bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vitro exosomal transfer of Nrf2 led to the oxaliplatin resistance in human colorectal cancer LS174T cells
Authors: Mostafazadeh Mostafa , Kahroba Houman , Haiaty Sanya , TazeKand Abbas P. , Samadi Nasser , Rahbarghazi Reza , Nouri Mohammad 
Published: April 2022

AbstractChemotherapy resistance is a serious pitfall in the treatment of colon cancers (CCs). Previous studies have found that exosomes (Exo) play a pivotal role in tumor drug resistance via the transfer of proteins and genetic materials to the acceptor cells. To date, the mechanisms orchestrating Exo‐derived resistance in cancer cells have been the center of attention. Herein, we aimed to evaluate the role of exosomal nuclear factor erythroid 2‐related factor 2 (Nrf2) on oxaliplatin (1‐OHP) resistance in human colorectal cancer LS174T cells in vitro. To this end, exosomal‐Nrf2‐mediated 1‐OHP resistance was examined using different assays. Exo was isolated from resistant LS174T cells (LS174T/R) and added to the culture medium of sensitive LS174T cells (LS174T/S). According to our data, LS174T/S cells successfully adsorbed PKH26‐Exo driven from LS174T/R cells. Western blotting showed an increased Nrf2 level in Exo isolated from LS174T/R cells compared to LS174T/S cell‐derived Exo (p < .05). The incubation of LS174T/S cells with LS174T/R‐derived Exo increased half‐maximal inhibitory concentration values in response to treatment with 1‐OHP (p < .05). Besides this, the apoptotic changes were diminished in LS174T/S cells after incubation with LS174T/R‐derived Exo. Of note, the exposure of LS174T/S cells to LS174T/R cell‐derived Exo increased the expression of Nrf2 and P‐glycoprotein (P‐gp) compared to the nontreated LS174T/S cells (p < .05). In line with these changes, lower intracellular Rhodamin 123 content was detected in Exo‐treated cells compared to the nontreated LS174T/S cells. Exo increased migration and clonogenic capacity of LS174T/S cells after incubation with Exo‐derived from resistant cells. Of note, inhibition of Nrf2 with a specific blocker, brusatol, blunted these effects. Taken together, Exo‐mediated transfer of Nrf2 is involved in the development of oxaliplatin resistance in CC cells by upregulating P‐gp.
Investigation of β‐Substitution Activity of O‐Acetylserine Sulfhydrolase from Citrullus vulgaris
Authors: Smith Jamorious L. , Harrison Isa Madrigal , Bingman Craig A. , Buller Andrew R. 
Published: April 2022

AbstractPyridoxal‐5’‐phosphate (PLP)‐dependent enzymes have garnered interest for their ability to synthesize non‐standard amino acids (nsAAs). One such class of enzymes, O‐acetylserine sulfhydrylases (OASSs), catalyzes the final step in the biosynthesis of l‐cysteine. Here, we examine the β‐substitution capability of the OASS from Citrullus vulgaris (CvOASS), a putative l‐mimosine synthase. While the previously reported mimosine synthase activity was not reproducible in our hands, we successfully identified non‐native reactivity with a variety of O‐nucleophiles. Optimization of reaction conditions for carboxylate and phenolate substrates led to distinct conditions that were leveraged for the preparative‐scale synthesis of nsAAs. We further show this enzyme is capable of C−C bond formation through a β‐alkylation reaction with an activated nitroalkane. To facilitate understanding of this enzyme, we determined the crystal structure of the enzyme bound to PLP as the internal aldimine at 1.55 Å, revealing key features of the active site and providing information that may guide subsequent development of CvOASS as a practical biocatalyst.
Time to lift the fog of iatrogenic complications in mechanical support
Authors: Gilchrist Ian C. 
Published: April 2022

Key Points
Vascular complications plague patients treated with mechanical circulatory support.
These complications are associated with significant morbidity and risk erasing the benefits of the technology.
Standardized care with across the spectrum of indication, access, care, and ultimate removal of mechanical support is a promising concept to reduce complications in this high‐risk patient group.
Better early than later!
Authors: Yildiz Mehmet , Henry Timothy D. 
Published: April 2022

Key Points
Timing to administer antiplatelet and antithrombin inhibitor in ST‐segment elevation myocardial infarction (STEMI) patients remains a matter of debate despite the guideline's recommendation of “as early as possible.”
This pre–post study with heparin and ticagrelor pretreatment in STEMI patients improved pre‐PCI TIMI flow grade with lower peak cardiac troponin levels and higher left ventricular ejection fraction without any difference in bleeding risk.
The results provide further support for the use of standardized STEMI protocols, including pretreatment with aspirin, heparin bolus, and P2Y12 inhibitor at the first‐medical contact in an effort to improve infarct‐related artery patency without risk of bleeding.
First case of concomitant cytomegalovirus (CMV) viremia in non‐immunocompromised COVID‐19 patient and ICU management strategy in Qatar with literature review
Authors: Iqbal Phool , Menik Arachchige Suresh , Ali Yousra , Qamar Muhammad Sohaib , Jaouni Hani Walid , Abdussalam Ahmed Lutfe Mohamad 
Published: April 2022

AbstractCOVID‐19 has created one of the world's worst pandemics and is associated with various life‐threatening complications and infections, possibly due to various internal and external host factors. Cytomegalovirus (CMV) coinfection is one of those infections. We present a challenging case of severe COVID‐19 infection managed in our ICU care facility with concomitant CMV infection. We aim to highlight the significance of early diagnosis and prompt management for a better outcome.
Two‐Dimensional Covalent and Supramolecular Polymers: From Monolayer to Bilayer and the Thicker
Authors: Yu Shang‐Bo , Lin Furong , Tian Jia , Liu Yi , Zhang Dan‐Wei , Li Zhan‐Ting 
Published: April 2022

AbstractSelective preparation of two‐dimensional polymers (2DPs) and supramolecular polymers (2DSPs) with defined thickness is crucially important for controlling and maximizing their functions, yet it has remained as a synthetic challenge. In the past decade, several approaches have been developed to allow selective preparation of discrete monolayer 2DPs and 2DSPs. Recently, crystal exfoliation and self‐assembly strategies have been employed to successfully prepare bilayer 2DP and 2DSP, which represent the first step towards the controlled “growth” of 2D polymers from the thinnest monolayers to thicker few‐layers along the third dimension. This Concept review discusses the concept of accurate synthesis of 2D polymers with defined layers. Advances in this research area will pave the way to rational synthetic strategies for 2D polymers with controlled thickness.
Combining Functional Prototyping of 3D Printed Reactors with a Modular Reactor Setup for Continuous Emulsion Polymerization
Authors: Zentel Kristina M. , Reinbeck Andreas , Deckert Christian , Pauer Werner , Luinstra Gerrit A. 
Published: April 2022

AbstractThe potential for fast and specific process optimization by functional prototyping with 3D printed reactors was shown for a known continuous emulsion polymerization in a modular setup. Three tubular reactors, two with static mixing elements and a continuously stirred tank reactor (CSTR) were printed from polylactic acid. Thermal imaging of the reactors allows to map the basically adiabatic progress of the redox‐started radical polymerization in a space‐resolved way. The application of static mixing elements led to a higher conversion stability and a more uniform product, as expected for a better mass transfer. Polymerization in combinations of CSTR and a tubular reactor showed further improvements of process stability and product uniformity in terms of particle size and mol masses.
Stereoselective Synthesis of a Tetrasaccharide Fragment from Rhamnogalacturonan II Side Chain A
Authors: Lei Jin‐Cai , Jiang Yuan‐Yuan , Xia Yi‐Fei , Fang Qing , Duan Shi‐Chao , Ruan Yu‐Xiong , Yang Jin‐Song 
Published: April 2022

Comprehensive SummaryAn efficient synthesis of a complex tetrasaccharide fragment 1 structurally related to rhamnogalacturonan II side chain A has been accomplished through a stepwise glycosylation strategy. Challenges involved in the synthesis include the facile construction of the sterically crowded l‐fucopyranose core and the stereoselective formation of two 1,2‐cis‐glycosidic linkages. The 3,4‐disubstituted l‐fucopyranoside structure was successfully constructed through a ‘counterclockwise’ glycosylation sequence, namely, the less reactive axial 4‐OH group of the central fucose unit was glycosylated first, then the 3‐OH. Besides, a 2‐pyridinecarbonyl‐assisted α‐d‐xylosylation was developed to synthesize the α‐d‐xylopyranosidic linkage and a 3,4‐O‐benzoyl‐controlled α‐l‐galactosylation reaction was used for the stereoselective synthesis of the corresponding α‐l‐galactopyranosidic linkage.
Computer‐Aided Design of Fluorinated Flavin Derivatives by Modulation of Intersystem Crossing and Fluorescence
Authors: Bracker Mario , Kubitz Mira K. , Czekelius Constantin , Marian Christel M. , Kleinschmidt Martin 
Published: April 2022

AbstractThis study aims at finding fluorinated flavin derivatives with modified intersystem crossing (ISC) and fluorescence properties. In total, photophysical properties of 8 derivatives were investigated computationally using combined density functional theory and multireference configuration interaction methods. On top of a screening procedure, the excited‐state decay mechanisms of selected chromophores were investigated in detail. Kinetic schemes including fluorescence, ISC as well as internal conversion (IC) channels were set up to unravel the complex excited‐state decay kinetics. We find two chromophores that exhibit promising properties with respect to fluorescence microscopy. Distinctive stabilization of the brightππ* state results in absorption in the green wavelength region and emission of (infra‐)red light. The1(πHπL)⤳3(πH–1πL) ISC channel of the flavin chromophore was found to be deactivated upon both modifications, but nonradiative deactivation of the fluorescence by IC appears to be a problem. Alternative modifications of the pteridine dione moiety were found to result in a marked stabilization ofnπ* states along with activation of El‐Sayed allowed ISC channels. For the latter two compounds, we predict fluorescence to be quenched by ISC followed by efficient population of the long‐livedstate via IC.
Cyclin C: A new responser for chemosensitivity in cancer
Authors: Fang Shuai , Jin Xiaofeng , Zhou Chengwei , Gong Zhaohui 
Published: April 2022

AbstractThe resistance to cisplatin‐based chemotherapy is a common cause of poor prognosis in cancer patients. Cisplatin stimulation causes cyclin C translocating to mitochondria, and in turn induces mitochondrial fission. However, little is known about the role of cyclin C in mitochondrial dysfunction in cancer cells challenged with cisplatin. In the present commentary, we bring to the attention of readers the recent report by Jiang et al which revealed the importance of ubiquitylation and translocation of cyclin C in gastric cancer cells in response to cisplatin stimulation for mitochondrial stability. This finding provides new insights into exploring the novel mechanisms of chemoresistance and developing the new chemotherapy synergistic agents in the era of precision oncology.
Epicardial adipose tissue related to left atrial and ventricular function in heart failure with preserved versus reduced and mildly reduced ejection fraction
Authors: Jin Xuanyi , Hung Chung‐Lieh , Tay Wan Ting , Soon Dinna , Sim David , Sung Kuo‐Tzu , Loh Seet Yoong , Lee Sheldonn , Jaufeerally Fazlur , Ling Lieng Hsi , Richards A Mark , van Melle Joost P. , Voors Adriaan A. , Lam Carolyn S.P. 
Published: April 2022

AimDifferent associations between epicardial adipose tissue (EAT) and cardiac function have been suggested in patients with heart failure with preserved (HFpEF) versus reduced and mildly reduced ejection fraction (HFrEF/HFmrEF). However, few studies have directly compared the association between EAT and left atrial (LA) and left ventricular (LV) function in patients with HFpEF and HFrEF/HFmrEF.Methods and resultsWe studied EAT thickness using transthoracic echocardiography in a multicentre cohort of 149 community‐dwelling controls without heart failure, 99 patients with HFpEF, and 366 patients with HFrEF/HFmrEF. EAT thickness was averaged from parasternal long‐axis and short‐axis views, respectively, and off‐line speckle tracking analysis was performed to quantify LA and LV function. Data were validated in an independent cohort of 626 controls, 243 patients with HFpEF, and 180 patients with HFrEF/HFmrEF. For LV function, LV global longitudinal strain (GLS) was measured in both derivation and validation cohorts. For LA function, LAGLS at reservoir, contractile and conduit phase were measured in the derivation cohort, and only LAGLS at reservoir phase was measured in the validation cohort. In the derivation cohort, EAT thickness was lower in HFrEF/HFmrEF (7.3 ± 2.5 mm) compared to HFpEF (8.3 ± 2.6 mm, p < 0.05) and controls (7.9 ± 1.8 mm, p < 0.05). Greater EAT thickness was associated with better LV and contractile LA function in HFrEF/HFmrEF, but not in HFpEF (p for interaction <0.05). These findings were confirmed in the validation cohort, where EAT thickness was lower in HFrEF/HFmrEF (6.7 ± 1.4 mm) compared to HFpEF (9.6 ± 2.8 mm; p < 0.05) and controls (7.7 ± 2.3 mm; p < 0.05). Greater EAT thickness was associated with better LV and reservoir LA function in patients with HFrEF/HFmrEF but worse LV and reservoir LA function in patients with HFpEF (p for interaction <0.05). Thickened EAT (EAT thickness >10 mm) was associated with LA dysfunction (LAGLS at reservoir phase <23%) in HFpEF, but not in HFrEF/HFmrEF.ConclusionEpicardial adipose tissue thickness is greater in patients with HFpEF than HFrEF/HFmrEF. Increased EAT thickness is associated with worse LA and LV function in HFpEF but the opposite in HFrEF/HFmrEF.
Electrochemical Sensing of Dopamine and Epinephrine Using Self‐assembled Fe3O4 Magnetic Nanoparticles on a Pyridine‐grafted Glassy Carbon Electrode
Authors: Mahanta Abhinandan , Akond Umme Solaem , Barman Koushik , Jasimuddin Sk. 
Published: April 2022

AbstractA magnetic nanomaterial based electrochemical sensor was developed by immobilizing Fe3O4 nanoparticles (ca. 12 nm d.) on a pyridine molecule grafted glassy carbon electrode (Py‐GCE) for the selective and sensitive determination of two important neurotransmitters, dopamine (DA) and epinephrine (EP) at neutral pH. The synthesised Fe3O4 magnetic nanoparticleswere characterized by FTIR, UV‐Vis, TEM, XRD and XPS methods, whereas thefabricated electrodeswere characterized by using SEM, ATR‐FTIR, CV and EIS techniques. Differential pulse voltammetry was used for the determination of DA and EP in the linear range of 0.2 to 1.2 μM with the detection limits (S/N=3) of 0.34 nM and 0.61 nM, respectively. The sensor electrode exhibited high stability, reproducibility, good selectivity in the presence of potential interfering agents viz. ascorbic acid, uric acid, citric acid, glucose, etc. Theproposed method was successfully applied for the simultaneous determination of DA and EP in human blood sample and the recovery result was excellent.
Joint Effects of Fragmentation and Mercury Contamination on Marsh Periwinkle (Littoraria irrorata) Movement
Authors: Krull Marcos , Newman Michael C. 
Published: April 2022

Abstract
There are different ways contaminants can interact and enhance the effects of habitat fragmentation, such as modifying the movement of organisms. The present study tested the hypothesis that mercury exacerbates the effects of fragmentation by affecting the movement of the marsh periwinkle Littoraria irrorata and reducing the probability of snails crossing fragmented microlandscape experimental systems. How these changes could affect the search efficiency of organisms in the long term was assessed using hidden Markov models and random walks simulations. Bayesian nonlinear models were used to analyze the effects of fragmentation and contamination on the mean speed and mean directional change of organisms. Snail movement for control and two mercury-exposure treatments were recorded in microlandscapes with six different levels of habitat cover and three landscape replicates. The results indicated that exposed organisms had lower probabilities of crossing the landscape, reduced speed, and shifts in step length distributions. Both mercury exposure and habitat fragmentation affected the movement of the marsh periwinkle. Mercury exacerbated the effects of habitat fragmentation by affecting the cognition (e.g., route planning, orientation, and spatial learning) and movement of L. irrorata. Hence, the interaction of these stressors could further reduce the functional connectivity of landscapes and reduce the search efficiency of organisms. Environ Toxicol Chem 2022;41:1742–1753. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Overnight volatility, realized volatility, and option pricing
Authors: Wang Tianyi , Cheng Sicong , Yin Fangsheng , Yu Mei 
Published: April 2022

AbstractThe equity market is not trading around the clock, and the overnight information has been proved be important for understanding pricing anomalies, improving volatility forecasting accuracy, and so forth. However, there is little research investigating its impact on option pricing. In this paper, we provide a framework that integrates intraday, overnight returns, and realized volatility simultaneously within an augmented Autoregressive Volatility model. The analytical option‐pricing formula for the new model is derived through the closed‐form moment generation function. The empirical results based on S&P 500 index options show that distinguishing the overnight component from daily returns has the potential capability to reduce the pricing errors, both in‐sample and out‐of‐sample.
Functional adaptation of glial cells at neuromuscular junctions in response to injury
Authors: Perez‐Gonzalez Anna P. , Provost Frédéric , Rousse Isabelle , Piovesana Roberta , Benzina Ouafa , Darabid Houssam , Lamoureux Benoit , Wang Yu Shi , Arbour Danielle , Robitaille Richard 
Published: April 2022

AbstractSynaptic elements from neuromuscular junctions (NMJs) undergo massive morphological and functional changes upon nerve injury. While morphological changes of NMJ‐associated glia in response to injury has been investigated, their functional properties remain elusive. Perisynaptic Schwann cells (PSCs), glial cells at the NMJ, are essential for NMJ maintenance and repair, and are involved in synaptic efficacy and plasticity. Importantly, these functions are regulated by PSCs ability to detect synaptic transmission through, notably, muscarinic (mAChRs) and purinergic receptors' activation. Using Ca2+ imaging and electrophysiological recordings of synaptic transmission at the mouse NMJ, we investigated PSC receptors activation following denervation and during reinnervation in adults and at denervated NMJs in an ALS mouse model (SOD1G37R). We observed reduced PSCs mAChR‐mediated Ca2+ responses at denervated and reinnervating NMJs. Importantly, PSC phenotypes during denervation and reinnervation were distinct than the one observed during NMJ maturation. At denervated NMJs, exogenous activation of mAChRs greatly diminished galectin‐3 expression, a glial marker of phagocytosis. PSCs Ca2+ responses at reinnervating NMJs did not correlate with the number of innervating axons or process extensions. Interestingly, we observed an extended period of reduced PSC mAChRs activation after the injury (up to 60 days), suggesting a glial memory of injury. PSCs associated with denervated NMJs in an ALS model (SOD1G37R mice) did not show any muscarinic adaptation, a phenotype incompatible with NMJ repair. Understanding functional mechanisms that underlie this glial response to injury may contribute to favor complete NMJ and motor recovery.
The orbitofrontal cortex represents advantageous choice in the Iowa gambling task
Authors: Zha Rujing , Li Peng , Liu Ying , Alarefi Abdulqawi , Zhang Xiaochu , Li Jun 
Published: April 2022

AbstractA good‐based model, the central neurobiological model of economic decision‐making, proposes that the orbitofrontal cortex (OFC) represents binary choice outcome, that is, the chosen good. A good is defined by a group of determinants characterizing the conditions in which the commodity is offered, including commodity type, cost, risk, time delay, and ambiguity. Previous studies have found that the OFC represents the binary choice outcome in decision‐making tasks involving commodity type, cost, risk, and delay. Real‐life decisions are often complex and involve uncertainty, rewards, and penalties; however, whether the OFC represents binary choice outcomes in a complex decision‐making situation, for example, Iowa gambling task (IGT), remains unclear. Here, we propose that the OFC represents binary choice outcome, that is, advantageous choice versus disadvantageous choice, in the IGT. We propose two hypotheses: first, the activity pattern in the human OFC represents an advantageous choice; and second, choice induces an OFC‐related functional network. Using functional magnetic resonance imaging and advanced machine‐learning tools, we found that the OFC represented an advantageous choice in the IGT. The OFC representation of advantageous choice was related to decision‐making performance. Choice modulated the functional connectivity between the OFC and the superior medial gyrus. In conclusion, the OFC represents an advantageous choice during the IGT. In the framework of a good‐based model, the results extend the role of the OFC to complex decision‐making situation when making a binary choice.
Correcting for discounting and loss aversion in composite time trade‐off
Authors: Lipman Stefan A. , Attema Arthur E. , Versteegh Matthijs M. 
Published: April 2022

AbstractTime trade‐off utilities have been suggested to be biased upwards. This bias is a result of the method being applied assuming linear utility of life duration, which is violated when individuals discount future life years or are loss averse for health. Applying a “corrective approach”, that is, measuring individuals' discount function and loss aversion and correcting time trade‐off utilities for these individual characteristics, may reduce this bias in utilities. Earlier work has developed this approach for time trade‐off in a student sample. In this study, the corrective approach was extended to composite time trade‐off (cTTO) methodology, which enabled correcting utilities for health states worse than dead. In digital interviews a sample of 150 members of the general public completed cTTO tasks for six health states, and afterward they completed measurements of loss aversion and discounting. cTTO utilities were corrected using these measurements under multiple specifications. Respondents were also asked to reflect on and adjust their cTTO utilities directly. Our results show considerable loss aversion and both positive and negative discounting were prevalent. As predicted, correction generally resulted in lower utilities. This was in accordance with the direction of adjustments made by respondents themselves.