-based indoor residual spraying in previously unsprayed districts: an observational analysis using health facility register data from Côte d’Ivoire, 2018–2022
Authors: Hilton Emily R , Gning-Cisse Ndombour , Assi Auguste , Eyakou Mathieu , Koffi John , Gnakou Barthelemy , Kouassi Bernard , Flatley Cecilia , Chabi Joseph , Gbalegba Constant , Alex Aimain Serge , Yah Kokrasset Colette , Antoine Tanoh Mea , N'Gotta Sylvain , Yao Octavie , Egou Assi Hughes , Konan Philomène , Davis Kelly , Constant Edi , Belemvire Allison , Yepassis-Zembrou Patricia , Zinzindohoue Pascal , Kouadio Blaise , Burnett Sarah 
Published: March 2024

BackgroundIndoor residual spraying (IRS) using neonicotinoid-based insecticides (clothianidin and combined clothianidin with deltamethrin) was deployed in two previously unsprayed districts of Côte d’Ivoire in 2020 and 2021 to complement standard pyrethroid insecticide-treated nets. This retrospective observational study uses health facility register data to assess the impact of IRS on clinically reported malaria case incidence.MethodsHealth facility data were abstracted from consultation registers for the period September 2018 to April 2022 in two IRS districts and two control districts that did not receive IRS. Malaria cases reported by community health workers (CHWs) were obtained from district reports and District Health Information Systems 2. Facilities missing complete data were excluded. Controlled interrupted time series models were used to estimate the effect of IRS on monthly all-ages population-adjusted confirmed malaria cases and cases averted by IRS. Models controlled for transmission season, precipitation, vegetation, temperature, proportion of cases reported by CHWs, proportion of tested out of suspected cases and non-malaria outpatient visits.ResultsAn estimated 10 988 (95% CI 5694 to 18 188) malaria cases were averted in IRS districts the year following the 2020 IRS campaign, representing a 15.9% reduction compared with if IRS had not been deployed. Case incidence in IRS districts dropped by 27.7% (incidence rate ratio (IRR) 0.723, 95% CI 0.592 to 0.885) the month after the campaign. In the 8 months after the 2021 campaign, 14 170 (95% CI 13 133 to 15 025) estimated cases were averted, a 24.7% reduction, and incidence in IRS districts dropped by 37.9% (IRR 0.621, 95% CI 0.462 to 0.835) immediately after IRS. Case incidence in control districts did not change following IRS either year (p>0.05) and the difference in incidence level change between IRS and control districts was significant both years (p<0.05).ConclusionDeployment of clothianidin-based IRS was associated with a reduction in malaria case rates in two districts of Côte d’Ivoire following IRS deployment in 2020 and 2021.
Abstract 1022: Integration of cerebrospinal fluid methylome and proteome can obviate the need for biopsy in central nervous system lymphoma
Authors: Landry Alex P. , Zuccato Jeffrey A. , Patil Vikas , Voisin Mathew , Wang Justin Z. , Ellenbogen Yosef , Gui Chloe , Ajisebutu Andrew , Nassiri Farshad , Zadeh Gelareh 
Published: March 2024

Abstract
Background: The diagnosis of intra-axial brain tumors requires histopathological examination of tissue obtained by neurosurgery in current clinical practice, which comes with inherent risks. Some patients, particularly those with primary CNS lymphoma (PCNSL), only undergo surgery to obtain a diagnosis and do not derive any therapeutic benefit from surgical resection or debulking. Less-invasive techniques for diagnosis, such as liquid biopsy, therefore provides an opportunity to mitigate surgical risk in these patients.
Methods: Patients with histopathology confirmed glioblastoma (GBM, IDH wild type), brain metastases (BM), and PCNSL with accompanying cerebrospinal fluid (CSF) samples were included in our study. Cell-free DNA methylation profiling and shotgun proteomics were obtained for all patients and used to train classifiers to distinguish each tumour entity from others. Specifically, binomial elastic net regression models were built by combining both data modalities using established early and late integration paradigms and performance was compared to classifiers built from individual data types alone. Each model was repeated 100 fold and performance assessed on an untouched testing subset.
Results: Our cohort includes 20 patients with GBM, 17 with BM, and 14 with PCNSL, each with matching CSF cell-free DNA methylation and shotgun proteomic profiling. We show that these data can be integrated to fully discriminate PCNSL from its major diagnostic counterparts with a perfect median AUC of 1.00 (95% CI 1-1) and 100% specificity. Integrated "lymphoma vs other" models significantly outperform models trained on methylation or protein data alone, though the same dramatic improvement was not demonstrated in GBM or BM, suggesting synergistic biological information is specific to lymphoma.
Conclusions: There is a critical need to diagnose patients with intra-axial tumours, particularly PCNSL, without relying on invasive and costly surgery. We present the most specific and accurate CNS lymphoma classifier to date by integrating the methylome and proteome of CSF. This has the potential for immediate clinical utility, eliminating the need for biopsy in an important subset of these patients.
Citation Format: Alex P. Landry, Jeffrey A. Zuccato, Vikas Patil, Mathew Voisin, Justin Z. Wang, Yosef Ellenbogen, Chloe Gui, Andrew Ajisebutu, Farshad Nassiri, Gelareh Zadeh. Integration of cerebrospinal fluid methylome and proteome can obviate the need for biopsy in central nervous system lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1022.
Abstract 107: Application of MSD on the lung cancer associated idiopathic pulmonary fibrosis
Authors: Bao Wei , Li Ying-Ji , Gu Jin-Fan , Yang Cong-Lin , Wang Yi-Da , Bing Tie-Jun , Yu Wen-Jen 
Published: March 2024

Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible chronic disease that kill ten thousand of people in China every year. The risk of IPF is highly correlated with smoke, air pollution, dust, virus infection and aging. Average survival period of patients diagnosed as IPF is around 2.8 years which is less than several types of cancers, therefore, IPF is also thought to be a lung cancer-like disease. In the past few decades, many animal models were created to mimic human IPF, however, induction materials, animal species and strain differences, sex, physiology structure and progress of disease make the choice of IPF animal models selection more difficult. In addition, lack of strong evidence of cytokines biomarker detection hampered the discovery of anti-IPF drugs. Meso Scale Discovery (MSD) instrument is an efficient tool to high throughput analyze the lowest level of several cytokines and other biomarkers in the same time and was used to detect the bleomycin (BLM) induced mouse lung fibrosis. Meanwhile, animal sex and dose effects of BLM were also tested to define the proper mouse model for anti-IPF drugs development. Our results indicated that 0.6-0.8 mg/kg of intratracheal injection of single dose BLM is sufficient to create the IPF model without sex differences by examining the lung weight, lung ratio, soluble hydroxyproline, HE staining and mason staining. However, male mice were more resistant to the lethal effect of BLM due to the larger size or bodyweight. Using MSD detection, several mouse cytokines were measured simultaneously and showed that IFN-γ, IL-5, TNF-α, and IL-10 were increased in the IPF mouse model and were recovered after pirfenidone treatment at day 14 which mimics the cytokines profile in IPF patients. In summary, the MSD detection and pathological evaluation prove that male mouse treated with 0.8 mg/kg BLM through intratracheal injection is a suitable mouse model for the development of anti-IPF dugs.
Citation Format: Wei Bao, Ying-Ji Li, Jin-Fan Gu, Cong-Lin Yang, Yi-Da Wang, Tie-Jun Bing, Wen-Jen Yu. Application of MSD on the lung cancer associated idiopathic pulmonary fibrosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 107.
Abstract 1074: Plasma EV profiling facilitates low abundance biomarker discovery in pancreatic cancer
Authors: Bansal Shivani , Wang Shu , Li Yaoxiang , Bansal Sunil , Smith Jill , Tyburski John B. , Unger Keith , Cheema Amrita 
Published: March 2024

Abstract
The lack of reliable biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) results in poor prognosis due to advanced disease at diagnosis. Biopsies for pancreatic cancer are known to be particularly difficult to perform because of the location of the pancreas and low volume of primary tumors that metastasize aggressively. Currently, there is no blood test or other screening modality in use, for stratification of individuals with higher-than-average risk (5-8-fold) of developing PDAC in their lifetime. Given this existing void in the US and worldwide, an FDA-compliant, minimally invasive, quantitative biomarker test for the early detection of PDAC would be critical for screening subpopulations with, a) inherent genetic or familial predisposition; history of chronic pancreatitis; c) precursor lesions of pancreas; and d) older patients (&gt;50 years) with new onset diabetes or sudden weight loss. Extracellular vesicles (EVs) are shed by normal and cancer cells and carry a rich molecular cargo that can be leveraged for biomarker discovery. Whereas molecular profiling of bio-fluids poses intrinsic limitations for detection of low abundant, disease-specific biomarkers due to matrix effects; EVs, on the other hand, offer promise as a robust and minimally invasive biomarker resource. Mass spectrometry data were developed in our laboratory, based on multi-omics (proteomics, lipidomics and metabolomics) analyses of plasma EVs derived from patients diagnosed with early-stage PC (N=60), pancreatitis (N=39), precursor lesions of pancreas (N=45) as well as normal controls (N=50). These clinically annotated samples were made available by the Georgetown University Medical Center (GUMC) repository. Feature selection using a training-validation design allowed the development of a multiplexed biomarker panel comprising of 12-analytes (5-lipids, 2-metabolites and 5-proteins) that can robustly stratify early-stage PC from normal controls with high accuracy (AUC&gt;95%). Availability of a FDA compliant, multi-analyte-based classification algorithm that can stratify patients with precursor lesions of the pancreas that are at potential risk of progression to PC with &gt; 90% specificity and sensitivity is a critical clinical need. Refinement of panel to improve positive predictive value as well as identification of markers predictive of progression of precursor lesions to malignant transformation is ongoing.
Citation Format: Shivani Bansal, Shu Wang, Yaoxiang Li, Sunil Bansal, Jill Smith, John B. Tyburski, Keith Unger, Amrita Cheema. Plasma EV profiling facilitates low abundance biomarker discovery in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1074.
Abstract 1093: Small molecule inhibitors of the PAX3::FOXO1 fusion protein in rhabdomyosarcoma
Authors: Shaw Taryn , Nakazawa Kay , Tiwari Purushottam , Nelson Eryn , Formen Jeffrey , Wolf Christian , Toretsky Jeffrey , Üren Aykut 
Published: March 2024

Abstract
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. It is commonly divided into subtypes based on histopathological appearance. The oncogenic fusion proteins PAX3::FOXO1 or PAX7::FOXO1 are present in the alveolar subtype of RMS (ARMS). These chimeric proteins are formed by reciprocal chromosomal translocations and consist of an N-terminal portion of the PAX3 or PAX7 transcription factor fused to a C-terminal portion of the FOXO1 transcription factor. These fusion proteins have been shown to drive malignant transformation in ARMS, and patients with fusion-positive ARMS have a worse prognosis than patients with fusion-negative ARMS and embryonal RMS. We recently reported that piperacetazine, a phenothiazine derivative and first-generation antipsychotic, is capable of binding to and inhibiting the transcriptional activity of PAX3::FOXO1, reducing the expression of PAX3::FOXO1 target genes, and inhibiting the ability of fusion-positive RMS cells to grow in soft agar. We hypothesize that other phenothiazine derivatives may have stronger binding affinity for PAX3::FOXO1 and greater ability to reduce tumor growth in vivo. We employed a structure-activity relationship campaign to develop new phenothiazine derivatives that may be more potent inhibitors of PAX3::FOXO1 than piperacetazine. We synthesized and tested 10 new compounds, in addition to 9 existing FDA-approved phenothiazine derivatives, for their ability to bind to PAX3::FOXO1 and inhibit its transcriptional activity and target gene expression as well as inhibiting the growth of fusion-positive RMS cells in 3D culture. Seven derivatives inhibited PAX3::FOXO1 reporter activity better than piperacetazine, nine of them performed worse, and three of them showed comparable activity to piperacetazine. We demonstrated that piperacetazine does not alter PAX3::FOXO1 levels, subcellular localization, binding to a PAX3::FOXO1 target DNA sequence, or phosphorylation at Ser256 in the FOXO1 portion of the fusion protein. We therefore hypothesize that piperacetazine may be disrupting interactions between PAX3::FOXO1 and its partner proteins. We are employing a proximity-based biotinylation method to identify proteins that are competed away from PAX3::FOXO1 by piperacetazine. Our data suggest that it is possible to target PAX3::FOXO1 protein using small molecules that can directly bind to it and inhibit its activity in fusion-positive RMS cells.
Citation Format: Taryn Shaw, Kay Nakazawa, Purushottam Tiwari, Eryn Nelson, Jeffrey Formen, Christian Wolf, Jeffrey Toretsky, Aykut Üren. Small molecule inhibitors of the PAX3::FOXO1 fusion protein in rhabdomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1093.
Abstract 1111: Poor radiation sensitivity and potential radiosensitizers for betel-nuts related head and neck squamous cell carcinoma in Taiwan
Authors: Chen Jo-Pai , Chang Jui-Ying , Hong Ruey-Long 
Published: March 2024

Abstract
Background: Betel nut chewing might contribute to strong invasion & treatment refractoriness in HNSCC from Taiwan. Betel-nuts exposed HNSCC cell line, TW2.6, had high PDL1, defective p53 mutation, p16 loss, & BCL2 overexpression. In our studies, PI3K/AKT/mTOR inhibitors, anti-angiogenesis therapies, CDK4/6 inhibitors, DDR interventions, epigenetic modifications, and immunotherapy-containing regimens will be future combination options. The genomic signature of TW2.6 has been figured out in our study(AACR2020 & 2023), too, mainly with PIK3CA H1047R mutation, high TMB(8.42 muts/Mb)/MSS, VEGF-A amplification, p53/MYC/HRAS/DDR2/PDGFRbeta/EPHB1/ATM mutations, FAT1 loss, amplification of TERT/FGF10/CCND3/SOX9/IL-7R/SDHA/RICTOR/FLCN, CDK12/PTPRD loss of function, CDK8 mutation, & deletions of STK11/ARID1B/MITF/TNFAIP3 and molecularly-guided novel interventions will be designed. Purpose & Methods: Polo-like kinase 1 inhibitor(volasertib), gluconate(blocking citrate transport & glucose metabolism), IAP inhibitor(Debio1143), glutaminase 1 inhibitor(CB839) were tested on TW2.6 to evaluate synergistic effects with radiation. Results: TW2.6 was resistant to volasertib, gluconate, or radiation alone; but sensitive to Debio1143 and CB839. Volasertib significantly enhanced radiation. The flow cytometry revealed volasertib and radiation resulted in a significant G2/M arrest. Western blotting showed volasertib and radiation increased p-histone3, p-CDK1, & cyclin B levels and induced apoptosis. Gluconate, CB839, or Debio1143 each had significant synergistic effects with radiation. The radiosensitization efficacy would be volasertib&gt;gluconate&gt;CB839&gt;Debio1143. Conclusions: In Taiwan, patients with R/M HNSCC progressing within 3 months after CCRT could be rescued by early ICIs. Recently, sequential CCRT followed by ICI or Debio-1143 with CCRT showed potential survival benefits. In our studies, novel agents such as PLK inhibitor, gluconate, and CB839 had even better radiosensitization compared with Debio1143. Sequential CCRT with novel agents followed by ICI will be the future trend, esp. in biology-aggressive betel-nuts related locally advanced HNSCC in Taiwan.
Citation Format: Jo-Pai Chen, Jui-Ying Chang, Ruey-Long Hong. Poor radiation sensitivity and potential radiosensitizers for betel-nuts related head and neck squamous cell carcinoma in Taiwan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1111.