bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive Prognostic Model for Hepatocellular Carcinoma Based on Seven Genes Participating in Arachidonic Acid Metabolism
Authors: Gu Xinyu , Wang Jing , Guan Jun , Li Guojun , Ma Xiao , Ren Yanli , Wu Shanshan , Chen Chao , Zhu Haihong 
Published: November 2024

ABSTRACTBackgroundThe occult onset and rapid progression of hepatocellular carcinoma (HCC) lead to an unsatisfactory overall survival (OS) rate. Established prognostic predictive models based on tumor‐node‐metastasis staging and predictive factors do not report satisfactory predictive efficacy. Arachidonic acid plays pivotal roles in biological processes including inflammation, regeneration, immune modulation, and tumorigenesis. We, therefore, constructed a prognostic predictive model based on seven genes linked to arachidonic acid metabolism, using samples of HCC patients from databases to analyze the genomic profiles. We also assessed the predictive stability of the constructed model.MethodsSample data of 365 patients diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA, training set) and HCCDB18, GSE14520, and GSE76427 databases (validation sets). Patient samples were clustered using ConsensusClusterPlus analysis based on the expression levels of 12 genes involved in arachidonic acid metabolism that were significantly associated with HCC prognosis. Differentially expressed genes (DEGs) within different clusters were distinguished and compared using WebGestaltR. Immunohistochemistry (IHC) analysis was performed using a human HCC tissue microarray (TMA). Tumor immune microenvironment assessment was performed using ESTIMATE, ssGSEA, and TIDE.ResultsSamples of patients with HCC were classified into three clusters, with significant differences in OS. Cluster 2 showed the best prognosis, whereas cluster 1 presented the worst. The three clusters showed significant differences in immune infiltration. We then performed Cox and LASSO regression analyses, which revealed CYP2C9, G6PD, CDC20, SPP1, PON1, TRNP1, and ADH4 as prognosis‐related hub genes, making it a simplified prognostic model. TMA analysis for the seven target genes showed similar results of regression analyses. The high‐risk group showed a significantly worse prognosis and reduced immunotherapy efficacy. Our model showed stable prognostic predictive efficacy.ConclusionsThis seven‐gene–based model showed stable outcomes in predicting HCC prognosis as well as responses to immunotherapy.
A Novel Gene Expression Scoring System Predicts Recurrence in Non‐Muscle‐Invasive Bladder Cancer Patients
Authors: Kayama Emina , Uemura Motohide , Onagi Akifumi , Meguro Satoru , Ogawa Soichiro , Yaginuma Kei , Matsuoka Kanako , Hoshi Seiji , Koguchi Tomoyuki , Hata Junya , Sato Yuichi , Akaihata Hidenori , Honma Reiko , Watanabe Shinya , Kojima Yoshiyuki 
Published: November 2024

ABSTRACTBackgroundDespite the high recurrence rate of non‐muscle‐invasive bladder cancer (NMIBC), there are limitations in accurately predicting recurrence after transurethral resection of bladder tumor (TURBT) based on clinicopathological factors alone. However, prediction of recurrence using biomolecular characteristics of bladder tumors has not been applied to clinical practice. The objective of this study was to establish a new gene expression scoring system for identifying patients at high risk of recurrence.MethodsNMIBC and normal bladder samples were subjected to microarray analysis to obtain gene expression profiles. We identified 6 genes that were specifically upregulated in bladder cancer and also in recurrent cases. All patients were randomly grouped into a discovery cohort (n = 59) and a validation cohort (n = 30). Gene expression score (GES) was defined as the mean Z‐score of the 6 genes specific for recurrent bladder cancer.ResultsThe intravesical recurrence rate of the high GES group (n = 38) was higher than the low GES group (n = 21). GES was significantly associated with recurrence‐free survival in the validation cohort as well. In prognostic analysis, the European Organization for Research and Treatment of Cancer (EORTC) risk classification was not related to recurrence after TURBT in either univariate or multivariate analysis. On the other hand, the GES we developed was an independent factor for recurrence in NMIBC.ConclusionsA novel gene expression scoring system was shown to predict recurrence in NMIBC patients after TURBT and might be helpful in clinical decision‐making for NMIBC patients.
Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and In Silico Studies
Authors: Abdallah Abdallah E. , Eissa Ibrahim H. , Mehany Ahmed B. M. , Celik Ismail , Sakr Helmy , Metwaly K. H. , El‐Adl Khaled , El‐Zahabi Mohamed Ayman 
Published: November 2024

AbstractNew thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7 a and 28, and phthalazine based 20 a against HepG‐2, MCF‐7, PC3, and HCT‐116 cell lines, compared to thalidomide. In particular, compound 20 a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF‐α, IL‐6, caspase 3, COX‐I/II, and VEGFR‐2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF‐7 cells, the most sensitive cell line to the current new molecules. Compound 20 a caused reduction in levels of TNF‐α and IL‐6 by 75.22 % and 82.51 %, respectively. It elevated the caspase‐3 level by 7.21‐fold. Furthermore, IC50 against COX‐I, COX‐II, and VEGFR‐2 were 0.65 μM, 0.33 μM, and 232 nM, respectively. In addition, it raised the apoptosis rate from 65.65 % to 99.89 %. Moreover, 20 a was further examined through a docking study and a 200 ns molecular dynamics simulation for its complex with VEGFR‐2, along with computational ADME properties. This work suggests the high significance of compounds 20 a, 7 a and 28, as lead compounds for development of new effective immunomodulatory antitumor drugs.
Synthesis and Biomedical Applications of Covalent Organic Frameworks for Disease Diagnosis and Therapy
Authors: Wang Anyun , Liu Xinli , Feng Shujun , Wang Yanping , Song Yujun , Gao Yanfeng 
Published: November 2024

AbstractCovalent organic frameworks (COFs) have emerged as a distinguished class of porous materials. Owing to their ability to be constructed through covalent bonds involving light elements, such as hydrogen, boron, carbon, nitrogen, and oxygen, COFs offer greater stability and lower cytotoxicity than metal–organic frameworks do, addressing critical limitations in in vivo applications. Their unique attributes, such as high surface area, customizable pore sizes, and versatile surface functionalities, make them ideal for various biomedical applications. This review aims to provide an overview of the recent advancements in modern COFs for biomedical uses. First, a variety of methods for the synthesis of COFs are outlined, which ensures their suitability for medical use. Next, we delve into innovative biomedical applications, emphasizing their roles in disease diagnosis and therapies. Finally, challenges, such as clinical translation, biocompatibility, and controlled drug release, are critically discussed, providing comprehensive insight into the potential of COFs in revolutionizing biomedical technologies. Overall, this review offers a comprehensive overview of COFs’ capabilities and future prospects in enhancing biomedical technologies.
Better Together: Synergic Effect of Gallium‐Based Catalyst and Porous Support for Reduction Reactions
Authors: Sánchez Marco Aurelio Jiménez , Carl Simon , Taccardi Nicola , Haumann Marco , Zubiri Benjamin Apeleo , Wasserscheid Peter , Spiecker Erdmann , Vogel Nicolas , Bachmann Julien , Magnabosco Giulia 
Published: November 2024

AbstractLiquid metal solutions are a new class of catalysts with outstanding properties in terms of catalytic conversion and resistance to coking. Finding the perfect combination of catalytic particles with homogeneous size distribution and support material able to stabilize them during catalysis is key for preparing model systems to gain understanding of these complex catalytic processes. In this work, we present a method for the preparation of small and narrowly distributed gallium–palladium particles supported on inverse opals, interconnected 3‐D porous networks with a very narrow pore size distribution. Our platform is a promising candidate as supported liquid metal catalytic system thanks to its permeability to fluids and its confined pore environment, which prevents the coalescence of the metal alloy, thus maximizing the surface area available for the catalytic reaction. We demonstrate their enhanced performance when compared to other state of the art systems giving a proof of concept of their application as catalysts for a simple model reaction, the reduction of methylene blue.
Changes in Secondary Structure Upon Pr to Pfr Transition in Cyanobacterial Phytochrome Cph1 Detected by DNP NMR
Authors: Gerland Lisa , Diehl Anne , Erdmann Natalja , Hiller Matthias , Lang Christina , Teutloff Christian , Hughes Jon , Oschkinat Hartmut 
Published: November 2024

AbstractPhytochromes perceive subtle changes in the light environment and convert them into biological signals by photoconversion between the red‐light absorbing (Pr) and the far‐red‐absorbing (Pfr) states. In the primitive bacteriophytochromes this includes refolding of a tongue‐like hairpin loop close to the chromophore, one strand of an antiparallel β‐sheet being replaced by an α‐helix. However, the strand sequence in the cyanobacterial phytochrome Cph1 is different from that of previously investigated bacteriophytochromes and has a higher β‐sheet propensity. We confirm here the transition experimentally and estimate minimum helix length using dynamic nuclear polarisation (DNP) magic angle spinning NMR. Sample conditions were optimized for protein DNP NMR studies at high field, yielding Boltzmann enhancements ϵB of 19 at an NMR field of 18.801 T. Selective labelling of Trp, Ile, Arg, and Val residues with 13C and 15N enabled filtering for pairs of labelled amino acids by the 3D CANCOCA technique to identify signals of the motif 483Ile‐Val‐Arg485 (IVR) present in both sheet and helix. Those signals were assigned for the Pfr state of the protein. Based on the chemical shift pattern, we confirm for Cph1 the formation of a helix covering the IVR motif.
Nivolumab and sunitinib in patients with advanced bone sarcomas: A multicenter, single‐arm, phase 2 trial
Authors: Palmerini Emanuela , Lopez Pousa Antonio , Grignani Giovanni , Redondo Andres , Hindi Nadia , Provenzano Salvatore , Sebio Ana , Lopez Martin Jose Antonio , Valverde Claudia , Martinez Trufero Javier , Gutierrez Antonio , de Alava Enrique , Aparisi Gomez Maria Pilar , D’Ambrosio Lorenzo , Collini Paola , Bazzocchi Alberto , Moura David S. , Ibrahim Toni , Stacchiotti Silvia , Broto Javier Martin 
Published: November 2024

AbstractBackgroundHerein, we present the results of the phase 2 IMMUNOSARC study (NCT03277924), investigating sunitinib and nivolumab in adult patients with advanced bone sarcomas (BS).MethodsProgressing patients with a diagnosis of BS were eligible. Treatment was comprised of sunitinib (37.5 mg/day on days 1–14, 25 mg/day afterword) plus nivolumab (3 mg/kg every 2 weeks). Primary end point was progression‐free survival rate (PFSR) at 6 months based on central radiology review. Secondary end points were overall survival (OS), overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, and safety.ResultsA total of 46 patients were screened, 40 patients entered the study, and 38 underwent central radiological review and were evaluable for primary end point. Median age was 47 years (range, 21–74). Histologies include 17 (43%) osteosarcoma, 14 chondrosarcoma (35%, 10 conventional, four dedifferentiated [DDCS]), eight (20%) Ewing sarcoma, and one (2%) undifferentiated pleomorphic sarcoma. The PFSR at 6 months was 42% (95% confidence interval [CI], 27–58). With a median follow‐up of 39.8 months (95% CI, 37.9–41.7), the median PFS and OS were 3.8 months (95% CI, 2.7–4.8) and 11.9 months (95% CI, 5.6–18.2). ORR by RECIST was 5%, with two of 38 partial responses (one of four DDCS and one of 17 osteosarcoma), 19 of 38 (50%) stable disease, and 17 of 38 (45%) progressions. Grade ≥3 adverse events were neutropenia (six of 40, 15%), anemia (5/40, hypertension (6/40, 15%), 12.5%), ALT/AST elevation (5/40, 12.5%), and pneumonitis (1/40, 2.5%). Seventeen percent of patients discontinued treatment due to toxicity, including a treatment‐related grade 5 pneumonitisConclusionThe trial met its primary end point in the BS cohort with >15% of patients progression‐free at 6 months. However, the toxicity profile of this regimen was relevant.
Implantable cardioverter defibrillators in people dying with cancer: A SEER‐Medicare analysis of ICD prevalence and association with aggressive end‐of‐life care
Authors: Mullins Megan A. , Wang Tianci , Shahan Kathryn , Zaha Vlad G. , Goswami Rachna , Sulistio Melanie , Gerber David E. , Pruitt Sandi L. 
Published: November 2024

AbstractIntroductionThe shared risk profiles for cancer and heart disease suggest many individuals with cancer may have an implantable cardioverter defibrillator (ICD). ICDs can have dramatic cancer end‐of‐life care implications including painful and distressing shocks. ICD prevalence and association with aggressive end‐of‐life care among individuals with breast, colorectal, and pancreatic cancer was evaluated using the Surveillance, Epidemiology, and End Results‐Medicare dataset.MethodsA total of 37,306 Medicare beneficiaries aged ≥66 years with stage 3 or 4 cancer who died between 2005 and 2016 were identified. ICD prevalence, ICD‐related care utilization that might present opportunities to discuss end‐of‐life implications and association with aggressive end‐of‐life care (>1 emergency department visit, intensive care unit admission, >1 hospitalization, terminal hospitalization, chemotherapy, and invasive or life‐extending procedures) in the last month of life was assessed using multivariable logistic regression.ResultsAmong cancer decedents, 6% had an ICD. More individuals with an ICD (31%) died in the hospital than individuals without an ICD (25%; p < .001). Half (46%) of individuals with an ICD had device programming or interrogation visits that could be an opportunity for device discussion. In adjusted models, ICD presence was associated with higher odds of every indicator of aggressive end‐of‐life care other than chemotherapy.ConclusionMany older cancer decedents in the United States had an ICD, and those with ICDs received more aggressive care at the end of life. Results suggest there are opportunities to discuss ICD and goals of care, raise awareness and encourage shared decision‐making for this population to ensure goal‐concordant care, and improve end‐of‐life care quality.
Vacancy Enriched Structurally Modulated Nickel Ferrite for Oxygen Evolution Reaction
Authors: Senapati Shraddhanjali , Bal Rajaram , Mohapatra Manoj , Jena Bijayalaxmi 
Published: November 2024

AbstractGeneration of clean hydrogen fuel from renewable source like water by electrocatalytic water splitting is an advanced energy conversion technology. The idea of water splitting attracts the researcher to focus on the synthesis of active and stable catalysts. We modulated nickel ferrite using different surfactants and developed an active two‐dimensional (2D), economic and sturdy catalyst for the study of oxygen evolution reaction (OER) in basic electrolytic solution. Nickel ferrite with CTAB named as NF(C), with ascorbic acid named as NF(A), with oxalic acid named as NF(O) and Nickel ferrite without surfactant is named as NF. NF(O) having 2D structure shows better catalytic activity among all. The catalytic activity of NF(O) was further enhanced through reduction process. We reduced NF(O) using hydrazine hydrate along with ultrasonication power treatment to induce vacancy in the material namely Vo‐NF(O). Vo‐NF(O) exhibits low overpotential of 260 mV at 10 mA/cm2 with Tafel slope of 25 mV/dec and stability of 18 h. Creation of vacancy boosts the catalytic activity of the electrocatalyst by increasing the surface area and number of reactive sites of the catalyst, which improve electrical conductivity, thus facilitating the transfer of charges.
Solvothermal Synthesis of Medium‐Entropy Oxide Spheres for Thermocatalytic Conversion of CO2 to Methanol
Authors: Mielniczuk Monika , Knorpp Amy J. , Shukla Rishabh , Erni Rolf , Kata Dariusz , Graule Thomas , Drożdż Ewa , Stuer Michael 
Published: November 2024

AbstractNew chemical compositions and structures for medium‐ and high‐entropy oxides (HEOs) currently represent a promising new avenue in materials research for a wide range of applications including catalysis, energy storage, and ceramics. To speed up further development, synthesis methods for multicationic oxides are needed for controlling features like morphology, porosity, and chemical compositions. In this work, mesoporous spinel oxide spheres with five cations are synthesized using solvothermal synthesis techniques. The targeted chemistry included Co, Al, Fe, and Cr as the first four cations, where the fifth cation was varied by increasing cation radii (Ga, In, Yb, Ho, or Ce). After calcination, all as‐synthesized precursors led to mesoporous oxide spheres with spinel oxide structures. In order to demonstrate an example of applicability for targeting different M3+ cations, the sample containing Co, Al, Fe, Cr, and In was tested in a model reaction of thermocatalytic CO2 hydrogenation and is shown to be active with a preference to methanol formation (58 % selectivity, 7.8 % conversion at 300 °C). The synthesis of multicationic mesoporous spheres appears to be quite flexible in terms of possible M3+ cations compositions and is a potential material to combine targeted chemistry for applications like catalysis.
On the Non‐Catalytic Role of Lytic Polysaccharide Monooxygenases in Boosting the Action of PETases on PET Polymers
Authors: Corrêa Thamy L. R. , Román Ellen K. B. , Costa Carlos A. R. , Wolf Lucia D. , Landers Richard , Biely Peter , Murakami Mario T. , Walton Paul H. 
Published: November 2024

AbstractSynthetic polymers are resistant to biological attack, resulting in their long‐term accumulation in landfills and in natural aquatic and terrestrial habitats. Lytic polysaccharide monooxygenases (LPMOs) are enzymes which oxidatively cleave the polysaccharide chains in recalcitrant polysaccharides such as cellulose. It has been widely hypothesised that LPMOs could be used to aid in the enzymatic breakdown of synthetic polymers. Herein, through the use of biochemical assays, X‐ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) we show that LPMOs can bind to polyethylene terephthalate (PET), and – in doing so – the hydrophobic surface of PET becomes more hydrophilic such that product release is boosted by subsequent treatment with classical PETases. The boosting effect is however, only observed in reactions when the LPMO and the PETase are added sequentially rather than simultaneously to the PET. Moreover, the same boosting effect is also seen when a catalytically‐inactive mutant of LPMO is used, showing that the principal means by which AA9 LPMOs boost the degradation of synthetic polymers is through their role as a “hydrophobin” rather than as an oxygenase. Indeed, in accord with this role of LPMOs, we further show that this effect can be extended to other ostensibly ‘non‐catalytic’ proteins beyond LPMOs, such as bovine serum albumin and lactate dehydrogenase.
Dual‐Boost Inverter Without Leakage Current
Authors: Hu Xuefeng , Dong Songsheng , Xu Zijun , Wen Bo , Chen Jiawei 
Published: November 2024

ABSTRACTThe output AC side voltage of traditional full‐bridge inverter is lower than the input DC side voltage, which is limited in low‐voltage power generation. The conventional boost circuit and the modified boost circuit structure are effectively combined, thus putting forward a kind of no leakage current of single‐phase single‐stage booster inverter. The inverter has the characteristics of common ground, which can suppress the leakage current from the structure and avoid the problem of shoot‐through and improve the reliability of the system. The working mode, modulation strategy, and steady‐state performance of the proposed circuit structure are analyzed in detail. Finally, a 250‐W experimental prototype is designed in the laboratory, and the experimental results verify the feasibility and superiority of the proposed inverter.
Molecular characterization of human HSPCs with different cell fates in vivo using single‐cell transcriptome analysis and lentiviral barcoding technology
Authors: Hua Junnan , Wang Ke , Chen Yue , Xu Xiaojing , Dong Guoyi , Li Yue , Liu Rui , Xiong Yecheng , Ding Jiabin , Zhang Tingting , Zeng Xinru , Li Yuxi , Sun Haixi , Gu Ying , Liu Sixi , Ouyang Wenjie , Liu Chao 
Published: November 2024

AbstractHematopoietic stem and progenitor cells (HSPCs) possess the potential to produce all types of blood cells throughout their lives. It is well recognized that HSPCs are heterogeneous, which is of great significance for their clinical applications and the treatment of diseases associated with HSPCs. This study presents a novel technology called Single‐Cell transcriptome Analysis and Lentiviral Barcoding (SCALeBa) to investigate the molecular mechanisms underlying the heterogeneity of human HSPCs in vivo. The SCALeBa incorporates a transcribed barcoding library and algorithm to analyze the individual cell fates and their gene expression profiles simultaneously. Our findings using SCALeBa reveal that HSPCs subset with stronger stemness highly expressed MYL6B, ATP2A2, MYO19, MDN1, ING3, and so on. The high expression of COA3, RIF1, RAB14, and GOLGA4 may contribute to the pluripotent‐lineage differentiation of HSPCs. Moreover, the roles of the representative genes revealed in this study regarding the stemness of HPSCs were confirmed with biological experiments. HSPCs expressing MRPL23 and RBM4 genes may contribute to differentiation bias into myeloid and lymphoid lineage, respectively. In addition, transcription factor (TF) characteristics of lymphoid and myeloid differentiation bias HSPCs subsets were identified and linked to previously identified genes. Furthermore, the stemness, pluripotency, and differentiation‐bias genes identified with SCALeBa were verified in another independent HSPCs dataset. Finally, this study proposes using the SCALeBa‐generated tracking trajectory to improve the accuracy of pseudo‐time analysis results. In summary, our study provides valuable insights for understanding the heterogeneity of human HSPCs in vivo and introduces a novel technology, SCALeBa, which holds promise for broader applications.Key points
SCALeBa and its algorithm are developed to study the molecular mechanism underlying human HSPCs identity and function.
The human HSPCs expressing MYL6B, MYO19, ATP2A2, MDN1, ING3, and PHF20 may have the capability for high stemness.
The human HSPCs expressing COA3, RIF1, RAB14, and GOLGA4 may have the capability for pluripotent‐lineage differentiation.
The human HSPCs expressing MRPL23 and RBM4 genes may have the capability to differentiate into myeloid and lymphoid lineage respectively in vivo.
The legitimacy of the identified genes with SCALeBa was validated using biological experiments and a public human HSPCs dataset.
SCALeBa improves the accuracy of differentiation trajectories in monocle2‐based pseudo‐time analysis.