bluuebunny/crossref_metadata_2025 huggingface dataset:
Deletion of Alzheimer's disease‐associated CD33 results in an inflammatory human microglia phenotype
Authors: Wißfeld Jannis , Nozaki Ichiro , Mathews Mona , Raschka Tamara , Ebeling Christian , Hornung Veit , Brüstle Oliver , Neumann Harald
Published: February 2021

Genome‐wide association studies demonstrated that polymorphisms in the CD33/sialic acid‐binding immunoglobulin‐like lectin 3 gene are associated with late‐onset Alzheimer's disease (AD). CD33 is expressed on myeloid immune cells and mediates inhibitory signaling through protein tyrosine phosphatases, but the exact function of CD33 in microglia is still unknown. Here, we analyzed CD33 knockout human THP1 macrophages and human induced pluripotent stem cell‐derived microglia for immunoreceptor tyrosine‐based activation motif pathway activation, cytokine transcription, phagocytosis, and phagocytosis‐associated oxidative burst. Transcriptome analysis of the macrophage lines showed that knockout of CD33 as well as knockdown of the CD33 signaling‐associated protein tyrosine phosphatase, nonreceptor type 6 (PTPN6) led to constitutive activation of inflammation‐related pathways. Moreover, deletion of CD33 or expression of Exon 2‐deleted CD33 (CD33ΔE2/CD33m) led to increased phosphorylation of the kinases spleen tyrosine kinase (SYK) and extracellular signal‐regulated kinase 1 and 2 (ERK1 and 2). Transcript analysis by quantitative real‐time polymerase chain reaction confirmed increased levels of interleukin (IL) 1B, IL8, and IL10 after knockout of CD33 in macrophages and microglia. In addition, upregulation of the gene transcripts of the AD‐associated phosphatase INPP5D was observed after knockout of CD33. Functional analysis of macrophages and microglia showed that phagocytosis of aggregated amyloid‐β1‐42 and bacterial particles were increased after knockout of CD33 or CD33ΔE2 expression and knockdown of PTPN6. Furthermore, the phagocytic oxidative burst during uptake of amyloid‐β1‐42 or bacterial particles was increased after CD33 knockout but not in CD33ΔE2‐expressing microglia. In summary, deletion of CD33 or expression of CD33ΔE2 in human macrophages and microglia resulted in putative beneficial phagocytosis of amyloid β1‐42, but potentially detrimental oxidative burst and inflammation, which was absent in CD33ΔE2‐expressing microglia.
Resting cerebral oxygen metabolism exhibits archetypal network features
Authors: Hubbard Nicholas A. , Turner Monroe P. , Sitek Kevin R. , West Kathryn L. , Kaczmarzyk Jakub R. , Himes Lyndahl , Thomas Binu P. , Lu Hanzhang , Rypma Bart
Published: February 2021

Standard magnetic resonance imaging approaches offer high‐resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low‐frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO2). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies. Seventeen participants underwent 20 min of resting imaging during dual‐echo, pseudocontinuous arterial spin labeling, and blood‐oxygen‐level dependent (BOLD) signal acquisition. Participants also underwent a 10 min normocapnic and hypercapnic procedure. Brain‐wide, CMRO2low‐frequency fluctuations were subjected to graph‐based and voxel‐wise functional connectivity analyses. Results demonstrated that connections derived from resting CMRO2fluctuations exhibited complex, small‐world topological properties (i.e., high integration and segregation, cost efficiency) consistent with those observed in previous studies using functional and anatomical connectivity approaches. Voxel‐wise CMRO2connectivity also exhibited spatial patterns consistent with four targeted resting‐state subnetworks: two association (i.e., frontoparietal and default mode) and two perceptual (i.e., auditory and occipital‐visual). These are the first findings to support the use of calibration‐derived CMRO2low‐frequency fluctuations for detecting brain‐wide organizational properties typical of healthy participants. We discuss interpretations, advantages, and challenges in using calibration‐derived oxygen metabolism signals for examining the intrinsic organization of the human brain.
Regression dynamic causal modeling for resting‐state fMRI
Authors: Frässle Stefan , Harrison Samuel J. , Heinzle Jakob , Clementz Brett A. , Tamminga Carol A. , Sweeney John A. , Gershon Elliot S. , Keshavan Matcheri S. , Pearlson Godfrey D. , Powers Albert , Stephan Klaas E.
Published: February 2021

“Resting‐state” functional magnetic resonance imaging (rs‐fMRI) is widely used to study brain connectivity. So far, researchers have been restricted to measures of functional connectivity that are computationally efficient but undirected, or to effective connectivity estimates that are directed but limited to small networks. Here, we show that a method recently developed for task‐fMRI—regression dynamic causal modeling (rDCM)—extends to rs‐fMRI and offers both directional estimates and scalability to whole‐brain networks. First, simulations demonstrate that rDCM faithfully recovers parameter values over a wide range of signal‐to‐noise ratios and repetition times. Second, we test construct validity of rDCM in relation to an established model of effective connectivity, spectral DCM. Using rs‐fMRI data from nearly 200 healthy participants, rDCM produces biologically plausible results consistent with estimates by spectral DCM. Importantly, rDCM is computationally highly efficient, reconstructing whole‐brain networks (>200 areas) within minutes on standard hardware. This opens promising new avenues for connectomics.
Surgeon‐performed ultrasound with fine‐needle aspiration biopsy for the diagnosis of parotid gland tumors
Authors: Lanišnik Boštjan , Levart Primož , Čizmarevič Bogdan , Švagan Matija
Published: February 2021

Background

Ultrasound (US) with or without fine‐needle aspiration cytology (FNAC) are readily available and can offer in office and rapid diagnosis of parotid lumps.

Methods

We analyzed 398 of patients who underwent blind FNAC or US with FNAC performed by an operating head and neck surgeon. Specificity, sensitivity, as well as accuracy were calculated for US alone, FNAC alone, and US–FNAC combined.

Results

Nondiagnostic US‐guided FNAC rate was 3.1% and 7.2% for blind FNAC. With those cases removed, final accuracy for US alone in diagnosis of malignancy, pleomorphic adenoma (PA), and Warthin tumor (WT) were 90.8%, 81%, and 77.4% respectively. For US–FNAC accuracy for malignancy, PA, and WT were 92.1%, 94 0.8%, and 95.4% respectively.

Conclusion

US with FNAC is cost‐effective and rapid diagnostic tool and may help surgeon to deliver more accurate informed consent to a patient.
Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T-Cell Responses in a Mouse Model
Authors: Du Yanqin , Yan Hu , Zou Shi , Khera Tanvi , Li Jia , Han Meihong , Yang Xiaoli , Wang Baoju , Liu Jia , Sun Shuilin , Zheng Xin , Dittmer Ulf , Lu Mengji , Yang Dongliang , Wedemeyer Heiner , Wu Jun
Published: February 2021

Functional maturation of liver sinusoidal endothelial cells (LSECs) plays an important role in intrahepatic T-cell activation and control of viral infections. Natural killer (NK) cells have been reported to prompt the maturation of antigen-presenting cells (APCs), especially for dendritic cells (DCs), but the interaction between NK cells and LSECs is elusive. Here, we investigated whether and how NK cells are involved in regulating LSEC maturation and if this has a role in controlling hepatitis B virus (HBV) infection in a mouse model. A chronic HBV replication mouse model was established by hydrodynamic injection (HI) of 6 μg adeno-associated virus plasmid (pAAV)/HBV 1.2. The nucleotide-binding oligomerization domain-containing protein 1 (NOD1) ligand diaminopemelic acid (DAP) was imported into liver by HI at day 14 after plasmid injection. We found that HI of DAP recruited conventional NK cells (cNK) into the liver and promoted tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) production of NK cells in a chemokine (C-X-C motif) receptor 3 (CXCR3)-dependent manner. Importantly, the maturation of LSECs and the anti-HBV effects of DAP were impaired in CXCR3−/− mice; this possibly was associated with the decreased number of intrahepatic cNK cells. Consistently, depleting cNK cells but not liver-resident NK cells also impaired the maturation and antigen-presenting function of LSECs, which reduced intrahepatic HBV-specific T-cell responses and thus inhibited HBV clearance both in wild-type and in Rag1−/− mice. Moreover, TNF-α or IFN-γ stimulation as well as coculture with intrahepatic NK cells partly promoted LSEC phenotypic and functional maturation in vitro. Conclusion: NOD1-triggered NK cell activation may lead to the enhancement of intrahepatic T-cell responses by promoting maturation of LSECs through soluble cytokines and cell–cell contact, thereby controlling HBV replication and expression.

NK cells promote intrahepatic T cell responses by regulating LSEC maturation. The potential mechanisms by which NK cells regulate the maturation of LSECs may involve soluble cytokines as well as cell-cell contact. The recruitment and activation of conventional NK cells (cNK) cells after NOD1 activation depend on CXCR3 axis.
Variability of stream extents controlled by flow regime and network hydraulic scaling
Authors: Lapides Dana A. , Leclerc Christine D. , Moidu Hana , Dralle David N. , Hahm W. Jesse
Published: February 2021

Stream networks expand and contract through time, impacting chemical export, aquatic habitat, and water quality. Although recent advances improve prediction of the extent of the wetted channel network (L) based on discharge at the catchment outlet (Q), controls on the temporal variability of L remain poorly understood and unquantified. Here we develop a quantitative, conceptual framework to explore how flow regime and stream network hydraulic scaling factors co‐determine the relative temporal variability in L (denoted here as the total wetted channel drainage density). Network hydraulic scaling determines how much L changes for a change in Q, while the flow regime describes how Q changes in time. We compiled datasets of co‐located dynamic stream extent mapping and discharge to analyze all globally available empirical data using the presented framework. We found that although variability in L is universally damped relative to variability in Q (i.e., streamflow is relatively more variable in time than network extent), the relationship is elastic, meaning that for a given increase in the variability in Q, headwater catchments will experience greater‐than‐proportional increases in the variability of L. Thus, under anticipated climatic shifts towards more volatile precipitation, relative variability in headwater stream network extents can be expected to increase even more than the relative variability of discharge itself. Comparison between network extents inferred from the L‐Q relationship and blue lines on USGS topographic maps shows widespread underestimation of the wetted channel network by the blue line network.
Strive towards investment efficiency among Egyptian companies: Do board characteristics and information asymmetry matter?
Authors: Menshawy Ibrahim M. , Basiruddin Rohaida , Mohd‐Zamil Nor‐Aiza , Hussainey Khaled
Published: February 2021

This study examines the impact of the board of directors (BoD) characteristics, namely BoD independence, compensation, leadership, and CEO career concerns on investment efficiency, using information asymmetry as a mediator. Using a sample of 326 firm‐year observations of non‐financial firms listed in the EGX 100 Index of the Egyptian stock market from 2014 to 2018, we find that board independence, board compensation, and board leadership are negatively associated with inefficient investment and information asymmetry, whereas the opposite is true for CEO career concerns. Furthermore, a positive relationship between information asymmetry and inefficient investment is documented. Finally, we find that information asymmetry mediates the relationship between the three BoD characteristics (i.e., board independence, leadership, and compensation) and inefficient investment. Conversely, it does not interfere with the relationship between CEO career concerns and inefficient investment. These findings are consistent in both under‐investment and over‐investment scenarios and across the pooled sample. Our findings contribute to corporate governance and investment literature by addressing new relationships, providing empirical evidence from a one‐tier board model in developing countries, and offering a useful explanation for the inconsistent results in prior studies. These findings help regulators, investors, and policymakers realize the importance of BoD characteristics in mitigating information asymmetry and improving corporate investment efficiency.
Expression profiling and bioinformatics analysis of exosomal long noncoding RNAs in patients with myasthenia gravis by RNA sequencing
Authors: Lu Wei , Lu Yao , Wang Chun‐Feng , Chen Ting‐Ting
Published: February 2021

Background

Myasthenia gravis (MG) is an autoimmune disease mediated by acetylcholine receptor antibodies. Exosomes were shown to be involved in the immune modulation and autoimmune diseases. However, the expression and function of exosomal long noncoding RNAs (lncRNAs) in MG are still unclear.

Methods

We conducted high‐throughput sequencing to detect the lncRNA profiles of serum exosomes in 6 MG patients (2 grade I, 2 grade IIa, and 2 grade IIb) and 6 healthy controls (HC). Then, differentially expressed (DE) lncRNAs with the greatest difference between the MG and HC groups were selected for further quantitative real‐time polymerase chain reaction (qRT‐PCR) validation in additional 30 MG patients and 10 HC. The DE lncRNAs were used to construct the coding/noncoding network and perform enrichment analysis.

Results

We identified 378 significantly upregulated and 348 significantly downregulated lncRNAs in MG patients compared with HC. The top 5 lncRNAs (NR_104677.1, ENST00000583253.1, NR_046098.1, NR_022008.1, and ENST00000581362.1) were validated and shown to be significantly increased in the serum exosome of MG, and the expression level of NR_046098.1 significantly increased with the MG grading. Enrichment analysis showed that DE genes mainly participated in the basic biological regulation of MG and immune‐related pathways, such as autoimmune thyroid disease pathway and T‐cell receptor signaling pathway. A specific lncRNA‐miRNA‐mRNA regulatory network associated with the 5 lncRNAs, 14 MG‐related miRNAs and 30 mRNAs was constructed.

Conclusions

We conducted a comprehensive analysis of exosomal lncRNAs to reveal potential biomarkers for the MG diagnosis and severity assessment.
Pharmacokinetics of Ribociclib in Subjects With Hepatic Impairment
Authors: Samant Tanay S. , Yang Shu , Miller Michelle , Ji Yan
Published: February 2021

Ribociclib is an orally bioavailable, highly selective small‐molecule inhibitor of cyclin‐dependent kinases 4 and 6. It is currently approved for the treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer with a starting dose of 600 mg. Both in vitro and in vivo studies indicate that ribociclib is primarily metabolized in the liver via cytochrome P450 3A4. A phase 1, open‐label, multicenter, parallel cohort, single‐oral‐dose study was conducted to characterize the pharmacokinetics of ribociclib in subjects with varying degrees of hepatic impairment as measured by the Child‐Pugh classification. Subjects were divided into 4 cohorts determined by their degree of hepatic impairment: normal, mild, moderate, or severe. Thirty subjects were enrolled and received a single 400 mg dose of ribociclib. Ribociclib exposure was similar in subjects with mild hepatic impairment compared with subjects with normal hepatic function, but was increased by approximately 30% in subjects with moderate and severe hepatic impairment. At a dose of 400 mg, ribociclib was generally well tolerated in all subjects regardless of the level of hepatic impairment. These results indicate that no dose adjustment (recommended dose of ribociclib is 600 mg daily, 3 weeks on and 1 week off) is necessary for patients with mild hepatic impairment but that a reduced dose of 400 mg daily, 3 weeks on and 1 week off in patients with moderate or severe hepatic impairment is recommended.
The role of college knowledge and proactive behavior on participation in cocurricular activities
Authors: Millunchick Joanna Mirecki , Brennan‐Wydra Emma , Henderson Trevion , Johnson Aaron , Finelli Cynthia J.
Published: February 2021

Background

Demographic characteristics are known to influence participation in cocurricular activities. Less studied are the effects of other background characteristics.

Purpose

We hypothesize that considering college knowledge and students' proactive behaviors in tandem with demographics provides better models for predicting such participation.

Method

We developed a questionnaire and administered it to 3,618 domestic third‐ and fourth‐year undergraduate engineering students at a large public R1 Midwestern university, yielding 860 responses. Logistic regression models predicting five types of cocurricular participation were constructed with demographic characteristics, college knowledge, and proactive behaviors in all combinations as predictors.

Results

Four of five types of cocurricular participation were better modeled using factors beyond demographics. Two were better modeled using only proactive behavior as predictors and two were better modeled using demographics in combination with either college knowledge or proactive behavior. Only one type of participation could be best predicted by demographics alone.

Conclusions

These findings contribute quantitative evidence establishing relationships between participation in engineering cocurricular activities and a wider range of factors than previously reported. Furthermore, they provide guidance for creating intervention programs because, unlike demographics, college knowledge and proactive behavior can be shaped by either the individual or the institution.
Conditional cash transfers, female bargaining power and parental labour supply
Authors: Novella Rafael , Ripani Laura , Vazquez Claudia
Published: February 2021

Recent empirical evidence shows that conditional cash transfer (CCT) programmes do not have an aggregate effect on the adult labour supply. However, little attention has been paid to the role of other intrahousehold dynamics. This paper examines how the parental labour supply response to CCT programmes varies with the bargaining power structure of households. We analyse a randomized experimental CCT design from rural areas of Honduras (PRAF) and found that women with more bargaining power in the household are four percentage points less likely to be employed than other women.
Seizure phenotype in CLN3 disease and its relation to other neurologic outcome measures
Authors: Abdennadher Myriam , Inati Sara , Soldatos Ariane , Norato Gina , Baker Eva H. , Thurm Audrey , Bartolini Luca , Masvekar Ruturaj , Theodore William , Bielekova Bibiana , Porter Forbes D. , Dang Do An N.
Published: February 2021

CLN3 disease is a pediatric neurodegenerative condition wherein seizures are common. The most common disease‐causing variant is an ~1‐kb deletion in CLN3. We investigated seizure phenotype in relation to genotype and to adaptive behavior, MR spectroscopy and CSF biochemical markers in a CLN3 cohort. We performed seizure phenotyping using clinical history, EEG, and the Unified Batten Disease Rating Scale (UBDRS) seizure score. We assessed correlations of seizure severity with disease severity (UBDRS capability), adaptive behavior composite score (ABC; Vineland‐3), glutamate+glutamine+GABA and N‐acetylaspartate+N‐acetylaspartyl glutamate (MR spectroscopy), and CSF neurofilament light chain (NEFL) levels. In 20 participants, median age was 10.7 years (IQR = 7.8). Eighteen completed baseline EEG; 12 had a 1‐year follow‐up. Seizures were reported in 14 (8 1‐kb deletion homozygotes), with median age at onset of 10.0 (IQR = 6.8). Epileptiform discharges were noted in 15 (9 homozygotes). Bilateral tonic clonic (n = 11) and nonmotor seizures (n = 7) were most common. UBDRS seizure score correlated with age (rp = 0.50; [0.08,0.77]; P = .02), UBDRS capability (rp = −0.57; [−0.81,−0.17]; P = .009) and ABC (rp = −0.66; [−0.85,−0.31]; P = .001) scores, glutamate+glutamine+GABA (rp = −0.54; [−0.80,−0.11]; P = .02) and N‐acetylaspartate+N‐acetylaspartyl glutamate (rp = −0.54; [−0.80,−0.11]; P = .02), and CSF NEFL (rp = 0.65; [0.29,0.85]; P = .002) levels. After controlling for age, correlations with ABC and CSF NEFL remained significant. In our CLN3 cohort, seizures and epileptiform discharges were frequent and often started by age 10 years without significant difference between genotypes. ABC and CSF NEFL correlate with UBDRS seizure score, reflecting the role of seizures in the neurodegenerative process. Longitudinal evaluations in a larger cohort are needed to confirm these findings.
A tripole pattern of summer surface air temperature anomalies over northern Eurasia and its precursory signals in the tropical Atlantic and northern Asian land
Authors: He Kejun , Liu Ge , Wu Renguang , Li Jingxin , Wang Huimei , Yue Xiaoyuan
Published: February 2021

This study investigates the variability of summer surface air temperature (SAT) over northern Eurasia and its precursory signals in the tropical Atlantic and northern Asian land. The leading mode of summer SAT variations features a northern Eurasian SAT tripole (NEST) pattern, with two same‐sign SAT anomaly regions over eastern Europe–western Siberia and the Far East region and an opposite‐sign SAT anomaly region around the Baikal Lake. It is found that sea surface temperature (SST) or SAT anomalies in the tropical Atlantic and rainfall‐soil moisture anomalies around the Baikal Lake during May can modulate the NEST pattern. The SST anomalies in the tropical Atlantic persist from May to summer and induce a downstream zonal wave train across northern Eurasia, consequently causing the variation in the summer NEST pattern. May rainfall anomalies around the Baikal Lake affect the overlying atmospheric circulation during summer through the ‘memory’ effect of soil moisture and the soil moisture‐rainfall interaction, correspondingly modulating the downstream wave train and the associated NEST pattern. Based on the above results, a statistical prediction model is established using the two precursory signals, that is, SAT in the tropical Atlantic and rainfall around the Baikal Lake during May. The leave‐three‐out cross‐validation shows that the model has a high skill in predicting the summer NEST pattern, with a correlation coefficient of 0.51 (significant at the 99.8% confidence level) between observation and prediction during the period 1980–2016.
Effect of Core‐Crosslinking on Protein Corona Formation on Polymeric Micelles
Authors: Alberg Irina , Kramer Stefan , Leps Christian , Tenzer Stefan , Zentel Rudolf
Published: February 2021

Most nanomaterials acquire a protein corona upon contact with biological fluids. The magnitude of this effect is strongly dependent both on surface and structure of the nanoparticle. To define the contribution of the internal nanoparticle structure, protein corona formation of block copolymer micelles with poly(N‐2‐hydroxypropylmethacrylamide) (pHPMA) as hydrophilic shell, which are crosslinked—or not—in the hydrophobic core is comparatively analyzed. Both types of micelles are incubated with human blood plasma and separated by asymmetrical flow field‐flow fractionation (AF4). Their size is determined by dynamic light scattering and proteins within the micellar fraction are characterized by gel electrophoresis and quantified by liquid chromatography‐high‐resolution mass spectrometry‐based label‐free quantitative proteomics. The analyses reveal only very low amounts of plasma proteins associated with the micelles. Notably, no significant enrichment of plasma proteins is detectable for core‐crosslinked micelles, while noncrosslinked micelles show a significant enrichment of plasma proteins, indicative of protein corona formation. The results indicate that preventing the reorganization of micelles (equilibrium with unimers) by core‐crosslinking is crucial to reduce the interaction with plasma proteins.
Localized corrosion of (lean) duplex stainless steels in immersion units of urban wastewater treatment plants
Authors: Larché Nicolas , Emo Benoit , Allion Audrey , Johansson Elisabeth , Thierry Dominique
Published: February 2021

With lower alloying cost and higher mechanical properties, lean duplex stainless steels can be an alternative to the more commonly used austenitic stainless steels. However, these alloys are still not the preferred choice, probably due to a lack of field experience. A study was thus initiated in view of defining the limits of use of selected (lean) duplexes for urban wastewater treatment units. The present paper shows the localized corrosion performance of selected lean duplexes in chloride contaminated solutions. The results are compared with austenitic S30403 and S31603 and with the more standard duplexes S82441 and S32205. The effect of welding was also investigated. Exposures in field municipal wastewater plants were conducted for 1 year in low and high chloride content units. The results show that lean duplexes S32101 and S32202 can be used as alternatives to S30403 and S31603 in low chloride electrolytes. At 500 ppm of chloride content, duplex stainless steel S32304 showed better corrosion resistance than S30403 and S31603. For higher chloride contents (1000 ppm and above) the standard duplexes S82441 and S32205 shall be preferred.
Benzo/Naphthodifuranone‐Based Polymers: Effect of Perpendicular‐Extended Main Chain π‐Conjugation on Organic Field‐Effect Transistor Performances
Authors: Li Rui , Dai Zhicheng , Zheng Meng , Wang Cheng , Deng Zhifeng , Zhuang Tao , Feng Kui , Yang Wenjun , Yang Kun , Zhang Haichang
Published: February 2021

For polymer semiconductors, the backbone structure plays an essential role in determining their physicochemical properties and charge transport behaviors. In this work, two donor–acceptor‐type polymers (P‐BDF and P‐NDF) based on benzodifuranone (BDF) and naphthodifunarone (NDF) as electron‐deficient moieties and indaceno‐dithiophene as electron‐rich groups are designed, synthesized and, for the first time, applied in organic field‐effect transistor. P‐BDF and P‐NDF differ from their backbone structures while P‐BDF has a more planar backbone conformation due to its smaller conjugated core size and P‐NDF features a perpendicular‐extended main chain structure. As a result, P‐BDF polymer exhibits bathochromic optical absorption, deeper molecular orbital energy levels, and more importantly, closer π‐stacking and stronger aggregation in the solid state and thus affords a more promising hole mobility of up to 0.85 cm2 V−1 s−1 in OFET devices, while that of the P‐NDF‐based devices is only 0.55 cm2 V−1 s−1. The results suggest the great potential of BDF/NDF‐type chromophores in constructing novel organic semiconductors and also indicate that the main chain coplanarity of polymer semiconductors is more essential than the sole extension of π‐conjugations (especially at the perpendicular direction of polymer main chains) for the design of high‐performance OFET materials.
No man's land: Species‐specific formation of exclusion zones bordering Actinomyces graevenitzii microcolonies in nanoliter cultures
Authors: Jalali Fatemeh , Ellett Felix , Balani Pooja , Duncan Margaret J. , Dewhirst Floyd E. , Borisy Gary G. , Irimia Daniel
Published: February 2021

To survive within complex environmental niches, including the human host, bacteria have evolved intricate interspecies communities driven by competition for limited nutrients, cooperation via complementary metabolic proficiencies, and establishment of homeostatic relationships with the host immune system. The study of such complex, interdependent relationships is often hampered by the challenges of culturing many bacterial strains in research settings and the limited set of tools available for studying the dynamic behavior of multiple bacterial species at the microscale. Here, we utilize a microfluidic‐based co‐culture system and time‐lapse imaging to characterize dynamic interactions between Streptococcus species, Staphylococcus aureus, and Actinomyces species. Co‐culture of Streptococcus cristatus or S. salivarius in nanoliter compartments with Actinomyces graevenitzii revealed localized exclusion of Streptococcus and Staphylococcus from media immediately surrounding A. graevenitzii microcolonies. This community structure did not occur with S. mitis or S. oralis strains or in co‐cultures containing other Actinomycetaceae species such as S. odontolyticus or A. naeslundii. Moreover, fewer neutrophils were attracted to compartments containing both A. graevenitzii and Staphylococcus aureus than to an equal number of either species alone, suggesting a possible survival benefit together during immune responses.
Game of names: Blockchain premium in corporate names
Authors: Sharma Prateek , Paul Samit
Published: February 2021

We examine stock price response around cryptocurrency‐related corporate name change announcements using an event study framework. We find that cryptocurrency‐related name changes generate larger gains in share price and volume than other corporate name changes. The valuation gains associated with cryptocurrency‐related name changes cannot be explained by standard asset pricing factors, firm and stock characteristics, industry specific shocks, or by the presence of outliers. These gains are higher when the announcements happen during periods of high sentiment for cryptocurrencies. There is evidence that shareholders with better access to private information about such name changes are able to front‐run other shareholders.
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

Background

The 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.

Methods

We 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.

Results

Whole 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.

Conclusions

To 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
The dynamics of the stock of workers at the firm level and threshold calculation
Authors: Ren Jie , Zhang Qimin , Li Xining
Published: February 2021

In this paper, we extend the state equations for the stock of unskilled and skilled workers by introducing internal training and study the dynamics of the number of skilled workers at the firm level. A threshold (R0) is defined, which can be used to judge whether skilled workers continue to exist. However, R0 is difficult to explicitly calculate because of its abstract form in infinite‐dimensional spaces. Therefore, a numerical approximation method to calculate R0 is provided. The factors affecting R0 are discussed through numerical examples. Based on the calculation results, we provide some suggestions for hiring/firing and training strategies in firms.
Fibonacci polynomials for the numerical solution of variable‐order space‐time fractional Burgers‐Huxley equation
Authors: Heydari M. H. , Avazzadeh Z.
Published: February 2021

In this article, the variable‐order (VO) space‐time fractional version of the Burgers‐Huxley equation is introduced with fractional differential operator of the Caputo type. The collocation technique based on the Fibonacci polynomials (FPs) is developed for finding the approximate solution of this equation. In order to implement the presented method, some novel operational matrices of derivative (including ordinary and fractional derivatives) are extracted for the FPs. Moreover, the roots of the Chebyshev polynomials of the first kind are chosen as the collocation points which reduce the equation to a system of algebraic equations more efficiency. Ultimately, we obtain the solution of the VO space‐time fractional Burgers‐Huxley equation in terms of the FPs. The devised method is validated by finding an error bound for the truncated series of the Fibonacci expansion in two dimensions. The accuracy of approximation is verified through various illustrative examples.
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

Scope

The 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 Results

A 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.

Conclusion

This 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

Purpose

To quantify the use of anterior torso skin surface position measurement as a breathing surrogate.

Methods

Fourteen 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.

Results

A 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%.

Conclusions

The 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

Purpose

Increased 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.

Methods

In 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.

Results

The 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).

Conclusion

This 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

Purpose

This study aimed to investigate the role of regionalinhomogeneity in spiral hyperpolarized13C image quality and to develop measures to alleviate these effects.

Methods

Field 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.

Results

Mean 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

Purpose

Radial 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.

Methods

The 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).

Results

RMSE 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.

Conclusions

PIV is feasible for application‐specific 4D flow MRI protocol optimization. PC‐VIPR is better‐suited to dual‐Venc LV imaging with short scan times.
Docetaxel chemotherapy response in PC3 prostate cancer mouse model detected by rotating frame relaxations and water diffusion
Authors: Laakso Hanne , Ylä‐Herttuala Elias , Sierra Alejandra , Jambor Ivan , Poutanen Matti , Liljenbäck Heidi , Virtanen Helena , Merisaari Harri , Aronen Hannu , Minn Heikki , Roivainen Anne , Liimatainen Timo
Published: February 2021

MRI is a common method of prostate cancer diagnosis. Several MRI‐derived markers, including the apparent diffusion coefficient (ADC) based on diffusion‐weighted imaging, have been shown to provide values for prostate cancer detection and characterization. The hypothesis of the study was that docetaxel chemotherapy response could be picked up earlier with rotating frame relaxation timesTRAFF2andTRAFF4than with the continuous waveT1ρ, adiabaticT1ρ, adiabaticT2ρ,T1,T2or water ADC. Human PC3 prostate cancer cells expressing a red fluorescent protein were implanted in 21 male mice. Docetaxel chemotherapy was given once a week starting 1 week after cell implantation for 10 randomly selected mice, while the rest served as a control group (n= 11). The MRI consisted of relaxation along a fictitious field (RAFF) in the second (RAFF2) and fourth (RAFF4) rotating frames,T1andT2, continuous waveT1ρ, adiabaticT1ρand adiabaticT2ρrelaxation time measurements and water ADC. MRI was conducted at 7 T, once a week up to 4 weeks from cell implantation. The tumor volume was monitored usingT2‐weighted MRI and optical imaging. The histology was evaluated after the last imaging time point. Significantly reduced RAFFn,T1ρ,T2ρand conventional relaxation times 4 weeks after tumor implantation were observed in the treated tumors compared with the controls. The clearest short‐ and long‐term responses were obtained withT1, while no clear improvement in response to treatment was detected with novel methods compared with conventional methods or with RAFFncompared with all others. The tumor volume decreased after a two‐week time point for the treated group and increased significantly in the control group, which was supported by increasing red fluorescent light emission in the control tumors. Decreased relaxation times were associated with successful chemotherapy outcomes. The results indicate altered relaxation mechanisms compared with higher dose chemotherapies previously published.