bluuebunny/crossref_metadata_2025_split huggingface dataset:
First Observations With a GNSS Antenna to Radio Telescope Interferometer
Authors: Skeens J. , York J. , Petrov L. , Munton D. , Herrity K. , Ji‐Cathriner R. , Bettadpur S. , Gaussiran T. 
Published: August 2023

AbstractWe describe the design of a radio interferometer composed of a Global Navigation Satellite Systems (GNSS) antenna and a Very Long Baseline Interferometry radio telescope. Our eventual goal is to use this interferometer for geodetic applications including local tie measurements. The GNSS element of the interferometer uses a unique software‐defined receiving system and modified commercial geodetic‐quality GNSS antenna. We ran three observing sessions in 2022 between a 25 m radio telescope in Fort Davis, Texas (FD‐VLBA), a transportable GNSS antenna placed within 100 m, and a GNSS antenna placed at a distance of about 9 km. We have detected a strong interferometric response with a Signal‐to‐Noise Ratio (SNR) of over 1,000 from Global Positioning System and Galileo satellites. We also observed natural radio sources including Galactic supernova remnants and Active Galactic Nuclei located as far as one gigaparsec, thus extending the range of sources that can be referenced to a GNSS antenna by 18 orders of magnitude. These detections represent the first observations made with a GNSS antenna to radio telescope interferometer. We have developed a novel technique based on a Precise Point Positioning solution of the recorded GNSS signal that allows us to extend integration time at 1.5 GHz to at least 20 min without any noticeable SNR degradation when a rubidium frequency standard is used.
Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial
Authors: Yang Yunpeng , Min Jie , Yang Nong , Yu Qitao , Cheng Ying , Zhao Yanqiu , Li Manxiang , Chen Hong , Ren Shou’an , Zhou Jianying , Zhuang Wu , Qin Xintian , Cao Lejie , Yu Yan , Zhang Jian , He Jianxing , Feng Jifeng , Yu Hao , Zhang Li , Fang Wenfeng 
Published: August 2023

AbstractAnaplastic lymphoma kinase (ALK) rearrangements are present in about 5–6% of non-small cell lung cancer (NSCLC) cases and associated with increased risks of central nervous system (CNS) involvement. Envonalkib, a novel ALK inhibitor, demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study. This phase III trial (ClinicalTrials.gov NCT04009317) investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases. Totally 264 participants were randomized 1:1 to receive envonalkib (n = 131) or crizotinib (n = 133). Median independent review committee (IRC)-assessed progression-free survival (PFS) times were 24.87 (95% confidence interval [CI]: 15.64–30.36) and 11.60 (95% CI: 8.28–13.73) months in the envonalkib and crizotinib groups, respectively (hazard ratio [HR] = 0.47, 95% CI: 0.34–0.64, p < 0.0001). IRC-assessed confirmed objective response rate (ORR) was higher (81.68% vs. 70.68%, p = 0.056) and duration of response was longer (median, 25.79 [95% CI, 16.53–29.47] vs. 11.14 [95% CI, 9.23–16.59] months, p = 0.0003) in the envonalkib group compared with the crizotinib group. In participants with baseline brain target lesions, IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib (78.95% vs. 23.81%). Overall survival (OS) data were immature, and median OS was not reached in either group (HR = 0.84, 95% CI: 0.48–1.47, p = 0.5741). The 12-month OS rates were 90.6% (95% CI, 84.0%–94.5%) and 89.4% (95% CI, 82.8%–93.6%) in the envonalkib and crizotinib groups, respectively. Grade ≥3 treatment-related adverse events were observed in 55.73% and 42.86% of participants in the envonalkib and crizotinib groups, respectively. Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC.
High-density lipoprotein regulates angiogenesis by long non-coding RNA HDRACA
Authors: Mo Zhi-Wei , Peng Yue-Ming , Zhang Yi-Xin , Li Yan , Kang Bi-Ang , Chen Ya-Ting , Li Le , Sorci-Thomas Mary G. , Lin Yi-Jun , Cao Yang , Chen Si , Liu Ze-Long , Gao Jian-Jun , Huang Zhan-Peng , Zhou Jia-Guo , Wang Mian , Chang Guang-Qi , Deng Meng-Jie , Liu Yu-Jia , Ma Zhen-Sheng , Hu Zuo-Jun , Dong Yu-Gang , Ou Zhi-Jun , Ou Jing-Song 
Published: August 2023

AbstractNormal high-density lipoprotein (nHDL) can induce angiogenesis in healthy individuals. However, HDL from patients with coronary artery disease undergoes various modifications, becomes dysfunctional (dHDL), and loses its ability to promote angiogenesis. Here, we identified a long non-coding RNA, HDRACA, that is involved in the regulation of angiogenesis by HDL. In this study, we showed that nHDL downregulates the expression of HDRACA in endothelial cells by activating WW domain-containing E3 ubiquitin protein ligase 2, which catalyzes the ubiquitination and subsequent degradation of its transcription factor, Kruppel-like factor 5, via sphingosine 1-phosphate (S1P) receptor 1. In contrast, dHDL with lower levels of S1P than nHDL were much less effective in decreasing the expression of HDRACA. HDRACA was able to bind to Ras-interacting protein 1 (RAIN) to hinder the interaction between RAIN and vigilin, which led to an increase in the binding between the vigilin protein and proliferating cell nuclear antigen (PCNA) mRNA, resulting in a decrease in the expression of PCNA and inhibition of angiogenesis. The expression of human HDRACA in a hindlimb ischemia mouse model inhibited the recovery of angiogenesis. Taken together, these findings suggest that HDRACA is involved in the HDL regulation of angiogenesis, which nHDL inhibits the expression of HDRACA to induce angiogenesis, and that dHDL is much less effective in inhibiting HDRACA expression, which provides an explanation for the decreased ability of dHDL to stimulate angiogenesis.
An integrated organoid omics map extends modeling potential of kidney disease
Authors: Lassé Moritz , El Saghir Jamal , Berthier Celine C. , Eddy Sean , Fischer Matthew , Laufer Sandra D. , Kylies Dominik , Hutzfeldt Arvid , Bonin Léna Lydie , Dumoulin Bernhard , Menon Rajasree , Vega-Warner Virginia , Eichinger Felix , Alakwaa Fadhl , Fermin Damian , Billing Anja M. , Minakawa Akihiro , McCown Phillip J. , Rose Michael P. , Godfrey Bradley , Meister Elisabeth , Wiech Thorsten , Noriega Mercedes , Chrysopoulou Maria , Brandts Paul , Ju Wenjun , Reinhard Linda , Hoxha Elion , Grahammer Florian , Lindenmeyer Maja T. , Huber Tobias B. , Schlüter Hartmut , Thiel Steffen , Mariani Laura H. , Puelles Victor G. , Braun Fabian , Kretzler Matthias , Demir Fatih , Harder Jennifer L. , Rinschen Markus M. 
Published: August 2023

AbstractKidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 322 proteins is significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression is increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing with human data, we provide crucial evidence for the functional relevance of the kidney organoid model to human kidney disease.
Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing
Authors: Wimberger Sandra , Akrap Nina , Firth Mike , Brengdahl Johan , Engberg Susanna , Schwinn Marie K. , Slater Michael R. , Lundin Anders , Hsieh Pei-Pei , Li Songyuan , Cerboni Silvia , Sumner Jonathan , Bestas Burcu , Schiffthaler Bastian , Magnusson Björn , Di Castro Silvio , Iyer Preeti , Bohlooly-Y Mohammad , Machleidt Thomas , Rees Steve , Engkvist Ola , Norris Tyrell , Cadogan Elaine B. , Forment Josep V. , Šviković Saša , Akcakaya Pinar , Taheri-Ghahfarokhi Amir , Maresca Marcello 
Published: August 2023

AbstractGenome editing, specifically CRISPR/Cas9 technology, has revolutionized biomedical research and offers potential cures for genetic diseases. Despite rapid progress, low efficiency of targeted DNA integration and generation of unintended mutations represent major limitations for genome editing applications caused by the interplay with DNA double-strand break repair pathways. To address this, we conduct a large-scale compound library screen to identify targets for enhancing targeted genome insertions. Our study reveals DNA-dependent protein kinase (DNA-PK) as the most effective target to improve CRISPR/Cas9-mediated insertions, confirming previous findings. We extensively characterize AZD7648, a selective DNA-PK inhibitor, and find it to significantly enhance precise gene editing. We further improve integration efficiency and precision by inhibiting DNA polymerase theta (Polϴ). The combined treatment, named 2iHDR, boosts templated insertions to 80% efficiency with minimal unintended insertions and deletions. Notably, 2iHDR also reduces off-target effects of Cas9, greatly enhancing the fidelity and performance of CRISPR/Cas9 gene editing.
Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial
Authors: Yuan Li , Jia Guo-Dong , Lv Xiao-Fei , Xie Si-Yi , Guo Shan-Shan , Lin Da-Feng , Liu Li-Ting , Luo Dong-Hua , Li Yi-Fu , Deng Shen-Wen , Guo Ling , Zeng Mu-Sheng , Cai Xiu-Yu , Liu Sai-Lan , Sun Xue-Song , Li Xiao-Yun , Li Su-Chen , Chen Qiu-Yan , Tang Lin-Quan , Mai Hai-Qiang 
Published: August 2023

AbstractImmunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6–80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0–51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.
The Marginal Ice Zone as a dominant source region of atmospheric mercury during central Arctic summertime
Authors: Yue Fange , Angot Hélène , Blomquist Byron , Schmale Julia , Hoppe Clara J. M. , Lei Ruibo , Shupe Matthew D. , Zhan Liyang , Ren Jian , Liu Hailong , Beck Ivo , Howard Dean , Jokinen Tuija , Laurila Tiia , Quéléver Lauriane , Boyer Matthew , Petäjä Tuukka , Archer Stephen , Bariteau Ludovic , Helmig Detlev , Hueber Jacques , Jacobi Hans-Werner , Posman Kevin , Xie Zhouqing 
Published: August 2023

AbstractAtmospheric gaseous elemental mercury (GEM) concentrations in the Arctic exhibit a clear summertime maximum, while the origin of this peak is still a matter of debate in the community. Based on summertime observations during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition and a modeling approach, we further investigate the sources of atmospheric Hg in the central Arctic. Simulations with a generalized additive model (GAM) show that long-range transport of anthropogenic and terrestrial Hg from lower latitudes is a minor contribution (~2%), and more than 50% of the explained GEM variability is caused by oceanic evasion. A potential source contribution function (PSCF) analysis further shows that oceanic evasion is not significant throughout the ice-covered central Arctic Ocean but mainly occurs in the Marginal Ice Zone (MIZ) due to the specific environmental conditions in that region. Our results suggest that this regional process could be the leading contributor to the observed summertime GEM maximum. In the context of rapid Arctic warming and the observed increase in width of the MIZ, oceanic Hg evasion may become more significant and strengthen the role of the central Arctic Ocean as a summertime source of atmospheric Hg.
Photoredox-active Cr(0) luminophores featuring photophysical properties competitive with Ru(II) and Os(II) complexes
Authors: Sinha Narayan , Wegeberg Christina , Häussinger Daniel , Prescimone Alessandro , Wenger Oliver S. 
Published: August 2023

AbstractCoordination complexes of precious metals with the d6 valence electron configuration such as Ru(II), Os(II) and Ir(III) are used for lighting applications, solar energy conversion and photocatalysis. Until now, d6 complexes made from abundant first-row transition metals with competitive photophysical and photochemical properties have been elusive. While previous research efforts focused mostly on Fe(II), we disclose that isoelectronic Cr(0) gives access to higher photoluminescence quantum yields and excited-state lifetimes when compared with any other first-row d6 metal complex reported so far. The luminescence behaviour of the metal-to-ligand charge transfer excited states of these Cr(0) complexes is competitive with Os(II) polypyridines. With these Cr(0) complexes, the metal-to-ligand charge transfer states of first-row d6 metal complexes become exploitable in photoredox catalysis, and benchmark chemical reductions proceed efficiently under low-energy red illumination. Here we demonstrate that appropriate molecular design strategies open up new perspectives for photophysics and photochemistry with abundant first-row d6 metals.
In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis
Authors: Lara-Astiaso David , Goñi-Salaverri Ainhoa , Mendieta-Esteban Julen , Narayan Nisha , Del Valle Cynthia , Gross Torsten , Giotopoulos George , Beinortas Tumas , Navarro-Alonso Mar , Aguado-Alvaro Laura Pilar , Zazpe Jon , Marchese Francesco , Torrea Natalia , Calvo Isabel A. , Lopez Cecile K. , Alignani Diego , Lopez Aitziber , Saez Borja , Taylor-King Jake P. , Prosper Felipe , Fortelny Nikolaus , Huntly Brian J. P. 
Published: August 2023

AbstractCellular differentiation requires extensive alterations in chromatin structure and function, which is elicited by the coordinated action of chromatin and transcription factors. By contrast with transcription factors, the roles of chromatin factors in differentiation have not been systematically characterized. Here, we combine bulk ex vivo and single-cell in vivo CRISPR screens to characterize the role of chromatin factor families in hematopoiesis. We uncover marked lineage specificities for 142 chromatin factors, revealing functional diversity among related chromatin factors (i.e. barrier-to-autointegration factor subcomplexes) as well as shared roles for unrelated repressive complexes that restrain excessive myeloid differentiation. Using epigenetic profiling, we identify functional interactions between lineage-determining transcription factors and several chromatin factors that explain their lineage dependencies. Studying chromatin factor functions in leukemia, we show that leukemia cells engage homeostatic chromatin factor functions to block differentiation, generating specific chromatin factor–transcription factor interactions that might be therapeutically targeted. Together, our work elucidates the lineage-determining properties of chromatin factors across normal and malignant hematopoiesis.
Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity
Authors: Garner Lucy C. , Amini Ali , FitzPatrick Michael E. B. , Lett Martin J. , Hess Gabriel F. , Filipowicz Sinnreich Magdalena , Provine Nicholas M. , Klenerman Paul 
Published: August 2023

AbstractMucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing, a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles but intriguingly was not associated with the capacity to produce IL-17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment and clonotype.
A novel Corchorus olitorius-derived biochar/Bi12O17Cl2 photocatalyst for decontamination of antibiotic wastewater containing tetracycline under natural visible light
Authors: Samy Mahmoud , Gar Alalm Mohamed , abodlal Ribh S. , El-Dissouky Ali , Khalil Mohamed N. , El-Helow Ehab R. , E. Khalil Tarek , Tawfik Ahmed 
Published: August 2023

AbstractHerein, a novel composite of Corchorus olitorius-derived biochar and Bi12O17Cl2 was fabricated and utilized for the degradation of tetracycline (TC) in a solar photo-oxidation reactor. The morphology, chemical composition, and interaction between the composite components were studied using various analyses. The biochar showed a TC removal of 52.7% and COD mineralization of 59.6% using 150 mg/L of the biochar at a pH of 4.7 ± 0.5, initial TC concentration of 163 mg/L, and initial COD of 1244 mg/L. The degradation efficiency of TC increased to 63% and the mineralization ratio to 64.7% using 150 mg/L of bare Bi12O17Cl2 at a pH of 4.7 ± 0.5, initial TC concentration of 178 mg/L, and COD of 1034 mg/L. In the case of biochar/Bi12O17Cl2 composite, the degradation efficiency of TC and COD mineralization ratio improved to 85.8% and 77.7% due to the potential of biochar to accept electrons which retarded the recombination of electrons and holes. The synthesized composite exhibited high stability over four succeeding cycles. According to the generated intermediates, TC could be degraded to caprylic acid and pentanedioic acid via the frequent attack by the reactive species. The prepared composite is a promising photocatalyst and can be applied in large-scale systems due to its high degradation and mineralization performance in a short time besides its low cost and stability.
Population-level prevalence, effect on quality of life, and treatment behavior for erectile dysfunction and premature ejaculation in Poland
Authors: Przydacz Mikolaj , Chlosta Marcin , Rajwa Pawel , Chlosta Piotr 
Published: August 2023

AbstractThe prevalence of erectile dysfunction (ED) and premature ejaculation (PE) has been investigated in many population-based studies in different regions of the world. However, reliable data are lacking for Eastern Europe. Therefore, the aim of this study was to analyze the prevalence, effect on quality of life, and treatment-related behaviors for ED and PE in a population-representative sample of Polish men. We used an Internet interview format and rigorously adapted, widely accepted instruments for ED and PE evaluation. The study included 3001 men, representative for age and place of residence and adequate proportions of respondents from urban and rural areas. The prevalence of ED was 30.1–61.1%, and the prevalence of PE was 19.3–38.1%; there were no differences between urban and rural areas. Whereas the prevalence of ED increased with age, the prevalence of PE did not increase. More than 50% of respondents with ED and more than 60% of respondents with PE had concerns about their quality of life. However, less than one fourth of participants with ED and PE were seeking treatment, most of whom received treatment. The results of our nationwide analysis, reflecting the entire Polish population of men, are consistent with other epidemiologic studies of ED and PE and may support educational campaigns and health improvement programs in Poland.
Economic statistical model of the np chart for monitoring defectives
Authors: Haridy Salah , Alamassi Batool , Maged Ahmed , Shamsuzzaman Mohammad , Al Owad Ali , Bashir Hamdi 
Published: August 2023

AbstractWhen monitoring manufacturing processes, managing an attribute quality characteristic is easier and faster than a variable quality characteristic. Yet, the economic-statistical design of attribute control charts has attracted much less attention than variable control charts in the literature. This study develops an algorithm for optimizing the economic-statistical performance of the np chart for monitoring defectives, based on Duncan’s economic model. This algorithm has the merit of the economic model to minimize expected total cost, and the benefit of the statistical design to enhance the effectiveness of detecting increasing shifts in defectives. The effectiveness of the developed np chart is investigated under different operational scenarios. The results affirm a considerable superiority of the proposed np chart over the traditional np chart. Real-life data are used to demonstrate the applicability of the proposed np scheme, in comparison to the traditional np chart.