bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triazoloquinazoline derived classical DNA intercalators: Design, synthesis, in silico ADME profile, docking, and antiproliferative evaluations
Authors: El‐Adl Khaled , Ibrahim Mohamed‐Kamal , Alesawy Mohamed S. , Eissa Ibrahim H. 
Published: March 2022

AbstractThirteen novel [1,2,4]triazolo[4,3‐c]quinazoline derivatives as DNA intercalators were synthesized and their anticancer activities evaluated against HepG2 and HCT‐116 cells. A docking study was carried out to explore how the new derivatives bind to active sites of DNA. The docking data were highly interrelated with that of biological testing. The HCT‐116 cell line was the most sensitive one to the effect of the new derivatives. Compound 7c exhibited the highest anticancer activities against both the HepG2 and HCT116 cancer cell lines. Despite this compound displaying less activity than doxorubicin, it could be useful as a template for future manipulation, optimization, and investigation to produce other analogs with potential activity. The most active derivatives, 7c, 7b, and 7a were evaluated as DNA binders. Compound 7c displayed the highest binding affinity. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile was calculated for the four most active compounds in comparison to doxorubicin as reference drug. Our derivatives 7a, 7b, and 7c displayed a very good calculated ADMET profile in comparison to doxorubicin.
Androgen‐targeting therapeutics mitigate the adverse effect of GnRH agonist on the risk of neurodegenerative disease in men treated for prostate cancer
Authors: Branigan Gregory L. , Torrandell‐Haro Georgina , Soto Maira , Gelmann Edward P. , Vitali Francesca , Rodgers Kathleen E. , Brinton Roberta Diaz 
Published: March 2022

AbstractBackgroundProstate cancer and multiple neurodegenerative diseases (NDD) share an age‐associated pattern of onset. Therapy of prostate cancer is known to impact cognitive function. The objective of this study was to determine the impact of multiple classes of androgen‐targeting therapeutics (ATT) on the risk of NDD.MethodsA retrospective cohort study of men aged 45 and older with prostate within the US‐based Mariner claims data set between January 1 and 27, 2021. A propensity score approach was used to minimize measured and unmeasured selection bias. Disease risk was determined using Kaplan–Meier survival analyses.ResultsOf the 1,798,648 men with prostate cancer, 209,722 met inclusion criteria. Mean (SD) follow‐up was 6.4 (1.8) years. In the propensity score‐matched population, exposure to ATT was associated with a minimal increase in NDD incidence (relative risk [RR], 1.07; 95% CI, 1.05–1.10; p < 0.001). However, GnRH agonists alone were associated with significantly increased NDD risk (RR, 1.47; 95% CI, 1.30–1.66; p <0.001). Abiraterone, commonly administered with GnRH agonists and low‐dose prednisone, was associated with a significantly decreased risk (RR, 0.77; 95% CI, 0.68–0.87; p < 0.001) of any NDD.ConclusionsAmong patients with prostate cancer, GnRH agonist exposure was associated with an increased NDD risk. Abiraterone acetate reduced the risks of Alzheimer's disease and Parkinson's disease conferred by GnRH agonists, whereas the risk for ALS was reduced by androgen receptor inhibitors. Outcomes of these analyses contribute to addressing controversies in the field and indicate that GnRH agonism may be a predictable instigator of risk for NDD with opportunities for risk mitigation in combination with another ATT.
Blood donation motivation in the United States and Russia: What keeps donors coming back?
Authors: Sheldon Kennon M. , Osin Evgeny , Lapka Samantha , Rasskazova Elena , Titova Liudmila , Khrushev Sergei , Vybornykh Dmitry , Gaponova Tatiana 
Published: March 2022

AbstractWhat keeps regular blood donors coming back, despite the inconvenience and discomfort, thereby maintaining the community's blood supply? We approached 494 people waiting to give blood, 229 Americans and 265 Russians, with a survey that assessed their motivations to donate, their contextual emotions, and their future donation intentions. The Russian sample was older, and many were regulars at the donation centre. The U.S. sample was younger, attending a 3‐day college blood drive. Multigroup path analysis results showed that, as hypothesised, in both samples, autonomous donation motivations predicted contextual emotions and future donation intentions. Furthermore, contextual emotions partially mediated the motivation‐to‐future intentions effect. Small differences in results for the two samples, as well as differences in the two national systems for maintaining blood supplies, are discussed.
Hexavalent chromium induces centrosome amplification through ROS‐ATF6‐PLK4 pathway in colon cancer cells
Authors: Bian Xue K. , Guo Jia L. , Xu Si X. , Han Ya W. , Lee Shao C. , Zhao Ji Z. 
Published: March 2022

AbstractCentrosome amplification (CA) refers to a numerical increase in centrosomes resulting in cells with more than two centrosomes. CA has been shown to initiate tumorigenesis and increase the invasive potential of cancer cells in genetically modified experimental models. Hexavalent chromium is a recognized carcinogen that causes CA and tumorigenesis as well as promotes cancer metastasis. Thus, CA appears to be a biological link between chromium and cancer. In the present study, we investigated how chromium triggers CA. Our results showed that a subtoxic concentration of chromium‐induced CA in HCT116 colon cancer cells, resulted in the production of reactive oxygen species (ROS), activated ATF6 without causing endoplasmic reticulum stress, and upregulated the protein level of PLK4. Inhibition of ROS production, ATF6 activation, or PLK4 upregulation attenuated CA. Inhibition of ROS using N‐acetyl‐l‐cysteine (NAC) inhibited chromium‐induced activation of ATF6 and upregulation of PLK4. ATF6‐specific siRNA knocked down the protein level and activation of ATF6, and upregulated PLK4, with no effect on ROS production. Knockdown of PLK4 protein had no effect on chromium‐induced ROS production or activation of ATF6. In conclusion, our results suggest that hexavalent chromium induces CA via the ROS‐ATF6‐PLK4 pathway and provides molecular targets for inhibiting chromium‐mediated CA, which may be useful for the assessment of CA in chromium‐promoted tumorigenesis and cancer cell metastasis.
KLF11 promotes the progression of glioma via regulating Holliday junction recognition protein
Authors: Li Jian , Wang Chunhong , Cheng Rui , Su Haiyang , Wang Lijun , Ji Lei , Ji Hongming 
Published: March 2022

AbstractUnderstanding the molecular mechanism of glioma is very important for the diagnosis and treatment of glioma. Recently, a new study illustrated that KLF11 could be a potential prognostic and diagnostic biomarker in glioma, but the critical role is not illustrated. In this study, we found that KLF11 was highly expressed in glioma cancer tissues and cells, and KLF11 high expression of glioblastoma (GBM) and lower‐grade glioma (LGG) were correlated with poorer overall survival and disease‐free survival percentages. KLF11 knockdown inhibited glioma cell proliferation and migration, while KLF11 overexpression enhanced cell proliferation and migration. In vivo, knockdown of KLF11 reduced the tumor size of glioma. With regard to the molecular regulatory mechanism, we clarified that the Holliday junction recognition protein (HJURP) was positively regulated by KLF11. Meanwhile, we demonstrated that HJURP knockdown also inhibited glioma carcinoma progression. Overexpression of HJURP rescued the suppressed proliferation and migration function of glioma cells with depletion of KLF11. Therefore, our study demonstrated the function of KLF11 in glioma and showed KLF11 and HJURP could be prognostic and diagnostic markers in glioma, which provides a new insight of glioma therapy.
Apaf‐1 interacting protein, a new target of microRNA‐146a‐3p, promotes prostate cancer cell development via the ERK1/2 pathway
Authors: Wang Nan , Li Rou , Jia Huizhen , Xie Hui , Liu Chi , Jiang Shan , Zhang Ke , Lin Ping , Yu Xiaoguang 
Published: March 2022

AbstractThe Apaf‐1 interacting protein (APIP), a ubiquitously expressed antiapoptotic molecule, is aberrantly expressed and of great significance in various cancers. However, little is known regarding the potential value and underlying mechanisms of APIP in prostate cancer. Here, we demonstrated that APIP expression is significantly upregulated in prostate cancer cell lines. APIP overexpression promoted tumor cell proliferation and migration and induced extracellular regulated protein kinases 1/2 (ERK1/2) activation. Pharmacological inhibition of ERK1/2 signaling reversed APIP‐induced increase in cell proliferation and migration induced by APIP overexpression. Expression of APIP was hampered by miR‐146a‐3p. A dual luciferase reporter gene assay identified the regulatory relationship between APIP and miR‐146a‐3p in prostate cancer, suggesting that APIP is a direct target of miR‐146a‐3p. miR‐146a‐3p reduced cell proliferation and migration in prostate cancer. Furthermore, miR‐146a‐3p inhibited ERK1/2 activation. Application of an ERK1/2 inhibitor reversed the increase in cell proliferation and migration induced by miR‐146a‐3p inhibition. In summary, this study focused on the role of APIP in regulating cell growth and migration and proposes a theoretical basis for APIP as a promising biomarker in prostate cancer development.
Rare case of umbilical urachal sinus mimicking infected umbilical abscess: A case report
Authors: Torabi Hossein , Shirini Kasra , Ghaffari Rona 
Published: March 2022

AbstractIncomplete obliteration of urachus during the fetal period can lead to urachal abnormalities. One of these abnormalities is the urachal sinus that can be asymptomatic, or it can be symptomatic by becoming infected or being malignant, and it can mimic other diseases' symptoms. Although it is rare in adults, it should be considered a significant differential diagnosis in patients with abdominal pain or umbilical discharge. This article presents a young patient with urachal sinus mimicking umbilical pilonidal sinus symptoms.
First report of emerged pulmonary lophomoniasis in two Afghanian medical tourists
Authors: Sharifpour Ali , Zarrinfar Hossein , Fakhar Mahdi , Zakariaei Zakaria , Soleymani Mostafa , Banimostafavi Elham Sadat , Nakhaei Maryam 
Published: March 2022

AbstractLophomonas is a neglected and emerging protozoan that infects the lower and upper respiratory tracts of humans. Here, we present two cases of lophomoniasis from Afghanistan that include symptoms such as fever, cough, hemoptysis, and pleural effusion.
Mixing Characteristics for Scale‐up of an Orbital Shaken Bioreactor
Authors: Lee Hyunwoo , Lee Joon-Chul , Seo Youngjin 
Published: March 2022

AbstractTwo types of culture bags are typically used. Among the criteria for evaluating the bioreactor performance, mixing time and shear stress are important indicators. Experiments and numerical analyses are conducted to evaluate and predict the performance of an orbital shaken bioreactor by analyzing mixing time and shear stress. Reliability is ensured by performing numerical analysis under the same conditions using FLUENT. The error between the experimental and numerical analysis results is within the error range of the experiments. For two different working fluid volumes the mixing time and shear stress are predicted using validated numerical models.
Hollow Co‐Based Layered Double Hydroxide Decorated with Ag Nanoparticles for the Oxygen Evolution Reaction
Authors: Gan Xingyu , Guo Xinjie , Li Suozhu , Wang Yun , Wang Fengxiang , Lv Xiaoxia 
Published: March 2022

AbstractDeveloping cost‐effective and efficient oxygen evolution reaction (OER) catalysts is very important for electrochemical water splitting devices. Herein, hollow Co‐based layered double hydroxide (LDH) decorated with Ag nanoparticles (Ag@H−Co‐−LDH) was constructed using ion etching of zeolitic imidazolate frameworks‐67 (ZIF‐67), followed by simple stirring with Ag salts. Hollow double layered structure could expose rich active centers and improve electron transfer and mass transport. Meanwhile, the introduction of Ag species greatly increases the electrical conductivity and enhances cobalt species to form highly catalytically active Co4+. Therefore, the as‐obtained Ag@H−Co−LDH exhibits a distinguished OER activity with a low overpotential of 298 mV to provide an oxygen evolution current density of 10 mA cm−2, which is superior to that of Co−LDH and even commercial RuO2.
Fully Bridged Triphenylamines Comprising Five‐ and Seven‐Membered Rings
Authors: Michalsky Ina , Gensch Viktoria , Walla Christian , Hoffmann Marvin , Rominger Frank , Oeser Thomas , Tegeder Petra , Dreuw Andreas , Kivala Milan 
Published: March 2022

AbstractA family of fully bridged triphenylamines with embedded 5‐ and 7‐membered rings is presented. The compounds are potent electron donors capable to undergo donor/acceptor interactions with strong cyano‐based acceptors both in the solid state and solution. These interactions were evaluated by IR and UV/vis spectroscopy as well as X‐ray crystallography. The vinylene‐bridged compound was oxidized to the corresponding 1,2‐diketone which readily underwent acid‐catalyzed condensation with selected 1,2‐phenylenediamines. The resulting π‐extended quinoxaline derivatives represent valuable building blocks for the development of functional chromophores upon appropriate functionalization.
Diarylcuprates for Selective Syntheses of Multifunctionalized Ketones from Thioesters under Mild Conditions
Authors: Kato Daiki , Murase Tomoya , Talode Jalindar , Nagae Haruki , Tsurugi Hayato , Seki Masahiko , Mashima Kazushi 
Published: March 2022

AbstractKetones were selectively synthesized from thioesters by using diarylcuprates(I) generated in situ from copper(I) salts and aryl Grignard reagents in a 1 : 1.3–1.5 ratio under ambient temperature. During the ketone synthesis, various functional groups, such as carbonyl (ketones, esters, and amides), O‐protecting groups, halogens, and heteroarenes, were tolerated to afford multifunctionalized ketones in excellent yields. This copper‐mediated ketone synthesis could be applied to the synthesis of not only gluconolactone‐derived ketone 6, a synthetic intermediate in the transformation to the SGLT2 inhibitor canagliflozin, but also thiolactol 8, a valuable synthetic intermediate for (+)‐biotin. Control experiments on an isolated diphenylcuprate(I), [CuPh2]− (12), and DFT calculations revealed that this ketone synthesis proceeded by oxidative addition of the C−S bond of thioesters to [CuPh2]−, while reductive elimination from the CuIII intermediate produced the corresponding ketone and an inactive species [(RS)CuPh]−, the latter reacted with [CuPh]4 (11) to regenerate the reactive diphenylcuprate(I).
Fast selection of compiler optimizations using performance prediction with graph neural networks
Authors: do Rosario Vanderson Martins , da Silva Anderson Faustino , Zanella André Felipe , Napoli Otávio O. , Borin Edson 
Published: March 2022

AbstractTuning application performance on modern computing infrastructures involves choices in a vast design space as modern computing architectures can have several complex structures impacting performance. Moreover, different applications use these structures in different ways, leading to a challenging performance function. Consequently, it is hard for compilers or experts to find optimal compilation parameters for an application that maximizes such performance function. One approach to tackle this problem is to evaluate many possible optimization plans and select the best among them. However, executing an application to measure its performance for every plan can be very expensive. To tackle this problem, previous work has investigated the use of Machine Learning techniques to predict the performance of the applications without executing them quickly. In this work, we evaluate the use of graph neural networks (GNN) to make fast predictions without executing the application to guide the selection of good optimization sequences. We propose a GNN architecture to make such predictions. We train and test it using 30 thousand different compilation plans applied to 300 different applications, using ARM64 and LLVM IR code representations as input. Our results indicate that the control and data flow graph can then learn features from the control and data flow graph to outperform nongraph‐aware Machine Learning models. Our GNN architecture achieved 91% accuracy in our dataset compared to 79% when using a nongraph‐aware architecture–taking only 16ms to predict a given input. If the application been optimized took an average of 10 s to execute, and we evaluated 1000 optimization sequences, it would take almost 9 h to assess all pairs, but only 16 s with our GNN .
Ligand‐Induced Tuning of the Electronic Structure of Rhombus Tetraboron Cluster
Authors: Zhao Ya , Wang Tiantong , Wang Chong , Zhang Zhaoyan , Zheng Huijun , Jiang Shuai , Yan Wenhui , Xie Hua , Li Gang , Yang Jiayue , Wu Guorong , Zhang Weiqing , Dai Dongxu , Zheng Xiucheng , Fan Hongjun , Jiang Ling , Yang Xueming , Zhou Mingfei 
Published: March 2022

AbstractA neutral boron carbonyl complex B4(CO)3 is generated in the gas phase and is characterized by infrared plus vacuum ultraviolet (IR+VUV) two‐color ionization spectroscopy and quantum chemical calculations. The complex is identified to have a planar C2v structure with three CO ligands terminally coordinated to a rhombus B4 core. It has a closed‐shell singlet ground state that correlates to an excited state of B4. Bonding analyses on B4(CO)3 as well as the previously reported B4 and B4(CO)2 indicate that the electronic structure of rhombus tetraboron cluster changes from a close‐shell singlet to an open‐shell singlet in B4(CO)2 and to a close‐shell singlet in B4(CO)3, demonstrating that the electronic structures of boron clusters can be effectively tuned via sequential CO ligand coordination.
Effect of Cyclosporin A and Impact of Dose Staggering on OATP1B1/1B3 Endogenous Substrates and Drug Probes for Assessing Clinical Drug Interactions
Authors: Mochizuki Tatsuki , Zamek‐Gliszczynski Maciej J. , Yoshida Kenta , Mao Jialin , Taskar Kunal , Hirabayashi Hideki , Chu Xiaoyan , Lai Yurong , Takashima Tadayuki , Rockich Kevin , Yamaura Yoshiyuki , Fujiwara Kaku , Mizuno Tadahaya , Maeda Kazuya , Furihata Kenichi , Sugiyama Yuichi , Kusuhara Hiroyuki 
Published: March 2022

This study was designed to assess the quantitative performance of endogenous biomarkers for organic anion transporting polypeptide (OATP) 1B1/1B3‐mediated drug‐drug interactions (DDIs). Ten healthy volunteers orally received OATP1B1/1B3 probe cocktail (0.2 mg pitavastatin, 1 mg rosuvastatin, and 2 mg valsartan) and an oral dose of cyclosporin A (CysA, 20 mg and 75 mg) separated by a 1‐hour interval (20 mg (−1 hour), and 75 mg (−1 hour)). CysA 75 mg was also given with a 3‐hour interval (75 mg (−3 hours)) to examine the persistence of OATP1B1/1B3 inhibition. The area under the plasma concentration‐time curve ratios (AUCRs) were 1.63, 3.46, and 2.38 (pitavastatin), 1.39, 2.16, and 1.81 (rosuvastatin), and 1.42, 1.77, and 1.85 (valsartan), at 20 mg, 75 mg (−1 hour) and 75 mg (−3 hours) of CysA, respectively. CysA effect on OATP1B1/1B3 was unlikely to persist at the dose examined. Among 26 putative OATP1B1/1B3 biomarkers evaluated, AUCR and maximum concentration ratio (CmaxR) of CP‐I showed the highest Pearson’s correlation coefficient with CysA AUC (0.94 and 0.93, respectively). Correlation between AUCR of pitavastatin, and CmaxR or AUCR of CP‐I were consistent between this study and our previous study using rifampicin as an OATP1B1/1B3 inhibitor. Nonlinear regression analysis of AUCR−1 of pitavastatin and CP‐I against CysA Cmax yielded Ki,OATP1B1/1B3,app (109 ± 35 and 176 ± 42 nM, respectively), similar to the Ki,OATP1B1/1B3 estimated by our physiologically‐based pharmacokinetic model analysis described previously (107 nM). The endogenous OATP1B1/1B3 biomarkers, particularly CmaxR and AUCR of CP‐I, corroborates OATP1B1/1B3 inhibition and yields valuable information that improve accurate DDI predictions in drug development, and enhance our understanding of interindividual variability in the magnitude of DDIs.
Epitaxial Core‐Shell Oxide Nanoparticles: First‐Principles Evidence for Increased Activity and Stability of Rutile Catalysts for Acidic Oxygen Evolution
Authors: Lee Yonghyuk , Scheurer Christoph , Reuter Karsten 
Published: March 2022

AbstractDue to their high activity and favorable stability in acidic electrolytes, Ir and Ru oxides are primary catalysts for the oxygen evolution reaction (OER) in proton‐exchange membrane (PEM) electrolyzers. For a future large‐scale application, core‐shell nanoparticles are an appealing route to minimize the demand for these precious oxides. Here, we employ first‐principles density‐functional theory (DFT) and ab initio thermodynamics to assess the feasibility of encapsulating a cheap rutile‐structured TiO2 core with coherent, monolayer‐thin IrO2 or RuO2 films. Resulting from a strong directional dependence of adhesion and strain, a wetting tendency is only obtained for some low‐index facets under typical gas‐phase synthesis conditions. Thermodynamic stability in particular of lattice‐matched RuO2 films is instead indicated for more oxidizing conditions. Intriguingly, the calculations also predict an enhanced activity and stability of such epitaxial RuO2/TiO2 core‐shell particles under OER operation.
Phloem water isotopically different to xylem water: Potential causes and implications for ecohydrological tracing
Authors: Nehemy Magali F. , Benettin Paolo , Allen Scott T. , Steppe Kathy , Rinaldo Andrea , Lehmann Marco M. , McDonnell Jeffrey J. 
Published: March 2022

AbstractThe stable isotopes of hydrogen and oxygen in xylem water are often used to investigate tree water sources. But this traditional approach does not acknowledge the contribution of water stored in the phloem to transpiration and how this may affect xylem water and source water interpretations. Additionally, there is a prevailing assumption that there is no isotope fractionation during tree water transport. Here, we systematically sampled xylem and phloem water at daily and subdaily resolutions in a large lysimeter planted with Salix viminalis. Stem diurnal change in phloem water storage and transpiration rates were also measured. Our results show that phloem water is significantly less enriched in heavy isotopes than xylem water. At subdaily resolution, we observed a larger isotopic difference between xylem and phloem during phloem water refilling and under periods of tree water deficit. These findings contrast with the expectation of heavy‐isotope enriched water in phloem due to downward transport of enriched leaf water isotopic signatures. Because of previous evidence of aquaporin mediated phloem and xylem water transport and higher osmotic permeability of lighter hydrogen isotopologues across aquaporins, we propose that radial water transport across the xylem–phloem boundary may drive the relative depletion of heavy isotopes in phloem and their relative enrichment in xylem.