bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction and characterization of novel bifunctional fusion proteins composed of alcohol dehydrogenase and NADH oxidase with efficient oxidized cofactor regeneration
Authors: Wu Xi , Zhang Chong , Xing Xin‐Hui , Yun Zhenyu , Zhao Lin , Wu Qi 
Published: July 2021

AbstractTo tune the efficiency of oxidized cofactor recycling between alcohol dehydrogenase (ADH) and NADH oxidase (NOX) for the production of aromatic chiral alcohols, we designed and constructed four novel bifunctional fusion proteins composed of thermostable ADH and NOX from Thermococcus kodakarensis KOD1. ADH was linked to the N‐ or C‐terminus of NOX with a typical rigid linker (EAAAK)3 and a flexible linker (GGGGS)3, respectively. Compared with the parental enzymes, the NOX moieties in the four fusion proteins exhibited higher specific activities (141%–282%), while the ADH moieties exhibited varying levels of specific activity (69%–167%). All fusion proteins showed decreased affinities toward the cofactors, with increased Km values toward NADH (159%–406%) and NAD+ (202%–372%). In the enantioselective oxidation of (RS)‐1‐phenylethanol coupled with cofactor regeneration, the four fusion proteins displayed different positive and negative effects on the recycling efficiency of the oxidized cofactor. The two fusion proteins composed of NOX at the N‐terminus exhibited higher total turnover numbers than the corresponding mixtures of individual enzymes with equal activities, particularly at low cofactor concentrations. These findings suggest high cofactor recycling efficiencies of the fusion proteins with appropriate design and their potential application in the biosynthesis of chiral alcohols.
Subclassification estimation of the weighted average treatment effect
Authors: Choi Byeong Yeob 
Published: July 2021

AbstractWeighting and subclassification are popular approaches using propensity scores (PSs) for estimation of causal effects. Weighting is appealing in that it gives consistent estimators for various causal estimands if appropriate weights are well defined and the PS model is correctly specified. Subclassification is known to be more robust to model misspecification than weighting, but its application to diverse causal estimands is limited. In this article, we propose generalized stratum weights to implement subclassification estimators for various causal estimands. These weights include stratum weights for the average treatment effect (ATE) of the overall population and those for the ATE of the treated as special cases. For this, we incorporate strata into the expression of the weighted average treatment effect (WATE). Particularly, we identify stratum weights for the ATE for the overlap population (ATO), for which the weighting estimator is known to be most efficient among the class of WATE estimators. We show that the identified stratum weights for ATO are equivalent to the optimal stratum weights, which are the inverse variances of the stratum‐specific estimators. Simulation studies demonstrate that the proposed subclassification estimator for ATO is more robust to model misspecification than the weighting estimator for ATO. We also propose augmented subclassification estimators, which are shown to be less biased than the subclassification estimators when only the outcome model is correctly specified. The practical utility of the proposed methods is illustrated in a study of right heart catheterization.
Kinetics of Asian and African Zika virus lineages over single‐cycle and multi‐cycle growth in culture: Gene expression, cell killing, virus production, and mathematical modeling
Authors: Shi Huicheng , Yin John 
Published: July 2021

AbstractSince 2014, an Asian lineage of Zika virus has caused outbreaks, and it has been associated with neurological disorders in adults and congenital defects in newborns. The resulting threat of the Zika virus to human health has prompted the development of new vaccines, which have yet to be approved for human use. Vaccines based on the attenuated or chemically inactivated virus will require large‐scale production of the intact virus to meet potential global demands. Intact viruses are produced by infecting cultures of susceptible cells, a dynamic process that spans from hours to days and has yet to be optimized. Here, we infected Vero cells adhesively cultured in well‐plates with two Zika virus strains: a recently isolated strain from the Asian lineage, and a cell‐culture‐adapted strain from the African lineage. At different time points post‐infection, virus particles in the supernatant were quantified; further, microscopy images were used to quantify cell density and the proportion of cells expressing viral protein. These measurements were performed across multiple replicate samples of one‐step infections every four hours over 60 h and for multi‐step infections every four to 24 h over 144 h, generating a rich data set. For each set of data, mathematical models were developed to estimate parameters associated with cell infection and virus production. The African‐lineage strain was found to produce a 14‐fold higher yield than the Asian‐lineage strain in one‐step growth and a sevenfold higher titer in multi‐step growth, suggesting a benefit of cell‐culture adaptation for developing a vaccine strain. We found that image‐based measurements were critical for discriminating among different models, and different parameters for the two strains could account for the experimentally observed differences. An exponential‐distributed delay model performed best in accounting for multi‐step infection of the Asian strain, and it highlighted the significant sensitivity of virus titer to the rate of viral degradation, with implications for optimization of vaccine production. More broadly, this study highlights how image‐based measurements can contribute to the discrimination of virus‐culture models for the optimal production of inactivated and attenuated whole‐virus vaccines.
Successful rechallenge with cetuximab after progression with nivolumab for recurrent cervical lymph node metastasis from carcinoma of the tongue
Authors: Asada Yasuyuki , Teramura Chitoshi , Wada Takuma , Machida Yoshisato , Koshinuma Shinya , Yamamoto Gaku 
Published: July 2021

AbstractWe can infer that the immunostimulatory effect of nivolumab and reactivation of cetuximab enhance the antitumor effect of the therapy.
Cyclopia with proboscis: A rare congenital anomaly
Authors: Kunwar Asma , Shrestha Bibek Man , Shrestha Suraj , Paudyal Pooja , Rawal Suniti 
Published: July 2021

AbstractCyclopia with a proboscis, a rare congenital anomaly, and a severe form of holoprosencephaly occur as a result of incomplete separation of prosencephalon into two halves of hemispheres during organogenesis. A prenatal anomaly scan can help in the early detection of the condition and timely termination of the pregnancy.
Adverse reaction of methylprednisolone pulse therapy: Acute respiratory distress syndrome
Authors: Ashtari Fereshteh , Soltani Rasool , Shokouhi Shervin , Rismanbaf Ali , Hajiahmadi Somayeh , Hakamifard Atousa 
Published: July 2021

AbstractMethylprednisolone pulse therapy has significant anti‐inflammatory effects in multiple sclerosis. Acute respiratory distress syndrome as a probable adverse effect of methylprednisolone pulse therapy in MS patients should be considered.
Tailgut cyst: 2 case reports
Authors: Kardoun Nizar , Hadrich Zied , Akrout Amira , Harbi Houssem , Boujelben Salah , Mzali Rafik 
Published: July 2021

AbstractTailgut cysts, or retrorectal cystic hamartomas, are rare congenital developmental lesions. It is a benign lesion, but there is a risk of degeneration, so surgical resection is necessary.
Transcutaneous ultrasound: An adjunct way to evaluate the intra–false vocal cord pathology—learning from a case of laryngeal Rosai‐Dorfman disease
Authors: Wang Cheng‐Ping , Chen Tseng‐Cheng 
Published: July 2021

AbstractIn clinical practice, it is sometimes difficult to evaluate the intra–false vocal fold lesion. Transcutaneous ultrasound can be an option to evaluate the soft tissue lesion within the right false vocal cord in a 65‐year‐old man with laryngeal Rosai‐Dorfman disease presenting with hoarseness and right false cord swelling.
Effects of nanopores and sulfur doping on hierarchically bunched carbon fibers to protect lithium metal anode
Authors: Jung Ji In , Park Sunwoo , Ha Son , Cho Se Youn , Jin Hyoung‐Joon , Yun Young Soo 
Published: July 2021

AbstractStudies on three‐dimensional structured carbon templates have focused on how to guide homogeneous lithium metal nucleation and growth for lithium metal anodes (LMAs). However, there is still insufficient evidence for a key factor to achieve their high electrochemical performance. Here, the effects of nanopores and sulfur doping on carbon‐based nanoporous host (CNH) electrode materials for LMAs were investigated using natural polymer‐derived CNHs. Homogeneous pore‐filling behaviors of lithium metal in the nanopores of the CNH electrode materials were first observed by ex situ scanning electron microscopy analysis, where the protective lithium metal nucleation and growth process led to significantly high Coulombic efficiency (CE) of ~99.4% and stable 600 cycles. In addition, a comparison study of CNH and sulfur‐doped CNH (S‐CNH) electrodes, which differ only in the presence or absence of sulfur, revealed that sulfur doping can cause lower electrochemical series resistance, higher CE value, and better cycling stability in a wide range of current densities and number of cycles. Moreover, S‐CNH‐based LMAs showed high electrochemical performance in full‐cell Li–S battery tests using a sulfur copolymer cathode, where a high energy density of 1370 W h kgelectrode−1 and an excellent power density of 4120 W kgelectrode−1 were obtained.
Design of Stimuli‐Responsive Dynamic Covalent Delivery Systems for Volatile Compounds (Part 2): Fragrance‐Releasing Cleavable Surfactants in Functional Perfumery Applications
Authors: Tchakalova Vera , Lutz Eric , Lamboley Serge , Moulin Emilie , Benczédi Daniel , Giuseppone Nicolas , Herrmann Andreas 
Published: July 2021

AbstractAmphiphilic imines prepared by condensation of a hydrophobic fragrance aldehyde with a hydrophilic amine derived from a poly(propylene oxide) and poly(ethylene oxide) diblock copolymer were investigated as cleavable surfactant profragrances in applications of functional perfumery. In water, the cleavable surfactants assemble into micelles that allow solubilization of perfume molecules that are not covalently attached to the surfactant. Dynamic headspace analysis on a glass surface showed that solubilized perfume molecules evaporated in a similar manner in the presence of the cleavable surfactant as compared with a non‐cleavable reference surfactant. Under application conditions, the cleavable surfactant imine hydrolysed to release the covalently linked fragrance aldehyde. The profragrances were stable during storage in aqueous media, and upon dilution showed a blooming effect for the hydrolytical fragrance release and a more balanced performance of a solubilized perfume by retaining the more volatile fragrances and boosting the evaporation of the less volatile fragrances.
An investigation on the bubbly flow of a Venturi channel based on the population balance model
Authors: Ding Guodong , Chen Jiaqing , Li Zhenlin , Cai Xiaolei , Ji Yipeng 
Published: July 2021

AbstractIn this paper, the bubbly flow characteristics of a Venturi channel was revealed by using the population balance model (PBM) within the framework of computational fluid dynamics (CFD) numerical simulation and focused on the bubble size distribution and pressure drop △P of different regions. The simulation results indicated that bubble breakup mainly occurred in the diverging section of the Venturi channel, and the average diameter of the daughter bubbles davg in the sidewall region was much smaller than that in the central region. Through the correlational analysis between the bubble size distribution and turbulent flow field, the bubble breakup in the diverging section was positively related to the turbulent flow. Considering the influence of geometric parameters on davg and △P, the davg decreased and △P increased with the increasing of the diverging angle β. As the throat diameter D increased, the davg increased and △P decreased gradually. In order to quantify the bubble breakup characteristics, the concept of bubble breakup ratio τ is introduced and defined as the ratio of inlet average bubble diameter di to the outlet average bubble diameter do. Through dimensionless transformation, the fitting relationship between τ or △P and angle ratio a was Sinusoidal function (SINE), respectively, and was Boltzmann with the throat length‐diameter ratio b. Due to the relationship of first‐order linear function between τ and △P, the bubble breakup ratio can be obtained by measuring the pressure drop of the Venturi tube, which was significant to the practical engineering application.
Discovery of GPR183 Agonists Based on an Antagonist Scaffold
Authors: Kjær Viktoria M. S. , Ieremias Loukas , Daugvilaite Viktorija , Lückmann Michael , Frimurer Thomas M. , Ulven Trond , Rosenkilde Mette M. , Våbenø Jon 
Published: July 2021

AbstractThe G protein‐coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)‐3‐(4‐bromophenyl)‐1‐(4‐(4‐methoxybenzoyl)piperazin‐1‐yl)prop‐2‐en‐1‐one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca2+ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure‐activity relationship trends, these were supplemented with five in‐house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy‐switch.
Gold(I) and Gold(III) N‐Heterocyclic Carbene Complexes as Antibacterial Agents and Inhibitors of Bacterial Thioredoxin Reductase
Authors: Büssing Rolf , Karge Bianka , Lippmann Petra , Jones Peter G. , Brönstrup Mark , Ott Ingo 
Published: July 2021

AbstractA series of (NHC)Au(I)Cl monocarbene complexes and their gold(III) analogues (NHC)Au(III)Cl3 were prepared and investigated as antibacterial agents and inhibitors of bacterial TrxR. The complexes showed stronger antibacterial effects against the Gram‐positive MRSA and E. faecium strains than against several Gram‐negative bacteria. All complexes were efficient inhibitors of bacterial thioredoxin reductase, indicating that inhibition of this enzyme might be involved in their mechanism of action. The efficacy of gold(I) and gold(III) analogues was comparable in most of the assays. The cytotoxicity of the gold NHC compounds against cancer and human cells was overall weaker than the activity against the Gram‐positive bacteria, suggesting that their optimization as antibacterials warrants further investigation.
Effect of Pantoprazole on the Absorption of Hydroxychloroquinea A Randomized Drug‐Drug Interaction Trial in Healthy Adults
Authors: Stoll Felicitas , Blank Antje , Mikus Gerd , Czock David , Foerster Kathrin I. , Hermann Simon , Gümüs Katja , Muhareb Amin , Hummler Simone , Sauter Max , Weiss Johanna , Burhenne Jürgen , Haefeli Walter E. 
Published: July 2021

AbstractHydroxychloroquine as a weak basic compound with two amines is strongly enriched in cell compartments with low pH, suggesting that modification of gastric pH by coadministered proton pump inhibitors might reduce its solubility and absorption and thus its efficacy in patients. We addressed this question in a single‐center, open‐label, randomized, parallel drug‐drug interaction trial in healthy adults (EudraCT No. 2020‐001470‐30). All participants received a single oral dose of 400‐mg hydroxychloroquine, and one group additionally received 40 mg of pantoprazole once daily for 9 days dosed to steady state. Whole‐blood samples were collected for 72 hours, and hydroxychloroquine was quantified by liquid chromatography–tandem mass spectrometry. Primary endpoints were whole‐blood hydroxychloroquine areas under the concentration‐time curve from 0 to 72 hours (AUC0‐72h) and peak concentrations (Cmax). Unpaired 2‐sided t‐tests of the log transformed pharmacokinetic parameters were performed to compare both groups. Twenty‐four participants (12 per group) were included. Hydroxychloroquine AUC0‐72h and Cmax did not differ between groups without and with pantoprazole (arithmetic mean; AUC0‐72h, 7649 ng/ml • h, and 8429 ng/ml • h, P = .50; Cmax, 448 ng/mL and 451.5 ng/mL, P = .96, respectively). Pantoprazole did not alter hydroxychloroquine absorption, indicating that proton pump inhibitors do not affect its bioavailability.
Interviewing anorexia: How do individuals given a diagnosis of anorexia nervosa experience Voice Dialogue with their eating disorder voice? A qualitative analysis
Authors: Chua Natalie , Serpell Lucy , Burnett‐Stuart Sarah , Pugh Matthew 
Published: July 2021

AbstractA proportion of individuals given an eating disorder diagnosis describe the experience of an eating disorder ‘voice’ (EDV). However, methods for working with this experience are currently lacking. Voice Dialogue (Stone & Stone, 1989) involves direct communication between a facilitator and parts of the self to increase awareness, understanding, and separation from inner voices. Adapted forms of this method have shown promise in working with voices in psychosis. This study aimed to explore the experience and acceptability of Voice Dialogue amongst individuals with anorexia nervosa who experience an EDV. Nine women participated in a semistructured interview following a single Voice Dialogue session. Interview transcripts were analysed using interpretative phenomenological analysis (IPA). Three overarching themes were identified as follows: (i) “separating from the EDV”; (ii) “better understanding of the EDV”; and (iii) “hopeful, motivated, and afraid of recovery”. The majority of participants found Voice Dialogue acceptable and helpful for exploring their EDV. Whilst preliminary, the results suggest that Voice Dialogue has potential in terms of helping individuals establish a more constructive relationship with their EDV and motivating change. Further research is needed to build upon these findings. Implications for addressing the EDV using voice‐focused interventions are explored.
The Posology of Dupilumab in Pediatric Patients With Atopic Dermatitis
Authors: Kamal Mohamed A. , Kovalenko Pavel , Kosloski Matthew P. , Srinivasan Kamal , Zhang Yi , Rajadhyaksha Manoj , Lai Ching‐Ha , Kanamaluru Vanaja , Xu Christine , Sun Xian , Simpson Eric L. , Paller Amy S. , Siegfried Elaine C. , Shumel Brad , Bansal Ashish , Al‐Huniti Nidal , Davis John D. 
Published: July 2021

Dupilumab demonstrated efficacy with an acceptable safety profile in two randomized, double‐blind, placebo‐controlled, parallel‐group, phase III trials in adolescents (12–17 years; LIBERTY AD ADOL) and children (6–11 years; LIBERTY AD PEDS) with atopic dermatitis (AD) treated for 16 weeks. Here, we present the pharmacokinetic profiles and exposure‐response (E‐R) relationships of dupilumab that guided the posology in these populations. A total of 251 adolescent patients with moderate‐to‐severe AD were randomized to subcutaneous dupilumab monotherapy every 2 weeks (q2w; 200 mg q2w, baseline weight < 60 kg; 300 mg q2w, ≥ 60 kg), dupilumab 300 mg every 4 weeks (q4w; non‐weight tiered), or placebo; 367 children with severe AD were randomized to dupilumab q2w (100 mg q2w, baseline weight < 30 kg; 200 mg q2w, ≥ 30 kg), dupilumab 300 mg q4w, or placebo. Children received concomitant topical corticosteroids in addition to dupilumab, and loading doses were administered at the start of therapy. Mean dupilumab trough concentrations at week 16 for weight subcategories in each dosing regimen were compared with adult exposures for the approved dupilumab 300 mg q2w regimen. Positive E‐R relationships were demonstrated between dupilumab trough concentrations and AD outcome measures across patient populations and regimens; no relationship was observed with treatment‐emergent conjunctivitis. Based on these analyses, a weight‐tiered posology was proposed for adolescents (200/300 mg q2w in patients 30–< 60 kg/≥ 60 kg) and children (300 mg q4w in patients 15–< 30 kg, 200 mg q2w in patients 30–< 60 kg) with moderate‐to‐severe AD.
Uncovering the genetic diversity of yams (Dioscorea spp.) in China by combining phenotypic trait and molecular marker analyses
Authors: Cao Tianxu , Sun Jingyu , Shan Nan , Chen Xin , Wang Putao , Zhu Qianglong , Xiao Yao , Zhang Hongyu , Zhou Qinghong , Huang Yingjin 
Published: July 2021

AbstractYam is an important edible tuber and root plant worldwide; China as one of the native places of yams has many diverse local resources. The goal of this study was to clarify the genetic diversity of the commonly cultivated yam landraces and the genetic relationship between the main yam species in China. In this study, 26 phenotypic traits of 112 yam accessions from 21 provinces in China were evaluated, and 24 simple sequence repeat (SSR) and 29 sequence‐related amplified polymorphism (SRAP) markers were used for the genetic diversity analysis. Phenotypic traits revealed that Dioscorea opposita had the highest genetic diversity, followed by D. alata, D. persimilis, D. fordii, and D. esculenta. Among the 26 phenotypic traits, the Shannon diversity indexes of leaf shape, petiole color, and stem color were high, and the range in the variation of tuber‐related traits in the underground part was higher than that in the aboveground part. All accessions were divided into six groups by phenotypic trait clustering, which was also supported by principal component analysis (PCA). Molecular marker analysis showed that SSR and SRAP markers had good amplification effects and could effectively and accurately evaluate the genetic variation of yam. The unweighted pair‐group method with arithmetic means analysis based on SSR‐SRAP marker data showed that the 112 accessions were also divided into six groups, similar to the phenotypic trait results. The results of PCA and population structure analysis based on SSR‐SRAP data also produced similar results. In addition, the analysis of the origin and genetic relationship of yam indicated that the species D. opposita may have originated from China. These results demonstrate the genetic diversity and distinctness among the widely cultivated species of Chinese yam and provide a theoretical reference for the classification, breeding, germplasm innovation, utilization, and variety protection of Chinese yam resources.