bluuebunny/crossref_metadata_2025 huggingface dataset:
Freedmen and freedwomen
Authors: Liu Jinyu
Published: June 2019

Upon manumission, a slave became a freedman/woman. In both Greece and Rome, freedman status was a legal category, and freedmen/women did not constitute a homogeneous social class. Although freedmen/women were all faced with legal limitations, at least until Justinian, and had various obligations to their former masters, there were also tremendous differences in terms of their socioeconomic connections, financial status, social mobility, and occupations. Children born to freedmen/women after manumission, however, were freeborn. In the Roman Empire, freedmen/women were well represented in the epigraphic material, which provides rich information concerning their aspirations and diverse roles in society.
Wine
Authors: Estreicher Stefan K.
Published: June 2019

The wild easternVitis vinifera sylvestriswas domesticated and the first wine made ca. 6000bcein Neolithic Transcaucasia and eastern Anatolia. Wine played important roles as a safe drink (normally mixed with water) as well as in religion, medicine, and trade. The Phoenicians introduced viticulture around the Mediterranean Basin and the Ancient Greeks made wine a drink accessible to all levels of society. The Romans perfected the technology for its mass production and expanded viticulture away from the Mediterranean coast.
Aquilius Gallus, Gaius
Authors: Tuori Kaius
Published: June 2019

Gaius Aquilius Gallus was a Roman jurist of the Late Republic. He is best known through his role in the lawsuit of Aulus Caecina, which produced Cicero's speech
pro Caecina
. Among lawyers, he is famous as the inventor of several important institutions of Roman law, such as the
stipulatio Aquiliana
, the
actio de dolo
, and the
exceptio doli
. However, very little is known of his life and works beyond the references in Cicero and in Pomponius (the latter included him in the canon of important jurists), and a number of quotations in the
Digest
of Justinian.
Ofilius (Aulus Ofilius)
Authors: Möller Cosima
Published: June 2019

Ofilius was a jurist in the last decades of the Roman Republic. As a pupil of Servius Sulpicius Rufus, he was involved in the codification project of Julius Caesar. He was the first jurist who commented on the Praetor's Edict extensively. Important subjects he dealt with are legacies and water law. Lenel lists 58 citations in the
Digest
of Justinian, none deriving directly from the original works.
No apparent effect of naproxen onCSFmarkers of innate immune activation
Authors: Meyer Pierre‐François , Labonté Anne , Rosa‐Neto Pedro , Poirier Judes , Breitner John C. S. ,   the PREVENT‐AD Research Group
Published: June 2019

We studied 78 participants having a parental or multiple‐sibling history of Alzheimer’s disease (AD) in a two‐year randomized placebo‐controlled trial of naproxen 220 mg b.i.d. for mitigation of early AD pathogenesis. Naproxen was detected in cerebrospinal fluid at concentrations ~100 times lower than in plasma, but produced negligible change in immune markers. The repeated lack of benefit in AD prevention trials using naproxen and related drugs may reflect limited CNS permeability, lack of expected drug effects, or both. These findings suggest reconsideration of implications from results of AD prevention trials using anti‐inflammatory drugs.
Electronically Nonadiabatic Structural Transformations Promoted by Electron Beams
Authors: Lingerfelt David B. , Ganesh Panchapakesan , Jakowski Jacek , Sumpter Bobby G.
Published: June 2019

The use of scanning transmission electron microscopes to manipulate substitutional defects in graphene has recently been demonstrated and modeled using ground state molecular dynamics, but the role of electronic excitations induced through inelastic electron scattering in promoting these transformations has so‐far remained unexplored. Here, probed are the effects of electronic excitation on the structural dynamics of graphene quantum dots of differing edge morphologies that are substitutionally doped with silicon or phosphorous. The ground and excited state potential energy barriers for pyramidal inversion of these nonplanar doped species are evaluated using time‐dependent density functional theory. Optically bright excited states in which the barrier is decreased are identified in the low energy region of the electronic spectrum, suggesting that photoexcitation can modulate the reactivity of defects in graphene under electron beam irradiation. Coupling matrix elements between these inversion‐favoring excited states and the ground state and time‐domain simulations of the material's response to a point charge impulse indicate that focusing an electron beam near the defect can also lead to population of these states, suggesting that beam electrons incident on a defect can both excite the material to an inversion‐favoring state and transfer momentum to the defect to initiate the inversion.
Enhancing Water Evaporation by Interfacial Silica Nanoparticles
Authors: Lin Kejun , Chen Ruoyang , Zhang Liyuan , Shen Wei , Zang Duyang
Published: June 2019

This study provides a simple nanoparticle–water system for enhancing the water evaporation in a low‐cost and energy‐efficient way. The particle–water system is achieved by depositing a layer of hydrophobic silica nanoparticles onto the water surface. The influence of the locally curved water surface, generated by interfacial nanoparticles, to the water evaporation rate is investigated. The experimental results show that the coverage of nanoparticle layer on the water surface enhances the water evaporation flux. A theoretical model based on Kelvin equation is proposed to explain the evaporation enhancement with the local curvature of water surface distorted by hydrophobic nanoparticles on water surface. The major influencing factors on the water evaporation enhancement are found to involve the coverage of nanoparticle layer, surface concentration of nanoparticles, and surface tension of water. The experimental findings offer a novel protocol for evaporation enhancement during water purification and salt mining.
Nanofluid Based on Glucose‐Derived Carbon Dots Functionalized with [Bmim]Cl for the Next Generation of Smart Windows
Authors: Gonçalves Helena M. R. , Pereira Rui F. P. , Lepleux Emmanuel , Carlier Thomas , Pacheco Louis , Pereira Sónia , Valente Artur J. M. , Fortunato Elvira , Duarte Abel J. , de Zea Bermudez Verónica
Published: June 2019

The design of new advanced materials and technologies is essential for the development of smart windows for the next generation of energy‐efficient buildings. Here, it is demonstrated that the functionalization of glucose‐derived carbon dots with 1‐butyl‐3‐methylimidazolium chloride results in a self‐standing, water‐soluble, viscous, reusable nanofluid with self‐improving conductivity, thermotropy around 30–40 °C, and ultraviolet blocking ability. Its synthesis is straightforward, clean, fast, and cheap. At 36 °C (hot summer day), a sun‐actuated thermotropic (TT) device incorporating a 95% w/w nanofluid aqueous solution exhibits a transmittance variation (ΔT) of 9% at 550/1000 nm, which is amplified to 47/31% via the surface plasmon resonance effect. An integrated self‐healing system enabling independent sun‐actuated TT and voltage‐actuated electrochromic (EC) operation is also produced. The low‐energy EC device offers bright hot and dark cold modes (ΔT = 68/64%), excellent cycling stability, unprecedented coloration efficiency values (−1.73 × 106/−1.67 × 106 cm2 C−1 (coloring) and +1.12 × 107/+1.08 × 107 cm2 C−1 (bleaching) at ±2.5 V), and impressive memory effect. The disruptive design and sustainable synthesis of the new nanofluid proposed here will foster the agile development of novel products with improved ecological footprint.
Optoelectronic Device Simulations Based on Macroscopic Maxwell–Bloch Equations
Authors: Jirauschek Christian , Riesch Michael , Tzenov Petar
Published: June 2019

Due to their intuitiveness, flexibility, and relative numerical efficiency, the macroscopic Maxwell–Bloch (MB) equations are a widely used semiclassical and semi‐phenomenological model to describe optical propagation and coherent light–matter interaction in media consisting of discrete‐level quantum systems. This review focuses on the application of this model to advanced optoelectronic devices, such as quantum cascade and quantum dot lasers. The Bloch equations are here treated as a density matrix model for driven quantum systems with two or multiple discrete energy levels, where dissipation is included by Lindblad terms. Furthermore, the 1D MB equations for semiconductor waveguide structures and optical fibers are rigorously derived. Special analytical solutions and suitable numerical methods are presented. Due to the importance of the MB equations in computational electrodynamics, an emphasis is placed on the comparison of different numerical schemes, both with and without the rotating wave approximation. The implementation of additional effects which can become relevant in semiconductor structures, such as spatial hole burning, inhomogeneous broadening, and local‐field corrections, is discussed. Finally, links to microscopic models and suitable extensions of the Lindblad formalism are briefly addressed.
Distillation of alcohol/water solution in hybrid metal–organic framework hollow fibers
Authors: Su Pengcheng , Zhang Xu , Li Yang , Chen Haofeng , Meng Qin , Zhang Guoliang
Published: June 2019

Distillation with multitudinous structured packings has shown great potential for chemical separation. However, there still remains a big challenge to prepare porous structured packings with more productive separation and better mass transfer efficiency due to materials limitations. Metal–organic framework (MOF) membranes have commendable porous structures that provide enough pathways for fast mass transport and superhydrophobic character for efficient separation. Herein, novel MOFs‐based hollow fiber structured packings were fabricated by a facile two‐step blending and post‐coating method and successfully applied in alcohol/water distillation. The ZIF‐8 nanoparticles with high surface area and hydrophobic framework in PDMS matrix greatly accelerated mass transfer rate of membrane. Especially, as hydrophobic ZIF‐8/PDMS layer was coated on the inner surface of fibers, the wetting behavior of membranes can be effectively prevented. The prepared ZIF‐8/PDMS structured packings can be easily operated far above the normal flooding limit and held the height of mass transfer unit as small as desired.
Nutritional transition in schoolchildren from Tucumán, Argentina: A cross‐sectional analysis of nutritional status and body composition
Authors: Cordero María L. , Cesani María F.
Published: June 2019

Objective

The aim of this article was to describe the nutritional status and body composition of schoolchildren from Tucumán (Argentina) and analyze variations according to sex, area of residence, and socioeconomic status (SES).

Methods

A cross‐sectional study was performed in 1948 schoolchildren aged 8.0 to 11.9 years. Body weight, height, triceps skinfold, waist, and upper arm circumferences were measured. Nutritional status and body composition were estimated using the NHANES III reference. SES was surveyed with the Family Affluence Scale. Area of residence was classified as urban or rural based on the criteria of the National Institute of Statistics and Censuses of Argentina. Logistic regression analysis was applied to evaluate nutritional status and body composition according to sex, area of residence, and SES.

Results

The prevalence of overweight and obesity was 12.3% and 18.2%, respectively, as compared with that of underweight (2.3%), stunting (3%), and wasting (2.1%). The prevalence of stunting and wasting was higher in girls, while that of obesity was higher in boys. Low SES schoolchildren registered a higher prevalence of stunting. Analysis of body composition indicated modifications in adipose and muscular tissues, especially in undernourished (underweight, stunting, or wasting) children and children with excess weight (overweight or obesity).

Conclusion

The child population from Tucumán is undergoing an accelerated process of nutritional transition, manifested by the double burden of malnutrition. The distribution of stunting, wasting, and obesity, and changes in fat and muscular tissues were not homogeneous, revealing differences according to sex, area of residence, and SES.
Stable poly (ionic liquids) with unique cross‐linked mesoporous‐macroporous structure as efficient catalyst for alkylation of o‐xylene and styrene
Authors: Sheng Xiaoli , Gao Huaying , Zhou Yuming , Wang Beibei , Sha Xiao
Published: June 2019

In this work, using divinylbenzene (D), 1‐vinylimidazole (V) and 1‐vinyl‐3‐butylimidazolium bromide ([VBIM][Br]) as monomers, the binary‐monomer poly (ionic liquids) (PILs) and ternary‐monomer PILs were successfully synthesized, via hydrothermal polymerization and anion exchange, sequentially. Compared with each other, the ternary polymeric acidic IL catalyst has a clear spongy porous structure, while having a more stable macroporous structure, a larger specific surface area, more acidic groups and more active sites. Catalytic performance of catalyst was investigated through the alkylation of o‐xylene and styrene. The effect of the amount of IL added and the length of the cation chain on the ternary polymerization of acidic IL was systematically investigated. Under optimal reaction conditions (molar ratio of monomers was D:V:[VBIM][Br] = 2:1:1, the most suitable cation chain length was C4), the synthesized MPD‐[C4V]‐[VBIM][SO3CF3] has a larger specific surface area (89.47 m2/g), large pore volume (0.29 cm3/g), and abundant mesopores and macropores, which help to improve the contact between the active site and reactants. Moreover, the catalyst could maintain a relatively high conversion of styrene (99.0%), 1,2‐diphenylethane yield (98.7%) and high thermostability under reaction and be easily be divided from the solution, which is critical for heterogeneous solid catalysts.
Freshwater conservation planning informed and validated by public participation: The Ebro catchment, Spain, as a case study
Authors: Cañedo‐Argüelles Miguel , Hermoso Virgilio , Herrera‐Grao Tony , Barquín José , Bonada Núria
Published: June 2019

Freshwater ecosystems generally lack adequate protection. In this regard, defining clear and objective conservation criteria through public participation is extremely important, as it can greatly enhance the feasibility of the conservation plans by building credibility, salience, and legitimacy.

This article presents an exercise of systematic freshwater conservation planning informed and validated by public participation using river protected areas (RPAs) in the Ebro catchment, Spain, as a case study. A public participation process was performed to define the conservation criteria that RPAs should meet, resulting in a detailed list of conservation features and constraints that were poorly covered by the present network of RPAs in Spain.

The present network of RPAs failed to adequately protect aquatic biodiversity, as 48% of the taxa did not meet the conservation target, including seven species of vulnerable invertebrates and three of vulnerable fish. marxan was used to identify a minimum set of additional areas that would help to meet the conservation target by adequately representing all conservation features and by increasing the efficiency of the network of protected areas. When marxan was run without restrictions, none of the present RPAs was selected, suggesting that the current network of RPAs is not efficiently meeting the conservation demands expressed through public participation.

Overall, this study shows that combining public participation and systematic conservation planning could result in more efficient and enhanced protection of freshwater ecosystems by integrating a wide variety of conservation preferences into the design of RPAs. Also, according to the results, having detailed and updated information on the distribution of invasive and endangered species, as well as increasing the frequency and spatial extension of ecological monitoring, are key to meeting the public demands of enhanced freshwater biodiversity protection and the preservation of sites with high ecological value.
Lorente de Nó: From Neuroanatomy to Neurophysiology
Authors: Espinosa‐Sanchez Juan M. , Espinosa‐Campos Lucía , Batuecas‐Caletrío Ángel
Published: June 2019

Rafael Lorente de Nó (1902–1990) was the youngest and last of Santiago Ramón y Cajal's students. With Fernando de Castro, Lorente de Nó helped to transition the focus of Ramón y Cajal's School from neuroanatomy to neurophysiology. His main contributions to neuroscience concerned the cytoarchitecture of the cerebral isocortex and hippocampus, neural networks, central vestibular system anatomy, vestibulo‐ocular reflex physiology, cochlear nuclei anatomy, and synaptic transmission mechanisms. This article pays tribute to the memory of Lorente de Nó by providing a comprehensive review of the life and work of this giant of neuroscience. Anat Rec, 303:1221–1231, 2020. © 2019 American Association for Anatomy
Inhibition of the Progression of Skin Inflammation, Fibrosis, and Vascular Injury by Blockade of the CX3CL1/CX3CR1 Pathway in Experimental Mouse Models of Systemic Sclerosis
Authors: Luong Vu H. , Utsunomiya Akira , Chino Takenao , Doanh Le H. , Matsushita Takashi , Obara Takashi , Kuboi Yoshikazu , Ishii Naoto , Machinaga Akihito , Ogasawara Hideaki , Ikeda Wataru , Kawano Tetsu , Imai Toshio , Oyama Noritaka , Hasegawa Minoru
Published: June 2019

Objective

To assess the preclinical efficacy and mechanism of action of an anti‐CX3CL1 monoclonal antibody (mAb) in systemic sclerosis (SSc).

Methods

Cultured human dermal fibroblasts were used to evaluate the direct effect of anti‐CX3CL1 mAb on fibroblasts. In addition, bleomycin‐induced and growth factor–induced models of SSc were used to investigate the effect of anti‐CX3CL1 mAb on leukocyte infiltration, collagen deposition, and vascular damage in the skin.

Results

Anti‐CX3CL1 mAb treatment significantly inhibited Smad3 phosphorylation (P < 0.05) and expression of type I collagen and fibronectin 1 (P < 0.01) in dermal fibroblasts stimulated with transforming growth factor β1 (TGFβ1). In the bleomycin model, daily subcutaneous bleomycin injection increased serum CX3CL1 levels (P < 0.05) and augmented lesional CX3CL1 expression. Simultaneous administration of anti‐CX3CL1 mAb or CX3CR1 deficiency significantly suppressed the dermal thickness, collagen content, and capillary loss caused by bleomycin (P < 0.05). Injection of bleomycin induced expression of pSmad3 and TGFβ1 in the skin, which was inhibited by anti‐CX3CL1 mAb. Further, the dermal infiltration of CX3CR1+ cells, macrophages (inflammatory and alternatively activated [M2‐like] subsets), and CD3+ cells significantly decreased following anti‐CX3CL1 mAb therapy (P < 0.05), as did the enhanced skin expression of fibrogenic molecules, such as thymic stromal lymphopoietin and secreted phosphoprotein 1 (P < 0.05). However, the treatment did not significantly reduce established skin fibrosis. In the second model, simultaneous anti‐mCX3CL1 mAb therapy significantly diminished the skin fibrosis induced by serial subcutaneous injection of TGFβ and connective tissue growth factor (P < 0.01).

Conclusion

Anti‐CX3CL1 mAb therapy may be a novel approach for treating early skin fibrosis in inflammation‐driven fibrotic skin disorders such as SSc.
Modeling physical activity data using L0‐penalized expectile regression
Authors: Wirsik Norman , Otto‐Sobotka Fabian , Pigeot Iris
Published: June 2019

In recent years accelerometers have become widely used to objectively assess physical activity. Usually intensity ranges are assigned to the measured accelerometer counts by simple cut points, disregarding the underlying activity pattern. Under the assumption that physical activity can be seen as distinct sequence of distinguishable activities, the use of hidden Markov models (HMM) has been proposed to improve the modeling of accelerometer data. As further improvement we propose to use expectile regression utilizing a Whittaker smoother with an L0‐penalty to better capture the intensity levels underlying the observed counts. Different expectile asymmetries beyond the mean allow the distinction of monotonous and more variable activities as expectiles effectively model the complete distribution of the counts. This new approach is investigated in a simulation study, where we simulated 1,000 days of accelerometer data with 1 and 5 s epochs, based on collected labeled data to resemble real‐life data as closely as possible. The expectile regression is compared to HMMs and the commonly used cut point method with regard to misclassification rate, number of identified bouts and identified levels as well as the proportion of the estimate being in the range of of the true activity level. In summary, expectile regression utilizing a Whittaker smoother with an L0‐penalty outperforms HMMs and the cut point method and is hence a promising approach to model accelerometer data.
Rapid structure identification of nineteen metabolites of ondansetron in human urine using LC/MSn
Authors: Duan Mingyu , Qin Li , Zhong Dafang , Zhang Peng
Published: June 2019

Ondansetron, a 5‐hydroxytryptamine type 3 (5‐HT3) receptor antagonist, is regarded as an excellent candidate to treat chemotherapy‐ and radiotherapy‐induced nausea and vomiting. To better understand the metabolic profiles of ondansetron in human urine, the metabolites were analyzed using liquid chromatography/mass spectrometry (LC/MSn). Urine samples were collected after oral administration of 8 mg ondansetron to healthy volunteers. Then samples were treated by solid‐phase extraction and detected with LC/MSn. Besides ondansetron, in human urine, a total of 19 metabolites including 13 new metabolites were detected and identified via comparing the retention time and product ion spectra with those of reference standards isolated and characterized. The results showed that ondansetron was metabolized via hydroxylation, glucuronidation, sulfation and minor N‐demethylation in human. LC/MSn was demonstrated to be useful and sensitive in the metabolic study of ondansetron.
Efficient succinic acid production from high‐sugar‐content beverages by Actinobacillus succinogenes
Authors: Ferone Mariateresa , Ercole Alessia , Raganati Francesca , Olivieri Giuseppe , Salatino Piero , Marzocchella Antonio
Published: June 2019

This study presents the production of succinic acid (SA) by Actinobacillus succinogenes using high‐sugar‐content beverages (HSCBs) as feedstock. The aim of this study was the valorization of a by‐product stream from the beverage industry for the production of an important building block chemical, such as SA. Three types of commercial beverages were investigated: fruit juices (pineapple and ace), syrups (almond), and soft drinks (cola and lemon). They contained mainly glucose, fructose, and sucrose at high concentration—between 50 and 1,000 g/L. The batch fermentation tests highlighted that A. succinogenes was able to grow on HSCBs supplemented with yeast extract, but also on the unsupplemented fruit juices. Indeed, the bacteria did not grow on the unsupplemented syrup and soft drinks because of the lack of indispensable nutrients. About 30–40 g/L of SA were obtained, depending on the type of HSCB, with yield ranging between 0.75 and 1.00 gSA/gS. The prehydrolysis step improved the fermentation performance: SA production was improved by 6–24%, depending on the HSCB, and sugar conversion was improved of about 30–50%.
The genus Laggera (Asteraceae) – Ethnobotanical and Ethnopharmacological Information, Chemical Composition as well as Biological Activities of Its Essential Oils and Extracts: A Review
Authors: Getahun Tokuma , Sharma Vinit , Gupta Neeraj
Published: June 2019

Most species of the genus Laggera are often used in traditional and folk medicines for the treatment of jaundice, inflammation, leukemia, removing phlegm, bronchitis and bacterial diseases. The essential oils obtained from Laggera plants are rich sources of oxygenated monoterpenes and sesquiterpenes. Among oxygenated monoterpenes, aromatic ether 2,5‐dimethoxy‐p‐cymene is the most abundant and dominant compound of many essential oils of the Laggera species. Till today, to the best of our knowledge, chemical compounds of the essential oils and/or extracts of only eight Laggera species were reported from different countries. Thus, this review presents the chemical compositions and biological activities of the essential oils of these plants studied in thirteen countries. In addition, it discusses the reported ethnobotanical and ethnopharmacological information as well as biological activities of the extracts and some of the isolated compounds of Laggera plants species.
Another tool for the fork‐in‐the‐road toolbox
Authors: Butman Samuel M.
Published: June 2019

Key Points

A provisional stent strategy for bifurcation disease is a good rule of thumb.

The Tryton bifurcation stent is an additional potential useful tool for use in complex coronary disease.

If and when this device has a drug‐eluting side branch, its true role may be clearer.
Integrative Reflective Model of Group Supervision: Practicum Students' Experiences
Authors: Stinchfield Tracy A. , Hill Nicole R. , Bowers Ryan
Published: June 2019

The authors conducted a phenomenological study of 10 practicum students' experiences of the integrative reflective model of group supervision. Six categories emerged: (a) intentional listening, (b) engaged in the process, (c) extension and application of the model, (d) personalization feedback, (e) mindful listening, and (f) dimensional feedback. An implication was students' openness to constructive feedback in group supervision.
Randomized trial of ofatumumab and bendamustine versus ofatumumab, bendamustine, and bortezomib in previously untreated patients with high‐risk follicular lymphoma: CALGB 50904 (Alliance)
Authors: Blum Kristie A. , Polley Mei‐Yin , Jung Sin‐Ho , Dockter Travis J. , Anderson Sarah , Hsi Eric D. , Wagner‐Johnston Nina , Christian Beth , Atkins Jim , Cheson Bruce D. , Leonard John P. , Bartlett Nancy L.
Published: June 2019

Background

This multicenter, randomized phase 2 trial evaluated complete responses (CRs), efficacy, and safety with ofatumumab and bendamustine and with ofatumumab, bendamustine, and bortezomib in patients with untreated, high‐risk follicular lymphoma (FL).

Methods

Patients with grade 1 to 3a FL and either a Follicular Lymphoma International Prognostic Index (FLIPI) score of 2 with 1 lymph node >6 cm or an FLIPI score of 3 to 5 were randomized to arm A (ofatumumab, bendamustine, and maintenance ofatumumab) or to arm B (ofatumumab, bendamustine, bortezomib, and maintenance ofatumumab and bortezomib).

Results

One hundred twenty‐eight patients (66 in arm A and 62 in arm B) received treatment. The median age was 61 years, and 61% had disease >6 cm; 29% had an FLIPI score of 2, and 71% had an FLIPI score of 3 to 5. In arm A, 86% completed induction, and 64% completed maintenance. In arm B, 66% and 52% completed induction and maintenance, respectively. Dose modifications were required in 65% and 89% in arms A and B, respectively. Clinically significant grade 3 to 4 toxicities included neutropenia (A, 36%; B, 31%), nausea/vomiting (A, 0%; B, 8%), diarrhea (A, 5%; B, 11%), and sensory neuropathy (A, 0%; B, 5%). The estimated CR rates were 62% (95% confidence interval [CI], 50%‐74%) and 60% (95% CI, 47%‐72%) in arms A and B, respectively (P = .68). With a median follow‐up of 3.3 years, the estimated 2‐year progression‐free survival (PFS) and overall survival (OS) rates were 80% and 97%, respectively, for arm A and 76% and 91%, respectively, for arm B.

Conclusions

The CR rates, PFS, and OS were not improved with the addition of bortezomib to ofatumumab and bendamustine in patients with high‐risk FL. Although grade 3 to 4 toxicities were similar, more patients treated with bortezomib required dose modifications and early discontinuation.
Assessment of Drug Interaction Potential Between the Hepatitis C Virus Direct‐Acting Antiviral Agents Elbasvir/Grazoprevir and the Nucleotide Analog Reverse‐Transcriptase Inhibitor Tenofovir Disoproxil Fumarate
Authors: Feng Hwa‐Ping , Guo Zifang , Caro Luzelena , Talaty Jennifer E. , Mangin Eric , Panebianco Deborah , Fandozzi Christine , Zhu Yali , Marshall William , Huang Xiaobi , Hanley William D. , Jumes Patricia , Valesky Robert , Martinho Monika , Butterton Joan R. , Iwamoto Marian , Yeh Wendy W.
Published: June 2019

Treatment of individuals coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) requires careful consideration of potential drug‐drug interactions. We evaluated the pharmacokinetic interaction of the direct‐acting antiviral agents elbasvir and grazoprevir coadministered with the nucleotide reverse transcriptase inhibitor tenofovir disoproxil fumarate (TDF). Three open‐label, multidose studies in healthy adults were conducted. In the first study (N = 10), participants received TDF 300 mg once daily, elbasvir 50 mg once daily, and elbasvir coadministered with TDF. In the second study (N = 12), participants received TDF 300 mg once daily, grazoprevir 200 mg once daily, and grazoprevir coadministered with TDF. In the third study (N = 14), participants received TDF 300 mg once daily and TDF 300 mg coadministered with coformulated elbasvir/grazoprevir 50 mg/100 mg once daily. Pharmacokinetics and safety were evaluated. Following coadministration, the tenofovir area under the plasma concentration‐time curve to 24 hours and maximum plasma concentration geometric mean ratios (90% confidence intervals) for tenofovir and coadministered drug(s) versus tenofovir were 1.3 (1.2, 1.5) and 1.5 (1.3, 1.6), respectively, when coadministered with elbasvir; 1.2 (1.1, 1.3) and 1.1 (1.0, 1.2), respectively, when coadministered with grazoprevir; and 1.3 (1.2, 1.4) and 1.1 (1.0, 1.4), respectively, when coadministered with the elbasvir/grazoprevir coformulation. TDF had minimal effect on elbasvir and grazoprevir pharmacokinetics. Elbasvir and/or grazoprevir coadministered with TDF resulted in no clinically meaningful tenofovir exposure increases and was generally well tolerated, with no deaths, serious adverse events (AEs), discontinuations due to AEs, or laboratory AEs reported. No dose adjustments for elbasvir/grazoprevir or TDF are needed for coadministration in HCV/HIV‐coinfected people.
Bemessungskonzept für Druckschächte bei Nutzung des passiven Gebirgswiderstands
Authors: Innerhofer Guntram , Greiner Richard , Innerhofer Guntram
Published: June 2019

The proposed method can be seen as an adaption of the ”Seeber“ concept considering developments in geomechanics, calculation methods and steel technology over the last decades. When exposed to inner pressure, the cracking condition is transgressed and steel linings will not protect the rock mass against cracking. Accordingly, the post‐failure behaviour of the rock mass is an essential basis for structural design. The effects of crack water pressure on radial displacements and the width of gaps are considered. The resistant behaviour of the rock mass is determined by its minor primary principal stress. Under mountain ridges and slopes, there is no correlation between the minor stresses and the height of overburden. Obviously damage cases in concrete lined tunnels are the result of inappropriate assessment of principal stresses. A better approach is proposed based on fundamental considerations and FE calculations. Crack water pressure close to the level of the minimal principal stress will induce progressive hydraulic fracturing in the rock mass, which requires safe waterproofing sealing of the shaft. Grouting the coaxial gap in rock mass is a firm part of any design concept. In shafts sealed by membranes, the capability to bridge fissures must be proved by tests. In steel lined shafts, the usable passive resistance of rock mass is determined by the acceptable radial displacement.
Großtechnische, wirtschaftliche und effiziente untertägige Energiespeicher
Authors: Pikl Franz Georg , Richter Wolfgang , Zenz Gerald
Published: June 2019

The conversion of the energy supply system towards renewable technologies is indispensable for climate and environmental protection. With the predominant use of inexhaustible but fluctuating renewable energy sources, energy storage capacities and physical networks are key infrastructure for sustainable functionality. Efficient pumped‐storage hydropower can meet these demands. However, suitable sites for conventional surface reservoirs are facing natural limits, and new storage capacities in ecologically sensitive mountainous valleys are increasingly difficult to license. To gap these aspects this article reflects the construction of fully underground pumped‐storage hydropower plants to cover multipurpose energy storage requirements.

Thus, the surface reservoirs are substituted by underground storage caverns with less water volume required by equivalent energy storage capacity since high heads are utilized. Proximity to urban areas improves the construction and operation through various infrastructure and close connection to existing power grids, power plants and consumers. Valuable surface resources remain untouched and the closed water cycle ensures a constant storage volume and independent operation against external influences. Furthermore pumped‐storage is combined with seasonal underground thermal energy storage. This system leads the well‐proven hydraulic energy storage technology into a new energetic age and ensures the demand‐based and cross‐sectoral renewable energy supply.
A framework for evaluating correspondence between brain images using anatomical fiducials
Authors: Lau Jonathan C. , Parrent Andrew G. , Demarco John , Gupta Geetika , Kai Jason , Stanley Olivia W. , Kuehn Tristan , Park Patrick J. , Ferko Kayla , Khan Ali R. , Peters Terry M.
Published: June 2019

Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject‐to‐template and template‐to‐template registration. Specifically, we found that commonly used voxel overlap metrics were relatively insensitive to focal misregistrations compared to AFID point‐based measures. Our entire protocol and study framework leverages open resources and tools, and has been developed with full transparency in mind so that others may freely use, adopt, and modify. This protocol holds value for a broad number of applications including alignment of brain images and teaching neuroanatomy.
Scoring system for the prediction of the successful treatment modality in women with cesarean scar pregnancy
Authors: Sun Qiu‐Lei , Luo Li , Gao Chun‐Yan , Yan Ping , Yang Ying , Chen Zheng‐Qiong
Published: June 2019

Objective

To establish a risk scoring system to predict the successful treatment of cesarean scar pregnancy.

Methods

A prospective observational study was conducted between June 2016 and March 2018 in a tertiary care center. Patients received evacuation followed by uterine artery embolization and laparoscopic local resection/hysterectomy successively as salvage measures if necessary. Optimal scaling regression determined the extent of each potential prognostic factor predicted.

Results

Out of 228 women, 144 cases required evacuation before recovery, 73 women required uterine artery embolization, and 11 women eventually required laparoscopic surgery. Six variables were included in the predictive model: number of cesarean deliveries; maximal diameter of gestational sac; remnant myometrial thickness; grading of Doppler signals; presence of fetal heartbeat; and location of gestational sac. A 10‐point scoring system was established by weighting their prediction of the method of successful treatment. In the risk score rank of 1–4, only 4 (2.8%) out of 142 women needed uterine artery embolization as a salvage treatment, while in the risk score rank of 8–10, 41 (80.4%) cases needed uterine artery embolization; laparoscopic operations were performed by physicians for the other 10 (19.6%) cases.

Conclusion

The successful treatment of cesarean scar pregnancy was accurately predicted by a 10‐point scoring system.

Chinese Clinical Trials Registry

ChiCTR‐OOC‐16008467.
Specific RANK Cytoplasmic Motifs Drive Osteoclastogenesis
Authors: Li Yuyu , Shi Zhenqi , Jules Joel , Chen Shenyuan , Kesterson Robert A , Zhao Dongfeng , Zhang Ping , Feng Xu
Published: June 2019

Upon receptor activator of NF-κB ligand (RANKL) binding, RANK promotes osteoclast formation through the recruitment of tumor necrosis factor (TNF) receptor-associated factors (TRAFs). In vitro assays identified two RANK intracellular motifs that bind TRAFs: PVQEET560–565 (Motif 2) and PVQEQG604–609 (Motif 3), which potently mediate osteoclast formation in vitro. To validate the in vitro findings, we have generated knock-in (KI) mice harboring inactivating mutations in RANK Motifs 2 and 3. Homozygous KI (RANKKI/KI) mice are born at the predicted Mendelian frequency and normal in tooth eruption. However, RANKKI/KI mice exhibit significantly more trabecular bone mass than age- and sex-matched heterozygous KI (RANK+/KI) and wild-type (RANK+/+) counterparts. Bone marrow macrophages (BMMs) from RANKKI/KI mice do not form osteoclasts when they are stimulated with macrophage colony-stimulating factor (M-CSF) and RANKL in vitro. RANKL is able to activate the NF-κB, ERK, p38, and JNK pathways in RANKKI/KI BMMs, but it cannot stimulate c-Fos or NFATc1 in the RANKKI/KI cells. Previously, we showed that RANK signaling plays an important role in Porphyromonas gingivalis (Pg)-mediated osteoclast formation by committing BMMs into the osteoclast lineage. Here, we show that RANKL-primed RANKKI/KI BMMs are unable to differentiate into osteoclasts in response to Pg stimulation, indicating that the two RANK motifs are required for Pg-induced osteoclastogenesis. Mechanistically, RANK Motifs 2 and 3 facilitate Pg-induced osteoclastogenesis by stimulating c-Fos and NFATc1 expression during the RANKL pretreatment phase as well as rendering c-Fos and NFATc1 genes responsive to subsequent Pg stimulation. Cell-penetrating peptides (CPPs) conjugated with RANK segments containing Motif 2 or 3 block RANKL- and Pg-mediated osteoclastogenesis. The CPP conjugates abrogate RANKL-stimulated c-Fos and NFATc1 expression but do not affect RANKL-induced activation of NF-κB, ERK, p38, JNK, or Akt signaling pathway. Taken together, our current findings demonstrate that RANK Motifs 2 and 3 play pivotal roles in osteoclast formation in vivo and mediate Pg-induced osteoclastogenesis in vitro.
Synthesis of Some Substituted Pyrazolopyrimidine Derivatives: An Environmentally Benign Approach
Authors: Pathak Arpit Kumar , Gupta Sharoni , Punjabi Pinki B. , Ameta Garima , Ameta Chetna
Published: June 2019

Pyrazolopyrimidines constitute a medicinally important class of heterocyclic compounds. Herein, we report an efficient and environmentally benign method for the synthesis of pyrazolo[3,4‐d]pyrimidin‐3‐ones from 2,4‐dinitrophenylhydrazine and diethyl malonate under microwave irradiation in 1,3‐dibutylimidazolium bromide ionic liquid. The synthesized compounds were analyzed by elemental analysis and standard spectroscopic techniques. The compounds were screened for their antibacterial and antifungal activities.
Application of amino‐based chitosan cyclodextrin derivatives for the extraction of catechins in green tea with high‐performance liquid chromatography
Authors: Dai Yunliang , Row Kyung Ho
Published: June 2019

Chitosan derivatives have been studied widely, but poor solubility in water restricts their applications. In this study, four types of amine‐based chitosan derivatives were prepared and modified further with beta‐cyclodextrin. The sequential microextraction of catechins ((+)‐catechin and (−)‐epigallocatechin gallate) from green tea powder by an optimized solid‐phase extraction method using these four derivatives was investigated. The optimal conditions for the extraction of catechins were 60°C for a 40 min extraction period. The purity and amount of each catechin were determined by high‐performance liquid chromatography. The different amines strengthened the extraction capacity of chitosan. Among the four types of amines, ethylene diamine grafted chitosan beta‐cyclodextrin had the highest extraction capacity to catechins. Therefore, this material was used in the extraction assay, and the standard curves of (+)‐catechin and (−)‐epigallocatechin gallate were linear over the concentration range, 0.25–500 µg/mL, after assaying five data points in duplicate. Solid‐phase extraction with the amino‐based chitosan beta‐cyclodextrin system is a new application of chitosan, which has potential applications in the extraction of bioactive compounds from plant materials or the removal of different impurities from specific extracts.
Correlation between hearing loss and middle ear volume in patients with a tympanic membrane perforation
Authors: Casale Garrett , Shaffrey Ellen , Kesser Bradley W.
Published: June 2019

Objective

To investigate a possible correlation between the degree of conductive hearing loss (CHL) caused by an isolated tympanic membrane (TM) perforation and mastoid‐middle ear volume.

Study Design

Retrospective chart, audiometry, and computed tomography (CT) imaging review.

Methods

Adult patients with a diagnosis of isolated TM perforation between 2010 and 2018 were identified and their audiometric data collected. Mastoid‐middle ear volume (MMEV) was then calculated based on segmentation analysis from the patient's head or temporal bone CT. Calculated MMEV was compared to MMEV derived by tympanometry. A Student's t‐test was performed to determine a correlation between the calculated MMEV on CT imaging and the degree of conductive hearing loss as measured by the air bone gap on standard audiometry.

Results

There was a statistically significant difference between MMEV as determined by segmentation analysis compared to that determined by tympanometry (absolute average percent difference = 33.8%; range ‐49.5% to +155.2%; P = .03). Greater MMEV determined by segmentation analysis correlated with smaller air bone gap; this trend approached but did not reach statistical significance (P = .09).

Conclusions

Calculated MMEV by segmentation analysis on CT imaging may be a more accurate estimate of MMEV than tympanometry. MMEV may be correlated to the degree of conductive hearing loss in the setting of isolated TM perforation where greater volume was associated with better hearing.

Level of Evidence

4 Laryngoscope, 130:E228–E232, 2020
α‐Mannosyl‐Functionalized Cationic Nanohydrogel Particles for Targeted Gene Knockdown in Immunosuppressive Macrophages
Authors: Leber Nadine , Kaps Leonard , Yang Aiting , Aslam Misbah , Giardino Mariacristina , Klefenz Adrian , Choteschovsky Niklas , Rosigkeit Sebastian , Mostafa Asmaa , Nuhn Lutz , Schuppan Detlef , Zentel Rudolf
Published: June 2019

Immunosuppressive M2 macrophages govern the immunophathogenic micromilieu in many severe diseases including cancer or fibrosis, thus, their re‐polarization through RNA interference is a promising concept to support combinatorial therapies. For targeted siRNA delivery, however, safe and stable carriers are required that manage cell specific transport to M2 macrophages. Here, siRNA‐loaded cationic nanogels are reported with α‐mannosyl decorated surfaces that target and modify M2 macrophages selectively. Via amphiphilic precursor block copolymers bearing one single α‐mannosyl moiety at their chain end mannosylated cationic nanohydrogel particles (ManNP) were obtained of 20 nm diameter determined by dynamic light scattering and cryogenic electron transmission microscopy. α‐Mannosyl surface modification is confirmed by agglutination with concanavalin A. SiRNA‐loaded ManNP preferentially targets the overexpressed mannose receptor CD206 on M2 macrophages, as shown by in vitro cell uptake studies in M2 polarized primary macrophages. This specificity is confirmed, since ManNP uptake could be reduced by blocking of CD206 with mannan. Effective ManNP‐guided siRNA delivery is confirmed by sequence‐specific gene knockdown of CSF‐1R in M2‐type macrophages exclusively, while the expression levels in M1‐polarized macrophages is not affected. In conclusion, α‐mannosyl‐functionalized ManNPs are promising universal siRNA carriers for targeted immunomodulatory treatment of immunosuppressive macrophages.
A Vinylic Rotaxane Cross‐Linker Containing Crown Ether for Hydrophilic and Hard Rotaxane‐Networked Polymers
Authors: Sawada Jun , Aoki Daisuke , Sogawa Hiromitsu , Nakajima Ken , Takata Toshikazu
Published: June 2019

Rotaxane‐cross‐linked polymers (RCP), which have rotaxane structures at the cross‐link points, show unique physical properties originating from the movable cross‐link points. Herein, poly(N,N‐dimethylacrylamide) (PDMAAm) and poly(N‐isopropylacrylamide) (PNIPAm) which are well known as hydrophilic polymers and whose glass transition temperatures are much higher than room temperature, were applied as matrix polymers for RCPs. These RCPs are easily and successfully synthesized by radical polymerization of vinyl monomers in the presence of small amounts of [2]rotaxane cross‐linker (RC) comprising one wheel and one axle component with a methacrylate group on each component. As the result, PDMAAm‐based RCP without any solvents and PNIPAm‐based RCP swelled with water were much tougher than corresponding covalently cross‐linked polymers. It is confirmed that RC endows both of the hard polymer networks and soft hydrogels with toughness.
Biodegradation of Poly(aspartamide) Based Hydrogels
Authors: Juriga Dávid , Zrínyi Miklós
Published: June 2019

Biocompatibility and biodegradability are one of the most important properties of polymer hydrogels for pharmaceutical or medical applications. Poly(aspartamide)s, due to their peptide like structure possess these properties. In this study, swelling behavior and biodegradation of poly(aspartamide) based hydrogels are reported. Degradation of poly(aspartic acid) based hydrogels was followed according to the mass and elastic modulus change of hydrogel cylinders in the presence of different enzymes and in minimal essential medium.
Selenium in Cardiac Surgery
Authors: Wendt Sebastian , Schomburg Lutz , Manzanares William , Stoppe Christian
Published: June 2019

Selenium (Se) is an essential trace element that plays a pivotal role in many of the body's regulatory and metabolic functions, especially during times of stress. After uptake, Se is incorporated into several Se‐dependent proteins, which have potent anti‐inflammatory and antioxidant capacities. Several observational clinical studies have demonstrated that Se deficiency can cause chronic cardiovascular diseases and aggravate organ dysfunction after cardiac surgery and that low levels of Se may be independently associated with the development of organ dysfunction after cardiac surgery. Based on these findings, several studies have investigated the effects of a perioperative Se supplementation strategy. Therefore, the present review describes in depth the pathophysiology and harmful stimuli during cardiac surgery, how Se may counteract these injuries, the different types of Se supplementation strategies that have been evaluated, and current evidence of its clinical significance.