bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking Penetrance and Transcription in DYT‐THAP1: Insights From a Human iPSC‐Derived Cortical Model
Authors: Baumann Hauke , Ott Fabian , Weber Joachim , Trilck‐Winkler Michaela , Münchau Alexander , Zittel Simone , Kostić Vladimir S. , Kaiser Frank J. , Klein Christine , Busch Hauke , Seibler Philip , Lohmann Katja 
Published: February 2021

AbstractBackgroundThe THAP1 gene encodes a transcription factor, and pathogenic variants cause a form of autosomal dominant, isolated dystonia (DYT‐THAP1) with reduced penetrance. Factors underlying both reduced penetrance and the disease mechanism of DYT‐THAP1 are largely unknown.MethodsWe performed transcriptome analysis on 29 cortical neuronal precursors derived from human‐induced pluripotent stem cell lines generated from manifesting and nonmanifesting THAP1 mutation carriers and control individuals.ResultsWhole transcriptome analysis showed a penetrance‐linked signature with expressional changes more pronounced in the group of manifesting (MMCs) than in nonmanifesting mutation carriers (NMCs) when compared to controls. A direct comparison of the transcriptomes in MMCs versus NMCs showed significant upregulation of the DRD4 gene in MMCs. A gene set enrichment analysis demonstrated alterations in various neurotransmitter release cycle pathways, extracellular matrix organization, and deoxyribonucleic acid methylation between MMCs and NMCs. When specifically considering transcription factors, the expression of YY1 and SIX2 differed in MMCs versus NMCs. Further, THAP1 was upregulated in the group of MMCs.ConclusionsTo our knowledge, this is the first report systematically analyzing reduced penetrance in DYT‐THAP1 in a human model using transcriptomes. Our findings indicate that transcriptional alterations during cortical development influence DYT‐THAP1 pathogenesis and penetrance. We reinforce previously linked pathways including dopamine and eukaryotic translation initiation factor 2 alpha signaling in the pathogenesis of dystonia including DYT‐THAP1 and suggest extracellular matrix organization and deoxyribonucleic acid methylation as mediators of disease protection. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Untargeted Metabolomics Reveals Elevated L‐Carnitine Metabolism in Pig and Rat Colon Tissue Following Red Versus White Meat Intake
Authors: Rombouts Caroline , Van Meulebroek Lieven , De Spiegeleer Margot , Goethals Sophie , Van Hecke Thomas , De Smet Stefaan , De Vos Winnok H. , Vanhaecke Lynn 
Published: February 2021

ScopeThe consumption of red and processed meat, and not white meat, associates with the development of various Western diseases such as colorectal cancer and type 2 diabetes. This work aims at unraveling novel meat‐associated mechanisms that are involved in disease development.Methods and ResultsA non‐hypothesis driven strategy of untargeted metabolomics is applied to assess colon tissue from rats (fed a high dose of beef vs. white meat) and from pigs (fed red/processed meat vs. white meat), receiving a realistic human background diet. An increased carnitine metabolism is observed, which is reflected by higher levels of acylcarnitines and 3‐dehydroxycarnitine (rats and pigs) and trimethylamine‐N‐oxide (rats). While 3‐dehydroxycarnitine is higher in HT29 cells, incubated with colonic beef digests, acylcarnitine levels are reduced. This suggests an altered response from colon cancer cell line towards meat‐induced oxidative stress. Moreover, metabolic differences between rat and pigs are observed in N‐glycolylneuraminic acid incorporation, prostaglandin, and fatty acid synthesis.ConclusionThis study demonstrates elevated (acyl)carnitine metabolism in colon tissue of animals that follow a red meat‐based diet, providing mechanistic insights that may aid in explaining the nutritional‐physiological correlation between red/processed meat and Western diseases.
Technical Note: Investigating internal–external motion correlation using fast helical CT
Authors: Lauria Michael , Navaratna Ruvini , O’Connell Dylan , Santhanam Anand , Lee Percy , Low Daniel A. 
Published: February 2021

PurposeTo quantify the use of anterior torso skin surface position measurement as a breathing surrogate.MethodsFourteen patients were scanned 25 times in alternating directions using a free‐breathing low‐mA fast helical CT protocol. Simultaneously, an abdominal pneumatic bellows was used as a real‐time breathing surrogate. The imaged diaphragm dome position was used as a gold standard surrogate, characterized by localizing the most superior points of the diaphragm dome in each lung. These positions were correlated against the bellows signal acquired at the corresponding scan times. The bellows system has been shown to have a slow linear drift, and the bellows‐to‐CT synchronization process had a small uncertainty, so the drift and time offset were determined by maximizing the correlation coefficient between the craniocaudal diaphragm position and the drift‐corrected bellows signal. The corresponding fit was used to model the real‐time diaphragm position. To estimate the effectiveness of skin surface positions as surrogates, the anterior torso surface position was measured from the CT scans and correlated against the diaphragm position model. The residual error was defined as the root‐mean‐square correlation residual with the breathing amplitude normalized to the 5th to 95th breathing amplitude percentiles. The fit residual errors were analyzed over the surface for the fourteen studied patients and reported as percentages of the 5th to 95th percentile ranges.ResultsA strong correlation was measured between the diaphragm motion and the abdominal bellows signal with an average residual error of 9.21% and standard deviation of 3.77%. In contrast, the correlations between the diaphragm position model and patient surface positions varied throughout the torso and from patient to patient. However, a consistently high correlation was found near the abdomen for each patient, and the average minimum residual error relating the skin surface to the diaphragm was 11.8% with a standard deviation of 4.61%.ConclusionsThe thoracic patient surface was found to be an accurate surrogate, but the accuracy varied across the surface sufficiently that care would need to be taken to use the surface as an accurate and reliable surrogate. Future studies will use surface imaging to determine surface patch algorithms that utilize the entire chest as well as thoracic and abdominal breathing relationships.
Assessment of carotid stiffness by measuring carotid pulse wave velocity using a single‐slice oblique‐sagittal phase‐contrast MRI
Authors: Heidari Pahlavian Soroush , Cen Steven Yong , Bi Xiaoming , Wang Danny J. J. , Chui Helena Chang , Yan Lirong 
Published: February 2021

PurposeIncreased arterial stiffness has been shown to be one of the earliest markers of cerebrovascular dysfunction. As a surrogate marker of arterial stiffness, pulse wave velocity (PWV) quantifications are generally carried out on central and peripheral arteries. The purpose of this study was to develop and evaluate an MRI approach to assess carotid stiffness by measuring carotid PWV (cPWV) using a fast oblique‐sagittal phase‐contrast MRI sequence.MethodsIn 29 volunteers, a single‐slice oblique‐sagittal phase‐contrast MRI sequence with retrospective cardiac gating was used to quantify blood velocity waveforms along a vessel segment covering the common carotid artery (CCA) and the internal carotid artery (ICA). The CCA‐ICA segment length was measured from a region of interest selected on the magnitude image. Phase‐contrast MRI‐measured velocities were also used to quantify the ICA pulsatility index along with cPWV quantification.ResultsThe mean value of cPWV calculated using the middle upslope area algorithm was 2.86 ± 0.71 and 3.97 ± 1.14 m/s in young and elderly subjects, respectively. Oblique‐sagittal phase‐contrast MRI–derived cPWV measurements showed excellent intrascan and interscan repeatability. cPWV and ICA pulsatility index were significantly greater in older subjects compared to those in the young subjects (P < .01 and P = .01, respectively). Also, increased cPWV values were associated with elevated systolic blood pressure (β = 0.05, P = .03).ConclusionThis study demonstrated that oblique‐sagittal phase‐contrast MRI is a feasible technique for the quantification of both cPWV and ICA pulsatility index and showed their potential utility in evaluating cerebroarterial aging and age‐related neurovascular disorders.
Characterization and compensation of inhomogeneity artifact in spiral hyperpolarized13C imaging of the human heart
Authors: Reed Galen D. , Ma Junjie , Park Jae Mo , Schulte Rolf F. , Harrison Crystal E. , Chen Albert P. , Pena Salvador , Baxter Jeannie , Derner Kelly , Tai Maida , Raza Jaffar , Liticker Jeff , Hall Ronald G. , Dean Sherry A. , Zaha Vlad G. , Malloy Craig R. 
Published: February 2021

PurposeThis study aimed to investigate the role of regionalinhomogeneity in spiral hyperpolarized13C image quality and to develop measures to alleviate these effects.MethodsField map correction of hyperpolarized13C cardiac imaging using spiral readouts was evaluated in healthy subjects. Spiral readouts with differing duration (26 and 45 ms) but similar resolution were compared with respect to off‐resonance performance and image quality. Anmap‐based image correction based on the multifrequency interpolation (MFI) method was implemented and compared to correction using a global frequency shift alone. Estimation of an unknown frequency shift was performed by maximizing a sharpness objective based on the Sobel variance. The apparent full width half at maximum (FWHM) of the myocardial wall on [13C]bicarbonate was used to estimate blur.ResultsMean myocardial wall FWHM measurements were unchanged with the short readout pre‐correction (14.1 ± 2.9 mm) and post‐MFI correction (14.1 ± 3.4 mm), but significantly decreased in the long waveform (20.6 ± 6.6 mm uncorrected, 17.7 ± 7.0 corrected,P= .007). Bicarbonate signal‐to‐noise ratio (SNR) of the images acquired with the long waveform were increased by 1.4 ± 0.3 compared to those acquired with the short waveform (predicted 1.32). Improvement of image quality was observed for all metabolites withcorrection.Conclusions‐map correction reduced blur and recovered signal from dropouts, particularly along the posterior myocardial wall. The low imageSNRof [13C]bicarbonate can be compensated with longer duration readouts but at the expense of increasedartifacts, which can be partially corrected for with the proposed methods.
A phantom study comparing radial trajectories for accelerated cardiac 4D flow MRI against a particle imaging velocimetry reference
Authors: Corrado Philip A. , Medero Rafael , Johnson Kevin M. , François Christopher J. , Roldán‐Alzate Alejandro , Wieben Oliver 
Published: February 2021

PurposeRadial sampling is one method to accelerate 4D flow MRI acquisition, making feasible dual‐velocity encoding (Venc) assessment of slow flow in the left ventricle (LV). Here, two radial trajectories are compared in vitro for this application: 3D radial (phase‐contrast vastly undersampled isotropic projection, PC‐VIPR) versus stack of stars (phase‐contrast stack of stars, PC‐SOS), with benchtop particle imaging velocimetry (PIV) serving as a reference standard.MethodsThe study contained three steps: (1) Construction of an MRI‐ and PIV‐compatible LV model from a healthy adult’s CT images. (2) In vitro PIV using a pulsatile flow pump. (3) In vitro dual‐Venc 4D flow MRI using PC‐VIPR and PC‐SOS (two repeat experiments). Each MR image set was retrospectively undersampled to five effective scan durations and compared with the PIV reference. The root‐mean‐square velocity vector difference (RMSE) between MRI and PIV images was compared, along with kinetic energy (KE) and wall shear stress (WSS).ResultsRMSE increased as scan time decreased for both MR acquisitions. RMSE was 3% lower in PC‐SOS images than PC‐VIPR images in 30‐min scans (3.8 vs. 3.9 cm/s) but 98% higher in 2.5‐min scans (9.5 vs. 4.8 cm/s). PIV intrasession repeatability showed a RMSE of 4.4 cm/s, reflecting beat‐to‐beat flow variation, while MRI had intersession RMSEs of 3.8/3.5 cm/s for VIPR/SOS, respectively. Speed, KE, and WSS were overestimated voxel‐wise in 30‐min MRI scans relative to PIV by 0.4/0.3 cm/s, 0.2/0.1 μJ/mL, and 36/43 mPa, respectively, for VIPR/SOS.ConclusionsPIV is feasible for application‐specific 4D flow MRI protocol optimization. PC‐VIPR is better‐suited to dual‐Venc LV imaging with short scan times.
Phenolic compound abundance in Pak choi leaves is controlled by salinity and dependent on pH of the leaf apoplast
Authors: Meyer Philipp , Förster Nadja , Huyskens‐Keil Susanne , Ulrichs Christian , Geilfus Christoph‐Martin 
Published: February 2021

AbstractOnset of salinity induces the pH of the leaf apoplast of Pak choi transiently to increase over a period of 2 to 3 hr. This pH event causes protein abundances in leaves to increase. Among them are enzymes that are key for the phenylpropanoid pathway. To answer the questions whether this short‐term salt stress also influences contents of the underlying phenylpropanoids and for clarifying as to whether the apoplastic pH transient plays a role for such a putative effect, Pak choi plants were treated with 37.5 mM CaCl2 against a non‐stressed control. A third experimental group, where the leaf apoplast of plants treated with 37.5 mM CaCl2, was clamped in the acidic range by means of infiltration of 5 mM citric acid/sodium citrate (pH 3.6), enabled validation of pH‐dependent effects. Microscopy‐based live cell imaging was used to quantify leaf apoplastic pH in planta. Phenolics were quantified shortly after the formation of the leaf apoplastic pH transient by means of HPLC‐DAD‐ESI‐MS. Results showed that different phenolic compounds were modulated at 150 and 200 min after the onset of chloride salinity. A pH‐independent reduction in phenolic acid abundance as well as an accumulation of phenolic acid:malate conjugates was quantified after 200 min of salt stress. However, at 150 min after the onset of salt stress, flavonoids were significantly reduced by salinity in a pH‐dependent manner. These results provided a strong indication that the pH of the apoplast is a relevant component for the short‐term metabolic response to chloride salinity.
Permafrost of the Oka Plateau (Eastern Sayan Ridge)
Authors: Alexeev Sergey V. , Alexeeva Ludmila P. , Vasil'chuk Yurij K. , Svetlakov Artem A. , Kulagina Natalia V. 
Published: February 2021

AbstractThis article presents the results of the first comprehensive study of permafrost and frost mounds in the Sentsa River valley on the Oka Plateau (Eastern Sayan Ridge). The lacustrine‐alluvial deposits are represented by clayey silts and silts with visible ice contents up to 90%. Ground ice mainly comprises bicarbonate calcium or bicarbonate magnesium, enriched in ammonium, aluminium, silicon, phosphorus, iron and zinc. Rare earth element content varies from 0.010 to 0.500 μg/L. The distribution of δ18O and δ2H in the ground ice to a depth of 20 m reflects repeated changes during the freezing of the deposit. The mean annual temperature of frozen rocks is −1.0°C. From 2016, mean annual ground temperatures have been observed to be gradually increasing at a depth of 1.0 m, which correlates with a stable, positive trend of the mean annual air temperatures on the Oka Plateau over the past 60 years. The species and quantitative composition of the palynospectra of the permafrost provides the evidence of repeated changes in the habitat area of forests, as well as changes in the sedimentation regime in the Holocene. According to 14C dating of the soil horizons in the upper parts of the frost mounds, after the emptying of the paleo‐lake, organic material intensely accumulated in the drained areas (from 0.5 to 0.2 ka) and ice‐mineral frost mounds began to form.
SuperGAG biopolymers for treatment of excessive bladder permeability
Authors: Towner Rheal A. , Greenwood‐Van Meerveld Beverley , Mohammadi Ehsan , Saunders Debra , Smith Nataliya , Sant Grannum R. , Shain Harrison C. , Jozefiak Thomas H. , Hurst Robert E. 
Published: February 2021

AbstractFew therapeutic options exist for treatment of IC/BPS. A novel high MW GAG biopolymer (“SuperGAG”) was synthesized by controlled oligomerization of CS, purified by TFF and characterized by SEC‐MALLS and 1H‐NMR spectroscopy. The modified GAG biopolymer was tested in an OVX female rat model in which bladder permeability was induced by a 10‐minute intravesicular treatment with dilute (1 mg/ml) protamine sulfate and measured by classical Ussing Chamber TEER measurements following treatment with SuperGAG, chondroitin sulfate, or saline. The effect on abrogating the abdominal pain response was assessed using von Frey filaments. The SuperGAG biopolymer was then investigated in a second, genetically modified mouse model (URO‐MCP1) that increasingly is accepted as a model for IC/BPS. Permeability was induced with a brief exposure to a sub‐noxious dose of LPS and was quantified using contrast‐enhanced MRI (CE‐MRI). The SuperGAG biopolymer restored impermeability to normal levels in the OVX rat model as measured by TEER in the Ussing chamber and reduced the abdominal pain response arising from induced permeability. Evaluation in the URO‐MCP1 mouse model also showed restoration of bladder impermeability and showed the utility of CE‐MRI imaging for evaluating the efficacy of agents to restore bladder impermeability. We conclude novel high MW SuperGAG biopolymers are effective in restoring urothelial impermeability and reducing pain produced by loss of the GAG layer on the urothelium. SuperGAG biopolymers could offer a novel and effective new therapy for IC/BPS, particularly if combined with MRI to assess the efficacy of the therapy.
Cross‐resistance, fitness costs, and biochemical mechanism of laboratory‐selected resistance to tenvermectin A in Plutella xylostella
Authors: Zhu Linying , Zhang Shaoyong , Lu Feng , Zhang Kui , Han Qunqi , Ying Qianwen , Zhang Xinwei , Zhang Cuilan , Zhou Shaa , Chen Anliang 
Published: February 2021

AbstractBACKGROUNDTenvermectin A is a new avermectin derivative that has good insecticidal and acaricidal effects. In order to study the resistance of Plutella xylostella to tenvermectin A, a sensitive strain (SS) and a laboratory‐selected tenvermectin A‐resistant strain (RS, 33.57‐fold) were used to evaluate cross‐resistance and fitness costs as well as to determine the resistance mechanism.RESULTSThere was no cross‐resistance with common pesticides except for moderate cross‐resistance with cypermethrin (resistance ratio = 10.26‐fold) observed in RS. The activities of metabolic enzymes were measured, and the results showed that mixed function oxidase (MFO) and carboxylate esterase (CarE) in RS increased significantly by 2.92‐ and 2.86‐fold, respectively, compared with SS. In addition, there was no obvious difference in glutathione‐S‐transferase (GST), which indicated that enhanced MFO and CarE activities may be the main mechanisms of detoxification. In the four typical resistance‐related genes, expression of GluCl (4.86‐fold), ABCC2 (3.85‐fold), and CYP6 (2.94‐fold) in RS were significantly promoted, but expression of GST was not. The clone and sequence of the PxGluClα subunit displayed six mutations that could lead to changes in the amino acid residues.CONCLUSIONHigh suitability related to tenvermectin A resistance was observed in RS, and it was found that the developmental stages of RS were significantly shortened and the survival rate of females was reduced. In addition, the mechanism of resistance to tenvermectin A may be regulated by the glutamate‐gated chloride channel, ATP‐binding cassette transporter, and MFO. In general, the study of resistance and biochemical mechanisms can provide beneficial and rational information for the management of resistance in P. xylostella.© 2021 Society of Chemical Industry
Representativity of cloud‐profiling radar observations for data assimilation in numerical weather prediction
Authors: Barker Howard W. , Gabriel Philip M. , Qu Zhipeng , Kato Seiji 
Published: February 2021

AbstractAn algorithm is presented that aims to enhance the use of satellite‐based cloud‐profiling radar (CPR) data for the purpose of NWP data assimilation. It resembles the EarthCARE mission's scene construction algorithm: off‐nadir passive radiances get spectrally matched with nadir passive radiances, and the latter's collocated CPR profile gets replicated at the former's location. This process gets repeated until all passive pixels that cover an NWP domain D have a proxy column of CPR data. Only domain‐averaged profiles of CPR reflectivity ⟨ZdB⟩ and cloud fraction Ac are sought after for NWP domains measuring, nominally, 25 × 25 km. If CPR measurements intersect D, then in addition to using just the intersecting values to represent ⟨ZdB⟩ and Ac, the full array of proxy values get used. This is referred to as local estimation. If, however, CPR measurements do not intersect D, but are not too distant, this is referred to as non‐local estimation; estimates of ⟨ZdB⟩ and Ac rest entirely on proxies. Current and planned satellite‐based CPRs have nadir‐pointing narrow fields‐of‐view, so it is difficult to see how to verify the algorithm with anything other than synthetic observations. Thus, it was assessed here with simulated cloudy atmospheres and 2D and 3D distributions of associated passive radiances and CPR reflectivities. In general terms, for local domains the algorithm performs slightly better than simply averaging intersecting CPR profiles. This at least demonstrates that the proxies are not detrimental. For non‐local domains, where there are no intersecting measurements to average, the algorithm appears to perform well enough to include two or three 25 × 25 km NWP domains either side of sequences of local domains.
Rubbing elbows with them: Building capacity in STEM through science and engineering fairs
Authors: Koomen Michele H. , Hedenstrom Mary N. , Moran Molly K. 
Published: February 2021

AbstractUsing social cultural career theory (SCCT) linked with tenets of equity, we examined the role of participation in science and engineering fairs (SEFs) on youth's science, technology, engineering, and mathematics (STEM) educational and career choices. We analyzed data for evidence of the SCCT constructs of self‐efficacy, interest, and learning experiences using constructs of Native American (NA), culturally responsive, and rural equitable pedagogies. Qualitative data included semi‐structured interviews, focus groups, practice presentations of SEF prtojects, classroom observations, and mentoring students. Quantitative data consisted of two surveys: STEM Semantics Survey and the Motivation Strategies for Learning Questionnaire. Qualitative results reveal how the teacher built self‐efficacy using equitable pedagogy by putting the students in control of their projects, created a network of experts in various science disciplines, developed a culture of mentorship that promoted belonging, and removed barriers for student participation by blending academics with culture for NA and rural mixed socioeconomic status students. She evoked asset‐based pedagogies that inspired students to further their education and go into STEM fields. Quantitative findings reveal former student's orientation to participation in science fair activities related to their high interests, perceptions of a challenge, curiosity, and emerging mastery, where students demonstrated high dispositions in science and engineering and self‐identified as STEM people. Implications include the use of SCCT, linked with equitable pedagogies to understand interest in STEM fields, mentoring, tapping into the expertise of local professionals to support development of projects, and navigating cultural barriers to provide access for underrepresented youth.