bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of sampling effort required to assess pollen species richness on pollinators using rarefaction
Authors: Nikkeshi Aoi , Hiraiwa Masayoshi K. , Ushimaru Atushi , Hoshizaki Kazuhiko , Makita Akifumi , Mizuki Inoue 
Published: February 2021

PremiseUnderstanding the flower visitation history of individual pollinators is key in the study of pollination networks, but direct tracking is labor intensive and, more important, does not capture information about the previous interactions of an individual. Therefore, a protocol to detect most of the pollen species on the body surfaces of an individual pollinator could elucidate its flower visitation history.Methods and ResultsUnder a microscope, we observed 6.0‐µL droplets from a sample solution (1.0 or 3.0 mL) containing pollen grains collected from individuals of six major pollinator functional groups. To clarify how many droplets need to be observed to detect all pollen species within the solution, we examined up to 10 droplets collected from each individual insect. Sample‐based rarefaction curve analyses of the data showed that we could detect ~90% of the pollen species and the plant–pollinator links in the networks by observing six droplets.ConclusionsThe rarefaction curve analysis for pollen‐on‐pollinator studies is a useful preliminary step for minimizing the time and labor required while maximizing the data on the flower visitation history of each individual pollinator and revealing any hidden flower–pollinator interactions.
CRISPR‐Cas12a System for Biosensing and Gene Regulation
Authors: Shi Yuyan , Fu Xiaoyi , Yin Yao , Peng Fangqi , Yin Xia , Ke Guoliang , Zhang Xiaobing 
Published: February 2021

AbstractClustered regularly interspaced short palindromic repeats (CRISPR) is a promising technology in the biological world. As one of the CRISPR‐associated (Cas) proteins, Cas12a is an RNA‐guided nuclease in the type V CRISPR‐Cas system, which has been a robust tool for gene editing. In addition, due to the discovery of target‐binding‐induced indiscriminate single‐stranded DNase activity of Cas12a, CRISPR‐Cas12a also exhibits great promise in biosensing. This minireview not only gives a brief introduction to the mechanism of CRISPR‐Cas12a but also highlights the recent developments and applications in biosensing and gene regulation. Finally, future prospects of the CRISPR‐Cas12a system are also discussed. We expect this minireview will inspire innovative work on the CRISPR‐Cas12a system by making full use of its features and advantages.
Total Synthesis of Panaginsene
Authors: Singh Vipin Kumar , Chakraborty Tushar Kanti 
Published: February 2021

AbstractThe total synthesis of panaginsene has been accomplished in 11 linear steps starting from methyl 3,3‐dimethyl‐5‐oxocyclopent‐1‐ene‐1‐carboxylate. The key steps are a Sharpless asymmetric epoxidation and Ti(III)‐mediated reductive epoxide opening‐radical cyclization to construct the chiral quaternary carbon stereocenter followed by a very challenging HWE olefination reaction on an 1,3‐keto aldehyde and a late stage McMurry olefination using low valent titanium to construct the highly constrained angular tetrasubstituted olefin in a five‐membered ring.
Across‐species meta‐analysis of dexamethasone pharmacokinetics utilizing allometric and scaling modeling approaches
Authors: Song Dawei , Jusko William J 
Published: February 2021

AbstractThe pharmacokinetic (PK) parameters of dexamethasone (DEX) in 11 species were collected from the literature and clearances (CL) assessed by basic allometric methods, and concentration–time course profiles were fitted using two PK models incorporating physiological or allometric scaling. Plots of log CL vs. log body weights (BW) correlated reasonably withR2 = 0.91, with a maximum ratio of actual to fitted CL of 6 (for pig). A minimal physiologically‐based pharmacokinetic (mPBPK) model containing blood and two lumped tissue compartments and integrated utilization of physiological parameters was compared to an allometric two‐compartment model (a2CM). The plasma PK profiles of DEX from 11 species were analyzed jointly, with the mPBPK model having conserved partition coefficients (Kp), physiologic blood and tissue volumes, and species‐specific CL values. The DEX PK profiles were reasonably captured by the mPBPK model for 9 of 11 species in the joint analysis with three fitted parameters (besides CL) including an overall tissue‐to‐plasma partition coefficient of 1.07. The a2CM with distribution CL and central and peripheral volumes scaled allometrically fitted the plasma concentration profiles similarly but required a total of six parameters (besides CL). Overall, the literature reported that DEX CL values exhibit moderate variability (mean = 0.64 L/h/kg; coefficient of variation = 105%), but distribution parameters were largely conserved across most species.
Enhancing protein A productivity and resin utilization within integrated or intensified processes
Authors: Brinkmann Alex , Elouafiq Sanaa 
Published: February 2021

AbstractRecent interest in continuous manufacturing of biologics has driven the development and evaluation of multicolumn chromatography systems to drive down resin costs by increasing productivity and maximizing resin utilization, especially for the expensive protein A capture step. Single‐pass tangential flow filtration can be used to reduce the volume of perfusion harvest, enabling a further increase in the productivity of the capture step by up to fivefold. However, there are expected to be practical limits for the productivity of the capture step, which must be determined based on the manufacturing batch size, duration, and frequency, especially as it relates to efficient utilization of the column lifetime. For short fed‐batch manufacturing campaigns, intensified capture processes may result in up to 82% lower resin consumption, while avoiding the long‐term storage of used resin. For perfusion processes and longer fed‐batch campaigns, it may be more efficient to operate at a lower productivity that enables the column lifetime to be routinely achieved and achieves the desired resin and buffer savings without introducing unnecessary process risk or complexity. An intensified batch capture process, “super‐batch,” will be compared as an alternative to multicolumn chromatography processes to achieve high productivity and resin utilization with a potentially simpler process.
Microbial fatty acid transport proteins and their biotechnological potential
Authors: Salvador López José M. , Van Bogaert Inge N. A. 
Published: February 2021

AbstractFatty acid metabolism has been widely studied in various organisms. However, fatty acid transport has received less attention, even though it plays vital physiological roles, such as export of toxic free fatty acids or uptake of exogenous fatty acids. Hence, there are important knowledge gaps in how fatty acids cross biological membranes, and many mechanisms and proteins involved in these processes still need to be determined. The lack of information is more predominant in microorganisms, even though the identification of fatty acids transporters in these cells could lead to establishing new drug targets or improvements in microbial cell factories. This review provides a thorough analysis of the current information on fatty acid transporters in microorganisms, including bacteria, yeasts and microalgae species. Most available information relates to the model organisms Escherichia coli and Saccharomyces cerevisiae, but transport systems of other species are also discussed. Intracellular trafficking of fatty acids and their transport through organelle membranes in eukaryotic organisms is described as well. Finally, applied studies and engineering efforts using fatty acids transporters are presented to show the applied potential of these transporters and to stress the need for further identification of new transporters and their engineering.
Spectrum–effect relationship between GC‐QTOF‐MS fingerprint and antioxidant, anti‐inflammatory activities of Schizonepeta tenuifolia essential oil
Authors: Bai Xi , Liu Liu , Zhang Junping , Chen Li , Wu Tao , Aisa Haji Akber , Maiwulanjiang Maitinuer 
Published: February 2021

AbstractSchizonepeta tenuifolia (Benth.) Briq, a traditional Chinese medicine, is an annual herbaceous plant that is widely distributed in China, Japan, and Korea. The essential oil (EO) of S. tenuifolia has antioxidant and anti‐inflammatory properties. However, the components contributing to its antioxidant and anti‐inflammatory activities remain unclear. This study was aimed at investigating the spectrum–effect relationship between GC–MS fingerprint and the antioxidant and anti‐inflammatory effects of S. tenuifolia EO. Here, the fingerprints of EO from 10 batches of S. tenuifolia from various sources were established using GC–MS, and the antioxidant and anti‐inflammatory bioactivities were evaluated using 2,2‐diphenyl‐1‐picrylhydrazyl and nitric oxide inhibitory assays, respectively. Finally, 13 common peaks were identified from 10 batches of S. tenuifolia by searching against the standard mass spectra in NIST 14 and comparing the literature retention index. The different sources of S. tenuifolia EO exhibit mild antioxidant activities and significant anti‐inflammatory effects. In particular, menthone (peak 3), isomenthone (peak 4), pulegone (peak 7), piperitone (peak 8), and β‐caryophyllene (peak 11) might be the dominant constituents responsible for the antioxidant and anti‐inflammatory activities of S. tenuifolia EO. This method may provide a time‐saving, convenient way to screen the potential effective components of S. tenuifolia EO.
Incidence of venous thromboembolism after standard treatment in patients with epithelial ovarian cancer in Korea
Authors: Shin Wonkyo , Lee Sanghee , Lim Myong Cheol , Jung Jipmin , Kim Hak Jin , Cho Hyunsoon 
Published: February 2021

AbstractBackgroundVenous thromboembolism (VTE) is a hospital‐associated severe complication that may adversely affect patient prognosis. In this study, we evaluated the incidence of VTE and its risk factors in patients with epithelial ovarian cancer (EOC).MethodsWe retrospectively analyzed the electronic health record data of 1268 patients with EOC who received primary treatment at the National Cancer Center, Korea between January 2007 and December 2017 to identify patients who developed VTE. Demographic, clinical, and surgical characteristics of these patients were ascertained. Competing risks analyses were performed to estimate the cumulative incidence of VTE according to the treatment type. The associations between putative risk factors and the incidence of VTE were evaluated using the Fine–Gray regression models accounting for competing risks of death.ResultsVTE was the most prevalent cardiovascular event, found in 9.6% (n = 122) of all patients. Of these VTE events, 115 (94.3%) occurred within 2 years of EOC diagnosis. Advanced cancer stage at diagnosis (distant vs. localized, hazards ratio [HR])= 14.49, p = 0.015) and extended hospital stay (≥15 days, HR =3.87, p = 0.004) were associated with the incidence of VTE. There was no significant difference in the cumulative incidence of VTE between primary cytoreductive surgery followed by adjuvant chemotherapy and neoadjuvant chemotherapy followed by interval cytoreductive surgery (HR =0.81, p = 0.390).ConclusionsApproximately 10% of patients with EOC were diagnosed with VTE, which was the most common cardiovascular disease found in this study. The assessment of VTE risks in patients with advanced‐stage EOC with an extended hospital stay is needed to facilitate adequate prophylactic treatment.
Psychogenic polydipsia in a female adolescent without a psychiatric background: A case report
Authors: Nauwynck Elise , Van De Maele Karolien , Vanbesien Jesse , Staels Willem , De Schepper Jean , Gies Inge 
Published: February 2021

AbstractPsychological stress is a risk factor for primary polydipsia in adolescents without psychiatric comorbidity. Taking a detailed family and social history can help to distinguish primary polydipsia from diabetes insipidus in adolescents with challenging presentations of polydipsia and polyuria.
High‐performance IO for seismic processing on the cloud
Authors: Guimarães Antonio , Lacalle Luis , Rodamilans Charles B. , Borin Edson 
Published: February 2021

SummaryMost of the applications in the seismology field rely on the processing of up to hundreds of terabytes of data and their performance is strongly affected by IO operations. In this article, we analyze the main file structures currently used to store seismic data and propose a new intermediate data structure to improve IO performance while still complying with established standards. We show that, throughout a common workflow in seismic data analysis, our IO performance gain greatly surpasses the overhead of translating data to the intermediate structure. This approach enables a speedup of up to 208 times in reading time when using classical standards (e.g., SEG‐Y) and our intermediate structure is up to 1.8 times more efficient than modern formats (e.g., ASDF). Considering cache‐friendly applications, our speedups over the direct use of SEG‐Y reach 8000 times. We also performed a cost analysis on the AWS cloud showing that, in our approach, HDDs can be 1.25 times more cost‐effective than SSDs.
Delineating the roles of Grhl2 in craniofacial development through tissue‐specific conditional deletion and epistasis approaches in mouse
Authors: de Vries Michael , Owens Harley G. , Carpinelli Marina R. , Partridge Darren , Kersbergen Ariena , Sutherland Kate D. , Auden Alana , Anderson Peter J. , Jane Stephen M. , Dworkin Sebastian 
Published: February 2021

AbstractBackgroundThe highly conserved Grainyhead‐like (Grhl) family of transcription factors play critical roles in the development of the neural tube and craniofacial skeleton. In particular, deletion of family member Grainyhead‐like 2 (Grhl2) leads to mid‐gestational embryonic lethality, maxillary clefting, abdominoschisis, and both cranial and caudal neural tube closure defects. These highly pleiotropic and systemic defects suggest that Grhl2 plays numerous critical developmental roles to ensure correct morphogenesis and patterning.ResultsHere, using four separate Cre‐lox conditional deletion models, as well as one genetic epistasis approach (Grhl2+/−;Edn1+/− double heterozygous mice) we have investigated tissue‐specific roles of Grhl2 in embryonic development, with a particular focus on the craniofacial skeleton. We find that loss of Grhl2 in the pharyngeal epithelium (using the ShhCre driver) leads to low‐penetrance micrognathia, whereas deletion of Grhl2 within the ectoderm of the pharynx (NestinCre) leads to small, albeit significant, differences in the proximal‐distal elongation of both the maxilla and mandible. Loss of Grhl2 in endoderm (Sox17‐2aiCre) resulted in noticeable lung defects and a single instance of secondary palatal clefting, although formation of other endoderm‐derived organs such as the stomach, bladder and intestines was not affected. Lastly, deletion of Grhl2 in cells of the neural crest (Wnt1Cre) did not lead to any discernible defects in craniofacial development, and similarly, our epistasis approach did not detect any phenotypic consequences of loss of a single allele of both Grhl2 and Edn1.ConclusionTaken together, our study identifies a pharyngeal‐epithelium intrinsic, non‐cell‐autonomous role for Grhl2 in the patterning and formation of the craniofacial skeleton, as well as an endoderm‐specific role for Grhl2 in the formation and establishment of the mammalian lung.
Low‐fat hypocaloric diet reduces neprilysin in overweight and obese human subjects
Authors: Henke Christine , Haufe Sven , Ziehl Doreen , Bornstein Stefan R. , Schulz‐Menger Jeanette , Heni Martin , Engeli Stefan , Jordan Jens , Birkenfeld Andreas L. 
Published: February 2021

AbstractAimsNeprilysin (NEP), a zinc metallopeptidase, degrades a variety of bioactive peptides including natriuretic peptides terminating their biological action on arterial blood pressure and natriuresis. Pharmacological inhibition of NEP reduces mortality in patients with heart failure with reduced ejection fraction. Physiological interventions reducing NEP levels are unknown in humans. Because obesity leads to increased NEP levels and increases the risk for heart failure, we hypothesized that weight loss reduces NEP concentrations in plasma and tissue.Methods and resultsWe randomized overweight to obese human subjects to a low‐fat or low‐carbohydrate hypocaloric 6 month weight loss intervention. Soluble NEP was determined in plasma, and NEP mRNA was analysed from subcutaneous adipose tissue before and after diet. Low‐fat diet‐induced weight loss reduced soluble NEP levels from 0.83 ± 0.18 to 0.72 ± 0.18 μg/L (P = 0.038), while subcutaneous adipose tissue NEP mRNA expression was reduced by both dietary interventions [21% (P = 0.0057) by low‐fat diet and 16% (P = 0.048) by low‐carbohydrate diet]. We also analysed the polymorphisms of the gene coding for NEP, rs9827586 and rs701109, known to be associated with plasma NEP levels. For both single‐nucleotide polymorphisms, minor allele carriers (A/A) had higher baseline plasma NEP levels (rs9827586: β = 0.53 ± 0.23, P < 0.0001; rs701109: β = 0.43 ± 0.22, P = 0.0016), and minor allele carriers of rs9827586 responded to weight loss with a larger NEP reduction (rs9827586: P = 0.0048).ConclusionsOur study identifies weight loss via a hypocaloric low‐fat diet as the first physiological intervention in humans to reduce NEP in plasma and adipose tissue. Specific single‐nucleotide polymorphisms further contribute to the decrease. Our findings may help to explain the beneficial effect of weight loss on cardiac function in patients with heart failure.
Anticancer Activity and Mode of Action of Copper(II)‐Bis(thiosemicarbazonato) Complexes with Pendant Nitrogen Heterocycles
Authors: Palma Elisa , Raposinho Paula , Campello Maria Paula Cabral , Belo Dulce , Guerreiro Joana F. , Alves Vítor , Fonseca Alexandra , Abrunhosa Antero J. , Paulo António , Mendes Filipa 
Published: February 2021

AbstractExploring the potential of bis(thiosemicarbazones) (BTSC), a new family of BTSC ligands derived from GTSM (glyoxal‐bis(N4‐methylthiosemicarbazonato) and respective CuIIBTSC complexes were synthesized. These complexes, having pendant nitrogen heterocycles, exhibited increased water‐solubility, lower lipophilicity at physiological pH and more negative Cu(II)/Cu(I) redox potential, when compared with the parental complex. The cytotoxic evaluation performed in a panel of cancer cells lines showed an important effect of the metal complexation, and furthermore correlated well with the cellular uptake of the compounds, which was determined using their 64Cu congeners. The radiolabelling of the complexes also allowed more detailed uptake studies, with the results suggesting an active transport or facilitated diffusion mechanism for the cellular uptake of 64CuGTSMpip and 64CuGTSMmor, with pendant piperidine and morpholine rings, respectively. Additionally, a comparative study with the corresponding Cu(II) complexes derived from ATSM (diacetyl‐bis(N4‐methylthiosemicarbazonato) that we have previously described, demonstrated a clear difference in their lysosomotropic properties in particular for the piperidine derivatives. From this study, CuGTSMpip emerged as the most promising compound to be further evaluated as an anticancer metallodrug.
Anthropogenic relief changes in a long‐lasting lignite mining area (‘Ville’, Germany) derived from historic maps and digital elevation models
Authors: Henselowsky Felix , Rölkens Julian , Kelterbaum Daniel , Bubenzer Olaf 
Published: February 2021

AbstractHumans constitute one of the main geomorphological agents in modern times. As an example, post‐mining regions represent a typical landscape of the Anthropocene. Strong relief modifications are particularly obvious with open pit mining. However, many existing mining areas are lacking detailed pre‐mining information for the quantification of anthropogenic relief changes, which is a considerable challenge in regions with historic mining activities.Here, the Ville (Rhenish lignite district, Germany) is used to quantify surface mining induced relief changes in one of the oldest and currently largest lignite districts in Europe. Historical maps from first geodetic mapping in 1893 enabled construction of a historic digital elevation model to quantify the relief changes in comparison to elevation data from 2000 and 2015. The vertical accuracy of the historic data is remarkably high, with relief differences < 2 m in areas not affected by mining. In total, 49.2% of the investigated area (184 km2) shows a relief deficit and 14.5% has positive relief differences. Absolute changes account for more than 80 m heightening (dumpsites of overburden) and lowering of the natural relief (pits). Besides these altitudinal changes, overall steeper slopes are significant for the new topography, but levelling exists likewise. The spatial variabilities are discussed in the context of the regional geology and the mining techniques.Undoubtedly, such large‐scale anthropogenic relief changes persist for a very long time and will last as a human legacy far into the future. Only the detailed reconstruction of the pre‐mining relief offers the ability to clarify the dimension of humans as geomorphological agents and to understand landscape perception. Due to the fact that the impact of open pit mining has such a large vertical and horizontal extension, their consideration as part of anthropogeomorphology can significantly contribute to support future Critical Zone research in the Anthropocene.
Replicating extensive brain structural heterogeneity in individuals with schizophrenia and bipolar disorder
Authors: Wolfers Thomas , Rokicki Jaroslav , Alnæs Dag , Berthet Pierre , Agartz Ingrid , Kia Seyed Mostafa , Kaufmann Tobias , Zabihi Mariam , Moberget Torgeir , Melle Ingrid , Beckmann Christian F. , Andreassen Ole A. , Marquand Andre F. , Westlye Lars T. 
Published: February 2021

AbstractIdentifying brain processes involved in the risk and development of mental disorders is a major aim. We recently reported substantial interindividual heterogeneity in brain structural aberrations among patients with schizophrenia and bipolar disorder. Estimating the normative range of voxel‐based morphometry (VBM) data among healthy individuals using a Gaussian process regression (GPR) enables us to map individual deviations from the healthy range in unseen datasets. Here, we aim to replicate our previous results in two independent samples of patients with schizophrenia (n1 = 94; n2 = 105), bipolar disorder (n1 = 116; n2 = 61), and healthy individuals (n1 = 400; n2 = 312). In line with previous findings with exception of the cerebellum our results revealed robust group level differences between patients and healthy individuals, yet only a small proportion of patients with schizophrenia or bipolar disorder exhibited extreme negative deviations from normality in the same brain regions. These direct replications support that group level‐differences in brain structure disguise considerable individual differences in brain aberrations, with important implications for the interpretation and generalization of group‐level brain imaging findings to the individual with a mental disorder.