bluuebunny/crossref_metadata_2025_split huggingface dataset:
A method to improve quantitative radiotracing‐based analysis of the in vivo biodistribution of drug carriers
Authors: Roki Nikša , Solomon Melani , Casta Lou , Bowers Jessica , Getts Robert C. , Muro Silvia 
Published: December 2020

AbstractBiodistribution studies are essential in drug carrier design and translation, and radiotracing provides a sensitive quantitation for this purpose. Yet, for biodegradable formulations, small amounts of free‐label signal may arise prior to or immediately after injection in animal models, causing potentially confounding biodistribution results. In this study, we refined a method to overcome this obstacle. First, we verified free signal generation in animal samples and then, mimicking it in a controllable setting, we injected mice intravenously with a radiolabeled drug carrier formulation (125I‐antibody/3DNA) containing a known amount of free radiolabel (125I), or free 125I alone as a control. Corrected biodistribution data were obtained by separating the free radiolabel from blood and organs postmortem, using trichloroacetic acid precipitation, and subtracting the confounding signal from each tissue measurement. Control free 125I‐radiolabel was detected at ≥85% accuracy in blood and tissues, validating the method. It biodistributed very heterogeneously among organs (0.6–39 %ID/g), indicating that any free 125I generated in the body or present in an injected formulation cannot be simply corrected to the free‐label fraction in the original preparation, but the free label must be empirically measured in each organ. Application of this method to the biodistribution of 125I‐antibody/3DNA, including formulations directed to endothelial target ICAM‐1, showed accurate classification of free 125I species in blood and tissues. In addition, this technique rendered data on the in vivo degradation of the traced agents over time. Thus, this is a valuable technique to obtain accurate measurements of biodistribution using 125I and possibly other radiotracers.
A practical nomogram and risk stratification system predicting the cancer‐specific survival for patients with early hepatocellular carcinoma
Authors: Yan Bing , Su Bing‐Bing , Bai Dou‐Sheng , Qian Jian‐Jun , Zhang Chi , Jin Sheng‐Jie , Jiang Guo‐Qing 
Published: December 2020

AbstractBackgroundOur purpose was to establish and validate a nomogram model in early hepatocellular carcinoma (HCC) patients for predicting the cancer‐specific survival (CSS).MethodsWe extracted eligible data of relevant patients between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Further, we divided all patients into two groups (training and validation cohorts) at random (7:3). Nomogram was established using effective risk factors based on univariate and multivariate analysis. The effective performance of nomogram was evaluated using concordance index (C‐index), calibration plots, decision curve analysis (DCA), and receiver operating characteristic curve (ROC).ResultsWe selected 3620 patients with early HCC including the training cohort (70%, 2536) and the validation cohort (30%, 1084). The nomogram‐related C‐indexes were 0.755 (95% CI: 0.739–0.771) and 0.737 (95% CI: 0.712–0.762), in the training and validation cohorts, respectively. The calibration plots showed good consistency of 3‐and 5‐year CSS between the actual observation and the nomogram prediction. The 3‐, 5‐year DCA curves also indicated that the nomogram has excellent clinical utility. The 3‐, 5‐year area under curve (AUC) of ROC in the training cohort were 0.783, 0.779, respectively, and 0.767, 0.766 in the validation cohort, respectively. With the establishment of nomogram, a risk stratification system was also established that could divide all patients into three risk groups, and the CSS in different groups (i.e., low risk, intermediate risk, and high risk) had a good regional division.ConclusionsWe developed a practical nomogram in early HCC patients for predicting the CSS, and a risk stratification system follow arisen, which provided an applicable tool for clinical management.
Lidocaine inhibits the metastatic potential of ovarian cancer by blocking NaV1.5‐mediated EMT and FAK/Paxillin signaling pathway
Authors: Liu Chang , Yu Ming , Li Yi , Wang Hao , Xu Chuanya , Zhang Xiaoqing , Li Min , Guo Hongyan , Ma Daqing , Guo Xiangyang 
Published: December 2020

AbstractLidocaine, one of the most commonly used local anesthetics during surgery, has been reported to suppress cancer cell growth via blocking voltage‐gated sodium channels (VGSCs). VGSC 1.5 (NaV1.5) is highly expressed in invasive cancers including ovarian cancer. This study aims to investigate whether lidocaine inhibits the malignancy of ovarian cancer through NaV1.5 blockage. Human ovarian cancer, its metastatic cancer and normal ovarian tissues were probed with anti‐NaV1.5 antibody in situ. Human ovarian cancer A2780 and SKOV3 cells were cultured and their growth, epithelial‐mesenchymal transition (EMT), migration, and invasion in the presence or absence of lidocaine together with underlying molecular mechanisms were assessed. Murine syngeneic ovarian cancer (ID8) model was also used to determine the chemotherapeutic efficiency of cisplatin in combination with lidocaine. The high level of NaV1.5 expression was found in human ovarian cancer and even higher in its metastatic cancer but not in normal ovarian tissues. Lidocaine decreased the growth, EMT, migration, and invasion of human ovarian cancer A2780 and SKOV3 cells. Lidocaine enhanced the chemotherapeutic efficiency of cisplatin in both ovarian cancer cell cultures and a murine ovarian metastatic model. Furthermore, a downregulation of NaV1.5 by siRNA transfection, or FAK inhibitor application, inhibited the malignant properties of SKOV3 cells through inactivating FAK/Paxillin signaling pathway. Our data may indicate that lidocaine suppresses the metastasis of ovarian cancer and sensitizes cisplatin through blocking NaV1.5‐mediated EMT and FAK/paxillin signaling pathway. The translational value of lidocaine local application as an ovarian cancer adjuvant treatment warrants further study.
HELLS, a chromatin remodeler is highly expressed in pancreatic cancer and downregulation of it impairs tumor growth and sensitizes to cisplatin by reexpressing the tumor suppressor TGFBR3
Authors: Hou Xuyang , Yang Leping , Wang Kunpeng , Zhou Yan , Li Qinglong , Kong Fanhua , Liu Xi , He Jun 
Published: December 2020

AbstractPancreatic cancer (PC) is the most malignant cancer type in the digestive system with a poor prognosis. Chemotherapy such as cisplatin is the last chance for PC patients diagnosed with advanced or metastatic disease. Obtaining a deep understanding of the molecular mechanism underlying PC tumorigenesis and identifying optimal biomarkers to estimate chemotherapy sensitivity are essential for PC treatment. The chromatin remodeler HELLS was found to regulate various tumor suppressors through an epigenetic pathway in several cancers. We analyzed HELLS expression in clinical samples by Western blotting and immunohistochemical staining. Next, we identified the variation in tumor growth and cisplatin sensitivity after knockdown of HELLS and explored the downstream mediators of HELLS in PC via RNA‐seq, chromatin immunoprecipitation, and gain‐ and loss‐of‐function assays. We found that HELLS is upregulated in PC tissues and correlates with advanced clinical stage and a poor prognosis, and the knockdown of HELLS leads to tumor growth arrest and increased sensitivity to cisplatin. Mechanistically, the tumor suppressor TGFBR3 is markedly reexpressed after HELLS knockdown; conversely, compromising TGFBR3 rescues HELLS knockdown‐mediated effects in PC cells. Thus, our data provide evidence that HELLS can serve as a potential oncogene and suitable biomarker to evaluate chemotherapy sensitivity via epigenetically silencing the tumor suppressor TGFBR3 in PC.
Styrene hydrogenation in inclined packed‐bed bubble reactors: A reaction‐transport model for the catalytic hydrogenation of pyrolysis gasoline on‐board floating reactors
Authors: Iliuta Ion , Larachi Faïçal 
Published: December 2020

AbstractTwo‐phase upflow/downflow and styrene hydrogenation were explored numerically in vertical and inclined packed‐bed bubble reactors using a dynamic three‐dimensional model which integrates the hydrodynamics via macroscopic volume‐averaged continuity and momentum balance equations, energy and mass conservative equations in liquid/gas phases, and simultaneous diffusion and chemical reaction inside Pd/Al2O3 catalyst particles. Packed‐bed bubble reactors non‐verticality divert the liquid phase from its normally expected axial trajectory and generate an excessive axial symmetry distortion because of amplified secondary liquid flow associated with a larger liquid holdup and because of liquid reversal flow (two‐phase upflow). The significant liquid maldistribution over the packed beds (especially in deeper beds) substantially reduces the performance of the styrene hydrogenation process in inclined packed‐bed bubble reactors, more than in inclined trickle‐bed reactors. This drop in hydrogenation performance is more noticeable in downflow packed‐bed bubble reactors, particularly at higher packed bed inclinations, because of the reduction of catalyst wetting efficiency and overall effectiveness factor of the catalyst particles. Increasing the height and diameter of packed bed is recommended to compensate for reduction in hydrogenation performance in inclined packed‐bed bubble reactors. However, the ratio between the reactor height and diameter should be limited to a maximum value to avoid the excessive liquid maldistribution in deeper beds with a significant bypassing in the vicinity of the bottom of the packed bed.
Simulation of a moving bed chemical looping system for electricity production from coal via chemical looping water splitting
Authors: Kong Fanhe , Tene Youmbi Darryl , Tong Andrew , Fan Liang‐Shih 
Published: December 2020

AbstractCoal is a crucial energy source for modern industry and society. Because coal is one of the most CO2‐intensive carbonaceous fuels, the combustion of coal with CO2 capture is of great environmental relevance. However, the conventional coal‐based power generation processes, including the pulverized coal (PC) boiler process and the integrated gasification combined cycle (IGCC) process, suffer a significant efficiency loss when integrated with conventional CO2 capture methods. Chemical looping technology is a promising alternative pathway for coal‐based power generation with intrinsic CO2 separation and capture. Process simulation of chemical looping processes can provide an overview on the viability of the processes, thereby quantifying their advantages over conventional processes. This study presents the process simulation of a chemical looping water splitting combined cycle (CLWS‐CC) system for electricity generation. The CLWS‐CC process directly uses coal as the feedstock to produce H2, which is subsequently combusted in a combined cycle to generate electricity. The oxygen carriers used in the chemical looping process are optimized in their composition. Autothermal operation is established within the chemical looping system. Four CLWS‐CC cases that operate at different pressures are considered. In two of the four cases, an unequal pressure operating strategy is adopted to minimize the compression power consumption in order to enhance the overall process energy efficiency. The process simulation shows that the CLWS‐CC process is able to achieve an 18% increase in net plant efficiency over the conventional IGCC process.
Influence of zeta potential of ZrO2 and Al2O3 nanoparticles on removal of metal ions by hybrid electrospun polyamide 6 membrane: Kinetics of adsorption and fouling mechanisms
Authors: Mosayebi Ali , Esfahani Hamid , Hoor Mehrnoosh 
Published: December 2020

AbstractElectrostatic charging of the adsorbent is a critical method for the selective removal of metal ions fromacidic wastewater. In this study, electrospun polyamide 6 (PA6) membranes were separately incorporated with Al2O3 and ZrO2 nanoparticles (NPs), and their ability in the removal of cations (eg, Al3+ and Fe3+) were evaluated by static adsorption and filtration methods. The impact of various parameters, namely microstructure, surface porosity, functional molecular groups, and hydrophobicity of membranes on the removal process, was investigated. By evaluating the zeta (ζ) potential of oxide ceramic NPs, it was found that the Al2O3 and ZrO2 NPs had positive and negative electrostatic charges inacidic solution, respectively. The results showed that the incorporation of negatively charged ZrO2 NPs improved both the static adsorption and filtration removal capability of the PA6 membrane. The maximum adsorption efficiency of Al3+ and Fe3+ cations was 52.43% and 54.11%, and the highest filtration efficiency of the mentioned cations obtained by electrospun hybrid ZrO2 incorporated PA6 membrane was 98.6% and 99.3%, respectively. It was also found that the adsorption of both Al3+ and Fe3+ cations correlated well with the pseudo‐second‐order kinetic model. The results also demonstrated that the dominant blocking models were switched with the increase in the initial concentration of metal ions from 5 ppm‐70 ppm.
Behaviour of agglomerates formed by liquid injection in fluidized beds
Authors: Briens Cedric , Bhatti Muhammad O. I. , Sanchez Francisco J. , Berruti Franco , McMillan Jennifer 
Published: December 2020

AbstractFormation of agglomerates in fluidized beds can cause operating problems, such as excessive stripper shed fouling, which can lead to premature unit shut down. The focus of this study is to reach a better understanding of how agglomerates move through a fluidized bed to improve the Fluid Cokers and minimize the risk of agglomerates reaching regions where they cause problems. Two experimental methods were used: first, a Gum Arabic binder solution was injected into a two‐dimensional (2D) fluidized bed under conditions that simulate agglomerate formation in Fluid Cokers, and the mass and density of recovered agglomerates were measured; second, a new 2D radioactive particle tracking (RPT) method was developed to track the motion of model agglomerates. The fluidized bed had a steel wall, resulting in significant and non‐uniform radiation absorption. The 2D RPT system was, thus, calibrated by placing the source at 290 locations in the bed, for each fluidization velocity. Since bubble flow patterns greatly affect agglomerate motion and segregation, a tribo‐electric method was used to determine bubble flow distribution in the fluidized bed. The RPT and liquid injection methods gave similar vertical distributions of agglomerates. The main results were that increasing the fluidization velocity reduced segregation, and larger agglomerates were more likely to segregate. There was a strong correlation between the bubbles and agglomerates flow patterns: establishing an asymmetric flow pattern by injecting more fluidization gas in one side of the bed greatly reduced agglomerate segregation.
Phospho‐regulation of mitotic spindle assembly
Authors: Ong Joseph Y. , Bradley Michelle C. , Torres Jorge Z. 
Published: December 2020

AbstractThe assembly of the bipolar mitotic spindle requires the careful orchestration of a myriad of enzyme activities like protein posttranslational modifications. Among these, phosphorylation has arisen as the principle mode for spatially and temporally activating the proteins involved in early mitotic spindle assembly processes. Here, we review key kinases, phosphatases, and phosphorylation events that regulate critical aspects of these processes. We highlight key phosphorylation substrates that are important for ensuring the fidelity of centriole duplication, centrosome maturation, and the establishment of the bipolar spindle. We also highlight techniques used to understand kinase–substrate relationships and to study phosphorylation events. We conclude with perspectives on the field of posttranslational modifications in early mitotic spindle assembly.
Experimental Medicine Study to Measure Immune Checkpoint Receptors PD‐1 and GITR Turnover Rates In Vivo in Humans
Authors: Lassman Michael E. , Chappell Derek L. , McAvoy Thomas , Cheng Amy , de Alwis Dinesh P. , Pruitt Scott K. , Laterza Omar F. , Li Claire , Stoch Aubrey , Mayawala Kapil 
Published: December 2020

Development of monoclonal antibodies (mAbs) targeting immune‐checkpoint receptors (IMRs) for the treatment of cancer is one of the most active areas of investment in the biopharmaceutical industry. A key decision in the clinical development of anti‐IMR mAbs is dose selection. Dose selection can be challenging because the traditional oncology paradigm of administering the maximum tolerated dose is not applicable to anti‐IMR mAbs. Instead, dose selection should be informed by the pharmacology of immune signaling. Engaging an IMR is a key initial step to triggering pharmacologic effects, and turnover (i.e., the rate of protein synthesis) of the IMR is a key property to determining the dose level needed to engage the IMR. Here, we applied the stable isotope labeling mass spectrometry technique using 13C6‐leucine to measure the in vivo turnover rates of IMRs in humans. The 13C6‐leucine was administered to 10 study participants over 15 hours to measure 13C6‐leucine enrichment kinetics in 2 IMR targets that have been clinically pursued in oncology: GITR and PD‐1. We report the first measurements of GITR and PD‐1 median half‐lives associated with turnover to be 55.6 and ≥ 49.5 hours, respectively. The approach outlined here can be applied to other IMRs and, more generally, to protein targets.
Characterizing Effects of Antidiabetic Drugs on Heart Rate, Systolic and Diastolic Blood Pressure
Authors: Maringwa John , Sardu Maria Luisa , Hang Yaming , Czerniak Richard , Vishnubhotla Manasa , Vakilynejad Majid , Pfister Marc 
Published: December 2020

A model‐based meta‐analysis was performed with reported data from obese subjects and patients with type 2 diabetes (T2DM) to characterize the effects of dipeptidyl peptidase 4 (DPP4) inhibitors, gastric inhibitory polypeptides (GIPs), glucagon‐like peptide‐1 (GLP1), and dual GIP/GLP1 agonists, or a combination of these antidiabetic drugs (ADs) on heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP). A systematic literature search and review after the Cochrane method identified sources for investigational and approved ADs resulted in a comprehensive database with data from 178 clinical studies in obese subjects and patients with T2DM. Results indicated that there were AD class‐dependent effects on HR and SBP, whereas no clear AD‐related effects on DBP were found. All AD classes, except for DPP4 inhibitors, increased HR. The largest increase of 12 bpm was seen with GLP1 receptor agonists. All AD classes appeared to decrease SBP. DPP4 inhibitors were associated with a marginal decrease of ~ 1 mmHg, whereas GLP1 and GIP/GLP1 dual agonists exhibited the largest decrease of ~ 3 mmHg in SBP. AD‐related effects were similar in obese subjects and patients with T2DM. In conclusion, there are clinically relevant AD‐related effects on both HR and SBP, but not on DBP. DPP4 inhibitors are associated with the smallest (if at all) effects on HR and SBP, whereas GLP1 inhibitors exhibited the largest effects on these two cardiovascular end points. Additional studies are warranted to further investigate how AD‐related SBP decreases combined with HR increases affect long‐term cardiovascular mortality.
Fishing, environment, and the erosion of a population portfolio
Authors: Stier Adrian C. , Olaf Shelton Andrew , Samhouri Jameal F. , Feist Blake E. , Levin Phillip S. 
Published: December 2020

AbstractMany organisms exhibit tremendous fluctuations in population abundance and experience unexpected collapse. Conservationists seeking to minimize region‐wide variability in resources and reduce extinction risk often seek to preserve a metapopulation portfolio of spatially asynchronous subpopulations connected by dispersal. However, portfolio properties are not necessarily static, and the erosion of a portfolio can fundamentally alter the population dynamics and services a species provides. In the Northeast Pacific, a portfolio of spatially asynchronous herring populations has historically provided regional reliability of herring to mobile predators and commercial fishermen as well as local subsistence and ceremonial harvest. Here, we fit a mechanistic time‐series model to herring spawn and catch records from 1950 to 2015 to quantify how population growth, climate, and fishing have contributed to a major shift in the herring portfolio over time. We document the erosion of the herring portfolio and a severe decline in herring population growth. Commercial harvest historically played a key role in herring dynamics, hovering around typical annual exploitation rates (15%) at the archipelago scale, but local harvest rates were much higher when fishing occurred (as high as 65%). Additionally, the Pacific Decadal Oscillation and population growth had equally strong effects on local and regional herring population dynamics. Our results highlight how spatially structured populations can undergo major shifts following disturbance and emphasize how ecological systems do not always rapidly recover and provide services following disturbance. Developing herring management strategies at a finer scale may ensure greater regional resource reliability by recovering previous levels of spatial population asynchrony. However, doing so may require higher implementation and monitoring costs in order to yield higher ecological, social, and economic benefits. Such place‐based solutions that match the spatial scale of governance to the spatial scale of ecological dynamics have the potential to improve future management and conservation in an increasingly dynamic world.
Isotopic niche breadth of a generalist mesopredator increases with habitat heterogeneity across its range
Authors: Walsh Lisa L. , Tucker Priscilla K. 
Published: December 2020

AbstractAlthough generalists are becoming increasingly abundant and widespread, little is known about their response to ecological variation they encounter across their range. For example, the generalist’s flexible diet is cited to help explain recent range expansions, but no study has directly examined this claim. Here, we use stable isotope values of the Virginia opossum (Didelphis virginiana), a true generalist, to examine an extension of MacArthur’s habitat heterogeneity hypothesis for a single generalist species. If a generalist’s diet reflects local food abundance, then more heterogeneous landscapes should result in broader niches. We used stable isotope analysis, landcover indices, and WorldClim data to further evaluate how the opossum’s use of its environment varies across ancestral regions, expansion fronts, and regions of human‐facilitated introductions. Niche breadth varied across its range, especially between expansion fronts. We found a positive relationship between landcover diversity and isotopic niche breadth. WorldClim variables linked to aridity and C4 plant abundance were most strongly associated with nitrogen (δ15N) and carbon (δ13C) values, respectively. Our results reveal that a generalist’s stable isotope signature reflects its local environment, demonstrating their flexible diet is captured with stable isotopes and supporting the generalist habitat heterogeneity hypothesis.