bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1 evaluation of the safety and tolerability of niraparib in combination with everolimus in advanced ovarian and breast cancers
Authors: Starks David , Rojas‐Espaillat Luis , Meissner Tobias , Elsey Rachel , Xu Bing , Koenen Maria , Feng Shelley , VanOosbree Annika , Slunecka John , Lee John , Williams Casey B. 
Published: August 2023

AbstractObjectivesPhase 1 trial to determine the safety and tolerability of everolimus and niraparib in patients with advanced ovarian and breast malignancies.ResultsFourteen heavily pretreated patients were enrolled (12 high‐grade serous ovarian cancer, 1 clear cell ovarian cancer, and 1 triple negative breast cancer). All patients were PARP naïve and received comprehensive genomic profiling prior to enrollment. Two DLTs were experienced in cohort 2 (niraparib 200 mg daily and everolimus 5 mg 3 days per week) with one patient experiencing prolonged thrombocytopenia and the other experiencing severe hypertension. Four additional patients were enrolled after dose de‐escalation with one patient again experiencing severe hypertension leading to conclusion of the study. The most frequent grade 3 or greater adverse events were thrombocytopenia, hypertension, anemia, fatigue, neutropenia, and elevated alkaline phosphatase. Two patients had a PR and five patients had SD. ORR was 18% and the CBR was 45% in 11 evaluable patients. Median PFS was 6 months, and median OS is approximately 18 months with three patients still alive at the data cutoff.ConclusionsThe combination of everolimus and niraparib demonstrated significant toxicity at lower doses and is not feasible due to rapid onset and severe hypertension. This limitation possibly blunted the efficacy of the combination as PFS was modest, but OS was surprisingly robust due to three patients with ovarian cancer remaining alive with platinum refractory disease. Further investigation of multiagent blockade of the PI3K pathway combined with PARP is warranted.
Risk management actions following genetic testing in the Cancer Health Assessments Reaching Many (CHARM) Study: A prospective cohort study
Authors: Guo Boya , Knerr Sarah , Kauffman Tia L. , Mittendorf Kathleen F. , Keast Erin , Gilmore Marian J. , Feigelson Heather Spencer , Lynch Frances L. , Muessig Kristin R. , Okuyama Sonia , Zepp Jamilyn M. , Veenstra David L. , Hsu Li , Phipps Amanda I. , Lindström Sara , Leo Michael C. , Goddard Katrina A. B. , Wilfond Benjamin S. , Devine Beth ,   the CHARM Study team
Published: August 2023

AbstractBackgroundGenetic testing can identify cancer risk early, enabling prevention and early detection. We describe use of risk management interventions following genetic testing in the Cancer Health Assessment Reaching Many (CHARM) study. CHARM assessed risk and provided genetic testing to low income, low literacy, and other underserved populations that historically face barriers to accessing cancer genetic services.MethodsCHARM was implemented in Kaiser Permanente Northwest (KPNW) and Denver Health (DH) between 2018 and 2020. We identified post‐testing screening (mammography, breast MRI, colonoscopy) and surgical (mastectomy, oophorectomy) procedures using electronic health records. We examined utilization in participants who did and did not receive actionable risk management recommendations from study genetic counselors following national guidelines.ResultsCHARM participants were followed for an average of 15.4 months (range: 0.4–27.8 months) after results disclosure. Less than 2% (11/680) received actionable risk management recommendations (i.e., could be completed in the initial years following testing) based on their test result. Among those who received actionable recommendations, risk management utilization was moderate (54.5%, 6/11 completed any procedure) and varied by procedure (mammogram: 0/3; MRI: 2/4; colonoscopy: 4/5; mastectomy: 1/5; oophorectomy: 0/3). Cancer screening and surgery procedures were rare in participants without actionable recommendations.ConclusionThough the number of participants who received actionable risk management recommendations was small, our results suggest that implementing CHARM's risk assessment and testing model increased access to evidence‐based genetic services and provided opportunities for patients to engage in recommended preventive care, without encouraging risk management overuse.
Exploring biomarkers for autophagy‐mediated macrophage pyroptosis in atherosclerosis
Authors: Yang Rongyuan , Wang Dawei , Ding Yu , Liu Qing 
Published: August 2023

AbstractThis study tried to investigate the macrophage autophagy‐related pyroptosis in atherosclerosis. The gene expression omnibus (GEO) dataset of GSE100927 was used for differentially expressed genes (DEG) screening, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG), CIBERSORT, weighted correlation network analysis (WGCNA), receiver operating characteristic (ROC), gene set enrichment analysis (GSEA), and correlation analysis, and GSE159677 was used for single‐cell analysis, all conducted in R software. Protein–protein interaction (PPI) was constructed in STRING and analyzed in Cytoscape. Transcription factors, drugs, and tissue co‐expression network were explored in NetworkAnalyst. A total of 110 autophagy‐related DEG (DEATG) were identified, and GO/KEGG revealed the top items enriched in autophagy, phagosome and lysosome. CIBERSORT showed 11 cell types were markedly differentially expressed (p < .05). WGCNA found the turquoise and yellow module were positively correlated with macrophage M0 (corr = 0.5, P = 6e‐6) and M2 (corr = 0.54, P = 1e‐6), respectively. Then 35 immune‐related DEATG were identified, and functional analysis showed immune effector process, interleukin‐6 and myeloid cell activation were enriched besides autophagy. PPI and MCC algorithm identified 6 hub genes in regulating macrophage‐related autophagy, and ROC indicated high prediction value (area under curve = 0.961). GSEA enriched 6 common pathways associated with autophagy and atherosclerosis pathogenesis, and immune correlation suggested these hub genes were correlated with macrophages M0/M1, monocytes and T cells. Then venn plot found 3 central genes in mediating macrophage autophagy‐associated pyroptosis in atherosclerosis, and single‐cell analysis demonstrated cell distribution, then validated in THPA human samples. Our data discovered hub genes responsible for macrophage autophagy‐mediated pyroptosis in atherosclerosis, and functional analysis with immune cell distribution evidenced their high phenotype‐trait prediction value.
The role of multidetector CT scan in the management of prosthetic aortic valve thrombosis: A case report
Authors: Dodoo Sheriff N. , Moyine Christelle Yakana , Agyemang‐Sarpong Alicia , Ismail Abdullah , Le Nina , Patel Falgun , Ghasemzadeh Nima , Ramadan Ronnie , Mohammed Khaja Salahuddin , Henry Glen , Parastatidis Ioannis 
Published: August 2023

Key Clinical MessageIn this case report, the utility of MDCT in elucidating the pathophysiology and etiology of prosthetic aortic valve dysfunction allowed us to distinguish thrombosis from pannus as an etiology of prosthetic valve dysfunction. MDCT also guided the success of therapy.AbstractThe diagnosis and management of prosthetic aortic valve thrombosis (PAVT) is challenging. The accurate diagnosis of this entity and its prompt management is vital to improving the prognosis of PAVT patients. Multidetector CT plays a central role in this effort. We present a case of PAVT in which the use of MDCT was useful in guiding management.
Recreational nitrous oxide‐induced injury to the soft palate
Authors: Rowson Antonia C. , Yii Matthew X. , Tan Hannah B. , Prasad Jessica 
Published: August 2023

Key Clinical MessageFrostbite arising from nitrous oxide (N2O) inhalation is rare. As such, there is no consensus on best treatment for these injuries. In all published reports, judicious use of corticosteroids and antibiotics has resulted in positive clinical outcomes; we endorse these agents in our case of a young man with oropharyngeal burns.
Prolonged SARS‐CoV‐2 infection during obinutuzumab and bendamustine treatment for follicular lymphoma: A case report
Authors: Kambe Ryosuke , Sato Masamichi , Uehara Daisuke , Iizuka Yutaka , Kakizaki Satoru 
Published: August 2023

Key Clinical MessageSARS‐CoV‐2 infection has been associated with a prolonged course and a poor prognosis in patients who receive anti‐CD20 antibodies. However, there are no established treatments for such patients. Serial changes in the SARS‐CoV‐2 antigen titer during the clinical course and treatment strategies for immunosuppressed patients are discussed.AbstractWe report a case of prolonged SARS‐CoV‐2 infection during obinutuzumab and bendamustine treatment for follicular lymphoma. Four years previously, the patient had been diagnosed with follicular lymphoma (Stage IIIA, Grade 2). She received several chemotherapy regimens, including rituximab and radiation therapy. Although these therapies achieved complete response temporally, they did not continue and recurred at 8 months before. Obinutuzumab and bendamustine therapy was selected, and she received five courses of obinutuzumab and bendamustine. She also received a SARS‐CoV‐2 mRNA vaccine two times. Although she did not have any symptoms, a routine check‐up just before the 6th course of obinutuzumab and bendamustine revealed SARS‐CoV‐2 infection. Because she was immunosuppressed and was considered to be at high risk for the exacerbation of her disease, molnupiravir was immediately administered, and her SARS‐CoV‐2 antigen decreased. However, it was not completely cleared and flared‐up at 6 weeks, with symptoms of COVID‐19 appearing. Despite intensive treatment for SARS‐CoV‐2 infection, including remdesivir, baricitinib, tocilizumab and intravenous immunoglobulin, her SARS‐CoV‐2 antigen titer never became negative, and she finally died of respiratory failure caused by prolonged SARS‐CoV‐2 infection. Serial changes in the SARS‐CoV‐2 antigen titer during the clinical course and treatment strategies for immunosuppressed patients are discussed.
Biochemical and Structural Characterization of a Uronic Acid Oxidase from Citrus sinensis
Authors: Boverio Alessandro , van Beek Hugo L. , Savino Simone , Ranoux Adeline , Huijgen Wouter J. J. , Raaijmakers Harry W. C. , Fraaije Marco W. , Lončar Nikola 
Published: August 2023

AbstractAldaric acids are attractive diacids that can be prepared by selective oxidation of carbohydrates. For this, effective biocatalysts are in demand. This work reports on the discovery, biochemical and structural characterization of a VAO‐type flavin‐containing carbohydrate oxidase from Citrus sinensis: URAOCs3. URAOCs3 could be overexpressed using prokaryotic and eukaryotic expression systems. Extensive biochemical characterization revealed that the enzyme displays a high thermostability and an exquisite selectivity for uronic acids, galacturonic acid and glucuronic acid. The enzyme was further investigated by determining the crystal structure. The selective oxidation of D‐galacturonic acid in a complex mixture was demonstrated, showing how URAOCs3 was found to be highly effective in selectively producing galactaric acid while leaving other carbohydrates untouched. In addition to the specific discovery of URAOCs3, these findings suggest that plant proteomes can be an interesting source for new biocatalysts.
Tuneable Plasmonic Resonances Of A Dynamic Thin Film Of Ultrasmall Nanocrystals Modified In the Anti‐Galvanic Reduction Process
Authors: Kołodziej Grzegorz , Szostak Szymon , Tomczyk Ewelina , Wójcik Michał 
Published: August 2023

AbstractUltrasmall gold nanoparticles (NPs) have revolutionized nanotechnology as they are an excellent starting substrate for the synthesis of organic‐inorganic hybrid materials with photonic or energy conversion applications, often with a responsive nature. However, ultrasmall NPs do not sustain plasmonic resonances, preventing their use in plasmon‐related applications. In the presented work, we show a method of chemical modification of ultrasmall gold nanoparticles in order to fabricate dynamically controlled plasmonic thin films. For this purpose, we used the Anti‐Galvanic Reduction process (AGR) to modify the surface of small gold nanoparticles, inducing plasmonic properties without notable size increases. Au@Ag NPs are then modified with liquid crystal‐like organic ligands. The obtained NPs can assemble into densely packed films with long‐range order and temperature‐dependent structural properties. Namely, we detect two, fully reversible phase transitions between the hexagonal and cubic symmetries. The combination of AGR and organic surface modifications enabled us to demonstrate the possibility of managing plasmonic properties in the thin film of ~2 nm diameter metallic NPs.
Improved Triplex‐Forming Isoorotamide PNA Nucleobases for A−U Recognition of RNA Duplexes**
Authors: Talbott John M. , Tessier Brandon R. , Harding Emily E. , Walby Grant D. , Hess Kyle J. , Baskevics Vladislavs , Katkevics Martins , Rozners Eriks , MacKay James A. 
Published: August 2023

AbstractFour new isoorotamide (Io)‐containing PNA nucleobases have been designed for A−U recognition of double helical RNA. New PNA monomers were prepared efficiently and incorporated into PNA nonamers for binding A−U in a PNA:RNA2 triplex. Isothermal titration calorimetry and UV thermal melting experiments revealed slightly improved binding affinity for singly modified PNA compared to known A‐binding nucleobases. Molecular dynamics simulations provided further insights into binding of Io bases in the triple helix. Together, the data revealed interesting insights into binding modes including the notion that three Hoogsteen hydrogen bonds are unnecessary for strong selective binding of an extended nucleobase. Cationic monomer Io8 additionally gave the highest affinity observed for an A‐binding nucleobase to date. These results will help inform future nucleobase design toward the goal of recognizing any sequence of double helical RNA.
Optimizing the separation of xylose/xylan from eucalyptus woodchips in the autohydrolysis process
Authors: Ni Jianping , Liang Yinchun , Gong Chen , Fan Shujie , Yang Bin , Zhang Yu , Cheng Chunzu , Su Zhenhua , Chen Xiaolu 
Published: August 2023

AbstractEffective separation of various components in biomass is critical for biorefinery. Autohydrolysis is a commercialized unit operation to remove hemicelluloses, such as xylan, in producing high‐quality cellulose (the so‐called dissolving pulp) in the pre‐hydrolysis kraft process. In the present study, the autohydrolysis of eucalyptus woodchips was investigated for the purpose of producing dissolving pulps, with a focus on the production of cellulose acetate grade dissolving pulp. First, the effects of liquid‐to‐solid ratio, maximum temperature, and time on hemicelluloses removal were comprehensively studied, and the total xylose saccharides concentration and total xylose saccharides yield were determined as a function of the P factor and log(Ro). The three‐variable Box–Behnken design of the response surface methodology was followed to optimize the autohydrolysis conditions, aiming to achieving the maximum removal of xylan. The as‐obtained optimal conditions were: liquid‐to‐solid ratio of 5.5 mL · g−1, maximum temperature of 165°C, and time of 120 min, with its P factor of 867 h and log(Ro) of 4.03. Under these conditions, the total xylose saccharides concentration was 16.43 g · L−1. Furthermore, the autohydrolysis yield was investigated. The results showed that the purity of as‐prepared cellulose substrate as a result of autohydrolysis at a P factor of 867 h (log(Ro) of 4.03) can meet the stringent requirement of cellulose acetate grade dissolving pulp. Furthermore, the pre‐hydrolysis liquor compositions were compared between the typical autohydrolysis conditions for rayon grade dissolving pulp (a P factor of 690 h and log(Ro) of 3.91) and the optimal conditions (a P factor of 867 h and log(Ro) of 4.03).
Anonymous federated learning framework in the internet of things
Authors: Du Ruizhong , Liu Chuan , Gao Yan 
Published: August 2023

AbstractWith the continuous development of the internet of things (IoT), federated learning is being widely applied. This technology keeps data locally to protect data security. However, during the process of uploading gradients from local clients, there is a possibility of leaking sensitive information such as identities. To address this issue, this paper presents a secure and efficient anonymous federated learning framework. In our proposed, we first design a lightweight key‐sharing protocol based on elliptic curve cryptography (ECC) to generate shared keys and ensure secure communication. We then describe the improved process of federated learning, where clients communicate with the cloud server using pseudonyms to achieve anonymity. The security of our protocol is analyzed from both formal and informal perspectives, demonstrating that our proposed protocol satisfies “session key security.” We also employ the formal verification tool ProVerif to validate the security of the protocol in terms of mutual authentication and key configuration in the Dolve–Yao threat model. Finally, the computational and communication costs of the proposed anonymous federated learning framework are evaluated, showing that both the computational and communication expenses are relatively low. A comparison was made between the proposed federated learning process and three other federated learning processes, demonstrating the clear advantages of our proposed.
Environmental stability and genetic effect of soybeans differing in mutant allele combinations between rs and mips1 genes for soluble carbohydrate profiles
Authors: Lee Dongho , Vuong Tri D. , Shannon Grover J. , Shi Haiying , Rainey Katy M. , Nguyen Henry T. 
Published: August 2023

AbstractRaffinose and stachyose (raffinose family oligosaccharides [RFOs]) in soybeans [Glycine max (L.) Merr.] are anti‐nutritional carbohydrate components. Previous studies identified mutant alleles of raffinose synthase (rs) 2 and 3 and d‐myo‐inositol‐3‐phosphate synthase 1 (mips1) to increase sucrose and reduce RFOs content. Although earlier studies investigated the effects of rs2 and rs3 mutations, a mips1 mutation has not been tested yet. The objectives of this study were (1) to investigate the genetic effects and environmental stabilities of rs2, rs3, and mips1 mutations across 18 environments and (2) to evaluate germination rates of genotypes carrying these mutations. Sucrose was significantly affected by all environmental factors (year, location, and planting dates). However, raffinose was not affected by planting dates, and stachyose was only affected by location. The rs2 mutant allele (rs2W331‐) and mips1 showed the highest environmental stability for sucrose and raffinose, respectively. For stachyose, the wild‐type check showed the highest environmental stability. The lines with mips1 mutation showed significantly higher sucrose (11.1%) and lower raffinose (0.5%) and stachyose (0.6%) content than other genotypes across environments. The lines tested in field emergence tests showed no significant difference from the check. Lines with mips1 and rs2W331‐, respectively, showed significantly higher germination rates than the check in the accelerated aging test. In contrast, a line with mips1 showed a significantly higher germination rate than the check in the standard germination test. Desirable carbohydrate allele combinations will facilitate the development of new cultivars with modified carbohydrate profiles that are beneficial to human food and animal feed.
Quantifying impacts of an environmental intervention using environmental DNA
Authors: Allan Elizabeth Andruszkiewicz , Kelly Ryan P. , D'Agnese Erin R. , Garber‐Yonts Maya N. , Shaffer Megan R. , Gold Zachary J. , Shelton Andrew O. 
Published: August 2023

AbstractEnvironmental laws around the world require some version of an environmental‐impact assessment surrounding construction projects and other discrete instances of human development. Information requirements for these assessments vary by jurisdiction, but nearly all require an analysis of the biological elements of ecosystems. Amplicon‐sequencing—also called metabarcoding—of environmental DNA (eDNA) has made it possible to sample and amplify the genetic material of many species present in those environments, providing a tractable, powerful, and increasingly common way of doing environmental‐impact analysis for development projects. Here, we analyze an 18‐month time series of water samples taken before, during, and after two culvert removals in a salmonid‐bearing freshwater stream. We also sampled multiple control streams to develop a robust background expectation against which to evaluate the impact of this discrete environmental intervention in the treatment stream. We generate calibrated, quantitative metabarcoding data from amplifying the 12s MiFish mtDNA locus and complementary species‐specific quantitative PCR data to yield multispecies estimates of absolute eDNA concentrations across time, creeks, and sampling stations. We then use a linear mixed effects model to reveal patterns of eDNA concentrations over time, and to estimate the effects of the culvert removal on salmonids in the treatment creek. We focus our analysis on four common salmonid species: cutthroat trout (Oncorhynchus clarkii), coho salmon (Oncorhynchus kisutch), rainbow trout (Oncorhynchus mykiss), and sockeye salmon (Oncorhynchus nerka). We find that one culvert in the treatment creek seemed to have no impact while the second culvert had a large impact on fish passage. The construction itself seemed to have only transient effects on salmonid species during the two construction events. In the context of billions of dollars of court‐mandated road culvert replacements taking place in Washington State, USA, our results suggest that culvert replacement can be conducted with only minimal impact of construction to key species of management concern. Furthermore, eDNA methods can be an effective and efficient approach for monitoring hundreds of culverts to prioritize culverts that are required to be replaced. More broadly, we demonstrate a rigorous, quantitative method for environmental‐impact reporting using eDNA that is widely applicable in environments worldwide.
TREM2 promotes glioma progression and angiogenesis mediated by microglia/brain macrophages
Authors: Chen Xuezhen , Zhao Yue , Huang Yimin , Zhu Kaichuan , Zeng Fan , Zhao Junyi , Zhang Huaqiu , Zhu Xinzhou , Kettenmann Helmut , Xiang Xianyuan 
Published: August 2023

AbstractTriggering receptor expressed on myeloid cell 2 (TREM2), a myeloid cell‐specific signaling molecule, controls essential functions of microglia and impacts on the pathogenesis of Alzheimer's disease and other neurodegenerative disorders. TREM2 is also highly expressed in tumor‐associated macrophages in different types of cancer. Here, we studied whether TREM2 influences glioma progression. We found a gender‐dependent effect of glioma growth in wild‐type (WT) animals injected with GL261‐EGFP glioma cells. Most importantly, TREM2 promotes glioma progression in male but not female animals. The accumulation of glioma‐associated microglia/macrophages (GAMs) and CD31+ blood vessel density is reduced in male TREM2‐deficient mice. A transcriptomic analysis of glioma tissue revealed that TREM2 deficiency suppresses immune‐related genes. In an organotypic slice model devoid of functional vascularization and immune components from periphery, the tumor size was not affected by TREM2‐deficiency. In human resection samples from glioblastoma, TREM2 is upregulated in GAMs. Based on the Cancer Genome Atlas Program (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases, the TREM2 expression levels were negatively correlated with survival. Thus, the TREM2‐dependent crosstalk between GAMs and the vasculature formation promotes glioma growth.