bluuebunny/crossref_metadata_2025 huggingface dataset:
Eine chemo‐enzymatische Modifizierung der 5′‐Kappe erhält die Translation und erhöht die Immunogenität der mRNA
Authors: van Dülmen Melissa , Muthmann Nils , Rentmeister Andrea
Published: March 2021

Eukaryotische mRNAs zählen zu den neuartigen Modalitäten für Proteinersatztherapien und Schutzimpfungen. Die 5′‐Kappe ist für die mRNA‐Translation und die Immunantwort von Bedeutung und kann naturgemäß durch S‐Adenosyl‐l‐Methionin (AdoMet)‐abhängige Methyltransferasen (MTasen) an verschiedenen Positionen methyliert werden. Wir berichten vom Cosubstrat‐Spektrum der MTase CAPAM, die für die Methylierung der N6‐Position von Adenosin‐Start‐Nukleotiden verantwortlich ist und verwenden dazu synthetische AdoMet‐Analoga. Die chemo‐enzymatische Propargylierung ermöglicht die Herstellung von ortsspezifisch modifizierten Reporter‐mRNAs. Diese Kappen‐propargylierten mRNAs wurden effizient translatiert und zeigten eine ≈3‐fach erhöhte Immunantwort in menschlichen Zellen. Derselbe Effekt wurde beobachtet, wenn die Rezeptorbindedomäne (RBD) von SARS‐CoV2 – ein aktuell getestetes Epitop für mRNA‐Impfungen – verwendet wurde. Die ortsspezifische chemo‐enzymatische Modifizierung von eukaryotischer mRNA könnte somit eine geeignete Strategie zur Modulierung der Translation und Immunantwort eukaryotischer mRNAs für zukünftige therapeutische Applikationen darstellen.
Dicyclopentaannelated Hexa‐peri‐hexabenzocoronenes with a Singlet Biradical Ground State
Authors: Chen Qiang , Baumgarten Martin , Wagner Manfred , Hu Yunbin , Hou Ian Cheng‐Yi , Narita Akimitsu , Müllen Klaus
Published: March 2021

Synthesis of two dicyclopentaannelated hexa‐peri‐hexabenzocoronene (PHBC) regioisomers was carried out, using nonplanar oligoaryl precursors with fluorenyl groups: mPHBC 8 with two pentagons in the “meta”‐configuration was obtained as a stable molecule, while its structural isomer with the “para”‐configuration, pPHBC 16, could be generated and characterized only in situ due to its high chemical reactivity. Both PHBCs exhibit low energy gaps, as reflected by UV‐vis‐NIR absorption and electrochemical measurements. They also show open‐shell singlet ground states according to electron paramagnetic resonance (EPR) measurements and density functional theory (DFT) calculations. The use of fully benzenoid HBC as a bridging moiety leads to significant singlet biradical characters (y0) of 0.72 and 0.96 for mPHBC 8 and pPHBC 16, respectively, due to the strong rearomatization tendency of the HBC π‐system; these values are among the highest for planar carbon‐centered biradical molecules. The incorporation of fully unsaturated pentagons strongly perturbs the aromaticity of the parent HBC and makes the constituted benzene rings less aromatic or antiaromatic. These results illustrate the high impact of cyclopentaannelation on the electronic structures of fully benzenoid polycyclic aromatic hydrocarbons (PAHs) and open up a new avenue towards open‐shell PAHs with prominent singlet biradical characters.
Structural Analysis of an Antigen Chemically Coupled on Virus‐Like Particles in Vaccine Formulation
Authors: Jaudzems Kristaps , Kirsteina Anna , Schubeis Tobias , Casano Gilles , Ouari Olivier , Bogans Janis , Kazaks Andris , Tars Kaspars , Lesage Anne , Pintacuda Guido
Published: March 2021

Structure determination of adjuvant‐coupled antigens is essential for rational vaccine development but has so far been hampered by the relatively low antigen content in vaccine formulations and by their heterogeneous composition. Here we show that magic‐angle spinning (MAS) solid‐state NMR can be used to assess the structure of the influenza virus hemagglutinin stalk long alpha helix antigen, both in its free, unformulated form and once chemically coupled to the surface of large virus‐like particles (VLPs). The sensitivity boost provided by high‐field dynamic nuclear polarization (DNP) and proton detection at fast MAS rates allows to overcome the penalty associated with the antigen dilution. Comparison of the MAS NMR fingerprints between the free and VLP‐coupled forms of the antigen provides structural evidence of the conservation of its native fold upon bioconjugation. This work demonstrates that high‐sensitivity MAS NMR is ripe to play a major role in vaccine design, formulation studies, and manufacturing process development.
Iron‐Catalyzed Radical Asymmetric Aminoazidation and Diazidation of Styrenes
Authors: Lv Daqi , Sun Qiao , Zhou Huan , Ge Liang , Qu Yanjie , Li Taian , Ma Xiaoxu , Li Yajun , Bao Hongli
Published: March 2021

Asymmetric aminoazidation and diazidation of alkenes are straightforward strategies to build value‐added chiral nitrogen‐containing compounds from feedstock chemicals. They provide direct access to chiral organoazides and complement enantioselective diamination. Despite the advances in non‐asymmetric reactions, asymmetric aminoazidation or diazidation based on acyclic systems has not been previously reported. Here we describe the iron‐catalyzed intermolecular asymmetric aminoazidation and diazidation of styrenes. The method is practically useful and requires relatively low loading of catalyst and chiral ligand. With mild reaction conditions, the reaction can be completed on a 20 mmol scale. Studies of the mechanism suggest that the reaction proceeds via a radical pathway and involves stereocontrol of an acyclic free radical which probably takes place through a group transfer mechanism.
Uncovering a Functional Motif of Nonlinear Optical Materials by In Situ Electron Density and Wavefunction Studies Under Laser Irradiation
Authors: Jiang Xiao‐Ming , Lin Shu‐Juan , He Chao , Liu Bin‐Wen , Guo Guo‐Cong
Published: March 2021

Exploring nonlinear optical (NLO) functional motifs (FM, the structural origin of NLO efficiency) is vital for the rational design of NLO materials. Normal spectrum techniques applied in studying photon exciting materials are invalid for NLO materials, in which electrons are not excited substantially but only distorted under laser. A general strategy of determining NLO FM is proposed by comparative studies of experimental electron density (ED) without and under the laser. The in situ experimental ED and wavefunction of typical NLO material LiB3O5 (LBO) under dark and 360 and 1064 nm lasers are investigated. Compared with the initial state under dark, the ED of [B3O5]− unit at functional states under laser irradiation exhibits remarkable changes of topological atomic and bond properties, confirming the NLO FM being [B3O5]−. The work extracts for the first time the FM of a NLO material experimentally and highlights the crucial role of in situ ED analysis in studying NLO mechanisms.
Occupational Exposures and Smoking in Eosinophilic Granulomatosis With Polyangiitis: A Case–Control Study
Authors: Maritati Federica , Peyronel Francesco , Fenaroli Paride , Pegoraro Francesco , Lastrucci Vieri , Benigno Giuseppe D. , Palmisano Alessandra , Rossi Giovanni M. , Urban Maria L. , Alberici Federico , Fraticelli Paolo , Emmi Giacomo , Corradi Massimo , Vaglio Augusto
Published: March 2021

Objective

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Environmental agents and occupational exposures may confer susceptibility to EGPA, but data are scarce. This study was undertaken to investigate the association between occupational exposures (e.g., silica, farming, asbestos, and organic solvents) and other environmental agents (e.g., smoking) and the risk of EGPA.

Methods

Patients with newly diagnosed EGPA (n = 111) and general population controls (n = 333) who were matched for age, sex, and geographic area of origin were recruited at a national referral center for EGPA. Exposures were assessed using a dedicated questionnaire administered by a specialist in occupational medicine, under blinded conditions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

Exposures to silica (OR 2.79 [95% CI 1.55–5.01], P = 0.001), organic solvents (OR 3.19 [95% CI 1.91–5.34], P < 0.001), and farming (OR 2.71 [95% CI 1.71–4.29], P < 0.001) were associated with an increased risk of EGPA. Co‐exposure to silica and farming yielded an OR of 9.12 (95% CI 3.06–27.19, P < 0.001), suggesting a multiplicative effect between these 2 exposures. Smoking (current and former smokers combined) was significantly less frequent among patients with EGPA compared to controls (OR 0.49 [95% CI 0.29–0.70], P < 0.001). The pack‐year index was also lower among patients with EGPA (OR 0.96 [95% CI 0.94–0.98], P < 0.001). The association of silica and farming was primarily aligned with ANCA‐positive EGPA, while the association of smoking status and organic solvents was primarily aligned with ANCA‐negative EGPA.

Conclusion

The environment can influence susceptibility to EGPA. Exposure to silica, farming, or organic solvents is associated with an increased risk of EGPA, while smoking is associated with a lower risk. These exposures seem to have distinct effects on different EGPA subsets.
The N170 event‐related potential reflects delayed neural response to faces when visual attention is directed to the eyes in youths with ASD
Authors: Parker Termara C. , Crowley Michael J. , Naples Adam J. , Rolison Max J. , Wu Jia , Trapani Julie A. , McPartland James C.
Published: March 2021

Atypical neural response to faces is thought to contribute to social deficits in autism spectrum disorder (ASD). Compared to typically developing (TD) controls, individuals with ASD exhibit delayed brain responses to upright faces at a face‐sensitive event‐related potential (ERP), the N170. Given observed differences in patterns of visual attention to faces, it is not known whether slowed neural processing may simply reflect atypical looking to faces. The present study manipulated visual attention to facial features to examine whether directed attention to the eyes normalizes N170 latency in ASD. ERPs were recorded in 30 children and adolescents with ASD as well as 26 TD children and adolescents. Results replicated prior findings of shorter N170 latency to the eye region of the face in TD individuals. In contrast, those with ASD did not demonstrate modulation of N170 latency by point of regard to the face. Group differences in latency were most pronounced when attention was directed to the eyes. Results suggest that well‐replicated findings of N170 delays in ASD do not simply reflect atypical patterns of visual engagement with experimental stimuli. These findings add to a body of evidence indicating that N170 delays are a promising marker of atypical neural response to social information in ASD.

Lay Summary

This study looks at how children's and adolescents' brains respond when looking at different parts of a face. Typically developing children and adolescents processed eyes faster than other parts of the face, whereas this pattern was not seen in ASD. Children and adolescents with ASD processed eyes more slowly than typically developing children. These findings suggest that observed inefficiencies in face processing in ASD are not simply reflective of failure to attend to the eyes.
Proposing effective strategies for meeting an environmental regulation with attainable technology improvement targets
Authors: Eguchi Shogo , Takayabu Hirotaka , Kaneko Mitsuki , Kagawa Shigemi , Hienuki Shunichi
Published: March 2021

The Japanese government will adopt the CAFE standard after 2020. By using a “modified” slacks‐based measure (SBM) model, this study analyzed the technical efficiency of 113 gasoline vehicle models (GVs) and 54 hybrid vehicle models (HVs) sold by Japanese manufacturers in 2016. We also estimated attainable fuel efficiency of specific vehicle models that can be further improved referring to the nearest point on the best practice frontier. The improved CAFE values and standards of the nine automobile manufacturers were calculated. The technology gap from the vehicle technology frontier was more noticeable among gasoline vehicles than among hybrids. Moreover, most automobile manufacturers can achieve the CAFE standard through an effective achievement strategy based on best practice technologies, whereas the others will not achieve the CAFE standard even given a rapid technology innovation beyond the best practice frontiers for GVs and HVs.
Early radial artery occlusion following the use of a transradial7‐Frenchsheath for complex coronary interventions in Chinese patients
Authors: Wang Hao , Wang Hao‐Yu , Yin Dong , Feng Lei , Song Wei‐Hua , Wang Hong‐Jian , Zhu Cheng‐Gang , Dou Ke‐Fei
Published: March 2021

Objectives

We aimed to explore the impact of 7‐Fr sheaths on the incidence of early radial artery occlusion (RAO) after transradial coronary intervention (TRI) in Chinese patients.

Background

RAO precludes future use of the vessel for vascular access. Transradial catheterization is usually performed via 5‐Fr or 6‐Fr catheters; 7‐Fr sheath insertion enables complex coronary interventions but may increase the RAO risk.

Methods

We prospectively enrolled 130 consecutive patients undergoing complex TRI using 7‐Fr sheaths. Radial artery ultrasound assessment was performed before and after TRI. Early RAO was defined as the absence of flow on ultrasound within 6–24 hr after TRI. Multivariate logistic regression was used to determine the factors related to early RAO after TRI.

Results

7‐Fr sheaths were mainly used for chronic total occlusion (44.6%), bifurcation (30.0%), and tortuous calcification (25.4%) lesions. All patients were successfully sheathed. Percutaneous coronary intervention (PCI) procedural success was 96.2%; 119 patients (91.5%) had preserved radial artery patency after TRI. All 11 RAO cases (8.5%) were asymptomatic. The radial artery diameter was significantly larger postoperatively (3.1 ± 0.4 mm) than preoperatively (2.6 ± 0.5 mm) (p < .001). No parameters significantly differed between patients with and without RAO. TRI history was the only independent risk factor of early RAO (odds ratio: 6.047, 95% confidence interval: 1.100–33.253,p= .039).

Conclusions

7‐Fr sheath use after transradial access for complex PCI is feasible and safe. Evaluating the radial artery within 24 hr after TRI allows timely RAO recognition, important for taking measures to maintain radial artery patency and preserve access for future TRIs.
Relationship between cooking quality of fresh pasta made from durum wheat and protein content and molecular weight distribution parameters
Authors: Moayedi Sara , Ohm Jae‐Bom , Manthey Frank A.
Published: March 2021

Background and objectives

Although proteins are known to have a dominant impact on pasta cooking quality for dry pasta, little information has been reported on associations between proteins and the cooking quality of fresh pasta. Therefore, the objective of this research was to assess associations between protein molecular weight distribution (MWD) parameters and cooking quality of fresh pasta made from durum wheat.

Findings

Semolina samples that had high protein contents produced fresh pasta with high cooked pasta firmness (CPF) and low cooked pasta weight (CPW) and cooking loss. Protein MWD parameters varied with their associations with pasta cooking quality. Variation in CPF was positively associated with combination of SDS extractable and unextractable gliadin and albumin +globulin fractions but negatively associated with SDS extractable polymeric protein fraction. The CPW was positively affected by extractable polymeric protein fraction, while impact of albumin +globulin fraction was negative.

Conclusions

Protein fractions had predominant and different roles on the variation of CPF and CPW of fresh pasta.

Significance and novelty

This research reports novel information on associations between fresh pasta cooking quality and protein MWD parameters. The research identified protein components that had dominant roles in determining pasta cooking quality of fresh pasta.
Light‐Off Support for Mobile DeNOx Systems
Authors: Schallhart Verena , Berthold Heinrich , Klemm Elias , Moeltner Lukas
Published: March 2021

The potential of direct heating of reactors is in this study exemplified by an aftertreatment system for passenger vehicles. Experimental and numerical investigations on thermal characteristics of catalyst supports were conducted for both a cordierite and a conductive hybrid ceramic substrate, whereby the latter offers the possibility of electric heating. A considerable reduction of critical heat‐up time after engine startup is evident for the conductive hybrid ceramic carrier, which consequently allows an increase in emission reduction efficiency.
Numerical analysis of the hemodynamics of rat aorta based on magnetic resonance imaging and fluid–structure interaction
Authors: Han Longzhu , Ren Quan , Lian Jianxiu , Luo Liyi , Liu Huawei , Ma Tianxiang , Li Xin , Deng Xiaoyan , Liu Xiao
Published: March 2021

Murine models have been widely used to investigate the mechanobiology of aortic atherosclerosis and dissections, which develop preferably at different anatomic locations of aorta. Based MRI and finite element analysis with fluid–structure interaction, we numerically investigated factors that may affect the blood flow and structural mechanics of rat aorta. The results indicated that aortic root motion greatly increases time‐averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), displacement of the aorta, and enhances helical flow pattern but has limited influence on effective stress, which is highly modulated by blood pressure. Moreover, the influence of the motion component on these indicators is different with axial motion more obvious than planar motion. Surrounding fixation of the intercostal arteries and the branch vessels on aortic arch would reduce the influence of aortic root motion. The compliance of the aorta has different influences at different regions, leading to decrease in TAWSS and helical flow, increase in OSI, RRT at the aortic arch, but has reversed effects on the branch vessels. When compared with the steady flow, the pulsatile blood flow would obviously increase the WSS, the displacement, and the effective stress in most regions. In conclusion, to accurately quantify the blood flow and structural mechanics of rat aorta, the motion of the aortic root, the compliance of aortic wall, and the pulsation of blood flow should be considered. However, when only focusing on the effective stress in rat aorta, the motion of the aortic root may be neglected.
Synthesis and Effective Thermal Conductivity Measurements of Hollow Mesoporous SiO2 Spheres for Heat‐Insulating Applications
Authors: Winkelmann Frederik , Albert Rene , Felderhoff Michael
Published: March 2021

Mesoporous silica hollow spheres are an excellent model system to investigate the thermal conductivity for an efficient heat‐insulating material with respect to its geometry. Four different monodisperse silica hollow spheres are synthesized via a three‐step synthesis consisting of emulsifier‐free emulsion polymerization, modified Stöber condensation process, and subsequent calcination. In this approach, cetyltrimethylammonium bromide (CTAB) is used as a structure directing component to produce a highly porous silica shell. The systematic investigations of the effective thermal conductivity (ETC) allow distinguishing the respective conduction pathways, such as solid conduction and gas conduction. The carried out thermal conductivity measurements reveal for all four samples promising low ETC values of ≈36 mW m−1 K−1 at 1013 mbar and 35 °C. In vacuum (0.03 mbar) all four samples showed, independent of shell thickness and inner diameter, a comparable reduced ETC of about 10 mW m−1 K−1. The comparison with previous studies on unstructured silica hollow spheres indicates that the solid state conductivity within the bulk is more dependent on the contact strengths and the number of contacts than on the thermal conductivity within the silica material, as the scattering probability of phonons is not influenced by an increased density of defects.
Flame retardant investigations on carbon fibre‐reinforced polyurethane resin parts for aircraft applications produced by wet compression moulding
Authors: Behnisch Felix , Höhne Carl‐Christoph , Manas Lukas , Rosenberg Philipp , Henning Frank
Published: March 2021

Epoxy resins are widely used in composite materials for aircraft applications. However, they are difficult to recycle, thus posing an increasing challenge to the aviation sector. By contrast, polyurethane resins (PUR) can be easily chemically recycled by solvolysis, but structural parts made of carbon fibre‐reinforced polyurethanes (CF‐PURs) are currently not in use in aircraft applications. This is due to a lack of knowledge about the properties of CF‐PURs, especially during exposure to higher temperatures and to fire. To increase the recyclability of aircraft parts, for example interior structures like seats, there is a need for CF‐PUR components which are able to fulfil the flame retardant regulations as well as the quality and production cycle time requirements of the aviation industry. It was found that a CF‐PUR formulation processed by wet compression moulding containing 9 wt% of a phosphorous polyol is able to fulfil these requirements for aviation interior applications.
Histology‐based molecular profiling improves mutation detection for advanced thyroid cancer
Authors: Eszlinger Markus , Khalil Moosa , Gillmor Aaron Hill , Huang Helen , Stewardson Paul , McIntyre John B. , Morrissy Sorana , Paschke Ralf
Published: March 2021

Advanced cancers frequently show histologic and molecular intratumoral heterogeneity. Therefore, we comprehensively characterized advanced, metastatic, radioiodine‐resistant (RAIR) thyroid carcinomas at the molecular level in the context of histologic heterogeneity with the aim to identify potentially actionable mutations that may guide the use of specific tyrosine kinase inhibitor (TKI) treatment. Whole exome sequencing (WES) was applied to 29 macrodissected tissue samples of histologically heterogeneous and homogeneous areas, lymph node and lung metastases from six clinically and histologically well‐characterized metastatic RAIR thyroid cancer patients with structural incomplete response to treatment. WES data were analyzed to identify potential driver mutations in oncogenic pathways, copy number alterations, microsatellite instability, mutant‐allele tumor heterogeneity, and the relevance of histologic heterogeneity to molecular profiling. In addition to known driver mutations in BRAF, NRAS, EIF1AX, NCOA4‐RET, and TERT, further potentially actionable drivers were identified in AKT1, ATM, E2F1, HTR2A, and MLH3. The analysis of the evolutionary history of the mutations and the reconstruction of the molecular phylogeny of the cancers show a remarkable association between histologic and molecular heterogeneity. A comprehensive molecular analysis of the primary tumor guided by histologic analysis may help to better stratify patients for precision medicine approaches. Given the association between the molecular and the histologic heterogeneity, the selection of tumor samples for molecular analysis should be based on meticulous histologic evaluation of the entire tumor.
Does the Civic Renewal Movement Have a Future?
Authors: Levine Peter
Published: March 2021

A civic ideal is an ideal of deliberative self‐governance. People who participate in discussing what their own groups should do are being civic. Civic venues, institutions, and habits have waned since the mid‐1900s. In the 1990s, a movement arose to restore them, under the banner of “civic renewal.” This movement was carefully nonpartisan, often impartial about specific issues, and interested in creating alternative settings that could complement such basic political institutions as Congress and elections. As the condition of democracy has worsened in recent years, this approach looks inadequate or irrelevant. The most promising sources of civic renewal now are parties and social movements that have substantive agendas, such as racial justice, and that improve civic life as a collateral benefit.

[Correction added on 27 September 2021, after first online publication: In the abstract, “mid‐1990s” has been changed to “mid‐1900s”.]
Quenched coumarin derivatives as fluorescence lifetime phantoms for NADH and FAD
Authors: Freymüller Christian , Kalinina Sviatlana , Rück Angelika , Sroka Ronald , Rühm Adrian
Published: March 2021

Two‐photon fluorescence lifetime imaging is a versatile laboratory technique in the field of biophotonics and its importance is also growing in the field of in vivo diagnostics for medical purposes. After years of experience in dermatology, endoscopic implementations of the technique are now posing new technical challenges. To develop, test, and compare instrumental solutions for this purpose suitable reference samples have been devised and tested. These reference samples can serve as reliable NADH‐ and FAD‐mimicking optical phantoms for 2‐photon fluorescence lifetime imaging, as they can be prepared relatively easily with reproducible and stable characteristics for this quite relevant diagnostic technique. The reference samples (mixtures of coumarin 1 and coumarin 6 in ethanol with suitable amounts of 4‐hydroxy‐TEMPO) have been tuned to exhibit spectral and temporal fluorescence characteristics very similar to those of NADH and FAD, the two molecules most frequently utilized to characterize cell metabolism.
Formation Dominates Resorption With Increasing Mineralized Density and Time Postfracture in Cortical but Not Trabecular Bone: A Longitudinal HRpQCT Imaging Study in the Distal Radius
Authors: Atkins Penny R , Stock Kerstin , Ohs Nicholas , Collins Caitlyn J , Horling Lukas , Benedikt Stefan , Degenhart Gerald , Lippuner Kurt , Blauth Michael , Christen Patrik , Müller Ralph
Published: March 2021

Clinical evaluation of fracture healing is often limited to an assessment of fracture bridging from radiographic images, without consideration for other aspects of bone quality. However, recent advances in HRpQCT offer methods to accurately monitor microstructural bone remodeling throughout the healing process. In this study, local bone formation and resorption were investigated during the first year post fracture in both the fractured (n = 22) and contralateral (n = 19) radii of 34 conservatively treated patients (24 female, 10 male) who presented with a unilateral radius fracture at the Innsbruck University Hospital, Austria. HRpQCT images and clinical metrics were acquired at six time points for each patient. The standard HRpQCT image acquisition was captured for all radii, with additional distal and proximal image acquisitions for the fractured radii. Measured radial bone densities were isolated with a voxel‐based mask and images were rigidly registered to images from the previous imaging session using a pyramid‐based approach. From the registered images, bone formation and resorption volume fractions were quantified for multiple density‐based thresholds and compared between the fractured and contralateral radius and relative to demographics, bone morphometrics, and fracture metrics using regression. Compared with the contralateral radius, both bone formation and resorption were significantly increased in the fractured radius throughout the study for nearly all evaluated thresholds. Higher density cortical bone formation continually increased throughout the duration of the study and was significantly greater than resorption during late‐stage healing in both the fractured and intact regions of the radius. With the small and diverse study population, only weak relationships between fracture remodeling and patient‐specific parameters were unveiled. However this study provides methods for the analysis of local bone remodeling during fracture healing and highlights relevant considerations for future studies, specifically that remodeling postfracture is likely to continue beyond 12‐months postfracture. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Assessing challenging intra‐ and inter‐molecular charge‐transfer excitations energies with double‐hybrid density functionals
Authors: Brémond Éric , Ottochian Alistar , Pérez‐Jiménez Ángel José , Ciofini Ilaria , Scalmani Giovanni , Frisch Michael J. , Sancho‐García Juan Carlos , Adamo Carlo
Published: March 2021

We investigate the performance of a set of recently introduced range‐separated double‐hybrid functionals, namely ωB2‐PLYP, ωB2GP‐PLYP, RSX‐0DH, and RSX‐QIDH models for hard‐to‐calculate excitation energies. We compare with the parent (B2‐PLYP, B2GP‐PLYP, PBE0‐DH, and PBE‐QIDH) and other (DSD‐PBEP86) double‐hybrid models as well as with some of the most widely employed hybrid functionals (B3LYP, PBE0, M06‐2X, and ωB97X). For this purpose, we select a number of medium‐sized intra‐ and inter‐molecular charge‐transfer excitations, which are known to be challenging to calculate using time‐dependent density‐functional theory (TD‐DFT) and for which accurate reference values are available. We assess whether the high accuracy shown by the newest double‐hybrid models is also confirmed for those cases too. We find that asymptotically corrected double‐hybrid models yield a superior performance, especially for the inter‐molecular charge‐transfer excitation energies, as compared to standard double‐hybrid models. Overall, the PBE‐QIDH and its corresponding range‐separated RSX‐QIDH functional are recommended for general‐purpose TD‐DFT applications, depending on whether long‐range effects are expected to play a significant role.
circHIPK3 regulates proliferation and differentiation of myoblast through the miR‐7/TCF12 pathway
Authors: Gao Mengjin , Li Xue , Yang Zuojun , Zhao Shuo , Ling Xingxing , Li Jingjing , Xing Kai , Qi Xiaolong , Wang Xiangguo , Xiao Longfei , Ni Hemin , Guo Yong , Sheng Xihui
Published: March 2021

Skeletal muscle development is a complex biological process involving multiple key genes, signaling pathways and noncoding RNAs, including microRNAs and circular RNAs (circRNAs). However, the regulatory relationship among them is so complicated that it has not yet been fully elucidated. In this study, we found that miR‐7 inhibited C2C12 cell proliferation and differentiation by targeting transcription factor 12 (TCF12). circHIPK3 acted as a competing endogenous RNA, and its overexpression effectively reversed the regulation of miR‐7 on C2C12 cell proliferation and differentiation by increasing TCF12 expression. Taken together, our findings provide evidence that circHIPK3 regulates skeletal muscle development through the miR‐7/TCF12 pathway. This study provides a scientific basis for further research on skeletal muscle development at the circRNA level.
Financial constraints on genetic counseling and further risk‐management decisions among U.S. women at elevated breast cancer risk
Authors: Meadows Rachel J. , Padamsee Tasleem J.
Published: March 2021

Clinical guidelines recommend that women at high risk of breast cancer should consider various risk‐management options, which remain widely underutilized. We conducted semi‐structured, qualitative interviews with 50 high‐risk women to understand how financial constraints affect use of genetic counseling, genetic testing, and further risk‐management decisions. Inductive analyses revealed three categories of health‐related financial constraint: (a) lack of insurance, (b) underinsurance, and (c) other financial constraints (e.g., medical debt, raising children, managing comorbidities). Various breast cancer risk‐management actions were limited by these financial constraints, including genetic counseling, genetic testing, enhanced screening, and prophylactic surgeries. Women's narratives also identified complex relationships between financial constraint and perceptions of healthcare providers and insurance companies, particularly as related to bias, price transparency, and potential genetic discrimination. Results from this study have implications for further research and expansion of genetic counseling services delivery to more economically and racially diverse women.
Cost‐effectiveness of statins for primary prevention of atherosclerotic cardiovascular disease among people living with HIV in the United States
Authors: Boettiger David C , Newall Anthony T , Phillips Andrew , Bendavid Eran , Law Matthew G , Ryom Lene , Reiss Peter , Mocroft Amanda , Bonnet Fabrice , Weber Rainer , El‐Sadr Wafaa , d’Arminio Monforte Antonella , de Wit Stephane , Pradier Christian , Hatleberg Camilla I , Lundgren Jens , Sabin Caroline , Kahn James G , Kazi Dhruv S
Published: March 2021

Background

Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States.

Methods

We developed a microsimulation model that randomly selected (with replacement) individuals from the Data‐collection on Adverse Effects of Anti‐HIV Drugs study with follow‐up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid‐lowering therapy. Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness‐to‐pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual’s probability of experiencing atherosclerotic cardiovascular disease over 20 years.

Results

Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost‐effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost‐effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal.

Conclusions

Pravastatin was projected to be cost‐effective compared with no statin. With substantial price reduction, pitavastatin may be cost‐effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV‐specific estimates on the efficacy of statins and the quality‐of‐life burden associated with taking an additional daily pill.
Shrub‐rings used to reconstruct drought history of the central Alxa desert, northwest China
Authors: Ding Ai‐Jun , Xiao Sheng‐Chun , Peng Xiao‐Mei , Tian Quan‐Yan , Han Chao
Published: March 2021

The climate history of the Alxa desert of northwestern China must be sought both in recent instrumental records (dating from 1960) and in high‐resolution proxy data. Climate proxies are scarce in desert areas; however, long‐lived desert shrubs can offer one such proxy. We have used shrub‐ring data from Zygophyllum xanthoxylum, collected in the central Alxa desert, to reconstruct the Self‐calibrating Palmer Drought Severity Index (scPDSI) for the period 1880–2015. The data covers the May–July growth season. When we compared the history constructed from the shrub‐ring data with the instrumental data collected 1960–2015, we found that the reconstructed history explained 41% of the variance in scPDSI data (40% after adjusting for loss of degrees of freedom). The reconstructed history shows that this region has experienced six persistent droughts and four seasons wetter than usual during the period under study. Of note is a severe drought event in 1920s that affected much of northern China (as noted in contemporary documents). The droughts and wet seasons identified in our reconstruction are consistent with reports from other researchers who have studied the climate history or the region. Our study suggests that it is feasible to reconstruct climate history using shrub‐ring data from long‐lived desert shrubs.
Clinico‐metabolic characterization improves the prognostic value of histological growth patterns in patients undergoing surgery for colorectal liver metastases
Authors: Bohlok Ali , Duran Derijckere Ivan , Azema Hugues , Lucidi Valerio , Vankerckhove Sophie , Hendlisz Alain , Van Laethem Jean Luc , Vierasu Irina , Goldman Serge , Flamen Patrick , Larsimont Denis , Demetter Pieter , Dirix Luc , Vermeulen Peter , Donckier Vincent
Published: March 2021

Background and Objectives

The histological growth pattern (HGP) represents a strong prognostic factor in patients undergoing surgery for colorectal liver metastases (CRLM). We evaluated whether the combination of HGP with clinico‐metabolic parameters could improve its prognostic value.

Methods

In a series of 108 patients undergoing resection of CRLM, the HGP of CRLM was scored according to international guidelines. Baseline clinico‐metabolic clinical status was evaluated using a metabolic‐Clinical Risk Score (mCRS), combining traditional Memorial Sloan Kettering‐CRS parameters with the tumor‐to‐liver glucose uptake ratio as measured with 18Fluorodeoxyglucose/positron emission tomography.

Results

In patients with desmoplastic HGP (DHGP) CRLM (20% of all patients), 5‐ and 10‐years overall survival (OS) and disease free survival (DFS) were 66% and 43% and 37% and 24.5%, as compared with 35% and 21% and 11% and 11% in the non‐DHGP group (p = 0.07 and 0.054). Among DHGP patients, those with a low‐risk mCRS had improved postoperative outcomes, 5‐ and 10‐years OS and DFS reaching 83.3% and 62.5% and 50% and 33%, as compared with 18% and 0% and 0% and 0% in high‐risk mCRS patients (p = 0.007 and 0.003). In contrast, mCRS did not influence postoperative survivals in non‐DHGP patients.

Conclusions

Combining the clinico‐metabolic characteristics with the HGP may improve prognostication in patients undergoing surgery for CRLM.
Managing codified content for reuse in knowledge work
Authors: Bosua Rachelle , Venkitachalam Krishna
Published: March 2021

Firm‐wide integrated organisational applications such as intranets, enterprise portals, content repositories, and wikis are often instrumental in supporting knowledge work. Serving as centralised “containers” of codified content that facilitate knowledge work, one essential requirement is continuous reuse and management of codified content. In this paper, our investigation aims to determine suitable perspectives to manage codified content, by focusing on one specific integrated organisational infrastructure application, namely intranets. Findings from three case studies identified three modes to manage codified content for knowledge work for enterprise content systems and are: (a) shared, (b) controlled, and (c) informal. In addition, based on the three modes (or ways), findings also highlight four elements that impact the management of codified content for knowledge work, that is, (a) content contributions, (b) content sharing, (c) access to expertise, and (d) control of codified content.
Long Term Olfactory Outcomes Following Frontal Sinus Surgery in Chronic Rhinosinusitis
Authors: Ninan Sen , Goldrich David Y. , Liu Katherine , Kidwai Sarah , McKee Sean , Williams Lauren , Del Signore Anthony , Govindaraj Satish , Iloreta Alfred M.
Published: March 2021

Objectives/Hypothesis

No studies have evaluated the impact of the types of frontal sinus surgery (FSS) on objective olfaction scores. This study evaluated olfactory function and quality of life (QOL) in chronic rhinosinusitis (CRS) patients before and after total ethmoidectomy with frontal sinusotomy (FS).

Study Design

Prospective cohort study.

Methods

A prospective study of adult CRS patients undergoing FSS (Draf 2 or Draf 3 procedures) was conducted at a tertiary care center. Primary outcomes included brief smell identification test (BSIT) and sinonasal outcome test‐22 (SNOT‐22), which were assessed during preoperative evaluation, 6 to 9 weeks postoperatively, and 12 to 24 weeks postoperatively. Normosmia was defined as BSIT ≥9. Statistical significance was determined using the Wilcoxon signed‐rank test with α = .05.

Results

Thirty‐eight patients followed up 12 to 24 weeks after FSS. The differences between baseline and long‐term outcomes for BSIT (6.11 vs. 8.24, P = .00034) and SNOT‐22 (55.49 vs. 24.32, P < .00001) scores were found to be statistically significant. Although both subgroups had clinically significant olfactory improvements, only the Draf 2 cohort experienced a statistically significant improvement in olfaction at long‐term follow‐up. There was no statistically significant change in data from 6 to 9 weeks to 12 to 24 weeks postoperatively.

Conclusions

Patients undergoing total ethmoidectomy with FS demonstrated statistically significant increases in olfaction and QOL at long‐term postoperative follow‐up. This study demonstrated that FS does not negatively impact the olfactory improvement seen in sinus surgery. The lack of statistically significant changes in these olfactory metrics from short to long‐term follow‐up suggests that there is no additional negative effect of FSS in the long term.

Level of Evidence

3 Laryngoscope, 131:2173–2178, 2021
The most human bot: Female gendering increases humanness perceptions of bots and acceptance of AI
Authors: Borau Sylvie , Otterbring Tobias , Laporte Sandra , Fosso Wamba Samuel
Published: March 2021

Companies have repeatedly launched Artificial Intelligence (AI) products such as intelligent chatbots and robots with female names, voices, and bodies. Previous research posits that people intuitively favor female over male bots, mainly because female bots are judged as warmer and more likely to experience emotions. We present five online studies, including four preregistered, with a total sample of over 3,000 participants that go beyond this longstanding perception of femininity. Because warmth and experience (but not competence) are seen as fundamental qualities to be a full human but are lacking in machines, we argue that people prefer female bots because they are perceived as more human than male bots. Using implicit, subtle, and blatant scales of humanness, our results consistently show that women (Studies 1A and 1B), female bots (Studies 2 and 3), and female chatbots (Study 4) are perceived as more human than their male counterparts when compared with non‐human entities (animals and machines). Study 4 investigates explicitly the acceptance of gendered algorithms operated by AI chatbots in a health context. We found that the female chatbot is preferred over the male chatbot because it is perceived as more human and more likely to consider our unique needs. These results highlight the ethical quandary faced by AI designers and policymakers: Women are said to be transformed into objects in AI, but injecting women's humanity into AI objects makes these objects seem more human and acceptable.
Recent Advances of Molecularly Imprinted Polymers Based on Cyclodextrin
Authors: Zhao Xiaoyue , Wang Yong , Zhang Pan , Lu Zhemiao , Xiao Yin
Published: March 2021

Molecular imprinting polymers (MIPs), generally considered as artificial mimics that are comparable to natural receptor, are polymers with tailor‐made specific recognition sites complementary to the template molecules in shape and size. As a class of supramolecular compounds, cyclodextrins (CDs) are flourishing in the field of molecular imprinting with their unique structural properties. This review presents recent advances in application of MIPs based on CDs during the past five years. The discussion is grouped according to the different role of CDs in MIPs, that is, functional monomer, carrier modifier, etc. Main focus is the application of CD‐based MIP on sample preparation, detection, and sensing. Additionally, drug delivery with CD‐based MIP is also briefly discussed. Finally, challenges and future prospects of application of CDs in MIP are elaborated.
Existence and nonexistence of solutions for the fractional nonlinear Schrödinger equation
Authors: Alarcón Salomón , Ritorto Antonella , Silva Analía
Published: March 2021

We consider the equation

where s ∈ (0, 1),
, N > 2s,
,
is such that
and ε > 0 is small. We study the existence and nonexistence of solutions concentrating at a local minimum point of V as ε → 0 without using any symmetry assumption on V. First, we prove that certain type of positive solutions exhibiting peaks does not exist. Then, we study the existence of sign‐changing solutions under a suitable configuration of positive and negative peaks. To guarantee the existence, we cannot neglect the interaction between peaks. In particular, by using a minimization argument, we found solutions exhibiting peaks at the vertices of a 2ℓ‐regular polygon, such that two adjacent peaks have alternate sign.
An examination of the pass‐through of disaggregated energy prices to real house price: Evidence from the United States
Authors: Uzuner Gizem , Usman Ojonugwa , Alola Andrew Adewale
Published: March 2021

Our study investigates the dynamic pass‐through of energy prices (crude oil price, electricity price, natural gas price, and coal price) to real house price in the United States using the data from 1970 to 2017. Based on the autoregressive distributed lag (ARDL) model, the empirical results suggest an incomplete pass‐through for all the energy prices to real house price both in the long run and short run except for long‐run pass‐through of crude oil price which is complete with statistically insignificant parameter. The Granger causality results reveal a feedback effect between natural gas price and real house price, output growth and real house price, natural gas price and crude oil price, coal price and electricity price, and output growth and coal price. In addition, a unidirectional causal relationship is found running from crude oil price, natural gas price, real house price, and coal price to electricity price. Again, we find that crude oil price is the cause of coal price in Granger sense. Therefore, our findings provide insights into proper design of energy policy that reduces the transmission of energy price shocks to house price in the United States.