bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of CYP2D6 and CYP2C9 gene polymorphisms on the efficacy and safety of the combination of tramadol and ketorolac used for postoperative pain management in patients after video laparoscopic cholecystectomy
Authors: Muradian Andranik Alexandrovich , Sychev Dmitry Alekseevich , Blagovestnov Dmitry Alekseevich , Sozaeva Zhannet Alimovna , Akmalova Kristina Anatolyevna , Zastrozhin Michael Sergeevich , Kerimova Leyla Nabievna , Koroshvili Vadim Teymurazovich , Epifanova Irina Alexandrovna 
Published: April 2022

Abstract

Objectives
One of the key components of ERAS is adequate pain control in the postoperative period. There are no rational schemes for postoperative pain relief. At the same time, adequate postoperative pain relief promotes early activation and early rehabilitation of patients and shortens the duration of the postoperative stay, and does not cause postoperative complications associated with analgesia (weakness, intestinal paresis, nausea and vomiting). The aims of the present study are to assess the possible association of CYP2D6 and CYP2C9 polymorphisms with the efficacy and safety of tramadol and ketorolac in postoperative pain.

Methods
A total of 107 patients were genotyped for CYP2D6 and CYP2C9 polymorphisms. All patients underwent laparoscopic cholecystectomy. Postoperative pain relief was carried out with ketorolac and tramadol. Postoperative pain syndrome was assessed using a visual analogue scale and McGill pain questionnaire. The profile of side effects was assessed by the dynamics of red blood counts as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers.

Results
Pain was statistically significantly lower in CYP2C9*2 carriers, according to visual analogue scale (VAS): after 12 h – by 1.5 (p=0.002); after 24 h – by 1.1 (p=0.012); after 36 h – by 1.05 (p=0.004); after 48 h – by 0.7 (p=0.026). In CYP2C9*3 carriers the results were not statistically significant. In carriers of CYP2D6*4 pain syndromes were higher at all-time intervals, but statistically reliable results were obtained only after 2 h – by 1.01 (p=0.054) and after 24 h – by 0.8 (p=0.035). The profile of adverse reactions for NSAIDs was evaluated by the dynamics of hemoglobin and erythrocyte indices. A more pronounced decrease in the relative difference in hemoglobin levels was noted in CYP2C9*2 and CYP2C9*3 polymorphism carriers – by 1.7 (p=0.00268) and-by 2.2 (p=0.000143), respectively.

Conclusions

CYP2D6 and CYP2C9 can predict analgesic effectiveness of tramadol and ketorolac. CYP2C9 can predict the risk of gastrointestinal bleeding, including those hidden to ketorolac.
MicroRNAs as novel biomarkers for rivaroxaban therapeutic drug monitoring
Authors: Rytkin Eric , Bure Irina V. , Bochkov Pavel O. , Akmalova Kristina A. , Mirzaev Karin B. , Cherniaeva Marina S. , Ostroumova Olga D. , Smirnov Valery V. , Grishina Elena A. , Saribekian Anna G. , Sychev Igor N. , Sychev Dmitry A. 
Published: April 2022

Abstract

Objectives
The aim of this study is to assess micro-RNAs miR-142 and miR-39 as potential biomarkers for drug-monitoring of rivaroxaban among elderly patients with atrial fibrillation.

Methods
The study involved 57 patients with median (ME) age 87 years [80–94 years old] with nonvalvular atrial fibrillation admitted to a multidisciplinary hospital in Moscow. High-performance liquid chromatography with mass-spectrometry detection (HPLC-MS) was carried out to measure rivaroxaban concentrations. Carriership of CYP3A4 and ABCB1 was detected. MiRNA expression levels were measured. The activity of CYP3A4 isoenzyme was measured as the ratio of the concentrations of 6β-hydroxycortisol and cortisol.

Results
The miR-142 expression levels of patients with CC allelic variant polymorphism ABCB1 3435 C>T (rs1045642) were significantly higher compared to CT and TT variants 31.69 ± 1.60 vs. 34.06 ± 1.66 vs. 33.16 ± 1.77 (p=0.021). Carriers of TT allelic variant polymorphism ABCB1 rs4148738 had a higher concentration of the 6-beta-hydroxycortisol in urine compared to CC and CT variants 3,467.35 ± 1,055.53 vs. 3,453.52 ± 1,516.89 vs. 2,593.30 ± 1,172.52 (p=0.029). As for CYP3A4*22, the carriers of CC allelic variant had higher prothrombin time 14.10 ± 2.17 vs. 11.87 ± 0.60 and INR 1.31 ± 0.20 vs. 1.1 ± 0.06 but lower Quick’s value 74.52 ± 16.84 vs. 97.55 ± 10.54 (p=0.059). A positive correlation between the Ct miR-142 and the aPTT p=0.019 was noted. Also miR-142 has a correlation with Quick’s value p=0.095. There is no statistically significant connection between miR-142 and miR-39 expression levels and the plasma concentration of rivaroxaban (b coefficient=−2.055, SE 3.952, p=0.605 and b coefficient=1.546, SE 9.887, p=0.876 in the linear regression model respectively).

Conclusions
This study has assessed new potential biomarkers for rivaroxaban therapeutic drug monitoring: miR-142 and miR-39.
CYP2D6 phenotype and ABCB1 haplotypes are associated with antipsychotic safety in adolescents experiencing acute psychotic episodes
Authors: Ivashchenko Dmitriy V. , Yudelevich Daria A. , Buromskaya Nina I. , Shimanov Pavel V. , Deitch Roman V. , Akmalova Kristina A. , Kachanova Anastasia A. , Dorina Irina V. , Nastovich Marina I. , Grishina Elena A. , Savchenko Lyudmila M. , Shevchenko Yuriy S. , Sychev Dmitriy A. 
Published: April 2022

Abstract

Objectives
To identify possible associations of CYP2D6, CYP3A4/5, and ABCB1 gene polymorphisms with the efficacy and safety of antipsychotics in adolescents with acute psychotic episodes.

Methods
We examined the associations of pharmacogenetic factors with the efficacy and safety of antipsychotics in 101 adolescents with acute psychotic episodes. The diagnosis on admission was “Brief psychotic disorder” (F23.0–23.9 by ICD-10). All patients were administered antipsychotics for 14 days. Treatment efficacy and safety were assessed using the PANSS, CGAS, CGI-S(I), UKU SERS, BARS, and SAS scales. Pharmacokinetic genotyping was performed for the CYP2D6*4, *10, ABCB1 1236C>T, 2677G>T, and 3435C>T genes.

Results
CYP2D6 intermediate metabolisers had “Micturition disturbances” more often than extensive metabolisers (24.2 vs. 7.4%; p=0.026). “Wild” homozygote ABCB1 3435C>T CC was associated with more prominent akathisia. Haplotype analysis of three ABCB1 polymorphisms revealed that the “wild” alleles “C-G-C” (ABCB1 1236-2677-3435) were associated with higher risk of “Reduced salivation” (OR=2.95; 95% CI=1.35–6.45; p=0.0078).

Conclusions
CYP2D6 intermediate metabolism was associated with the risk of urinary difficulties under treatment with antipsychotics. We found that “wild” homozygotes ABCB1 1236C>T, 2677G>T, and 3435C>T were predictors of adverse drug effects caused by treatment with antipsychotics.
Migraine (Shaqeeqa) and its management in Unani medicine
Authors: Riyazuddin Mohd. , Shahid Arisha , Nagaraj Renuka Bangalore , Alam Md Anzar 
Published: April 2022

Abstract
Out of many disease conditions suffered by mankind since ancient ages, Migraine holds a significant position. It is derived from the word “hemi-crania” and is a type of primary headache. This disease is mentioned in the ancient scriptures dating back to the Mesopotamian era. It has been documented by Hippocrates (460–377 BC) in his treatise, further explored and explained on the basis of cause and location by Galen (131–201 AD). Later its etiopathogenesis clinical features and management was described by Al-Razi (850–923 AD), an eminent Unani physician. Migraine is a disease majorly affecting one side of the head and characterized by recurrent attacks of pulsating headache, mostly associated with nausea, vomiting, photophobia and phonophobia, with or without an aura. It is triggered by noise and light, based on the brightness, intensity, wavelengths or type of light that is being emitted. According to Unani physicians, the word Shaqeeqa is derived from Arabic word ‘Shiq’, meaning ‘a part’ or ‘a side’, hence the name Shaqeeqa. They describe it as a type of headache (Suda) in which pain occurs only in one side of head, and the causative factors for it are the morbid matters and morbid vapours (Bukharat e Radiya) arising from morbid humours which are either excessive in amount, too hot or too cold. It often results due to abnormal substantial temperament (Su-e-Mizaj Maddi) giving two variants acute (Shaqeeqa haar) and chronic (Shaqeeqa barid). The treatment mainly consists of elimination of morbid matter which is accumulated in the body, and strengthening the brain using brain tonics (Muqawwiyat-e-Dimagh).
Debt Spillovers in a Monetary Union: A Novel Rationale for Central Bank Independence
Authors: Campoy Juan Cristóbal , Negrete Juan Carlos 
Published: April 2022

Abstract
Central bank independence has been championed on the grounds that it avoids political business cycles, the time-inconsistency problem of discretionary monetary policy, and political conflicts. However, after the financial crisis, central banks have resorted to unconventional monetary policies and embraced additional tasks, making monetary authorities more exposed to political interference. This new reality has put into question the long-lasting consensus on the desirability of central bank independence. We add to this debate a new argument in support of that independence, namely, it internalizes the fiscal spillovers that arise in a monetary union, which is not a full fiscal union.
The Effectiveness of Fiscal-Budgetary Measures to Counteract the COVID-19 Crisis. Evidence from EU Countries
Authors: Dornean Adina , Oanea Dumitru-Cristian 
Published: April 2022

Abstract
The aim of this study is to analyse the fiscal-budgetary measures, which have been taken by almost all governments around the world, including EU countries, in an attempt to limit the negative impact of the pandemic blockade. In most cases, these measures concerned the granting of technical unemployment, the postponement of tax payments, and the suspension or postponement of loan instalments or their maturity. The present study focuses especially on tax and expenditure measures that EU countries have introduced in response to the COVID-19 crisis. With this purpose, a paired sample t-test and multiple linear regression are used based on balanced panel data for the 27 EU countries for the period 2000Q1–2020Q3. The obtained results show that COVID-19 crisis had a significant negative impact on GDP growth. At the same time, a significant increase in public debt and government deficit occurred due to COVID-19 crisis. However, resuming the findings, the intensity, and implicitly, the effect of these measures depends on the specifics of each economy.
Green synthesis of manganese-doped superparamagnetic iron oxide nanoparticles for the effective removal of Pb(ii) from aqueous solutions
Authors: Rehman Ata Ur , Sharafat Uzma , Gul Saima , Khan Murad Ali , Khan Sher Bahadar , Ismail Muhammad , Khan M. I. 
Published: April 2022

Abstract
In the current study, pure and manganese-doped superparamagnetic iron oxide nanoparticles (Mn-doped SPIONPs) were successfully prepared by a green approach using a fresh aqueous extract of Asparagus officinalis as a reducing and stabilizing agent. Magnetic behaviors of pure and Mn-doped SPIONPs were measured at room temperature against various field strengths by a vibrating sample magnetometer (VSM). The saturation magnetization was in the range of 5.39–2.07 emu. Absorption at 340 nm in the UV-visible spectrum confirmed the presence of iron oxide nanoparticles (IONPs). The presence of plant extract as a capping agent was confirmed by Fourier transform infrared (FTIR) spectroscopy. The crystalline nature of IONPs was confirmed by X-ray diffraction. A gradual increase in size was observed with increasing concentration of Mn. The synthesized materials were applied successfully as sorbent for the effective removal of lead ions (Pb(ii)). Experimental results of adsorption were also analyzed by Langmuir and Freundlich isotherm equations at different temperatures. The results suggested that sorption processes were spontaneous, and the synthesized SPIONPs displayed PbII removal capacity at higher loadings with q
m of 21.3 and 29.56 mg·g−1 for undoped and 7% Mn-doped IOPNs, respectively, as compared to the commercial activated carbon.
Effect of stabilizers on Mn ZnSe quantum dots synthesized by using green method
Authors: Nguyen Van Khiem , Pham Duy Khanh , Tran Ngoc Quyen , Dang Le Hang , Nguyen Ngoc Hoa , Nguyen Thanh Mien , Viet Nguyen Thanh , Oh Jin-Woo , Bui Thi-Diem , Luong Bich Thi 
Published: April 2022

Abstract
Herein, the effect of three types of capping polymers, mercaptopropionic acid (MPA), polyethylene glycol (PEG), and starch on the photoluminescence of Mn(2+)-doped ZnSe (ZnSe:Mn) nanoparticles, has been investigated. ZnSe:Mn nanoparticles were successfully prepared with a green method of precipitation in aqueous solutions containing MPA, PEG, or starch as stabilizers. The X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy had proved the formation of ZnSe:Mn particles and the interaction between them and the capping agents. The resultant nanoparticles with different capping polymers were identical in optical property; however, photoluminescence quantum yields (PLQY) as well as the photoluminescence lifetime varied by capping agents. Starch-capped ZnSe:Mn nanoparticles had the biggest size compared to others, which was confirmed using transmission electron microscopy, dynamic light scattering, UV-Vis absorbance and Raman spectroscopy. Also, the PL intensity was significantly enhanced with starch-capped ZnSe:Mn nanoparticles. The PLQYs of starch archived 26%, which was 1.23 or 1.8 times lower than that of ZnSe:Mn nanoparticles capping with MPA or PEG, respectively. Furthermore, the highest decline of PL intensity was detected in PEG, which completely diminished in the 19th week, while both MPA and starch endowed ZnSe:Mn nanoparticles with outstanding PL lifetimes diminished over seven weeks.
Einsatzhärten – Ein Prozess mit neuen Entwicklungen und Perspektiven*
Authors: Edenhofer B. 
Published: April 2022

Abstract
Das Einsatzhärten ist seit vielen Jahren der dominierende Wärmebehandlungsprozess für hoch beanspruchte Bauteile in Motoren, Maschinen, Getrieben, Fahrzeugaufhängungen, Düsentriebwerken usw. Diese herausragende Stellung ist entstanden trotz einiger Nachteile, die mit der klassischen Gasaufkohlung verbunden sind, wie verhältnismäßig langsamer Kohlenstoffübergang und lange Prozesszeiten, Oberflächenanomalitäten, indirekte Prozesskontrolle, hoher Gasverbrauch, Verwendung von Abschreckölen, Emissionen und nicht ganz einfache Arbeitsbedingungen.
Neuere Entwicklungen in der Verfahrenstechnik versprechen jetzt, diese Nachteile zu beheben, und bestimmen somit die Entwicklung des Einsatzhärtungsprozesses von Öfen in separaten Härtereien zu Wärmebehandlungsmaschinen, die in Fertigungslinien integriert sind. Diese Entwicklung wurde durch die Verwendung zweier gasförmiger Medien in Gang gesetzt. Es handelt sich hierbei einmal um Kohlenwasserstoffgase für die Aufkohlung und zum anderen um inerte Gase für das Abschrecken.
In der vorliegenden Arbeit werden die Einflüsse und Wirkungen dieser beiden gasförmigen Medien auf den Kohlenstoffübergang, das Randgefüge, die Prozesssteuerung und das Abschreckverhalten sowie die Anlagentechnik untersucht.
Einfluss des Prozessgases auf Kohlenstoffaufnahme und Rußbildung in Niederdruck-und Plasmaaufkohlungsprozessen*
Authors: Clausen B. , Laumen C. , Holm T. , Hoffmann F. , Mayr P. 
Published: April 2022

Abstract
Niederdruck- und Plasmaaufkohlung sind Aufkohlungstechniken, denen zunehmend Interesse entgegengebracht wird. Beide bieten einen vergleichsweise hohen Kohlenstoffmassenstrom in die Werkstückoberfläche, der gerade bei einer Anhebung der Aufkohlungstemperatur unverzichtbar ist. Das hohe Kohlenstoffangebot bei Niederdruckaufkohlungsprozessen (mit oder ohne Plasma) begünstigt auf der anderen Seite Rußbildung im Ofen. Kohlenstoffablagerungen auf den isolierenden keramischen Bauteilen des Ofens können zu Kurzschlüssen führen und müssen möglichst verhindert werden. Die Keramikbauteile müssen daher spätestens ersetzt werden, sobald sie elektrisch leitend werden. Das Ziel der hier vorgestellten Untersuchung ist, festzustellen, ob die Qualität und die Zusammensetzung der eingesetzten Prozessgase einen Einfluss auf die Rußbildung und den Kohlenstoffmassenstrom in die aufzukohlenden Oberflächen hat. Die Ergebnisse zeigen, dass sowohl Qualität als auch Zusammensetzung des Prozessgases einen deutlichen Einfluss haben, dass es aber überraschenderweise nicht erforderlich ist, die beste erhältliche Gasqualität einzusetzen, um optimierte Aufkohlungsergebnisse zu erhalten.
Oberflächenhärtung von austenitischen Stählen unter Beibehaltung der Korrosionsbeständigkeit*
Authors: Günther D. , Hoffmann F. , Jung M. , Mayr P. 
Published: April 2022

Abstract
Es wird über Untersuchungen zur Steigerung der Verschleißbeständigkeit austenitischer Stähle durch Aufkohlen berichtet. Randbedingung war, dass die hohe Korrosionsbeständigkeit des austenitischen Werkstoffes nicht beeinträchtigt werden darf. Bei der Prozessführung kommt neben weiteren Parametern der Temperatur eine wesentliche Bedeutung zu, um eine Mikrostruktur einzustellen, bei der sich Kohlenstoff in Lösung befindet und keine Chromcarbide ausgeschieden werden. Die Durchführung der Versuche wird beschrieben und die Ergebnisse werden anhand röntgenographischer, chemischer sowie metallographischer Untersuchungen analysiert und bewertet.
Neue Erkenntnisse zum Plasmaborieren mit Trimethylborat*
Authors: Küper A. , Stock H.-R. , Mayr P. 
Published: April 2022

Abstract
Mit Hilfe von dünnen Nickel-Barriereschichten auf dem Stahl 42CrMo4 konnten in einem plasmaunterstützten Prozess mit der Verbindung Trimethylborat, B(OCH3)3, kompakte Boridschichten der Zusammensetzung (Ni,Fe)2B und Fe2B erzeugt werden. Es wurde der Einfluss der Nickelschichtdicke, des Nickel-Abscheideverfahrens sowie der Prozessparameter Druck und Zeit auf die Boridschichtausbildung untersucht. Je nach Behandlungszeit – bei einer 2 μm dicken Nickel-Barriereschicht – hat die resultierende Boridschicht eine Dicke bis zu 160 μm und weist eine Härte von maximal 2150 HV 0,025 auf.
Das Primärgefüge sprühkompaktierter Stähle
Authors: Schulz A. , Matthaei-Schulz E. , Spangel S. , Tinscher R. , Vetters H. , Mayr P. 
Published: April 2022

Abstract
Sprühkompaktieren ist als ein neu entwickeltes Produktionsverfahren für technische Werkstoffe bekannt, speziell für die Herstellung hochwertiger Stähle. Die Vorteile der Zerstäubung der Schmelze in kleine Tröpfchen begleitet von extrem schneller Abkühlung bedingen eine bemerkenswerte Erhöhung der Homogenität bei der Entstehung des Primärgefüges im Vergleich zum konventionell abgegossenen Werkstoff. Diese Vorzüge werden auch im Halbzeug nach thermisch-mechanischen Behandlungen gefunden. Untersuchungen der sehr homogenen Gefüge an einem Wälzlagerstahl (100Cr6) und einem Schnellarbeitsstahl (HS6-5-2C) zeigen auch die Vermeidung von Poren durch hohe Verdichtung und die Eliminierung von Makroseigerungen.
Energie- und ressourcenschonende Fertigungsprozesse in der Metallbearbeitung*
Authors: Eckebrecht J. , Brinksmeier E. 
Published: April 2022

Abstract
Das Thema Umweltschutz ist in der Metall verarbeitenden Industrie von zunehmender Bedeutung. Das ECO-Centrum des Instituts für Werkstofftechnik beschäftigt sich mit der Weiterentwicklung von Fertigungsverfahren und konzentriert sich in seiner Arbeit insbesondere auf die Umweltaspekte, die mit dem Einsatz unterschiedlicher Fertigungsverfahren verbunden sind. Ein Ziel von besonderer Wichtigkeit ist es hierbei, Betriebe bei Lösungen in diesem Bereich zu unterstützen. Der folgende Beitrag beschäftigt sich mit der umweltverträglichen Gestaltung von Fertigungsprozessen und mit der Problematik des umwelttechnischen Vergleichs alternierender Verfahrensführungen.
Einfluss von Brechwerkzeugen auf die Eigenschaften von Betonrezyklaten
Authors: Diedrich R. 
Published: April 2022

Abstract
Bei der Aufbereitung von mineralischen Abbruch- und Aufbruchmassen werden bevorzugt der Prallbrecher und der Backenbrecher und vereinzelt auch der Kegelbrecher eingesetzt. Im Rahmen eines Forschungsvorhabens sollte geprüft werden, wie sich Beton bei der Zerkleinerung mit diesen Brechern und deren unterschiedlichen Brechwerkzeugen verhält. Dazu wurden die Brecher in verschiedenen Anlagen miteinander kombiniert, so dass aus Betonquadern zweier unterschiedlich fester Betonsorten (B15 und B35) der Abmessung 50 cm × 50 cm × 25 cm ein Korngemisch 0/32 mm für die Wiederverwertung im Beton nach DIN 1045 hergestellt werden kann. Es wurde das Brechgut aus vier Anlagentypen, der Prallbrecheranlage mit Überkornrückführung, der Backen-/Prallbrecheranlage, der Backen-/Kegelbrecheranlage und der Prall-/Kegelbrecheranlage untersucht. In dem vorliegenden Artikel werden nur die Ergebnisse der wichtigsten Untersuchungen aus dem Forschungsprojekt wie die Korngrößenverteilung, Kornform, Widerstand gegen Frost, Kornrohdichte und stoffliche Zusammensetzung vorgestellt. Dabei konnten werkstoffliche Unterschiede zwischen den Rezyklaten aus den verschiedenen Aufbereitungsanlagen aufgezeigt werden. Generell blieb bei allen Anlagen der Betoncharakter (Rohdichte/ Porosität/Widerstand gegen Frost) in den Rezyklatfraktionen 4/8, 8/16 und 16/32 im Wesentlichen erhalten.
The Death and Disposal of Sacred Texts
Authors: El Shamsy Ahmed 
Published: April 2022

Abstract
Both Islamic and Jewish thought display a sensitivity to the treatment of texts, particularly sacred texts. This article investigates Muslim debates on how to dispose of worn-out sacred texts. It argues that these debates were rooted in the precedent formed by the reported destruction of noncanonical copies of the Qurʾān by the third caliph ʿUthmān, and they featured various preferred and rejected methods of text disposal, including burning, washing, shredding, and burying. By the thirteenth century CE, these debates had yielded a robust theorization of worn-out texts as analogous to human corpses and thus deserving of respectful burial.
On stable parameter estimation and short-term forecasting with quantified uncertainty with application to COVID-19 transmission
Authors: Smirnova Alexandra , Pidgeon Brian , Luo Ruiyan 
Published: April 2022

Abstract
A novel optimization algorithm for stable parameter estimation and forecasting from limited incidence data for an emerging outbreak is proposed.
The algorithm combines a compartmental model of disease progression with iteratively regularized predictor-corrector numerical scheme aimed at the reconstruction of case reporting ratio, transmission rate, and effective reproduction number.
The algorithm is illustrated with real data on COVID-19 pandemic in the states of Georgia and New York, USA.
The techniques of functional data analysis are applied for uncertainty quantification in extracted parameters and in future projections of new cases.
Hard-to-learn conjunctive expressions for advanced learners: a survey on storytelling in I-JAS
Authors: Sunakawa Yuriko 
Published: April 2022

Abstract
There are basic grammatical items that are difficult to learn even for advanced learners, although they are introduced early at the beginning of their learning. Conjunctive expressions that imply speakers’ subjective feelings such as suruto ‘then,’ sokode ‘then and there’ are one such item. We use storytelling data from the “International Corpus of Japanese as a Second Language” to investigate how Japanese native speakers and Japanese L2 learners whose first languages are Chinese and Korean use conjunctive expressions at the turning moments of a story. The results indicate that even learners at an advanced level do not use conjunctive expressions that native Japanese speakers do to make stories vivid and lively. We explain this phenomenon using the concept of “subjective construal.” We further consult previous research on Japanese teaching practices and consider how to instruct this type of expression.