bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solution‐Processed Lead‐Free Perovskite Nanocrystal Scintillators for High‐Resolution X‐Ray CT Imaging
Authors: Zhou Jiaer , An Kang , He Peng , Yang Jie , Zhou Chang , Luo Yi , Kang Wei , Hu Wei , Feng Peng , Zhou Miao , Tang Xiaosheng 
Published: March 2021

AbstractThe physical properties of scintillators determine X‐ray detection performance directly, which plays a vital role in computed tomography (CT) imaging for medical radiography and security checks. Recently, lead halide perovskite materials have shown higher photoluminescence quantum yield (PLQY) than conventional X‐ray scintillators, but there are still some limitations, including instability and the use of heavy metal lead. In this study, a low‐temperature solution method is used to prepare 0D lead‐free Cs3Cu2I5 perovskite nanocrystals (NCs), and a corresponding optical fiber panel with Cs3Cu2I5 NCs is fabricated for high‐resolution X‐ray CT imaging. The Cs3Cu2I5 NCs exhibit a high PLQY of 59% and outstanding stability for more than three months. Importantly, the Cs3Cu2I5 NCs show a high radioluminescence (RL) light yield, that is four times higher than that of CsPbBr3 NCs (80 kV, 70 µA). In addition, an X‐ray detector based on a Cs3Cu2I5 NC scintillator is designed. Using this system, a clear projection image of a chip is obtained, and a 3D CT image of a snail is reconstructed. Therefore, the use of lead‐free perovskite nanocrystal scintillators is a promising technique for commercial X‐ray detection.
Bayesian hybrid analytics for uncertainty analysis and real‐time crop management
Authors: Meenken Esther D. , Triggs Christopher M. , Brown Hamish E. , Sinton Sarah , Bryant Jeremy R. , Noble Alasdair D.L. , Espig Martin , Sharifi Mostafa , Wheeler David M. 
Published: March 2021

AbstractDynamic, deterministic agricultural models, and current machine learning technologies based on sensor data, enable and support decision making for on‐farm management. However, their predictions are subject to various sources of uncertainty. Hybrid analytics that leverage both modelled and sensor data provide predictive information that makes the best of both approaches in a timely fashion to inform operational decision making and enable inclusive uncertainty quantification. We describe and evaluate a probabilistic Bayesian data assimilation tool that combines the state variables from the Sirius wheat (Triticum aestivum L.) development model with time‐series environmental and leaf count data. Additionally, the uncertainty associated with input parameters is quantified via expert opinion. The Bayesian approach obtained point estimates through time that were accompanied by inclusive, probabilistic, 95% credible intervals. At the end of simulation, a typical model predicted a final leaf number of 6.6 leaves, Sirius alone predicted seven leaves and the mean of the observed data was 6.7 leaves. The 95% credible interval was estimated as 5.1–8.4 leaves. Importantly, the tool was able to “redirect” simulated outputs if input parameters such as minimum leaf number or base phyllochron were incorrectly specified, with the implication that on‐farm decision makers would have advance warning of variation in expected harvest date. Relatively few plants with time‐intensive data were sufficient to fit the model, however, more plants would be desirable to reduce the rather wide range of credible intervals. Nevertheless, the tool shows potential and could be readily implemented with low resource requirements, providing more finely tuned harvest date information, with probabilistic uncertainty quantification built‐in, for on‐farm decisions.
Effects of work stress, sleep, and shift work on suicidal ideation among female workers in an electronics company
Authors: Son Junseok , Lee Sangyoon 
Published: March 2021

AbstractBackgroundSuicide is the leading cause of death in young adults in Korea. Stress in the workplace affects the suicide rate; young female workers are particularly vulnerable to adverse work environments. We investigated the relationships of shift work, sleep, and work stress to suicidal ideation.MethodsThis study used data from 508 female workers aged 22–40 years in an electronics company. Data on baseline characteristics, work patterns, sleep quality (using the Pittsburgh Sleep Quality Index), and work stress levels using the Korean Occupational Stress Scale (KOSS) were obtained from questionnaires. We examined associations between suicidal ideation and shift work, sleep quality, and KOSS scores.ResultsSuicidal ideation was significantly higher among shift workers (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.31–4.32), those with poor sleep (OR, 2.84; 95% CI, 1.68–4.84), and those with high work stress (OR, 3.30; 95% CI, 1.82–6.00). Both 3 × 12 h shift workers (OR, 2.98; 95% CI, 1.35–6.57) and 4 × 8 h shift workers (OR, 2.14; 95% CI, 1.03–4.45) had increased suicidal ideation. High work stress (OR, 11.55; 95% CI, 2.93–45.48) had stronger associations with suicidal ideation than poor sleep (OR, 3.86; 95% CI, 1.21–12.33) in shift workers. The combined effect of poor sleep and high KOSS on suicidal ideation was stronger in shift workers (OR, 13.39; 95% CI, 3.22–55.62) than day workers (OR, 4.31; 95% CI, 1.03–18.01).ConclusionsShift workers are more vulnerable than day workers to the combination of work stress and poor sleep quality as well as to work stress alone.
Struktur eines an virusähnliche Partikel gekoppelten Antigens: Analyse einer Impfstoff‐Formulierung
Authors: Jaudzems Kristaps , Kirsteina Anna , Schubeis Tobias , Casano Gilles , Ouari Olivier , Bogans Janis , Kazaks Andris , Tars Kaspars , Lesage Anne , Pintacuda Guido 
Published: March 2021

AbstractDie Strukturbestimmung Wirkverstärker‐gekoppelter Antigene ist für eine rationale Impfstoffentwicklung unerlässlich, wurde aber bisher durch den recht geringen Antigengehalt in Impfstoff‐Formulierungen und durch deren heterogene Zusammensetzung erschwert. Wir zeigen, dass die Festkörper‐NMR mit Magic Angle Spinning (MAS) zur Bestimmung der Struktur des Influenza‐Virus‐Hämagglutinin‐Stiel‐Antigens verwendet werden kann, und dies sowohl in seiner freien Form sowie nach chemischer Kopplung an die Oberfläche großer virusähnlicher Partikel (VLPs). Die Steigerung der Sensitivität durch dynamische nukleare Polarisation (DNP) und Protonen‐Detektion bei schnellen MAS‐Raten ermöglicht es, den mit der Antigenverdünnung verbundenen Nachteil auszugleichen. Der Vergleich der MAS‐NMR‐Fingerabdrücke zwischen freier und VLP‐gekoppelter Antigenform liefert strukturelle Beweise für die Erhaltung seiner nativen Faltung nach der Bio‐Konjugation. Die hochempfindliche MAS‐NMR ist reif, um eine wichtige Rolle bei Impfstoffdesign, Formulierungsstudien und der Entwicklung von Herstellungsprozessen zu spielen.
NHC‐Catalyzed Desymmetrization of N‐Aryl Maleimides Leading to the Atroposelective Synthesis of N‐Aryl Succinimides
Authors: Barik Soumen , Shee Sayan , Das Soumik , Gonnade Rajesh G. , Jindal Garima , Mukherjee Subrata , Biju Akkattu T. 
Published: March 2021

AbstractAlthough the construction of axially chiral C−C bonds leading to the atroposelective synthesis of biaryls and allied compounds are well‐known, the related synthesis of compounds bearing axially chiral C−N bonds are relatively rare. Described herein is the N‐heterocyclic carbene‐catalyzed atroposelective synthesis of N‐aryl succinimides having an axially chiral C−N bond via the desymmetrization of N‐aryl maleimides. The NHC involved intermolecular Stetter‐aldol cascade of dialdehydes with prochiral N‐aryl maleimides followed by oxidation afforded N‐aryl succinimides in good yields and ee values. Preliminary studies on rotation barrier for the C−N bond, the temperature dependence, and detailed DFT studies on mechanism are also provided.
Beyond Classical Coordination Chemistry: The First Case of a Triply Bridging Phosphine Ligand
Authors: Baranov Andrey Y. , Pritchina Elena A. , Berezin Alexey S. , Samsonenko Denis G. , Fedin Vladimir P. , Belogorlova Nataliya A. , Gritsan Nina P. , Artem'ev Alexander V. 
Published: March 2021

AbstractThe first example of a triply bridging (μ3‐P) phosphine ligand has been discovered in the crown‐shaped [Cu3(μ2‐Hal)3L] (Hal=Cl, Br, or I) complexes supported by tris[2‐(2‐pyridyl)ethyl]phosphine (L). Theoretical analysis completely confirms the observed μ3‐P‐bridging pattern, revealing the interaction of the same lone pair of phosphorus with three valence 4s‐orbitals of Cu atoms. The presented complexes exhibit outstanding blue phosphorescence (λem=442–465 nm) with the quantum efficiency reaching 100 %. The complex [Cu3(μ2‐I)3L] also exhibits remarkable thermo‐ and mechanochromic luminescence resulting in a sharp change in the emission colour upon external stimuli. These findings essentially contribute to coordination chemistry of the pnictine ligands.
Chemo‐Enzymatic Modification of the 5′ Cap Maintains Translation and Increases Immunogenic Properties of mRNA
Authors: van Dülmen Melissa , Muthmann Nils , Rentmeister Andrea 
Published: March 2021

AbstractEukaryotic mRNAs are emerging modalities for protein replacement therapy and vaccination. Their 5′ cap is important for mRNA translation and immune response and can be naturally methylated at different positions by S‐adenosyl‐l‐methionine (AdoMet)‐dependent methyltransferases (MTases). We report on the cosubstrate scope of the MTase CAPAM responsible for methylation at the N6‐position of adenosine start nucleotides using synthetic AdoMet analogs. The chemo‐enzymatic propargylation enabled production of site‐specifically modified reporter‐mRNAs. These cap‐propargylated mRNAs were efficiently translated and showed ≈3‐fold increased immune response in human cells. The same effects were observed when the receptor binding domain (RBD) of SARS‐CoV‐2—a currently tested epitope for mRNA vaccination—was used. Site‐specific chemo‐enzymatic modification of eukaryotic mRNA may thus be a suitable strategy to modulate translation and immune response of mRNAs for future therapeutic applications.
Chemical Evolution of Antivirals Against Enterovirus D68 through Protein‐Templated Knoevenagel Reactions
Authors: Tauber Carolin , Wamser Rebekka , Arkona Christoph , Tügend Marisa , Abdul Aziz Umer Bin , Pach Szymon , Schulz Robert , Jochmans Dirk , Wolber Gerhard , Neyts Johan , Rademann Jörg 
Published: March 2021

AbstractThe generation of bioactive molecules from inactive precursors is a crucial step in the chemical evolution of life, however, mechanistic insights into this aspect of abiogenesis are scarce. Here, we investigate the protein‐catalyzed formation of antivirals by the 3C‐protease of enterovirus D68. The enzyme induces aldol condensations yielding inhibitors with antiviral activity in cells. Kinetic and thermodynamic analyses reveal that the bioactivity emerges from a dynamic reaction system including inhibitor formation, alkylation of the protein target by the inhibitors, and competitive addition of non‐protein nucleophiles to the inhibitors. The most active antivirals are slowly reversible inhibitors with elongated target residence times. The study reveals first examples for the chemical evolution of bio‐actives through protein‐catalyzed, non‐enzymatic C−C couplings. The discovered mechanism works under physiological conditions and might constitute a native process of drug development.
Synthesis of novel sulfonamides with anti‐Alzheimer and antioxidant capacities
Authors: Gök Nihal , Akıncıoğlu Akın , Erümit Binici Edanur , Akıncıoğlu Hülya , Kılınç Namık , Göksu Süleyman 
Published: March 2021

AbstractA series of novel dopamine analogs incorporating urea and sulfonamide functional groups was synthesized from 3,4‐dimethoxyphenethylamine. The reaction of 3,4‐dimethoxyphenethylamine with N,N‐dimethylcarbamoyl chloride, followed by the sulfonyl chlorination of the urea derivative, gave benzene‐1‐sulfonyl chloride 9, which was reacted with NH3 (aq) or N‐alkyl amines to give related sulfonamides. The O‐demethylation reaction of the subsequent compounds with BBr3 afforded four novel phenolic dopamine analogs including sulfonamide and urea in the same structure. The anticholinergic and antioxidant effects of the synthesized compounds were examined. Compound 13 exhibited inhibition at the micromolar level for both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The IC50 value of 13 was calculated as 298 ± 43 µM for AChE and 321 ± 29 µM for BChE. The antioxidant and antiradical effects of the molecules were investigated by five different methods. Among the synthesized compounds 10–18, the best antioxidant and antiradical activities belong to the phenolic compounds 15–18. Compounds 16 and 18 have a higher reducing power than the standards used, that is, butylated hydroxytoluene, butylated hydroxyanisole, Trolox, and α‐tocopherol, for Fe3+–Fe2+ and Cu2+–Cu+ reducing activities. For the DPPH• radical scavenging method, compounds 16–18 have a much better scavenging power than the standard molecules. In addition, it has been determined by the induced‐fit docking method that compound 13 is well‐fitted in the active site of the enzymes. ADME studies reveal that the pharmacokinetic and physicochemical properties of all synthesized compounds are within an acceptable range.
Reducing Immunogenicity of Pegloticase With Concomitant Use of Mycophenolate Mofetil in Patients With Refractory Gout: A Phase II, Randomized, Double‐Blind, Placebo‐Controlled Trial
Authors: Khanna Puja P. , Khanna Dinesh , Cutter Gary , Foster Jeff , Melnick Joshua , Jaafar Sara , Biggers Stephanie , Rahman A. K. M. Fazlur , Kuo Hui‐Chien , Feese Michelle , Kivitz Alan , King Charles , Shergy William , Kent Jeff , Peloso Paul M. , Danila Maria I. , Saag Kenneth G. 
Published: March 2021

ObjectivePegloticase is used for the treatment of severe gout, but its use is limited by immunogenicity. This study was undertaken to evaluate whether mycophenolate mofetil (MMF) prolongs the efficacy of pegloticase.MethodsParticipants were randomized 3:1 to receive 1,000 mg MMF twice daily or placebo for 14 weeks, starting 2 weeks before receiving pegloticase and continuing while receiving intravenous pegloticase 8 mg biweekly for 12 weeks. Participants then received pegloticase alone from week 12 to week 24. The primary end points were the proportion of patients who sustained a serum urate level of ≤6 mg/dl at 12 weeks and the rate of adverse events (AEs). Secondary end points included 24‐week durability of serum urate level ≤6 mg/dl. Fisher’s exact test and Wilcoxon’s 2‐sample test were used for analyses, along with Kaplan‐Meier estimates and log rank tests.ResultsA total of 32 participants received ≥1 dose of pegloticase. Participants were predominantly men (88%), with a mean age of 55.2 years, mean gout duration of 13.4 years, and mean baseline serum urate level of 9.2 mg/dl. At 12 weeks, a serum urate level of ≤6 mg/dl was achieved in 19 (86%) of 22 participants in the MMF arm compared to 4 (40%) of 10 in the placebo arm (P = 0.01). At week 24, the serum urate level was ≤6 mg/dl in 68% of MMF‐treated patients versus 30% of placebo‐treated patients (P = 0.06), and rates of AEs were similar between groups, with more infusion reactions occurring in the placebo arm (30% versus 0%).ConclusionOur findings indicate that MMF therapy with pegloticase is well tolerated and shows a clinically meaningful improvement in targeted serum urate level of ≤6 mg/dl at 12 and 24 weeks. This study suggests an innovative approach to pegloticase therapy in gout.
Prenatal developmental toxicity of alkyl dimethyl benzyl ammonium chloride and didecyl dimethyl ammonium chloride in CD rats and New Zealand White rabbits
Authors: Hostetler Keith A. , Fisher Louan C. , Burruss Benjamin L. 
Published: March 2021

AbstractThe prenatal developmental toxicity potential of alkyl dimethyl benzyl ammonium chloride (ADBAC) and didecyl dimethyl ammonium chloride (DDAC) was evaluated in regulatory‐compliant studies. Pregnant female CD rats (25/group) and New Zealand White rabbits (16/group) were administered ADBAC (0, 10, 30, or 100 mg/kg/day and 0, 1, 3, or 9 mg/kg/day, respectively), or DDAC (0, 1, 10, or 20 mg/kg/day and 0, 1, 3, or 10 mg/kg/day, respectively), by oral gavage on gestation days (GD) 6–15 for rats and GD 6–18 for rabbits. At scheduled termination (GD 21 for rats; GD 29 for rabbits), maternal necropsies were conducted and live fetuses were weighed and examined for external, visceral, and skeletal malformations and variations. Clinical signs of maternal toxicity were observed in rats and rabbits dosed with ADBAC, resulting in no‐observed‐adverse‐effect levels (NOAELs) of 10 and 3 mg/kg/day, respectively. Despite the treatment‐related maternal toxicity of ADBAC, the NOAEL for prenatal developmental toxicity was 100 and 9 mg/kg/day for rats and rabbits, respectively, the highest doses evaluated. Repeated oral doses of DDAC resulted in maternal toxicity in both species at the top two doses, with 25% mortality noted in rabbits at 10 mg/kg/day. No teratogenic effects were observed at any dose for either species. However, increased incidence of dead fetuses per litter and decreased fetal body weights were observed in rabbits at the maternally lethal dose of 10 mg/kg/day. The NOAEL for maternal toxicity of DDAC was 1 mg/kg/day for both species and the NOAEL for prenatal developmental toxicity was 20 and 3 mg/kg/day, for rats and rabbits, respectively.
Enantioselective Synthesis of 3‐Substituted 3‐Amino‐2‐oxindoles by Amination with Anilines
Authors: Yang Wenkun , Dong Pei , Xu Jian , Yang Jian , Liu Xiaohua , Feng Xiaoming 
Published: March 2021

AbstractA chiral N,N′‐dioxide‐nickel(II) complex‐catalyzed asymmetric amination of 3‐bromo‐3‐substituted oxindoles with anilines has been developed. A series of alkyl or aryl 3‐amino‐indolinones with quaternary stereocenters were obtained in high yields with excellent ee values in one step (up to 99 % yield, up to 96 % ee). The method provided a ready route to optically active intermediates of 3‐amino‐2‐oxindole‐based bioactive compounds. Moreover, a possible transition‐state model is proposed so as to elucidate the origin of the chirality based on the X‐ray crystal structure of the catalyst and the adduct.
Evaluation of Drug‐Drug Interaction Liability for Buprenorphine Extended‐Release Monthly Injection Administered by Subcutaneous Route
Authors: Kharidia Jahnavi , Howgate Eleanor M. , Laffont Celine M. , Liu Yongzhen , Young Malcolm A. 
Published: March 2021

AbstractBuprenorphine extended‐release (BUP‐XR) formulation is a once‐monthly subcutaneous injection for the treatment of opioid use disorder (OUD). Buprenorphine undergoes extensive cytochrome P450 (CYP) 3A4 metabolism, leading to potential drug‐drug interactions (DDIs) as reported for sublingual buprenorphine. Sublingual buprenorphine is subject to first‐pass extraction, as a significant proportion of the dose is swallowed. Because subcutaneous administration avoids first‐pass extraction, the DDI with CYP3A4 inhibitors is expected to be less than the 2‐fold increase reported for the sublingual route. The objective of this analysis was to predict the magnitude of DDI following coadministration of BUP‐XR with a strong CYP3A4 inhibitor or inducer using physiologically based pharmacokinetic (PBPK) modeling. Models were developed and verified by comparing predicted and observed data for buprenorphine following intravenous and sublingual dosing. Comparison of predicted and observed pharmacokinetic (PK) profiles and PK parameters demonstrated acceptable predictive performance of the models (within 1.5‐fold). Buprenorphine plasma concentrations following administration of a single dose of BUP‐XR (300 mg) were simulated using a series of intravenous infusions. Daily coadministration of strong CYP3A4 inhibitors with BUP‐XR predicted mild increases in buprenorphine exposures (AUC, 33%‐44%; Cmax, 17‐28%). Daily coadministration of a strong CYP3A4 inducer was also associated with mild decreases in buprenorphine AUC (28%) and Cmax (22%). In addition, the model predicted minimal increases in buprenorphine AUC (8%‐11%) under clinical conditions of 2 weeks’ treatment with CYP3A4 inhibitors administered after initiation of BUP‐XR. In conclusion, the PBPK predictions indicate that coadministration of BUP‐XR with strong CYP3A4 inhibitors or inducers would not result in clinically meaningful interactions.
Assessment of biological matrices for the detection of in utero cannabis exposure
Authors: Concheiro Marta , Gutierrez Frank Martin , Ocampo Alejandro , Lendoiro Elena , González‐Colmenero Eva , Concheiro‐Guisán Ana , Peñas‐Silva Patricia , Macías‐Cortiña Manuel , Cruz‐Landeira Angelines , López‐Rivadulla Manuel , de‐Castro‐Ríos Ana 
Published: March 2021

AbstractCannabis consumption has been increasing worldwide among pregnant women. Due to the negative effects of prenatal cannabis exposure, it is necessary to develop an objective, sensitive, and specific method to determine cannabinoids use during pregnancy. In this study, we compared four different biological samples, maternal hair, meconium, umbilical cord, and placenta, for the detection of in utero cannabis exposure. The biological samples were collected from 627 mother–newborn dyads. All hair and meconium samples were analyzed, and umbilical cord and placenta if hair and/or meconium were positive for cannabinoids. Meconium and hair showed to complement each other, with an agreement between hair and meconium results of 96.7% but only 34.3% if just positive results were considered. Umbilical cord and placenta results showed a better agreement with meconium (91.3% and 92.6%, respectively) than with hair (39.1% and 34.6%, respectively). The predominant metabolites in meconium were 11‐nor‐carboxy‐THC (THCCOOH) and 8,11‐dihydroxy‐THC (diOHTHC), and in umbilical cord and placenta was THCCOOH‐glucuronide. Cannabidiol (CBD) and cannabinol (CBN) were detected in meconium but not in any umbilical cord or placenta. For the first time, prenatal marijuana exposure was analyzed and compared in paired hair, meconium, umbilical cord, and placental samples. Hair and meconium positivity rate was similar, but a more sensitive and specific analytical method for the hair may resolve discrepancies between the matrices. Umbilical cord and placenta may be considered suitable alternative matrices to meconium through the determination of THCCOOH‐glucuronide as a biomarker of cannabis exposure.