bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk of Infection in Children With Psoriasis Receiving Treatment With Ustekinumab, Etanercept, or Methotrexate Before and After Labeling Expansion
Authors: Schneeweiss Maria C. , Savage Timothy J. , Wyss Richard , Jin Yinzhu , Schoder Katharina , Merola Joseph F. , Sidbury Robert , Oduol Theresa , Schneeweiss Sebastian , Glynn Robert J. 
Published: February 2023

ImportancePsoriasis in children is increasingly treated with systemic medications, yet their risk of serious infection is not well characterized in clinical practice. Pediatric clinical trials for these medications were often small and placebo controlled.ObjectiveTo estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate.Design, Setting, and ParticipantsThis cohort study used insurance claims data from clinical practices across the US on children aged 17 years or younger with psoriasis who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. The analysis was stratified by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021). Patient follow-up started 1 day after initiating treatment and ended at 6 months.ExposuresNew treatment with ustekinumab, etanercept, and methotrexate.Main Outcomes and MeasuresDuring follow-up, the frequency of inpatient serious infections and outpatient infections requiring treatment was compared. Event rates and rate ratios were estimated after propensity score decile stratification.ResultsAfter exclusions, we identified 2338 patients (1368 girls [57.8%]) who initiated new treatment with a targeted immunomodulating agent. In all, 379 patients started treatment with ustekinumab, 779 patients started treatment with etanercept, and 1180 patients started treatment with methotrexate from 2009 through 2021. The propensity score–adjusted incidence rate of serious infection was 18.4 per 1000 person-years (3 events) for ustekinumab users, 25.6 per 1000 person-years (9 events) for etanercept users, and 14.9 per 1000 person-years (8 events) for methotrexate users. The adjusted rate of outpatient infections was 254.9 per 1000 person-years (39 events) for ustekinumab users, 435.7 per 1000 person-years (139 events) for etanercept users, and 433.6 per 1000 person-years (209 events) for methotrexate users. The adjusted rate ratio of outpatient infections was 0.58 (95% CI, 0.41-0.83) for ustekinumab vs etanercept, 0.66 (95% CI, 0.48-0.91) for ustekinumab vs methotrexate, and 0.95 (95% CI, 0.75-1.21) for etanercept vs methotrexate. Rate ratios were similar during the off-label use era and after pediatric labeling.Conclusions and RelevanceAmong children with psoriasis who started treatment with immunomodulating agents, serious infections were infrequent. This cohort study suggests that there was no increase in the risk of outpatient infections for children who started treatment with ustekinumab compared with etanercept or methotrexate.
Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction
Authors: Köhler-Forsberg Kristin , Dam Vibeke H. , Ozenne Brice , Sankar Anjali , Beliveau Vincent , Landman Elizabeth B. , Larsen Søren V. , Poulsen Asbjørn S. , Ip Cheng-Teng , Jørgensen Anders , Meyer Michal , Stenbæk Dea S. , Eiberg Hans R. L. , Madsen Jacob , Svarer Claus , Jørgensen Martin B. , Frokjaer Vibe G. , Knudsen Gitte M. 
Published: February 2023

ImportanceThe cerebral serotonin 4 (5-HT4) receptor is a promising novel target for treatment of major depressive disorder (MDD), and pharmacological stimulation of the 5-HT4 receptor has been associated with improved learning and memory in healthy individuals.ObjectiveTo map the neurobiological signatures of patients with untreated MDD compared with healthy controls and to examine the association between cerebral 5-HT4 receptor binding and cognitive functions in the depressed state.Design, Setting, and ParticipantsThis case-control study used baseline data from the NeuroPharm clinical depression trial in Denmark. Adult participants included antidepressant-free outpatients with a current moderate to severe depressive episode and healthy controls. All participants completed positron emission tomography (PET) scanning with [11C]SB207145 for quantification of brain 5-HT4 receptor binding, but only the patients underwent cognitive testing. Data analyses were performed from January 21, 2020, to April 22, 2022.Main Outcomes and MeasuresThe main study outcome was the group difference in cerebral 5-HT4 receptor binding between patients with MDD and healthy controls. In addition, the association between 5-HT4 receptor binding and verbal memory performance in the patient group was tested. Other cognitive domains (working memory, reaction time, emotion recognition bias, and negative social emotions) were assessed as secondary outcomes.ResultsA total of 90 patients with untreated MDD (mean [SD] age, 27.1 [8.2] years; 64 women [71.1%]) and 91 healthy controls (mean [SD] age, 27.1 [8.0] years; 55 women [60.4%]) were included in the analysis. Patients with current MDD had significantly lower cerebral 5-HT4 receptor binding than healthy controls (−7.0%; 95% CI, −11.2 to −2.7; P = .002). In patients with MDD, there was a correlation between cerebral 5-HT4 receptor binding and verbal memory (r = 0.29; P = .02).Conclusions and RelevanceResults of this study show that cerebral 5-HT4 receptor binding was lower in patients with MDD than in healthy controls and that the memory dysfunction in patients with MDD was associated with lower cerebral 5-HT4 receptor binding. The cerebral 5-HT4 receptor is a promising treatment target for memory dysfunction in patients with MDD.
DNA‐Encoded Immunoassay in Picoliter Drops: A Minimal Cell‐Free Approach
Authors: Jacková Barbara , Mottet Guillaume , Rudiuk Sergii , Morel Mathieu , Baigl Damien 
Published: February 2023

AbstractImmunoassays have emerged as indispensable bioanalytical tools but necessitate long preliminary steps for the selection, production, and purification of the antibody(ies) to be used. Here is explored the paradigm shift of creating a rapid and purification‐free assay in picoliter drops where the antibody is expressed from coding DNA and its binding to antigens concomitantly characterized in situ. Efficient synthesis in bulk of various functional variable domains of heavy‐chain only antibodies (VHH) using reconstituted cell‐free expression media, including an anti‐green fluorescent protein VHH, is shown first. A microfluidic device is then used to generate monodisperse drops (30 pL) containing all the assay components, including a capture scaffold, onto which the accumulation of VHH:antigen produces a specific fluorescent signal. This allows to assess, in parallel or sequentially at high throughput (500 Hz), the VHH‐antigen binding and its specificity in less than 3 h, directly from a VHH‐coding DNA, for multiple VHH sequences, various antigens and down to DNA concentrations as low as 12 plasmids per drop. It is anticipated that the ultraminiaturized format, robustness, and programmability of this novel cell‐free immunoassay concept will constitute valuable assets in fields as diverse as antibody discovery, point‐of‐care diagnostics, synthetic biology, and/or bioanalytical assays.
Electronic States Regulation Induced by the Synergistic Effect of Cu Clusters and Cu‐S1N3 Sites Boosting Electrocatalytic Performance
Authors: Yu Fengshou , Zhan Jiayu , Chen Datong , Guo Jiangyi , Zhang Shaobo , Zhang Lu‐Hua 
Published: February 2023

AbstractThe precise coordination environment manipulation and interfacial electron redistribution are significant strategies for the modulation of electronic configuration and intermediates adsorption behaviors, while the complex synergistic effect is yet to materialize due to the lack of catalyst platform. Herein, an atomic‐scale catalyst platform containing single Cu site with tunable coordination environment (Cu‐N4 or Cu‐S1N3) and easy decoration of Cu cluster (Cux) for electrochemical O2 reduction reaction (ORR) is reported. Theoretical analysis shows that the charge redistribution and up‐shifting d‐band center of single Cu site induced by the asymmetrical coordination environment and Cux effectively strength *OOH adsorption. The modulation in intermediates adsorption enables Cu‐S1N3/Cux a superior ORR performance compared with the samples without S atom and/or Cux. Moreover, the adsorption behavior of *OOH and d‐band center of single Cu site tuned by coordination environment and interfacial interactions are correlated linearly with catalytic potential, e.g., half‐wave potential and reaction kinetic, e.g., Tafel slope for ORR, indicating the high applicability of the intermediate adsorption strength and d‐band center as the indicators for catalytic performance. This study provides a comprehensive modulation strategy for electron configuration and intermediates adsorption behaviors, and can be extended to facilitate other proton‐coupled electron transfer reactions.
Machine‐Learning Assisted Electronic Skins Capable of Proprioception and Exteroception in Soft Robotics
Authors: Shu Sheng , Wang Ziming , Chen Pengfei , Zhong Junwen , Tang Wei , Wang Zhong Lin 
Published: February 2023

AbstractInspired by natural biological systems, soft robots have recently been developed, showing tremendous potential in real‐world applications because of their intrinsic softness and deformability. The confluence of electronic skins and machine learning is extensively studied to create effective biomimetic robotic systems. Based on a differential piezoelectric matrix, this study presents a shape‐sensing electronic skin (SSES) that can recognize surface conformations with minimal interference from pressing, stretching, or other surrounding stimuli. It is then integrated with soft robots to reconstruct their shape during movement, serving as a proprioceptive sense. Additionally, the robot can utilize machine learning to identify various terrains, demonstrating exteroception and pointing toward more advanced autonomous robots capable of performing real‐world tasks in challenging environments.
Trichloromethyl‐Radical‐Initiated Three‐Component Reaction of Alkenes with CHCl3 and Quinoxalinones
Authors: Wu Yechun , Zhang Jie , Yu Jin‐Tao , Pan Changduo 
Published: February 2023

AbstractAn iron(II)‐catalyzed three‐component reaction was developed for the construction of trichloromethylated 3‐benzylquinoxalin‐2(1H)‐ones. This reaction was conducted through the trichloromethylation of alkenes with quinoxalin‐2(1H)‐ones using commercially available chloroform as trichloromethyl radical source, which provided a convenient approach toward trichloromethylated 3‐benzylquinoxalin‐2(1H)‐ones.magnified image
Atomic Scaled Depth Correlation to the Oxygen Reduction Reaction Performance of Single Atom Ni Alloy to the NiO2 Supported Pd Nanocrystal
Authors: Li Haolin , Dai Sheng , Wu Yawei , Dong Qi , Chen Jianjun , Chen Hsin‐Yi Tiffany , Hu Alice , Chou Jyh‐Pin , Chen Tsan‐Yao 
Published: February 2023

AbstractThis study demonstrates the intercalation of single‐atom Ni (NiSA) substantially reduces the reaction activity of Ni oxide supported Pd nanoparticle (NiO2/Pd) in the oxygen reduction reaction (ORR). The results indicate the transition states kinetically consolidate the adsorption energy for the chemisorbed O and OH species on the ORR activity. Notably, the NiO2/Ni1/Pd performs the optimum ORR behavior with the lowest barrier of 0.49 eV and moderate second‐step barrier of 0.30 eV consequently confirming its utmost ORR performance. Through the stepwise cross‐level demonstrations, a structure–Eads–ΔE correspondence for the proposed NiO2/Nin/Pd systems is established. Most importantly, such a correspondence reveals that the electronic structure of heterogeneous catalysts can be significantly differed by the segregation of atomic clusters in different dimensions and locations. Besides, the doping‐depth effect exploration of the NiSA in the NiO2/Pd structure intrinsically elucidates that the Ni atom doping in the subsurface induces the most fruitful NiSA/PdML synergy combining the electronic and strain effects to optimize the ORR, whereas this desired synergy diminishes at high Pd coverages. Overall, the results not only rationalize the variation in the redox properties but most importantly provides a precision evaluation of the process window for optimizing the configuration and composition of bimetallic catalysts in practical experiments.
Novel phenotype of aortic root dilatation and late‐onset metabolic decompensation in a patient with TMEM70 deficiency
Authors: Mackay Laura , Gijavanekar Charul , Streff Haley , Price Jack F. , Elsea Sarah H. , Scaglia Fernando 
Published: February 2023

AbstractTMEM70 deficiency causing mitochondrial complex V deficiency, nuclear type 2 (MIM: 614052) is the most common nuclear encoded defect affecting ATP synthase and has been well described in the literature as being characterized by neonatal or infantile onset of poor feeding, hypotonia, lethargy, respiratory compromise, heart failure, lactic acidosis, hyperammonemia, and 3‐methylglutaconic aciduria progressing to a phenotype of developmental delay, failure to thrive, short stature, nonprogressive cardiomyopathy, microcephaly, facial dysmorphisms, hypospadias, persistent pulmonary hypertension of the newborn, and Wolff–Parkinson–White syndrome, as well as metabolic crises followed by developmental regression. The patient with TMEM70 deficiency herein reported has the unique presentation of aortic root dilatation, differing facial dysmorphisms, and no history of neonatal metabolic decompensation or developmental delay, as well as a plasma metabolomics signature, including elevated 3‐methylglutaconic acid, 3‐methylglutarylcarnitine, alanine, and lactate, in addition to the commonly described increased 3‐methylglutaconic acid on urine organic acid analysis that helped aid in the diagnostic interpretation of variants of uncertain significance in TMEM70.
Complete Depolymerization of PET Wastes by an Evolved PET Hydrolase from Directed Evolution
Authors: Shi Lixia , Liu Pi , Tan Zijian , Zhao Wei , Gao Junfei , Gu Qun , Ma Hongwu , Liu Haifeng , Zhu Leilei 
Published: February 2023

AbstractPETase displays great potential in PET depolymerization. Directed evolution has been limited to engineer PETase due to the lack of high‐throughput screening assay. In this study, a novel fluorescence‐based high‐throughput screening assay employing a newly designed substrate, bis (2‐hydroxyethyl) 2‐hydroxyterephthalate (termed BHET‐OH), was developed for PET hydrolases. The best variant DepoPETase produced 1407‐fold more products towards amorphous PET film at 50 °C and showed a 23.3 °C higher Tm value than the PETase WT. DepoPETase enabled complete depolymerization of seven untreated PET wastes and 19.1 g PET waste (0.4 % Wenzyme/WPET) in liter‐scale reactor, suggesting that it is a potential candidate for industrial PET depolymerization processes. The molecular dynamic simulations revealed that the distal substitutions stabilized the loops around the active sites and transmitted the stabilization effect to the active sites through enhancing inter‐loop interactions network.
Simultaneous co‐Photocatalytic CO2Reduction and Ethanol Oxidation towards Synergistic Acetaldehyde Synthesis
Authors: Liu Qiong , Lin Jingjun , Cheng Hui , Wei Liling , Wang Fuxian 
Published: February 2023

AbstractPhotocatalytic conversion of CO2is of great interest but it often suffers sluggish oxidation half reaction and undesired by‐products. Here, we report for the first the simultaneous co‐photocatalytic CO2reduction and ethanol oxidation towards one identical value‐added CH3CHO product on a rubidium and potassium co‐modified carbon nitride (CN‐KRb). The CN‐KRb offers a record photocatalytic activity of 1212.3 μmol h−1g−1with a high selectivity of 93.3 % for CH3CHO production, outperforming all the state‐of‐art CO2photocatalysts. It is disclosed that the introduced Rb boosts the *OHCCHO fromation and facilitates the CH3CHO desorption, while K promotes ethanol adsorption and activation. Moreover, the H+stemming from ethanol oxidation is confirmed to participate in the CO2reduction process, endowing near ideal overall atomic economy. This work provides a new strategy for effective use of the photoexcited electron and hole for high selective and sustainable conversion of CO2paired with oxidation reaction into identical product.
Sustainable and high‐performance composites based on glycidyl methacrylate‐grafted poly(lactic acid) and cellulose nanofibrils
Authors: Kim Seok‐Ju , Eom Tae‐Gyeong , Kang Seokchan , Seo Minyoung , Jeong Young Gyu 
Published: February 2023

AbstractWe investigate the microstructure, thermal stability, melt‐rheological behavior, and mechanical properties of sustainable composites based on a modified poly(lactic acid) (PLA) matrix and cellulose nanofibril (CNF) fillers. For this purpose, glycidyl methacrylate (GMA)‐grafted PLA (PLA‐g‐GMA) was fabricated via reactive melt‐mixing of neat PLA with GMA and it was melt‐compounded with different CNF filler loadings (0.5–10.0 wt%). The NMR and FT‐IR spectroscopic analyses of PLA‐g‐GMA/CNF composites confirmed that GMA was successfully grafted on the PLA backbone and that there are intermolecular chemical reactions and specific interactions between the GMA group of the PLA‐g‐GMA matrix and the hydroxyl group of the CNF filler in the composites. As the result, the glass transition and cold‐crystallization temperatures of the PLA‐g‐GMA matrix in the composites were measured to increase with the increase of CNF loading. In addition, the thermal decomposition temperature of the PLA‐g‐GMA matrix as well as the residue at 500°C of the composites increased with the CNF loading, resulting from the barrier and flame retardation roles of CNFs to the PLA‐g‐GMA matrix. The elastic storage moduli, impact strength, and complex viscosity were found to be higher for the composites with higher CNF loadings, which is due to the good interfacial adhesion between the PLA‐g‐GMA matrix and the CNF filler in the composites at glassy, rubbery, and melt states.
Hydrophilic modification of PVDF membranes for oily water separation with enhanced anti‐fouling performance
Authors: Kan Jiahui , Zhang Zhixuan , Ren Liang , Han Jian , Zhang Huixin , Li Jihui , Wu Hong , Chen Jianxin 
Published: February 2023

AbstractThe main purpose of this work is to improve the hydrophilicity and antifouling properties of hydrophobic polyvinylidene fluoride (PVDF) microfiltration membranes through modification. Pyrogallol (PG), polyethyleneimine (PEI), and (3‐chloropropyl) trimethoxysilane (CTS) formed a stable hydrophilic network by Michael addition/Schiff reaction in alkaline solution Fourier transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), and scanning electron microscopy (SEM) were used to characterize the surface chemical composition, surface and cross‐section morphology of the membrane. In addition, the properties of the membrane were tested systematically. The as‐prepared PVDF‐PG/PEI/CTS membranes showed a smaller water contact angle down to 21.1± 4.8°. The pure water flux of the modified membrane increased significantly by about 18 folds, from 377.0 ± 61.0 to 6745.0 L m−2 h−1, the separation efficiency for the four types of oil‐in‐water emulsions were all greater than 98.8%. In addition, the modified membrane showed high stability under various conditions of acidity, weak alkalinity and high salt content, showing great potential in the actual treatment of oily wastewater.
Weyl and Majorana for neutral particles
Authors: Dvoeglazov Valeriy V. 
Published: February 2023

AbstractWe compare various formalisms for neutral particles. It is found that they contain unexplained contradictions. Next, we investigate the spin‐1/2 and spin‐1 cases in different bases. Next, we look for relations with the Majorana‐like field operator. We show explicit incompatibility of the Majorana ansatzen with the Dirac‐like field operators in both the original Majorana theory and its generalizations.
Dual‐targeting therapy against HER3/MET in human colorectal cancers
Authors: Yamasaki Akitaka , Miyake Rikuto , Hara Yuta , Okuno Hideki , Imaida Takuya , Okita Kouki , Okazaki Shogo , Akiyama Yasutoshi , Hirotani Kenji , Endo Yuichi , Masuko Kazue , Masuko Takashi , Tomioka Yoshihisa 
Published: February 2023

AbstractBackgroundColorectal cancer (CRC) is the most common malignancy in the world, and novel molecular targeted therapies for CRC have been vigorously pursued. We searched for novel combination therapies based on the expression patterns of membrane proteins in CRC cell lines.ResultsA positive correlation was observed between the expression of human pidermal growth factor receptor (HER) 3 and mesenchymal‐to‐epithelial transition factor (MET) on the cell surface of CRC cell lines. The brief stimulation of HER3/MET‐high SW1116 CRC cells with both neuregulin‐1 (NRG1) and hepatocyte growth factor enhanced ERK phosphorylation and cell proliferation more than each stimulation alone. In addition, a prolonged NRG1 stimulation resulted in the tyrosine phosphorylation of MET. In this context, the Forkhead Box protein M1 (FOXM1)‐regulated tyrosine phosphorylation of MET by NRG1 was demonstrated, suggesting the existence of a signaling pathway mediated by FOXM1 upon the NRG1 stimulation. Since the co‐expression of HER3 and MET was also demonstrated in in vivo CRC tissues by immunohistochemistry, we investigated whether the co‐inhibition of HER3 and MET could be an effective therapy for CRC. We established HER3‐and/or MET‐KO SW1116 cell lines, and HER3/MET‐double KO resulted in the inhibition of in vitro cell proliferation and in vivo tumor growth in nude mice by SW1116 cells. Furthermore, the combination of patritumab, an anti‐HER3 fully human mAb, and PHA665752, a MET inhibitor, markedly inhibited in vitro cell proliferation, 3D‐colony formation, and in vivo tumor growth in nude mice by SW1116 cellsConclusionThe dual targeting of HER3/MET has potential as CRC therapy.