bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of a prostate cancer‐specific targeted sequencing panel for credentialing of patient‐derived cell lines and genomic characterization of patient samples
Authors: Stover Elizabeth H. , Oh Coyin , Keskula Paula , Choudhury Atish D. , Tseng Yuen‐Yi , Adalsteinsson Viktor A. , Lohr Jens G. , Thorner Aaron R. , Ducar Matthew , Kryukov Gregory V. , Ha Gavin , Rosenberg Mara , Freeman Samuel S. , Zhang Zhenwei , Wu Xiaoyun , Van Allen Eliezer M. , Takeda David Y. , Loda Massimo , Wu Chin‐Lee , Taplin Mary‐Ellen , Garraway Levi A. , Boehm Jesse S. , Huang Franklin W. 
Published: January 2022

AbstractBackgroundPrimary and metastatic prostate cancers have low mutation rates and recurrent alterations in a small set of genes, enabling targeted sequencing of prostate cancer‐associated genes as an efficient approach to characterizing patient samples (compared to whole‐exome and whole‐genome sequencing). For example, targeted sequencing provides a flexible, rapid, and cost‐effective method for genomic assessment of patient‐derived cell lines to evaluate fidelity to initial patient tumor samples.MethodsWe developed a prostate cancer‐specific targeted next‐generation sequencing (NGS) panel to detect alterations in 62 prostate cancer‐associated genes as well as recurring gene fusions with ETS family members, representing the majority of common alterations in prostate cancer. We tested this panel on primary prostate cancer tissues and blood biopsies from patients with metastatic prostate cancer. We generated patient‐derived cell lines from primary prostate cancers using conditional reprogramming methods and applied targeted sequencing to evaluate the fidelity of these cell lines to the original patient tumors.ResultsThe prostate cancer‐specific panel identified biologically and clinically relevant alterations, including point mutations in driver oncogenes and ETS family fusion genes, in tumor tissues from 29 radical prostatectomy samples. The targeted panel also identified genomic alterations in cell‐free DNA and circulating tumor cells (CTCs) from patients with metastatic prostate cancer, and in standard prostate cancer cell lines. We used the targeted panel to sequence our set of patient‐derived cell lines; however, no prostate cancer‐specific mutations were identified in the tumor‐derived cell lines, suggesting preferential outgrowth of normal prostate epithelial cells.ConclusionsWe evaluated a prostate cancer‐specific targeted NGS panel to detect common and clinically relevant alterations (including ETS family gene fusions) in prostate cancer. The panel detected driver mutations in a diverse set of clinical samples of prostate cancer, including fresh‐frozen tumors, cell‐free DNA, CTCs, and cell lines. Targeted sequencing of patient‐derived cell lines highlights the challenge of deriving cell lines from primary prostate cancers and the importance of genomic characterization to credential candidate cell lines. Our study supports that a prostate cancer‐specific targeted sequencing panel provides an efficient, clinically feasible approach to identify genetic alterations across a spectrum of prostate cancer samples and cell lines.
Tapentadol shows lower intrinsic efficacy at µ receptor than morphine and oxycodone
Authors: Manandhar Preeti , Connor Mark , Santiago Marina 
Published: January 2022

AbstractTapentadol is a centrally acting analgesic with a dual mechanism of action. It acts as an agonist at the µ receptor and inhibitor of noradrenaline reuptake. Clinical trials suggest similar analgesic efficacy of tapentadol, oxycodone, and morphine in acute and chronic pain. Given the limited information about the molecular actions of tapentadol at the µ receptor, we investigated the intrinsic efficacy of tapentadol and compared it with other opioids. β‐chlornaltrexamine (β‐CNA, 100 nM, 20 min) was used to deplete spare receptors in AtT20 cells stably transfected with human µ receptor wild‐type (WT). Opioid‐mediated changes in membrane potential were measured in real‐time using a membrane potential‐sensitive fluorescent dye. Using Black and Leff’s operational model, intrinsic efficacy relative to DAMGO was calculated for each opioid. Tapentadol (0.05 ± 0.01) activated the GIRK channel with lesser intrinsic efficacy than morphine (0.17 ± 0.02) and oxycodone (0.16 ± 0.02). We further assessed the signaling of tapentadol in the common µ receptor variants (N40D and A6V) which are associated with altered receptor signaling. We found no difference in the response of tapentadol between these receptor variants.
Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics
Authors: Lu Jing , Wang Xian , Wu Anxin , Cao Yi , Dai Xiaolin , Liang Youdan , Li Xiaofang 
Published: January 2022

AbstractThe nervous system is one of the most complex physiological systems, and central nervous system diseases (CNSDs) are serious diseases that affect human health. Ginseng (Panax L.), the root ofPanaxspecies, are famous Chinese herbs that have been used for various diseases in China, Japan, and Korea since ancient times, and remain a popular natural medicine used worldwide in modern times. Ginsenosides are the main active components of ginseng, and increasing evidence has demonstrated that ginsenosides can prevent CNSDs, including neurodegenerative diseases, memory and cognitive impairment, cerebral ischemia injury, depression, brain glioma, multiple sclerosis, which has been confirmed in numerous studies. Therefore, this review summarizes the potential pathways by which ginsenosides affect the pathogenesis of CNSDs mainly including antioxidant effects, anti‐inflammatory effects, anti‐apoptotic effects, and nerve protection, which provides novel ideas for the treatment of CNSDs.
Proteomics discovery of pulmonary hypertension biomarkers: Insulin‐like growth factor binding proteins are associated with disease severity
Authors: Nies Melanie K. , Yang Jun , Griffiths Megan , Damico Rachel , Zhu Jie , Vaydia Dhananjay , Fu Zongming , Brandal Stephanie , Austin Eric D. , Ivy Dunbar D. , Hassoun Paul M. , Van Eyk Jennifer E. , Everett Allen D. 
Published: January 2022

AbstractPulmonary arterial hypertension (PAH) is a progressive disease characterized by sustained elevations of pulmonary artery pressure. To date, we lack circulating, diagnostic, and prognostic markers that correlate to clinical and functional parameters. In this study, we performed mass spectrometry‐based proteomics analysis to identify circulating biomarkers of PAH. Plasma samples from patients with idiopathic pulmonary arterial hypertension (IPAH, N = 9) and matched normal controls (N = 9) were digested with trypsin and analyzed using data‐dependent acquisition on an Orbitrap mass spectrometer. A total of 826 (false discovery rate [FDR] 0.047) and 461 (FDR 0.087) proteins were identified across all plasma samples obtained from IPAH and control subjects, respectively. Of these, 153 proteins showed >2 folds change (p < 0.05) between groups. Circulating levels of carbonic anhydrase 2 (CA2), plasma kallikrein (KLKB1), and the insulin‐like growth factor binding proteins (IGFBP1‐7) were quantified by immunoassay in an independent verification cohort (N = 36 PAH and N = 35 controls). CA2 and KLKB1 were significantly different in PAH versus control but were not associated with any functional or hemodynamic measurements. Whereas, IGFBP1 and 2 were associated with higher pulmonary vascular resistance, IGFBP2, 4, and 7 with decreased 6‐min walk distance (6MWD), and IGFBP1, 2, 4, and 7 with worse survival. This plasma proteomic discovery analysis suggests the IGF axis may serve as important new biomarkers for PAH and play an important role in PAH pathogenesis.
A case of acquired von Willebrand disease in severe pediatric pulmonary hypertension contributing to bleeding following reverse Potts shunt
Authors: Sullivan Rachel T. , Lo Clara , Martin Elisabeth , Kameny Rebecca J. , Hopper Rachel K. 
Published: January 2022

AbstractThe reverse Potts shunt is increasingly used as a palliative measure for end‐stage pulmonary arterial hypertension (PAH) as a means to offload the right ventricle and improve functional status. This case report describes a child who developed significant hemothorax after reverse Potts shunt that required surgical exploration, blood product administration, and prolonged intensive care hospitalization. Despite lack of preoperative bleeding symptoms, testing revealed acquired von Willebrand disease (aVWD), with subsequent resolution of bleeding. Alterations in von Willebrand factor, including aVWD, have been reported in children with severe PAH but have not previously been associated with bleeding after reverse Potts shunt procedure. As bleeding is a recognized postoperative morbidity in PAH patients undergoing reverse Potts shunt, we highlight a potential role for preoperative testing for aVWD as perioperative factor replacement therapy may improve postoperative outcomes.
Utility of plasma volume status in ambulatory patients with pulmonary hypertension
Authors: Sternberg Michael E. , Grinnan Daniel , Gertz Zachary M. 
Published: January 2022

AbstractPlasma volume status (PVS) is a noninvasive estimate of intravascular volume status. We studied the utility of PVS to predict short‐term outcomes in patients with pulmonary hypertension. Patients with lower PVS had decreased risk of hospitalization and death within 90 days of clinic visit, compared to those with higher PVS.
First report of Lophomonas infection in a patient with AML‐2 from Qeshm Island, Persian Gulf, southern Iran
Authors: Sharifpour Ali , Zarrinfar Hossein , Fakhar Mahdi , Zakariaei Zakaria , Soleymani Mostafa , Banimostafavi Elham Sadat , Nakhaei Maryam 
Published: January 2022

AbstractImmunocompromised patients are frequently more susceptible to pathogens such as protozoa. For the first time, we report a case of pulmonary lophomoniasis in a known case of acute myeloid leukaemia (AML‐2) from Qeshm Island, Persian Gulf, southern Iran. Diagnosis of lophomoniasis was confirmed using microscopy and molecular examinations of bronchoalveolar lavage fluid. She was completely treated with metronidazole (500 mg three times a day for 3 weeks). We conclude that immunocompromised patients with unjustified respiratory disorders should be screened for Lophomonas infection.
Approximate likelihood‐based estimation method of multiple‐type pathogen interactions: An application to longitudinal pneumococcal carriage data
Authors: Man Irene , Bogaards Johannes A. , Makwana Kishan , Trzciński Krzysztof , Auranen Kari 
Published: January 2022

AbstractWhile the serotypes of Streptococcus pneumoniae are known to compete during colonization in human hosts, our knowledge of how competition occurs is still incomplete. New insights of pneumococcal between‐type competition could be generated from carriage data obtained by molecular‐based detection methods, which record more complete sets of serotypes involved in co‐carriage than when detection is done by culture. Here, we develop a Bayesian estimation method for inferring between‐type interactions from longitudinal data recording the presence/absence of the types at discrete observation times. It allows inference from data containing co‐carriage of two or more serotypes, which is often the case when pneumococcal presence is determined by molecular‐based methods. The computational burden posed by the increased number of types detected in co‐carriage is addressed by approximating the likelihood under a multi‐state model with the likelihood of only those trajectories with minimum number of acquisition and clearance events between observation times. The proposed method's performance was validated on simulated data. The estimates of the interaction parameters of acquisition and clearance were unbiased in settings with short sampling intervals between observation times. With less frequent sampling, the estimates of the interaction parameters became more biased, but their ratio, which summarizes the total interaction, remained unbiased. Confounding due to unobserved heterogeneity in exposure could be corrected by including individual‐level random effects. In an application to empirical data about pneumococcal carriage in infants, we found new evidence for between‐serotype competition in clearance, although the effect size was small.
Ionic‐Liquid‐Based, Sustainable Wavelength‐Shifting Materials for Energy Conversion: A Minireview
Authors: Rahman Ziaur , Das Sudhir Kumar 
Published: January 2022

AbstractPhoton upconversion (UC) and down‐conversion (DC) are the technology that can increase solar utilization efficiencies.UC and DC are the major key factors for designing and developing efficient organic solar cells. In this mini‐review, we have focused on the recent progress on the ionic liquids (ILs) as novel sustainable media or building blocks for the fabrication of up and down‐converted materials in which energy is migrated through Dexter type of energy transfer by triplet‐triplet annihilation (TTA) and Förster resonance energy transfer (FRET) mechanism to overcome the problems for the use of these phenomena for solar utilization efficiencies associated with conventional solvents. We have surveyed most of the important, recent, and exemplary articles and tried to provide the latest information to help researchers to grab updated knowledge in this field. Finally, we critically assess the potentiality of these sustainable media‐based up and down‐converters to fulfill the requirements for solar utilization efficiencies conceptually.
Methimazole Analogs as Urease Inhibitors: Synthesis, In Silico and In Vitro Evaluation
Authors: Çapan İrfan 
Published: January 2022

AbstractUrease plays a key role in urinary tract and gastrointestinal infections for which inhibition of it could prove to be substantial as a potential therapeutic option. Here, synthesized thirty novel compounds in four different series based on methimazole skeleton, also known as thiamazole, a drug that is used for the treatment of hyperthyroidism. Characterization of novel compounds consisting oxadiazoles, hydrazine‐1‐carbothioamides and N′‐arylidenebenzohydrazides were performed by 1H‐, 13C‐NMR and high resolution mass spectrometry (HRMS). The synthesized molecules were examined for structure‐activity relationship in urease inhibition and found to exhibit inhibitory potency in a range of IC50=3.56–14.08 μM compared to urea and acetohydroxamic acid used as standard. Moreover, molecular docking was performed to understand ligand binding interactions in the active site of the enzyme (Jack bean urease, Protein Data Bank ID 3LA4). The promise of addressing urinary tract and gastrointestinal disorders through urease inhibition is discussed.
Properties and Potential Applications of Manganese‐doped Ceria Gained by Mechanochemical Synthesis
Authors: Ivković Ivana Katarina , Kurajica Stanislav , Duplančić Marina , Faraguna Fabio , Grbešić Tea 
Published: January 2022

AbstractManganese doped nanosized ceria samples were prepared by mechanochemical synthesis. Characterization was done using X‐ray diffraction (XRD), UV‐Vis diffuse reflectance spectroscopy (UV‐Vis DRS), X‐ray photoelectron spectroscopy (XPS) and others. Different conditions of synthesis were tried. Beside cerium carbonate, cerium chloride and amorphous phase remain in the product. Cerium carbonate decomposes around 250 °C, while the decomposition process centered at 330 °C was attributed to cerium chloride decomposition. Along with ceria, birnessite occurs in doped samples after thermal treatment and washing. Ceria lattice constant is reduced from 5.405 Å for pure sample to 5.401 Å for the 30 % doped sample as a consequence of manganese entrance in the ceria lattice. Ceria bandgap is significantly reduced with doping. Particle size was far greater than crystallite size due to a strong tendency toward agglomeration. All prepared powders proved to be efficient catalysts for toluene oxidation with the 30 % doped sample being the most promising.
Coincident Fluorescence‐Burst Analysis of the Loading Yields of Exosome‐Mimetic Nanovesicles with Fluorescently‐Labeled Cargo Molecules
Authors: Sanaee Maryam , Sandberg Elin , Ronquist K. Göran , Morrell Jane M. , Widengren Jerker , Gallo Katia 
Published: January 2022

AbstractThe possible targeting functionality and low immunogenicity of exosomes and exosome‐like nanovesicles make them promising as drug‐delivery carriers. To tap into this potential, accurate non‐destructive methods to load them and characterize their contents are of utmost importance. However, the small size, polydispersity, and aggregation of nanovesicles in solution make quantitative characterizations of their loading particularly challenging. Here, an ad‐hoc methodology is developed based on burst analysis of dual‐color confocal fluorescence microscopy experiments, suited for quantitative characterizations of exosome‐like nanovesicles and of their fluorescently‐labeled loading. It is applied to study exosome‐mimetic nanovesicles derived from animal extracellular‐vesicles and human red blood cell detergent‐resistant membranes, loaded with fluorescently‐tagged dUTP cargo molecules. For both classes of nanovesicles, successful loading is proved and by dual‐color coincident fluorescence burst analysis, size statistics and loading yields are retrieved and quantified. The procedure affords single‐vesicle characterizations well‐suited for the investigation of a variety of cargo molecules and biological nanovesicle combinations besides the proof‐of‐principle demonstrations of this study. The results highlight a powerful characterization tool essential for optimizing the loading process and for advanced engineering of biomimetic nanovesicles for therapeutic drug delivery.
A van der Waals Integrated Damage‐Free Memristor Based on Layered 2D Hexagonal Boron Nitride
Authors: Mao Jing‐Yu , Wu Shuang , Ding Guanglong , Wang Zhan‐Peng , Qian Fang‐Sheng , Yang Jia‐Qin , Zhou Ye , Han Su‐Ting 
Published: January 2022

Abstract2D materials with intriguing properties have been widely used in optoelectronics. However, electronic devices suffered from structural damage due to the ultrathin materials and uncontrolled defects at interfaces upon metallization, which hindered the development of reliable devices. Here, a damage‐free Au/h‐BN/Au memristor is reported using a clean, water‐assisted metal transfer approach by physically assembling Au electrodes onto the layered h‐BN which minimized the structural damage and undesired interfacial defects. The memristors demonstrate significantly improved performance with the coexistence of nonpolar and threshold switching as well as tunable current levels by controlling the compliance current, compared with devices with evaporated contacts. The devices integrated into an array show suppressed sneak path current and can work as both logic gates and latches to implement logic operations allowing in‐memory computing. Cross‐sectional scanning transmission electron microscopy analysis validates the feasibility of this nondestructive metal integration approach, the crucial role of high‐quality atomically sharp interface in resistive switching, and a direct observation of percolation path. The underlying mechanism of boron vacancies‐assisted transport is further supported experimentally by conductive atomic force microscopy free from process‐induced damage, and theoretically by ab initio simulations.
Anionic Redox Activities Boosted by Aluminum Doping in Layered Sodium‐Ion Battery Electrode
Authors: Cheng Chen , Ding Manling , Yan Tianran , Jiang Jinsen , Mao Jing , Feng Xuefei , Chan Ting‐Shan , Li Ning , Zhang Liang 
Published: January 2022

AbstractSodium‐ion batteries (SIBs) have attracted widespread attention for large‐scale energy storage, but one major drawback, i.e., the limited capacity of cathode materials, impedes their practical applications. Oxygen redox reactions in layered oxide cathodes are proven to contribute additionally high specific capacity, while such cathodes often suffer from irreversible structural transitions, causing serious capacity fading and voltage decay upon cycling, and the formation process of the oxidized oxygen species remains elusive. Herein, a series of Al‐doped P2‐type Na0.6Ni0.3Mn0.7O2 cathode materials for SIBs are reported and the corresponding charge compensation mechanisms are investigated qualitatively and quantitatively. The combined analyses reveal that Al doping boosts the reversible oxygen redox reactions through the reductive coupling reactions between orphaned O 2p states in NaOAl local configurations and Ni4+ ions, as directly evidenced by X‐ray absorption fine structure results. Additionally, Al doping also induces an increased interlayer spacing and inhibits the unfavorable P2 to O2 phase transition upon desodiation/sodiation, which is common in P2‐type Mn‐based cathode materials, leading to the great improvement in capacity retention and rate capability. This work provides deeper insights into the development of structurally stable and high‐capacity layered cathode materials for SIBs with anion–cation synergetic contributions.
Potential and limitations of machine-learning approaches to inclusive |Vub| determinations
Authors: Biekötter Anke , Kwok Ka Wang , Pecjak Benjamin D. 
Published: January 2022

Abstract
The determination of |Vub| in inclusive semileptonic B → Xuℓν decays will be among the pivotal tasks of Belle II. In this paper we study the potential and limitations of machine-learning approaches that attempt to reduce theory uncertainties by extending the experimentally accessible fiducial region of the B → Xuℓν signal into regions where the B → Xcℓν background is dominant. We find that a deep neural network trained on low-level single particle features offers modest improvement in separating signal from background, compared to BDT set-ups using physicist-engineered high-level features. We further illustrate that while the signal acceptance of such a deep neural network deteriorates in kinematic regions where the signal is small, such as at high hadronic invariant mass, neural networks which exclude kinematic features are flatter in kinematics but less inclusive in the sampling of exclusive hadronic final states at fixed kinematics. The trade-off between these two set-ups is somewhat Monte Carlo dependent, and we study this issue using the multipurpose event generator Sherpa in addition to the widely used B-physics tool EvtGen.