bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D and Clinical Cancer Outcomes: A Review of Meta‐Analyses
Authors: Sluyter John D , Manson JoAnn E , Scragg Robert 
Published: September 2020

ABSTRACTThe relationship between vitamin D status or supplementation and cancer outcomes has been examined in several meta‐analyses. To address remaining knowledge gaps, we conducted a systematic overview and critical appraisal of pertinent meta‐analyses. For meta‐analyses of trials, we assessed their quality using AMSTAR‐2 (A Measurement Tool to Assess Systematic Reviews), strength of associations using umbrella review methodology and credibility of evidence using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) criteria. Meta‐analyses of observational studies reported inverse associations of 25OHD with risk of cancer incidence and cancer mortality and, particularly for colorectal cancer, fulfilled some of Bradford‐Hill's causation criteria. In meta‐analyses of trials, vitamin D supplementation did not affect cancer incidence. However, we found credible evidence that vitamin D supplementation reduced total cancer mortality risk, with five out of six meta‐analyses reporting a relative risk (RR) reduction of up to 16%: RR, 0.84 (95% CI, 0.74–0.95). The strength of the association, however, was classified as weak. This was true among meta‐analyses of high, moderate, and lower quality (AMSTAR‐2–rated). Trials did not include large numbers of vitamin D‐deficient participants; many tested relatively low doses and lacked sufficiently powered data on site‐specific cancers. In conclusion, meta‐analyses show that, although observational evidence indicates that low vitamin D status is associated with a higher risk of cancer outcomes, randomized trials show that vitamin D supplementation reduces total cancer mortality, but not cancer incidence. However, trials with larger proportions of vitamin D‐insufficient participants and longer durations of follow‐up, plus adequately powered data on site‐specific common cancers, would provide further insight into the evidence base. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
A Neutralizing Antibody Targeting Oxidized Phospholipids Promotes Bone Anabolism in Chow-Fed Young Adult Mice
Authors: Palmieri Michela , Kim Ha-Neui , Gomez-Acevedo Horacio , Que Xuchu , Tsimikas Sotirios , Jilka Robert L , Manolagas Stavros C , Witztum Joseph L , Ambrogini Elena 
Published: September 2020

ABSTRACT
Oxidized phospholipids containing phosphocholine (OxPL) are pro-inflammatory lipid peroxidation products that bind to scavenger receptors (SRs), such as Scarb1, and toll-like receptors (TLRs). Excessive OxPL, as found in oxidized low-density lipoprotein (OxLDL), overwhelm these defense mechanisms and become pathogenic in atherosclerosis, nonalcoholic steatohepatitis (NASH), and osteoporosis. We previously reported that the innate IgM natural antibody E06 binds to OxPL and neutralizes their deleterious effects; expression of the single-chain (scFv) form of the antigen-binding domain of E06 (E06-scFv) as a transgene increases trabecular bone in male mice. We show herein that E06-scFv increases trabecular and cortical bone in female and male mice by increasing bone formation and decreasing osteoblast apoptosis in vivo. Homozygous E06-scFv mice have higher bone mass than hemizygous, showing a dose effect of the transgene. To investigate how OxPL restrain bone formation under physiologic conditions, we measured the levels of SRs and TLRs that bind OxPL. We found that osteoblastic cells primarily express Scarb1. Moreover, OxLDL-induced apoptosis and reduced differentiation were prevented in bone marrow–derived or calvaria-derived osteoblasts from Scarb1 knockout mice. Because Scarb1-deficient mice are reported to have high bone mass, our results suggest that E06 may promote bone anabolism in healthy young mice, at least in part, by neutralizing OxPL, which in turn promote Scarb1-mediated apoptosis of osteoblasts or osteoblast precursors. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
Deficient muscle regeneration potential in sarcopenic COPD patients: Role of satellite cells
Authors: Sancho‐Muñoz Antonio , Guitart Maria , Rodríguez Diego A. , Gea Joaquim , Martínez‐Llorens Juana , Barreiro Esther 
Published: September 2020

AbstractSarcopenia is a major comorbidity in chronic obstructive pulmonary (COPD). Whether deficient muscle repair mechanisms and regeneration exist in the vastus lateralis (VL) of sarcopenic COPD remains debatable. In the VL of control subjects and severe COPD patients with/without sarcopenia, satellite cells (SCs) were identified (immunofluorescence, specific antibodies, anti‐Pax‐7, and anti‐Myf‐5): activated (Pax‐7+/Myf‐5+), quiescent/regenerative potential (Pax‐7+/Myf‐5‐), and total SCs, nuclear activation (terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling [TUNEL]), and muscle fiber type (morphometry and slow‐ and fast‐twitch, and hybrid fibers), muscle damage (hematoxylin‐eosin staining), muscle regeneration markers (Pax‐7, Myf‐5, myogenin, and MyoD), and myostatin levels were identified. Compared to controls, in VL of sarcopenic COPD patients, myostatin content, activated SCs, hybrid fiber proportions, TUNEL‐positive cells, internal nuclei, and muscle damage significantly increased, while quadriceps muscle strength, numbers of Pax‐7+/Myf‐5‐ and slow‐ and fast‐twitch, and hybrid myofiber areas decreased. In the VL of sarcopenic and nonsarcopenic patients, TUNEL‐positive cells were greater, whereas muscle regeneration marker expression was lower than in controls. In VL of severe COPD patients regardless of the sarcopenia level, the muscle regeneration process is triggered as identified by SC activation and increased internal nuclei. Nonetheless, a lower regenerative potential along with significant alterations in muscle phenotype and damage, and increased myostatin were prominently seen in sarcopenic COPD.
Molecular pathophysiology of acute kidney injury: The role of sirtuins and their interactions with other macromolecular players
Authors: Rahbar Saadat Yalda , Hosseiniyan Khatibi Seyed Mahdi , Ardalan Mohammadreza , Barzegari Abolfazl , Zununi Vahed Sepideh 
Published: September 2020

AbstractAcute kidney injury (AKI), a rapid drop in kidney function, displays high mortality and morbidity, and its repeated or severe status can shift into chronic kidney disease or even end‐stage renal disease. How and which events cause AKI still is controversial. In addition, no specific therapies have emerged that can attenuate AKI or expedite recovery. Some central mechanisms including tubular epithelial cells injury, endothelial injury, renal cell apoptosis, and necrosis signaling cascades, and inflammation have been reported in the pathophysiology of AKI. However, the timing of the activation of each pathway, their interactions, and the hierarchy of these pathways remain unknown. The main molecular mechanisms that might be complicated in this process are the mitochondrial impairment and alteration/shifting of cellular metabolites (e.g., acetyl‐CoA and NAD+/NADH) acting as cofactors to alter the activities of many enzymes, for instance, sirtuins. Moreover, alteration of mitochondrial structure over the fusion and fission mechanisms can regulate cellular signaling pathways by modifying the rate of reactive oxygen species generation and metabolic activities. The aim of this review is to better understand the underlying pathophysiological and molecular mechanisms of AKI. In addition, we predicted the main other molecular players in interaction with sirtuins as energy/stresses monitoring proteins for the development of future approaches in the treatment or prevention of ischemic AKI.
Physiologically Based Pharmacokinetic Modeling of Doravirine and Its Major Metabolite to Support Dose Adjustment With Rifabutin
Authors: Yee Ka Lai , Cabalu Tamara D. , Kuo Yuhsin , Fillgrove Kerry L. , Liu Yang , Triantafyllou Ilias , McClain Sasha , Dreyer Daniel , Wenning Larissa , Stoch S. Aubrey , Iwamoto Marian , Sanchez Rosa I. , Khalilieh Sauzanne G. 
Published: September 2020

AbstractDoravirine, a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus 1 (HIV‐1), is predominantly cleared by cytochrome P450 (CYP) 3A4 and metabolized to an oxidative metabolite (M9). Coadministration with rifabutin, a moderate CYP3A4 inducer, decreased doravirine exposure. Based on nonparametric superposition modeling, a doravirine dose adjustment from 100 mg once daily to 100 mg twice daily during rifabutin coadministration was proposed. However, M9 exposure may also be impacted by induction, in addition to the dose adjustment. As M9 concentrations have not been quantified in previous clinical studies, a physiologically based pharmacokinetic model was developed to investigate the change in M9 exposure when doravirine is coadministered with CYP3A inducers. Simulations demonstrated that although CYP3A induction increases doravirine clearance by up to 4.4‐fold, M9 exposure is increased by only 1.2‐fold relative to exposures for doravirine 100 mg once daily in the absence of CYP3A induction. Thus, a 2.4‐fold increase in M9 exposure relative to the clinical dose of doravirine is anticipated when doravirine 100 mg twice daily is coadministered with rifabutin. In a subsequent clinical trial, doravirine and M9 exposures, when doravirine 100 mg twice daily was coadministered with rifabutin, were found to be consistent with model predictions using rifampin and efavirenz as representative inducers. These findings support the dose adjustment to doravirine 100 mg twice daily when coadministered with rifabutin.
Tucatinib Inhibits Renal Transporters OCT2 and MATE Without Impacting Renal Function in Healthy Subjects
Authors: Topletz‐Erickson Ariel R. , Lee Anthony J. , Mayor JoAl G. , Rustia Evelyn L. , Abdulrasool Layth I. , Wise Amanda L. , Dailey Ben , DeChenne Sharon , Walker Luke N. , Alley Stephen C. , Endres Christopher J. 
Published: September 2020

AbstractTucatinib is a potent tyrosine kinase inhibitor selective for human epidermal growth factor receptor 2 (HER2) approved by the US Food and Drug Administration for the treatment of HER2‐positive metastatic breast cancer and in development for other HER2‐positive solid tumors. Modest, reversible serum creatinine (SCr) elevations have been observed in tucatinib clinical trials. SCr is conveyed by the renal drug transporters organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) and 2‐K (MATE2‐K) and can increase in the presence of inhibitors of these transporters. In vitro, tucatinib inhibited OCT2‐, MATE1‐, and MATE2‐K‐mediated transport of metformin, with IC50 values of 14.7, 0.340, and 0.135 µM, respectively. Tucatinib also inhibited OCT2‐ and MATE1‐mediated transport of creatinine, with IC50 values of 0.107 and 0.0855 µM, respectively. A phase 1 study with metformin administered orally in the absence and presence of tucatinib was conducted in 18 healthy subjects. Renal function was assessed by measuring glomerular filtration rate (GFR; based on iohexol plasma clearance) and endogenous markers (SCr, cystatin C‐based estimated glomerular filtration rate [eGFR]) with and without tucatinib. Metformin exposure increased (1.4‐fold) and renal clearance decreased (29.99‐17.64 L/h) with tucatinib, with no effect on metformin maximum concentration. Creatinine clearance transiently decreased 23% with tucatinib. GFR and eGFR, which are unaffected by OCT2 and/or MATE1/2‐K transport, were unchanged with tucatinib. These data demonstrate that tucatinib inhibits OCT2‐ and MATE1/2‐K‐mediated tubular secretion of creatinine, which may manifest as mild SCr elevations that are not indicative of renal impairment.
Student performance comparisons for a critical thinking skill set (technology decision‐making) for classroom and remote (Zoom) facilitation
Authors: Holloway Julie A. , Johnsen David C. , Syrbu John 
Published: September 2020

AbstractA comparison of student learning in a critical thinking exercise for technology decision‐making occurred with the onset of coronavirus and the switch from face‐to‐face to distance with Zoom. Literature on explicit critical thinking skill sets is scant in any format, including distance learning. While face‐to‐face and Zoom have similarities, seizing this opportunity for comparison can set the stage to determine soundness of distance learning in critical thinking on a preliminary basis. The learning outcome, learning guide and assessment instrument remained the same for the exercise in both formats; student teams presented analyses of different technologies with assessment by 2 faculty as before. Forty students had not completed the exercise when the coronavirus shut down occurred. Students performed at as high a level using virtual/Zoom as with face‐to‐face.
Improving the effectiveness of saturated riparian buffers for removing nitrate from subsurface drainage
Authors: McEachran Andrea R. , Dickey Loulou C. , Rehmann Chris R. , Groh Tyler A. , Isenhart Thomas M. , Perez Michael A. , Rutherford Cassandra J. 
Published: September 2020

AbstractA saturated riparian buffer (SRB) is an edge‐of‐field conservation practice that reduces nitrate export from agricultural lands by redistributing tile drainage as shallow groundwater and allowing for denitrification and plant uptake. We propose an approach to improve the design of SRBs by analyzing a tradeoff in choosing the SRB width, and we apply the approach to six sites with SRBs in central Iowa. A larger width allows for more residence time, which increases the opportunity for removing nitrate that enters the buffer. However, because the SRBs considered here treat only a portion of the tile flow when it is large, for the same difference in hydraulic head, a smaller width allows more of the total tile flow to enter the buffer and therefore treats more of the drainage. By maximizing the effectiveness of nitrate removal, defined as the ratio of total nitrate removed by the SRB to total nitrate leaving the field in tile drainage, an equation for the optimal width was derived in terms of soil properties, denitrification rates, and head difference. All six sites with existing SRBs considered here have optimal widths smaller than the current width, and two are below the minimum width listed in current design standards. In terms of uncertainty, the main challenges in computing the optimal width for a site are estimating the removal coefficient for nitrate and determining the saturated hydraulic conductivity. Nevertheless, including a width that accounts for site conditions in the design standards would improve water quality locally and regionally.
Drivers of extreme wind events in Mexico for windpower applications
Authors: Thomas Simon Richard , Martínez‐Alvarado Oscar , Drew Daniel , Bloomfield Hannah 
Published: September 2020

AbstractIn this study, we use a k‐mean clustering approach to investigate the weather patterns responsible for extreme wind speed events throughout Mexico using 40 years of the ERA‐5 atmospheric reanalysis. Generally, we find a large geographical split between the weather patterns that generate the strongest winds across the country. The highest wind power production periods therefore occur at different times in different regions across the country. In the South, these are associated with cold surge events, where an anticyclone is present in the Gulf of Mexico resulting in a strong Northerly flow across the Isthmus of Tehuantepec. In the North‐East, Easterly trade winds are responsible for the strongest wind events, whereas in the North‐West, it is the proximity of the North Pacific High. However, the weakest winds and lowest power production periods occur at the same times for all stations with the exception of Baja California Sur, meaning that low wind power production may be unavoidable at these times. The El Niño Southern Oscillation is found to influence wind speeds at some locations across Mexico at sub‐seasonal time‐scales. We report that statistically stronger wind speeds are observed during the Summer during El Niño months than during La Niña months for both sites in Chiapas and Oaxaca.
Interdecadal change in the relationship between interannual variation of the South China Sea monsoon trough and tropical Indo‐Pacific sea surface temperature
Authors: Zhang Zeyu , Jian Maoqiu , Gao Si , Qiao Yunting 
Published: September 2020

AbstractThe South China Sea monsoon trough (SCSMT) presents remarkable year‐to‐year variability, which exerts great influences on the summer climate over the South China Sea and surrounding regions. The variation of SCSMT may be forced by the tropical Indo‐Pacific sea surface temperature anomalies (SSTAs). The relationship between interannual variability of the SCSMT and the SSTA in tropical Indo‐Pacific oceans experienced several interdecadal changes during 1958–2019, namely around the late 1970s, early 1990s, and mid‐2000s, respectively. In epoch 1 (1958–1977), the significant SSTA pattern associated with the weakening of the SCSMT features the warming in the eastern tropical Indian Ocean (TIO) and the Maritime Continent (MC) which contributes to interannual variation of the SCSMT via inducing anomalous local meridional circulation. In epoch 2 (1978–1992), there is strong warming in the whole Indian Ocean basin which induces southwest–northeast vertical circulation anomalies and excites warm Kelvin wave in tropospheric atmosphere, leading to the weakening of the SCSMT. The SSTA in epoch 3 (1993–2003) features significant warming in the eastern TIO and MC which influences the SCSMT via abnormal meridional circulation and Kelvin wave, and weak cooling in the central Pacific which partly contributes to the weakening of the SCSMT via Rossby wave response. The SSTA pattern in epoch 4 (2004–2014) is similar to that in epoch 3, while the warming in the MC is weaker with insignificant meridional circulation and Kelvin‐wave response, and the most significant feature is the cooling in the central to eastern Pacific (CEP) with strong Rossby wave response. These results suggest that, during different epochs, interannual variability of the SCSMT is modulated by SSTA in different key areas through different mechanisms, and the key area shifts eastward from the TIO to the CEP with time.
Ag and Au nanostructures for surface‐enhanced Raman spectroscopy of Mospilan 20 SP (acetamiprid)
Authors: Atanasov Petar Asenov , Nedyalkov Nikolay N. , Fukata Naoki , Jevasuwan Wipakorn 
Published: September 2020

AbstractThe paper describes the preparation of advanced Ag and Au nanostructures via thermal deposition on three gradual grades of microabrasive processed (100) SiO2 substrates and the investigation of their morphology and optical properties. The quartz substrates were manually dry scratched in advance with three grades (0.1, 0.5, or 1 μm) of diamond supper‐abrasive slurry coated on high precision polyester film. The deposition of Ag or Au was first applied, and then the films were laser annealed. The as‐prepared nanostructures were used for surface‐enhanced Raman spectroscopy analyses of neonicotinoid insecticide Mospilan 20 SP, which contains acetamiprid, in quantities much smaller than that usually applied in the agricultural medicine. The efficiency of the fabricated advanced structures was studied using the finite difference time domain method. The limit of detection of Mospilan 20 SP (acetamiprid) was estimated to be about 40 nM, and the enhancement factor of polished quartz was about 6.6 × 103. This study of harmful pollutant in small or residue quantities is very important in order to preserve the honey bees' health and thus for conservation of the environment.
A novel chromatographic separation method for rapid enrichment and isolation of novel flavonoid glycosides from Sphaerophysa salsula
Authors: Wang Weidong , Dang Jun , Shao Yun , Jiang Lei , Liu Zenggen , Mei Lijuan , Tao Yanduo 
Published: September 2020

AbstractFlavonoid glycosides exist widely in medicine herbs and often used as nutraceuticals because of their excellent bioactivity and low toxicity. For accurate quality control and bioactivity assessment of Sphaerophysa salsula, a rapid and productive method to isolate flavonoid glycosides is needed. Therefore, this work reports the development of a novel comprehensive strategy based on an online middle‐pressure chromatography and preparative high‐performance liquid chromatography for rapid enrichment and separation of flavonoid glycosides from S. salsula. First, the flavonoid glycosides were enriched using an online middle‐pressure chromatographic column containing stationary middle chromatogram isolated phase. During this process, the high‐volume injection of the extracting solution was realized by an empty precolumn positioned before the main chromatographic tower. Then, the compounds were separated through preparative high‐performance liquid chromatography with Megress C18. As a result, one new flavonol 3‐O‐glycoside (2) and two known flavonol 3‐O‐glycosides (1, 3) were targetedly isolated from S. salsula. The content of compounds 1–3 in S. salsula was 0.09, 0.11, and 0.18 wt%, respectively. Comparing to traditional enrichment and separation methods, our technique offers significantly shorter sample pretreatment time as well as high reproducibility. We believe that our separation method has a strong potential to be used for the processing of other medicinal plants.
Chemical profiling of Honghua Xiaoyao tablet and simultaneous determination of its quality markers by liquid chromatography–tandem mass spectrometry combined with chemometrics methods
Authors: Mi Rui , Li Xiaofeng , Zhang Zhen , Cheng Taofang , Tian Saisai , Xu Xike , Zhang Yuhao , Yuan Wenlin , Ye Ji , Liu Li , Zhang Xinrong 
Published: September 2020

AbstractDiscovering marker components of traditional Chinese medicine formulas is challenging because of the hundreds of components they inherently contain. This study first proposed a reliable and validated method for the comprehensive profiling of chemical constituents in Honghua Xiaoyao tablet by using high‐performance liquid chromatography coupled with mass spectrometry. After searching within the in‐house library, a total of 55 constituents were unambiguously characterized or tentatively identified through reference standards and by comparing mass spectrometry data with literature values. Quantitative analysis of 14 compounds, which were selected as the quality marker components based on a serum pharmacochemistry study, has been performed by triple‐quardrupole mass spectrometry technique. Multiple chemometric methods, including principal components analysis and hierarchical cluster analysis, were subsequently used to analyze the quantitative results, classify samples from three manufacturers, and distinguish the analytical markers. In method validation results, 14 quality marker compounds have shown good linearity (R2 ≥ 0.9965) with a relative wide concentration range and acceptable recovery at 98.39–102.46%. The proposed approach provides the chemical evidence for revealing the material basis of Honghua Xiaoyao tablet, and establishes a reliable statistical analysis‐based strategy of quality marker investigation for controlling its quality.