bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Cell‐Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis
Authors: Adams Cameron , Nair Nisha , Plant Darren , Verstappen Suzanne M. M. , Quach Hong L. , Quach Diana L. , Carvidi Alex , Nititham Joanne , Nakamura Mary , Graf Jonathan , Barton Anne , Criswell Lindsey A. , Barcellos Lisa F. 
Published: January 2023

ObjectiveWe undertook this study to estimate changes in cell‐specific DNA methylation (DNAm) associated with methotrexate (MTX) response using whole blood samples collected from rheumatoid arthritis (RA) patients before and after initiation of MTX treatment.MethodsPatients included in this study were from the Rheumatoid Arthritis Medication Study (n = 66) and the University of California San Francisco Rheumatoid Arthritis study (n = 11). All patients met the American College of Rheumatology RA classification criteria. Blood samples were collected at baseline and following treatment. Disease Activity Scores in 28 joints using the C‐reactive protein level were collected at baseline and after 3–6 months of treatment with MTX. Methylation profiles were generated using the Illumina Infinium HumanMethylation450 and MethylationEPIC v1.0 BeadChip arrays using DNA from whole blood. MTX response was defined using the EULAR response criteria (responders showed good/moderate response; nonresponders showed no response). Differentially methylated positions were identified using the Limma software package and Tensor Composition Analysis, which is a method for identifying cell‐specific differential DNAm at the CpG level from tissue‐level (“bulk”) data. Differentially methylated regions were identified using Comb‐p software.ResultsWe found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell‐specific differential global methylation associated with MTX response. After correction for multiple testing, 1 differentially methylated position was associated with differential DNAm between responders and nonresponders at baseline in CD4+ T cells, CD8+ T cells, and natural killer cells. Thirty‐nine cell‐specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples.ConclusionWe identified cell‐specific changes in DNAm that were associated with MTX treatment response in RA patients. Future studies of DNAm and MTX treatment response should include measurements of DNAm from sorted cells.image
Engineering of xylanases for the development of biotechnologically important characteristics
Authors: Sürmeli Yusuf , Şanlı‐Mohamed Gülşah 
Published: January 2023

AbstractXylanases are the main biocatalysts used for the reduction of the xylan backbone from hemicellulose, randomly splitting off β‐1,4‐glycosidic linkages between xylopyranosyl residues. Xylanase market has been annually estimated at 500 million US Dollars and they are potentially used in broad industrial process ranges such as paper pulp biobleaching, xylo‐oligosaccharide production, and biofuel manufacture from lignocellulose. The highly stable xylanases are preferred in the downstream procedure of industrial processes because they can tolerate severe conditions. Almost all native xylanases can not endure adverse conditions thus they are industrially not proper to be utilized. Protein engineering is a powerful technology for developing xylanases, which can effectively work in adverse conditions and can meet requirements for industrial processes. This study considered state‐of‐the‐art strategies of protein engineering for creating the xylanase gene diversity, high‐throughput screening systems toward upgraded traits of the xylanases, and the prediction and comprehensive analysis of the target mutations in xylanases by in silico methods. Also, key molecular factors have been elucidated for industrial characteristics (alkaliphilic enhancement, thermal stability, and catalytic performance) of GH11 family xylanases. The present review explores industrial characteristics improved by directed evolution, rational design, and semi‐rational design as protein engineering approaches for pulp bleaching process, xylooligosaccharides production, and biorefinery & bioenergy production.
Low‐volume plasma sampling for determination of dextromethorphan and dextrorphan in rat plasma: LC–MS/MS method and its application in pharmacokinetic study
Authors: Majhi Praful Kumar , Sayyad Samir , Mishra Pratyush , Kamte Sainath , Sahu Rajanikant , Ghosh Goutam , Subudhi Bharat Bhusan 
Published: January 2023

AbstractDextromethorphan (DM) and its metabolite dextrorphan (DX) continue to draw the attention of researchers owing to their diverse pharmacodynamics. Thus, there are possibilities for repurposing DM. Most of the pharmacodynamics of DM needs further validation in different preclinical models. Also, it is necessary to correlate the pharmacodynamics with relevant pharmacokinetics data. Multiple bioanalytical techniques developed for this purpose primarily use a high sample processing volume. Since sample volume is a limiting factor for many preclinical models, an effort was taken to develop an alternative method suitable for handling low sample processing volumes. An efficient solid‐phase extraction technique, robust liquid chromatographic (LC) separation and highly sensitive tandem mass spectrometric detection (MS/MS) showed suitability for use of a 30 μl sample processing volume. This led to the development of a highly specific, selective, accurate and precise‐bio‐analytical method for simultaneous quantification of DM and DX in rat plasma. The validated method was linear in the range of 0.196–403.356 ng/ml for DM and 0.102–209.017 ng/ml for DX. The application of the method was demonstrated through the estimation of pharmacokinetic parameters that showed good congruence with earlier studies.
Effect of light fluctuations on photosynthesis and metabolic flux in Synechocystis sp. PCC 6803
Authors: Imada Tatsumi , Yamamoto Chiaki , Toyoshima Masakazu , Toya Yoshihiro , Shimizu Hiroshi 
Published: January 2023

AbstractIn nature, photosynthetic organisms are exposed to fluctuating light, and their physiological systems must adapt to this fluctuation. To maintain homeostasis, these organisms have a light fluctuation photoprotective mechanism, which functions in both photosystems and metabolism. Although the photoprotective mechanisms functioning in the photosystem have been studied, it is unclear how metabolism responds to light fluctuations within a few seconds. In the present study, we investigated the metabolic response of Synechocystis sp. PCC 6803 to light fluctuations using 13C‐metabolic flux analysis. The light intensity and duty ratio were adjusted such that the total number of photons or the light intensity during the low‐light phase was equal. Light fluctuations affected cell growth and photosynthetic activity under the experimental conditions. However, metabolic flux distributions and cofactor production rates were not affected by the light fluctuations. Furthermore, the estimated ATP and NADPH production rates in the photosystems suggest that NADPH‐consuming electron dissipation occurs under fluctuating light conditions. Although we focused on the water–water cycle as the electron dissipation path, no growth effect was observed in an flv3‐disrupted strain under fluctuating light, suggesting that another path contributes to electron dissipation under these conditions.
Controlled Membrane Transport in Polymeric Biomimetic Nanoreactors
Authors: Cao Shoupeng , Ivanov Tsvetomir , de Souza Melchiors Marina , Landfester Katharina , Caire da Silva Lucas 
Published: January 2023

AbstractPolymersome‐based biomimetic nanoreactors (PBNs) have generated great interest in nanomedicine and cell mimicry due to their robustness, tuneable chemistry, and broad applicability in biologically relevant fields. In this concept review, we mainly discuss the state of the art in functional polymersomes as biomimetic nanoreactors with membrane‐controlled transport. PBNs that use environmental changes or external stimuli to adjust membrane permeability while maintaining structural integrity are highlighted. By encapsulating catalytic species, PBNs are able to convert inactive substrates into functional products in a controlled manner. In addition, special attention is paid to the use of PBNs as tailored artificial organelles with biomedical applications in vitro and in vivo, facilitating the fabrication of next‐generation artificial organelles as therapeutic nanocompartments.
Young children's career aspirations: Gender differences, STEM ambitions, and expected skill use
Authors: Conlon Rachel A. , Barroso Connie , Ganley Colleen M. 
Published: January 2023

AbstractThis study examines young children's career aspirations, gender differences in those aspirations, and children's perceptions of the amount of math and science used in careers. We asked 1634 students in first to third grades what job they wanted in the future and how much they thought they would use math or science in it. Career aspirations were sorted into 27 career categories, of which 12 showed significant gender differences. Notably, boys were more likely to indicate military, manual labor, and math/computer science careers, and girls were more likely to indicate stay at home parent, education, and animal care careers. Students aspiring to science, technology, engineering, and mathematics (STEM) careers thought they would use science, but not math, more than non‐STEM‐aspiring students did. School counseling interventions focused on specific STEM subfields, and education highlighting links between school subjects and careers requirements may benefit students and reduce gender inequality in STEM fields.
Alkoxyphosphorane/Borane Cooperative Alkylations: A Frustrated Lewis Pair Version of the Mitsunobu Reaction
Authors: Chen Ting , Mei Yanbo , Liu Liu Leo , Zhao Yufen , Wu Yile , Stephan Douglas W. 
Published: January 2023

AbstractThe combination of the alkoxyphosphoranes, Ph2P(OR)(O2C6Cl4) and the borane B(C6F5)3 generates the zwitterions 3 which act as FLP to effect the alkylation of several nucleophiles affording C−C, C−N, C−H and C−Cl coupling products. A DFT study shows the reaction proceeds via an FLP activation pathway generating an alkoxyphosphonium intermediate which effects the alkylation of the nucleophiles, akin to the Mitsunobu reaction.
Second‐Generation CD73 Inhibitors Based on a 4,6‐Biaryl‐2‐thiopyridine Scaffold
Authors: Ghoteimi Rayane , Braka Abdennour , Rodriguez Céline , Cros‐Perrial Emeline , Duvauchelle Valentin , Uttaro Jean‐Pierre , Mathé Christophe , Ménétrier‐Caux Christine , Jordheim Lars Petter , Chaloin Laurent , Peyrottes Suzanne 
Published: January 2023

AbstractVarious series of 4,6‐biaryl‐2‐thiopyridine derivatives were synthesized and evaluated as potential ecto‐5′‐nucleotidase (CD73) inhibitors. Two synthetic routes were explored and the coupling of 4,6‐disubstituted 3‐cyano‐2‐chloro‐pyridines with selected thiols allowed us to explore the structural diversity. Somehow divergent results were obtained in biological assays on CD73 inhibition using either the purified recombinant protein or cell‐based assays, highlighting the difficulty to target protein‐protein interface on proteins existing as soluble and membrane‐bound forms. Among the 18 new derivatives obtained, three derivatives incorporating morpholino substituents on the 4,6‐biaryl‐2‐thiopyridine core were shown to be able to reverse the adenosine‐mediated immune suppression on human T cells. The higher blockade efficiency was observed for 2‐((3‐cyano‐4,6‐bis(4‐morpholinophenyl)pyridin‐2‐yl)thio)‐N‐(isoxazol‐3‐yl)acetamide (with total reversion at 100 μM) and methyl 2‐((3‐cyano‐4,6‐bis(4‐morpholinophenyl)pyridin‐2‐yl)thio)acetate (with partial reversion at 10 μM). Thus, this series of compounds illustrates a new chemotype of CD73 allosteric inhibitors.
Adverse late health outcomes among children treated with 3D radiotherapy techniques: Study design of the Dutch pediatric 3D‐RT study
Authors: Beijer Josien G. M. , Kok Judith L. , Janssens Geert O. , Streefkerk Nina , de Vries Andrica C. H. , Slagter Cleo , Maduro John H. , Kroon Petra S. , Grootenhuis Martha A. , van Dulmen‐den Broeder Eline , Loonen Jacqueline J. , Wendling Markus , Tissing Wim J. E. , van der Pal Helena J. , Louwerens Marloes , Bel Arjan , den Hartogh Jaap , van der Heiden‐van der Loo Margriet , Kremer Leontien C. M. , Teepen Jop C. , Ronckers Cécile M. 
Published: January 2023

AbstractBackgroundAdverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side‐effects of two dimensional planned radiotherapy.AimsThe Dutch pediatric 3D‐planned radiotherapy (3D‐RT) study aims to gain insight in the long‐term health outcomes among children who had radiotherapy in the 3D era. Here, we describe the study design, data‐collection methods, and baseline cohort characteristics.Methods and ResultsThe 3D‐RT study represents an expansion of the Dutch Childhood Cancer Survivor study (DCCSS) LATER cohort, including pediatric cancer patients diagnosed during 2000–2012, who survived at least 5 years after initial diagnosis and 2 years post external beam radiotherapy. Individual cancer treatment parameters were obtained from medical files. A national infrastructure for uniform collection and archival of digital radiotherapy files (Computed Tomography [CT]‐scans, delineations, plan, and dose files) was established. Health outcome information, including subsequent tumors, originated from medical records at the LATER outpatient clinics, and national registry‐linkage. With a median follow‐up of 10.9 (interquartile range [IQR]: 7.9–14.3) years after childhood cancer diagnosis, 711 eligible survivors were identified. The most common cancer types were Hodgkin lymphoma, medulloblastoma, and nephroblastoma. Most survivors received radiotherapy directed to the head/cranium only, the craniospinal axis, or the abdominopelvic region.ConclusionThe 3D‐RT study will provide knowledge on the risk of adverse late health outcomes and radiation‐associated dose‐effect relationships. This information is valuable to guide follow‐up care of childhood cancer survivors and to refine future treatment protocols.
Enhancement of video demosaicing techniques using optimization algorithm
Authors: Alphonse Babitha , Alfred Sylam Boyed Wesley 
Published: January 2023

SummaryDemosaicing and denoising are the most significant steps in the imaging process for both images and videos. The correlation noise corrupts the image quality, such that an accurate interpretation of the image is avoided. Thus, demosaicing is utilized to restructure the full‐color image from imperfect color samples. In this article, cat shuffled shepherd optimization‐based local polynomial approximation and intersection of confidence intervals (Cat SSO‐based LPA‐ICI) approach is developed for video demosaicing. The LPA‐ICI model is employed for frame demosaicing in which the second‐order polynomial interpolation filter coefficients are produced using the devised optimization algorithm, named cat SSO technique. Similarly, generative adversarial network classifier is also applied for frame demosaicing. In addition, initialization and flow estimation is performed for the demosaicing process. Besides, spatio temporal demosaicing model is utilized in order to get a noise‐free sequence. However, the developed cat SSO technique is newly devised by the incorporation of the shuffled shepherd optimization algorithm and cat swarm optimization technique. The created video demosaicing model outperformed with peak signal‐to‐noise ratio, root mean square error, and second derivative‐like measure of enhancement values of 56.85 dB, 0.46, and 60.62, respectively.
Perfect Core‐Shell Octahedral B@B38+, Be@B38, and Zn@B38 with an Octa‐Coordinate Center as Superatoms Following the Octet Rule
Authors: Yan Qiao‐Qiao , Zhao XiaoYun , Zhang Ting , Li Si‐Dian 
Published: January 2023

AbstractPlanar, tubular, cage‐like, and bilayer boron clusters Bn+/0/− (n=3∼48) have been observed in joint experimental and theoretical investigations in the past two decades. Based on extensive global searches augmented with first‐principles theory calculations, we predict herein the smallest perfect core‐shell octahedral borospherene Oh B@B38+ (1) and its endohedral metallo‐borospherene analogs Oh Be@B38 (2), and Oh Zn@B38 (3) which, with an octa‐coordinate B, Be or Zn atom located exactly at the center, turn out to be the well‐defined global minima of the systems highly stable both thermodynamically and dynamically. B@B38+ (1) represents the first boron‐containing molecule reported to date which contains an octa‐coordinate B center covalently coordinated by eight face‐capping boron atoms at the corners of a perfect cube in the first coordination sphere. Detailed natural bonding orbital (NBO) and adaptive natural density partitioning (AdNDP) bonding analyses indicate that these high‐symmetry core‐shell complexes X@B38+/0/− (X=B, Be, Zn) as super‐noble gas atoms follow the octet rule in coordination bonding patterns (1S21P6), with one delocalized 9c‐2e S‐type coordination bond and three delocalized 39c‐2e P‐type coordination bonds formed between the octa‐coordinate X center and its octahedral Oh B38 ligand to effectively stabilize the systems. Their IR, Raman, and UV‐Vis spectra are computationally simulated to facilitate their spectroscopic characterizations.
A Further Study on Calcium Phosphate Gardens Grown from the Interface of κ‐Carrageenan‐based Hydrogels and Counterion Solutions
Authors: Fogde Anna , Rosqvist Emil , Le Trung‐Anh , Smått Jan‐Henrik , Sandberg Thomas , Huynh Tan‐Phat 
Published: January 2023

AbstractOriginating from the concept of classical chemical gardens, a new field coined ‘chemobrionics’ has recently emerged. In the present work, two chemobrionic systems grown from a hydrogel/liquid interface at different time scales (for 1, 7, 14 or 28 days) were investigated, i. e., a calcium‐based hydrogel with a phosphate counterion solution (Ca‐gel) and a phosphate‐based hydrogel with a calcium counterion solution (P‐gel). The initial pH changes of the systems were investigated, and the obtained tubular structures were studied using optical microscopy, SEM, AFM, PXRD and TGA. One of the important findings is that the tubes obtained in the Ca‐gel system were straight and long, which could be explained by the larger pH difference observed between the hydrogel and the counterion solution in this system (ΔpH∼2.1) compared to the P‐gel system (ΔpH∼0). The Ca‐gel structures remained overall more amorphous even though increased crystallinity was observed in both systems with increased time spent in counterion solution. Both systems contained hydroxyapatite phases, with additional calcite phases observed for the P‐gel structures and traces of κ‐carrageenan for the Ca‐gel structures. Our study provides a promising method for controlling tubular macrostructures through adjusting the reaction conditions such as maturation time and pH.
A Comprehensive Formulation of Aqueous Electrolytes for Low‐Temperature Supercapacitors
Authors: Ah‐Lung Guillaume , Flamme Benjamin , Maréchal Manuel , Ghamouss Fouad , Jacquemin Johan 
Published: January 2023

AbstractSafer‐by‐design and sustainable energy storage devices are envisioned to be among the required 2.0 solutions to satisfy the fast growing energy demands. Responding to this evolution cannot be freed from a global and synergetic approach to design the requisite electrolytes taking into account the toxicity, the eco‐compatibility and the cost of their constituents. To target low‐temperature applications, a non‐toxic and cost‐efficient eutectic system comprising LiNO3 in water with 1,3‐propylene glycol as co‐solvent was selected to design a ternary electrolyte with a wide liquid range. By using this electrolyte in an electrochemical double‐layer capacitor (EDLC), the operating voltage of the device reaches an optimum of 2.0 V at −40 °C over more than 100 h of floating. Moreover, after being set up at 20 °C, the temperature resilience of the capacitance is near total, demonstrating thus a promising feature related to the suitable thermal and electrochemical behaviours of the tested EDLC devices.
Evaluation of the detection of the homologous transfusion of a red blood cell concentrate in vivo for antidoping
Authors: Marchand Alexandre , Roulland Ingrid , Semence Florian , Jaffredo Franck , Dehainault Catherine , Le Guiner Soizic , Le Pajolec Marie‐Gaëlle , Donati Francesco , Mekacher Lamine Redouane , Lamek Kahina , Ericsson Magnus 
Published: January 2023

AbstractTwo doping cases of homologous blood transfusion (HBT) during Tokyo 2020 Summer Olympics have shown that more controls are needed. The method of detection using flow cytometry to evaluate the expression of minor blood group antigens from red blood cells (RBCs) and identify different RBC populations is efficient but still complex to perform with multiple antigens detection. Recently, the interest of using forensic DNA analysis was also highlighted as a potential new method to detect HBT, with possibility to start from dried blood spots (DBS) instead of fresh blood. After a first phase of development, a protocol was validated for HBT detection using DNA analysis after extraction from DBS. Presence of a second DNA was clear down to 2% of donor blood in vitro. A flow cytometry protocol was also developed with preparation and analysis in 96‐well plates and detection of two different antigens per well using two secondary antibodies with distinct fluorophores. The objective of the project was to evaluate the window of detection of an HBT performed in vivo with 150 mL of RBC concentrate. Blood samples obtained over 7 weeks post‐transfusion were analyzed. DNA profiling from DBS was not sensitive enough to detect the presence of a second DNA even 1 day after transfusion. On the contrary, the flow cytometry protocol was very efficient and allowed identification of several double populations of RBC (expressing/non‐expressing several antigens) until day 50 post‐transfusion. This protocol can be fully validated for a future application to doping control samples.
Still Elusive – Pd(II)‐Mediated Base Pairing by an Acetophenone Oxime Palladacycle within 15N‐Labelled Double‐Helical Oligonucleotides
Authors: Toiviala Maaret , Kleemola Vesa , Maity Sajal , Lönnberg Tuomas 
Published: January 2023

AbstractBoth α and β anomers of an acetophenone C‐nucleoside were synthesized and incorporated in the middle of short oligodeoxynucleotides. The ketone oligonucleotides were converted to 15N‐labelled oxime oligonucleotides by treatment with 15N‐hydroxylamine and, finally, cyclopalladated by treatment with lithium tetrachloropalladate. Comparison of the UV melting profiles of duplexes bearing the β anomer of either the palladacyclic or the metal‐free oxime C‐nucleoside suggested formation of a stable Pd(II)‐mediated base pair, especially with adenine or thymine as the base pairing partner. Melting profiles of the corresponding duplexes bearing the α anomer were much more convoluted, precluding meaningful comparison. 15N NMR spectra were obtained for the β anomeric oxime oligonucleotide as well as its palladacyclic derivative but the signals unfortunately diminished below detection limit when the latter was hybridized with a complementary strand placing a 15N3‐labelled thymine opposite to the palladacyclic residue.