bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Phosphate Binders and a Dietary Iron Supplement on the Pharmacokinetics of a Single Dose of Vadadustat in Healthy Adults
Authors: Paulson Susan K. , Martinez Jimena , Sawant Rishikesh , Burke Steven K. , Chavan Ajit 
Published: February 2022

AbstractVadadustat is a hypoxia‐inducible factor prolyl‐hydroxylase inhibitor being developed for the treatment of anemia in patients with chronic kidney disease. Sequelae of chronic kidney disease include hyperphosphatemia and anemia, which are frequently treated with phosphate binders and iron supplements, respectively. Two studies evaluating the pharmacokinetics, safety, and tolerability of a single oral dose of vadadustat coadministered with a phosphate binder or iron supplement were conducted in healthy adult participants. In study 1, 54 healthy women and men were administered vadadustat (300 mg) alone and 1 hour before, concurrently with, or 2 hours after a phosphate binder (sevelamer carbonate 1600 mg, calcium acetate 1334 mg, or ferric citrate 2000 mg). In study 2, 10 healthy men were administered vadadustat (450 mg) alone and concomitantly with the oral iron supplement ferrous sulfate (325 mg [equivalent to 65 mg of elemental iron]). Vadadustat exposure was reduced by coadministration with sevelamer carbonate, calcium acetate, ferric citrate, or ferrous sulfate. Geometric least squares mean ratios for area under the concentration‐time curve from time 0 to infinity were reduced 37% to 55% by phosphate binders and 46% by ferrous sulfate. However, when vadadustat was administered 1 hour before phosphate binders, 90% confidence intervals for vadadustat exposure were within the no‐effect boundaries of +50% to –33%, indicating that drug‐drug interactions can be reduced by administering vadadustat 1 hour before phosphate binders. Vadadustat was well tolerated when administered in conjunction with phosphate binders or an iron supplement.
Generation of Tumor Spheroids to Evaluate T Cell and NK Cell Cytotoxicity
Authors: Poggi Alessandro 
Published: February 2022

AbstractTumor cell spheroids are one of the three‐dimensional (3D) culture systems that can be used to study the features of tumor cells in a more physiologic condition. Indeed, this 3D culture system has been validated in preclinical studies to select anticancer drugs. Tumor cell spheroids can be obtained through employing different procedures, and here I describe in detail how to obtain spheroids from tumor cell lines of colorectal carcinoma (CRC). I analyze the procedures employed to evaluate the phenotype and growth of tumor cells in this 3D culture system. Also, interaction with immune cells is considered. Indeed, it is relevant to define whether the antitumor effects exerted by different cytotoxic lymphocyte subsets are similar when tumor cells are used either as cells adherent to a plastic substrate or floating spheroids. To obtain optimal results in this complex system, some parameters must be considered, such as those related to poorly defined experimental variables including biological and biophysical features of tumor cell lines and the quality (purity and time to use after generation) of antitumor effector lymphocyte subsets. Also, I describe in detail the methods to generate these lymphocyte subsets and to characterize their cytotoxic potential and effectiveness in killing tumor cells. Human natural killer cells and T lymphocytes expressing the γδ T cell receptor (in particular Vδ2 T cells) are considered among the cytotoxic lymphocyte populations. Eventually, it should be possible to obtain reliable and feasible results to study the molecular mechanisms involved in recognition and killing of CRC spheroids exerted by effector lymphocytes. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.Basic Protocol 1: Generation of tumor cell spheroidsBasic Protocol 2: Evaluation of ATP content of spheroidsBasic Protocol 3: Evaluation of antigen expression by cell spheroidsBasic Protocol 4: Generation of effector lymphocytesBasic Protocol 5: Coculture of spheroids and lymphocytesBasic Protocol 6: Evaluation of lymphocyte cytotoxicity using crystal violet staining
Quantitative trait loci mapping reveals the complexity of adult plant resistance to leaf rust in spring wheat ‘Copio’
Authors: Rauf Yahya , Lan Caixia , Randhawa Mandeep , Singh Ravi P. , Huerta‐Espino Julio , Anderson James A. 
Published: February 2022

AbstractThe spring wheat (Triticum aestivum L.) line ‘Copio’ has exhibited high level of adult plant resistance (APR) to the leaf rust (Puccinia triticina) pathogen in Mexico during field evaluations. To elucidate the genetic basis of leaf rust resistance in Copio, 176 F4‐derived F6‐recombinant inbred lines (RILs) from a cross of wheat lines ‘Apav’ and Copio were phenotyped in the field for two seasons in the United States and Mexico. A total of 762 genotyping‐by‐sequencing (GBS) single nucleotide polymorphic (SNP) markers were used to develop linkage maps. Composite interval mapping identified seven quantitative trait loci (QTL), all contributed by Copio. Three QTL on chromosome arms 1BL (QLr.umn‐1B), 2AS (QLr.umn‐2A), and 3BS (QLr.umn‐3B) were consistently expressed across all four environments. The QTL on 1BL represents Lr46, which is a pleiotropic APR gene, while the QTL on 2AS is colocated to the Lr37 gene in the 2NS/2AS translocation fragment. The QTL on 3BS, mapped to the Sr2/Yr30/Lr27 genomic region, is more likely to be a unique locus conferring APR to leaf rust races because all phenotyping environments had Lr27 virulent pathotypes. Moreover, the functionality of Lr27 is complimented by Lr31 on chromosome 4BS, which is lacking in both parents. Marker haplotypes identified seven RILs carrying a combination of resistance alleles at all three loci. This combination reduced leaf rust coefficient of infection up to 52 and 36% in the Mexican and U.S. environments, respectively. This study reports the complex genetic mechanism of APR to leaf rust in Copio and its importance as a potential resistance source for gene pyramiding through recombination breeding.
Protein disulfide isomerase a4 promotes lung cancer development via the Stat3 pathway in stromal cells
Authors: Chen Tzung‐Yan , Yang Chun‐Yen , Yang Meng‐Ting , Kuo Tien‐Fen , Chang Cicero Lee‐Tian , Chen Chih‐Li , Lee Tsung‐Han , Yang Greta , Yang Wen‐Chin , Chiu Ching‐Feng , Yu Alex Yang‐Hao 
Published: February 2022

AbstractBackgroundProtein disulfide isomerases a4 (Pdia4) is known to be involved in cancer development. Our previous publication showed that Pdia4 positively promotes cancer development via its inhibition of procaspase‐dependent apoptosis in cancer cells. However, nothing is known about its role in the cancer microenvironment.ResultsHere, we first found that Pdia4 expression in lung cancer was negatively correlated with patient survival. Next, we investigated the impact of host Pdia4 in stromal cells during cancer development. We showed that Pdia4 was expressed at a low level in stromal cells, and this expression was up‐regulated akin to its expression in cancer cells. This up‐regulation was stimulated by tumour cell‐derived stimuli. Genetics studies in tumour‐bearing wild‐type and Pdia4–/– mice showed that host Pdia4 promoted lung cancer development in the mice via cancer stroma. This promotion was abolished in Rag1–/– mice which lacked T and B cells. This promotion could be restored once T and B cells were added back to Rag1–/– mice. In addition, host Pdia4 positively regulated the number and immunosuppressive function of stromal cells. Mechanistic studies showed that host Pdia4 positively controlled the Stat3/Vegf pathway in T and B lymphocytes via its stabilization of activated Stat3 in a Thioredoxin‐like domain (CGHC)‐dependent manner.ConclusionsThese findings identify Pdia4 as a possible target for intervention in cancer stroma, suggesting that targeting Pdia4 in cancer stroma is a promising anti‐cancer approach.
Leukemia inhibitory factor receptor homodimerization mediated by acetylation of extracellular lysine promotes prostate cancer progression through the PDPK1/AKT/GCN5 axis
Authors: Ding Yufeng , Chi Honggang , Shao Jialiang , Shi Tiezhu , Yu Hua , Wang Xiang , Wang Xiongjun 
Published: February 2022

AbstractBackgroundProstate cancer (PCa), an inert tumour, has a long progression period, but valid biomarkers and methods for effectively and sensitively monitoring PCa progression are lacking, prompting us to identify new predictors for diagnosis and prognosis. Posttranslational modifications characterizing receptor activation are considered potentially strong indicators of disease progression.MethodsThe posttranscriptional regulation of leukaemia inhibitory factor receptor (LIFR) and its novel downstream signalling activity in PCa were studied using liquid mass spectrometry, genetically engineered mouse (GEM) models, organoid assays, lentivirus packaging, infection and stable cell line construction.ResultsIn this study, the level of acetylated K620 on LIFR in its extracellular domain was shown to predict the progression and prognosis of PCa. In PCa cells, LIFR‐K620 acetylation is reversibly mediated by GCN5 and SIRT2. GEM experiments and organoid assays confirmed that the loss of LIFR‐K620 acetylation inhibits PCa progression. Mechanistically, K620 acetylation facilitates LIFR homodimerization and subsequently promotes LIFR‐S1044 phosphorylation and activation, which further recruits PDPK1 to activate AKT signalling and sequentially enhances the GCN5 protein level to sustain the protumour level of LIFR‐K620 acetylation by preventing GCN5 degradation via CRL4Cdt2 E3 ligase.ConclusionsAcetylation of extracellular K620 on LIFR reinforces its homodimerization and integrates the activities of PDPK1, AKT, GSK3β and GCN5 to form a novel positive feedback loop in PCa; this modification is thus a promising biomarker for monitoring PCa progression.
A dual‐band circular patch antenna using hexagon‐shaped slots
Authors: Krishnan Thiyagarajan , Sennan Sankar , Ravi Vinayakumar , Harshavardhan reddy Dwarakacharla 
Published: February 2022

SummaryThis paper presents the design of a dual‐band circular patch antenna for the application requirements of wireless handheld devices and various wireless sensor modules operating in WiMax and 5G NR Bands. The design originated from a single‐band conventional circular patch antenna and ended up with a dual‐band circular patch. A novel hexagon‐shaped slot was preferred to achieve dual‐band performance in the circular patch antenna. The simulation level performance of the antenna is verified using the Advanced Design System 2019 tool. An FR4 material with a height of 1.6 mm is selected as a substrate for the patch antennas. The return loss and radiation pattern behaviour of the patch antennas are measured using a network analyser and an anechoic chamber. The fabricated prototype achieves dual‐band performance at 3.47 and 6.96 GHz. Simulated and measured results show that the proposed hexagonal‐shaped slot in the circular patch provides a dual‐band behaviour.
Experimentelle Untersuchungen zum Out‐of‐Plane‐Verhalten von Mauerwerkswänden
Authors: Helm Lukas , Sadegh‐Azar Hamid , Schüßler Jan , Teutsch Roman 
Published: February 2022

AbstractMauerwerk besitzt sehr gute Eigenschaften zum vertikalen Lastabtrag, dagegen können horizontale Lasten z. B. durch Erdbeben, insbesondere quer zur Ebene (Out of Plane, Plattenschub), nur begrenzt aufgenommen werden. Das Out‐of‐Plane‐Verhalten von unbewehrten Mauerwerkswänden ist von einer Vielzahl an Einflussfaktoren abhängig und aufgrund der starken Nichtlinearität sehr komplex. Trotz der baupraktischen Relevanz hat sich in Literatur und Normung kein einheitliches Modell zur Berechnung der Tragfähigkeit etabliert. In diesem Beitrag werden Rütteltischversuche mit Ziegelmauerwerk zur Untersuchung des Out‐of‐Plane‐Verhaltens von einachsig spannenden unbewehrten Mauerwerkswänden vorgestellt und die wesentlichen Ergebnisse aufgeführt. Weiterhin wird ein analytisches Ingenieurmodell zur Bestimmung der Tragfähigkeit unter Berücksichtigung der maßgebenden Parameter mithilfe der Versuche verifiziert.
Vertikale Begrünung mit UNIKA‐Pflanzsteinen – Hintergründe zur Anwendung, Bemessung und Konstruktion
Authors: Brinkmann Maximilian , Armenat Jannick 
Published: February 2022

AbstractDer UNIKA‐Pflanzstein ist ein innovativer Mauerstein, welcher es ermöglicht, freistehende Mauerwerkswände sowie Vorsatzschalen von zweischaligem Mauerwerk als vertikale Begrünungsflächen zu nutzen. Durch die vielfältigen Einsatzmöglichkeiten des Pflanzsteins können nicht nur architektonische Akzente gesetzt, sondern auch Beiträge zur Luftreinigung und Temperaturregelung im städtischen Raum geleistet werden. Da der Pflanzstein aufgrund seiner außergewöhnlichen Geometrie nicht nach den Regelungen des Eurocode 6 bemessen werden kann, ist die Nachweisführung innerhalb einer allgemeinen Bauartgenehmigung mithilfe eines anwenderfreundlichen Tabellenverfahrens geregelt. Der nachfolgende Beitrag erläutert relevante Hintergründe des Bemessungskonzepts und gibt sowohl Hinweise für die Anwendung als auch für die Konstruktion von vertikalen Begrünungsflächen aus Pflanzsteinen.
Investigations into the stability of 17 psychoactive drugs in a “simulated postmortem blood” model
Authors: Castle Jared W. , Butzbach Danielle M. , Reith Frank , Walker G. Stewart , Lenehan Claire E. , Costello Samuel P. , Kirkbride K. Paul 
Published: February 2022

AbstractIn the postmortem environment, some drugs and metabolites may degrade due to microbial activity, even forming degradation products that are not produced in humans. Consequently, underestimation or overestimation of perimortem drug concentrations or even false negatives are possible when analyzing postmortem specimens. Therefore, understanding whether medications may be susceptible to microbial degradation is critical in order to ensure that reliable detection and quantitation of drugs and their degradation products is achieved in toxicology screening methods. In this study, a “simulated postmortem blood” model constructed of antemortem human whole blood inoculated with a broad population of human fecal microorganisms was used to investigate the stability of 17 antidepressant and antipsychotic drugs. Microbial communities present in the experiments were determined to be relevant to postmortem blood microorganisms by 16S rRNA sequencing analyses. After 7 days of exposure to the community at 37°C, drug stability was evaluated using liquid chromatography coupled with diode array detection (LC‐DAD) and with quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS). Most of the investigated drugs were found to be stable in inoculated samples and noninoculated controls. However, the 1,2‐benzisothiazole antipsychotics, ziprasidone and lurasidone, were found to degrade at a rate comparable with the known labile control, risperidone. In longer experiments (7 to 12 months), where specimens were stored at −20°C, 4°C, and ambient temperature, N‐dealkylation degradation products were detected for many of the drugs, with greater formation in specimens stored at −20°C than at 4°C.
Does the punishment fit the crime? Consequences and diagnosis of misspecified detection functions in Bayesian spatial capture–recapture modeling
Authors: Dey Soumen , Bischof Richard , Dupont Pierre P. A. , Milleret Cyril 
Published: February 2022

AbstractSpatial capture–recapture (SCR) analysis is now used routinely to inform wildlife management and conservation decisions. It is therefore imperative that we understand the implications of and can diagnose common SCR model misspecifications, as flawed inferences could propagate to policy and interventions. The detection function of an SCR model describes how an individual's detections are distributed in space. Despite the detection function's central role in SCR, little is known about the robustness of SCR‐derived abundance estimates and home range size estimates to misspecifications. Here, we set out to (a) determine whether abundance estimates are robust to a wider range of misspecifications of the detection function than previously explored, (b) quantify the sensitivity of home range size estimates to the choice of detection function, and (c) evaluate commonly used Bayesian p‐values for detecting misspecifications thereof. We simulated SCR data using different circular detection functions to emulate a wide range of space use patterns. We then fit Bayesian SCR models with three detection functions (half‐normal, exponential, and half‐normal plateau) to each simulated data set. While abundance estimates were very robust, estimates of home range size were sensitive to misspecifications of the detection function. When misspecified, SCR models with the half‐normal plateau and exponential detection functions produced the most and least reliable home range size, respectively. Misspecifications with the strongest impact on parameter estimates were easily detected by Bayesian p‐values. Practitioners using SCR exclusively for density estimation are unlikely to be impacted by misspecifications of the detection function. However, the choice of detection function can have substantial consequences for the reliability of inferences about space use. Although Bayesian p‐values can aid the diagnosis of detection function misspecification under certain conditions, we urge the development of additional custom goodness‐of‐fit diagnostics for Bayesian SCR models to identify a wider range of model misspecifications.
A preliminary comparison of a songbird’s song repertoire size and other song measures between an urban and a rural site
Authors: Brewer Dustin E. , Fudickar Adam M. 
Published: February 2022

AbstractCharacteristics of birdsong, especially minimum frequency, have been shown to vary for some species between urban and rural populations and along urban–rural gradients. However, few urban–rural comparisons of song complexity—and none that we know of based on the number of distinct song types in repertoires—have occurred. Given the potential ability of song repertoire size to indicate bird condition, we primarily sought to determine if number of distinct song types displayed by Song Sparrows (Melospiza melodia) varied between an urban and a rural site. We determined song repertoire size of 24 individuals; 12 were at an urban (‘human‐dominated’) site and 12 were at a rural (‘agricultural’) site. Then, we compared song repertoire size, note rate, and peak frequency between these sites. Song repertoire size and note rate did not vary between our human‐dominated and agricultural sites. Peak frequency was greater at the agricultural site. Our finding that peak frequency was higher at the agricultural site compared to the human‐dominated site, contrary to many previous findings pertaining to frequency shifts in songbirds, warrants further investigation. Results of our pilot study suggest that song complexity may be less affected by anthropogenic factors in Song Sparrows than are frequency characteristics. Additional study, however, will be required to identify particular causal factors related to the trends that we report and to replicate, ideally via multiple urban–rural pairings, so that broader generalization is possible.
Do microplastics impair male dominance interactions in fish? A test of the vector hypothesis
Authors: Swank Ally , Blevins Kadijah , Bourne Abby , Ward Jessica 
Published: February 2022

AbstractMicroplastics (MPs) are widespread in aquatic environments and have become a critical environmental issue in recent years due to their adverse impacts on the physiology, reproduction, and survival of aquatic animals. Exposure to MPs also has the potential to induce sub‐lethal behavioral changes that can affect individual fitness, but these effects are understudied. Many plastic additives introduced during the manufacture of MPs are known endocrine‐disrupting chemicals (EDCs) that mimic the action of natural hormones, alter sexual and competitive behavior, and impair reproductive success in fish. In addition, EDCs and other aquatic contaminants may adhere to MPs in the environment, the latter of which may serve as transport vectors for these compounds (i.e., the vector hypothesis). In this study, we staged territorial contests between control males, and males exposed to virgin MP particles or to MPs previously immersed in one of two environmentally relevant concentrations of 17‐alpha ethinyl estradiol (EE2; 5 ng/L and 25 ng/L) to evaluate the independent and synergistic effects of exposure to MPs and a common environmental estrogen on male–male aggression and competitive territory acquisition in a freshwater fish, Pimephales promelas. Short‐term (30 days) dietary exposure to MPs did not impair the ability of males to successfully compete for and obtain a breeding territory. Overall levels of aggression in control and exposed males were also similar across trial series. These results help to fill a critical knowledge gap regarding the direct and indirect (vector‐borne) effects of MPs on the reproductive behavior of aquatic vertebrates in freshwater systems.
Chemistry of surface water, precipitation, throughfall, leaves, sediment, soil, and air near a gold mining region in Peru
Authors: Gerson Jacqueline R. , Szponar Natalie , Agostini Arianna , Alotaibi Rand , Bergquist Bridget , Chen Arabella , Fernandez Luis E. , Lansdale Kelsey N. , Lee Anne H. , Machicao Maria F. , Marchese Melissa J. , Topp Simon N. , Vega Claudia , Bernhardt Emily S. 
Published: February 2022

AbstractArtisanal and small‐scale gold mining (ASGM) is the primary global source of anthropogenic mercury (Hg) emissions and a large source of landscape change. ASGM occurs throughout the world, including in the Peruvian Amazon. This data set contains measurements of surface water, precipitation, throughfall, leaves, sediment, soil, and air samples from across the Madre de Dios region of Peru, in locations near and remote from ASGM. These data were collected to determine the fate and transport of Hg across the landscape. Samples were collected in 2018 and 2019. Data predominantly included total Hg and methyl Hg concentrations in surface water, precipitation, throughfall, leaves, sediment, soil, and air. Additional water and soil parameters were also measured to better characterize their chemistry. There are no copyright restrictions; please cite this data paper when the data are used in publication.