bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug cost savings in phase III hematological oncology clinical trials in a university hospital
Authors: Herledan Chloé , Ranchon Florence , Schwiertz Vérane , Baudouin Amandine , Karlin Lionel , Ghesquières Hervé , Salles Gilles , Rioufol Catherine
Published: May 2020

The rapid emergence of expensive anticancer therapies is leading to exponential growth in healthcare expenses. In clinical trials, most investigational drugs are provided free of charge by industrial and academic sponsors. This results in drug cost savings for healthcare payers, who are no longer charged with the cost of the standard‐of‐care treatment, which would have been administered outside the trial. This study aims to estimate drug cost savings resulting from patient enrolment in hematological oncology clinical trials, from a public payer perspective. Retrospective screening identified all patients with hematological malignancies included from 2011 to 2016 in a phase III trial and having received at least one sponsor‐provided cycle. Drug cost savings were defined as the standard treatment costs not charged to the payer due to sponsor provision of treatment. For each patient, cost savings were determined by the number of cycles received in the trial and the cost of standard (control arm) treatment. Of the 345 patients included in eligible trials during study period, 272 received sponsor‐provided drugs. Drug cost savings could be estimated for 177 patients (65.1%) included in 27 trials. Total cost savings were €5218 million (US$ 6804 million) for 1720 sponsor‐provided cycles. Mean cost saving per patient was €19 182.7 ± 29 865.7 ($25 015.24 ± 39 478.25). Most cost‐saving trials were industry‐sponsored (77.8%), although academic trials generated 40.15% of total cost savings. Enrolling patients in clinical trials, whether industry‐sponsored or academic, leads to substantial drug cost savings for payers. Implications are significant for public payers facing increasing financial constraints, as savings can be reallocated to patient care.
Challenges and solutions for maternity and gynecology services during the COVID‐19 crisis in Jordan
Authors: Alsharaydeh Ibrahim , Rawashdeh Hasan , Saadeh Noura , Obeidat Basil , Obeidat Nail
Published: May 2020

Objective

To describe regional experiences and measures implemented to safely maintain obstetrics and gynecology services during the COVID‐19 pandemic at King Abdullah University Hospital in Jordan.

Methods

All policies and measures were implemented in keeping with World Health Organization and other international recommendations and guidelines.

Results

With concerted effort and a multidisciplinary approach, most maternity and gynecology services were provided and all other training and educating responsibilities were maintained.

Conclusion

COVID‐19 caused an unprecedented global healthcare crisis. Our institution addressed the challenges and implemented several measures at different levels to maintain services and facilitate the training and teaching of trainees and medical students.
Optimal water allocation and distribution management in irrigation networks under uncertainty by multi‐stage stochastic case study: Irrigation and drainage networks of Maroon*
Authors: Amanat Behbahani Leila , Moghaddasi Mahnoosh , Ebrahimi Hossein , Babazadeh Hossein
Published: May 2020

In the present research the aim was to prepare a spatial and temporal optimization model for allocating irrigation water and cropping pattern in the Maroon irrigation and drainage networks, which are located in the province of Khoozestan, under uncertainty. Hydrometrical data were gathered from the Maroon network station. Meteorological data were prepared from Idenak station in Behbahan City during 2006–2016. Therefore a model was designed and developed to maximize the total gross benefit of the irrigation networks of Maroon. The presented model is capable of adjusting the optimal water distribution among networks, crops and their different growing stages, determining water shortage, allocating surplus water, and the gross benefit under three scenarios of arid, normal and wet years in two sub‐models of actual intra‐network optimal management and optimal management from the reservoir output to the inside network by applying multi‐stage stochastic programming under uncertainty. The findings show the priority of the second sub‐model over the first run. In the upper and lower bounds model it was illustrated that the cropping areas were increased by respectively 33 and 19%, and of course the benefit amount had an increase of 67 and 7% in the second sub‐model. © 2020 John Wiley & Sons, Ltd.
An edge‐based scheme to support heart rate estimation for different physical exercises
Authors: Pan Wenwen , Ma Shuai
Published: May 2020

As an emerging computing paradigm for smart cities, edge computing has received widespread attention. A huge amount of healthcare data in smart city poses more severe issues to the resource‐constrained wearable platform. Meanwhile, this type of platform can not load some complex models to simultaneously improve the accuracy and real‐time performance of algorithms, particularly for heart rate (HR) estimation strongly contaminated by motion artifacts. In this paper, we propose an edge‐based scheme to estimate heart rate during different physical exercises, for example, walking and running with varying speed. This scheme utilizes two‐channel PPG signals and runs on two resource‐constrained edge clusters. The estimation of HR is divided into two stages and runs on edge cluster 1 (C1) and edge cluster 2 (C2), respectively. Firstly, the recursive least squares (RLS) filter running on the C1 is used to discard runaway errors and generate an initial estimate of HR. Second, on the C2, we use particle filters to track HR and can quickly recover the correct value of HR from the incorrect estimates. Our proposed algorithm is validated on a public dataset of 12 subjects recorded during running and walking, compared with some state‐of‐the‐art methods. Experimental results show that our algorithm has a better absolute average error and real‐time performance.
Differencing versus nondifferencing in factor‐based forecasting
Authors: Choi In , Jeong Hanbat
Published: May 2020

This paper studies performance of factor‐based forecasts using differenced and nondifferenced data. Approximate variances of forecasting errors from the two forecasts are derived and compared. It is reported that the forecast using nondifferenced data tends to be more accurate than that using differenced data. This paper conducts simulations to compare root mean squared forecasting errors of the two competing forecasts. Simulation results indicate that forecasting using nondifferenced data performs better. The advantage of using nondifferenced data is more pronounced when a forecasting horizon is long and the number of factors is large. This paper applies the two competing forecasting methods to 68I(1) monthly US macroeconomic variables across a range of forecasting horizons and sampling periods. We also provide detailed forecasting analysis on US inflation and industrial production. We find that forecasts using nondifferenced data tend to outperform those using differenced data.
Study on the mechanism of cantharidin‐induced hepatotoxicity in rat using serum and liver metabolomics combined with conventional pathology methods
Authors: Zhang Jianyong , Chen Qihong , Wang Le , Chen Kuan , Mu Wenbi , Duan Cancan , Li Xiaofei
Published: May 2020

Cantharidin (CTD), a compound secreted from Mylabris species, exhibits strong antitumor properties; however, hepatotoxicity restricts its clinical application. The mechanism by which CTD induces toxicity remains unclear. In the present study, the hepatotoxicity of CTD in the rat was investigated using a metabolomic approach combined with conventional pathology methods. A total of 30 rats were intragastrically treated with two doses of CTD (0.75 and 1.5 mg/kg) for 15 days to evaluate hepatotoxicity. Serum and liver samples were collected for biochemical dynamics analyses, histopathological examination and metabolomic analysis. It was found that liver index and serum biochemical indices were significantly increased. Furthermore, the pathology results showed that hepatocytes and subcellular organelles were damaged. Metabolomics analysis found 4 biomarkers in serum and 15 in the liver that were associated with CTD‐induced hepatotoxicity. In addition, these were responsible for CTD hepatotoxicity by glycerophospholipid metabolism, sphingolipid metabolism, and steroid hormone biosynthesis. In conclusion, conventional pathology and metabolomics for exploring hepatotoxicity can provide useful information about the safety and potential risks of CTD.
Visibility of microvessels in Optical Coherence Tomography angiography depends on angular orientation
Authors: Zhu Jun , Bernucci Marcel T. , Merkle Conrad W. , Srinivasan Vivek J.
Published: May 2020

Optical Coherence Tomography angiography (OCTA) is a widespread tool for depth‐resolved imaging of chorioretinal vasculature with single microvessel resolution. To improve the clinical interpretation of OCTA, the conditions affecting visualization of microvessels must be defined. Here we inject a scattering plasma tracer (Intralipid) during OCTA imaging of the anesthetized rat eye. In the retina, we find that interlaminar (vertical) vessels that connect laminae have one‐fourth to one‐third the OCTA red blood cell to tracer (RBC‐to‐tracer) signal ratio of intralaminar (horizontal) vessels. This finding suggests that the OCTA signal from microvessels depends on angular orientation, making vertically‐oriented vessels more difficult to visualize using intrinsic contrast alone. Clinicians should be aware of this potential artifact when interpreting OCTA.
Examining witness interviewing environments
Authors: Hoogesteyn Katherine , Meijer Ewout , Vrij Aldert
Published: May 2020

The literature on information elicitation in psycholegal settings has predominantly focused on the investigator–interviewee dynamic, with little attention to the environment in which the interview takes place. The present study compared the impact of two interview locations on the disclosure of crime‐related information and perceptions of rapport building. Participants experienced a virtual reality mock crime, and 1 week later were interviewed at either their homes, or a formal room akin to a real‐world police interview room. Participants in the home setting reported feeling more at ease and in control compared to participants interviewed in the formal room. However, we found no differences between conditions on the quantity and quality of information disclosure and participants' perceptions of rapport building. Based on our findings, we found no advantages or disadvantages for conducting witness interviews at their homes. However, these results underscore the practicality of interviewing witnesses outside the police interview room if deemed as more convenient.
The impact of El Niño Southern Oscillation on cropping season rainfall variability across Central Brazil
Authors: Heinemann Alexandre Bryan , Ramirez‐Villegas Julian , Stone Luís Fernando , Silva Ana Paula Garcia Abreu , da Matta David Henriques , Diaz Mario Ernesto Piscoya
Published: May 2020

Local‐level understanding of within‐season rainfall variability and its relationship with the El Niño Southern Oscillation (ENSO) can shed light on crop yield variations and establish appropriate cropping calendars in rainfed systems. This requires information on the growing season, including its length, the total rainfall, the onset and cessation of rainfall, the number of wet and dry days, and the optimal sowing window. The objective of this study was to examine the onset and cessation of both the rainy and growing seasons using historical daily rainfall datasets (1980–2013) from 50 weather stations distributed across the main grain production region of Brazil. We then correlated the interannual variability of the climate variables and crop water availability with ENSO (using the Oceanic Niño Index, ONI). Across the study region, the onset of the rainy period ranged from late September to early November, and the cessation period ranged from late March to mid‐April. The onset of the growing season followed that of the rainy season, beginning across central and northern Mato Grosso in mid‐October, followed by Goiás and Tocantins, and finally Rondônia by the end of October. The length of the sowing window was reduced, and the mean optimal sowing date was delayed during La Niña years for most weather stations in the study region. Our results infer the need to adjust the cropping calendars for specific ENSO phases only in regions that conduct crop rotations. Based on rice crop model simulations of water availability, we propose a mean optimal crop sowing calendar for annual crops in Central Brazil.

Highlights

We analysed the impact of El Niño Southern Oscillation (ENSO) on the growing season characteristics of Central Brazil.

The length of the sowing period is markedly reduced during La Niña years across the region.

We propose a mean optimal crop sowing calendar for Central Brazil based on crop modelling results of ENSO effects.
Resonance Raman investigation of dithionite‐reduced cobalamin
Authors: Mieda‐Higa Kaoru , Mamun Abdullah Al , Ogura Takashi , Kitagawa Teizo , Kozlowski Pawel M.
Published: May 2020

Absorption (Abs) and resonance Raman (rR) spectroscopy along with density functional theory (DFT) have been applied to investigate the derivatives of vitamin B12 (or cobalamins = Cbls). Cbls are cobalt‐containing corrin complexes, vibrations of which can be probed using rR spectroscopy. The oxidation state of Co ion in Cbls can range between Co3+, Co2+, and Co1+, and axially, cobalt can be coordinated by variety of ligands. Recent spectroscopic study revealed that Co2+Cbl reduced by dithionite (DTH) exhibited a unique property distinct from other Co2+Cbls. Accordingly, in this study, rR spectra of Co2+Cbls reduced by DTH were compared with these reduced by dithiothreitol (DTT). The DTT‐reduced Cbl gave ordinary rR spectrum at pH 3 and 8. On the other hand, the DTH‐reduced Cbl gave different rR spectra at pH 3 and 8 and contained a new rR band at 987 cm−1, which is absent with the DTT‐reduced one. The α and γ Abs bands of DTH‐reduced Cbls were also shifted to shorter wavelengths and exhibited broadening. To understand these rR spectra, geometry optimization and frequency calculations using DFT have been carried out for different structural models of Cbls and compared with experiment. Based on current spectroscopic studies and computation, we deduced that the DTH‐reduced Cbl has SO2‐. radical anion at an axial coordination position of Co2+ and that the ππ* transition of corrin ring is partially mixed with π bond of SO2‐. radical anion, giving rise to the S=O stretching rR band in resonance with the γ Abs band.
Besov regularity for solutions of elliptic equations with variable exponents
Authors: Giova Raffaella
Published: May 2020

We establish the higher fractional differentiability of the solutions of a problem in divergence form of the type
The main features consist in assuming that the partial map has ‐growth, the datum F is Besov regular and both the partial map and the function are Orlicz–Besov regular.
Webinar: New services should achieve more than preserving status quo
Authors: Enos Gary
Published: May 2020

New modes of service delivery brought on by the COVID‐19 crisis will fall short if they simply try to duplicate what was being offered in behavioral health organizations before the pandemic, three leaders of prominent provider agencies suggested in a May 20 webinar.
Trauma healing program addresses challenges front‐line professionals face
Authors: Canady Valerie A.
Published: May 2020

A Tucson, Arizona–based mental health and addictions treatment center has incorporated elements of its specialized trauma healing programs to help nurses, psychologists, physicians, social workers, health care technicians, respiratory therapists and other front‐line health care workers receive comprehensive, personalized services to help them process traumatic experiences and improve their mental health.
APA stress report amid COVID‐19 points to parental challenges
Authors: Canady Valerie A.
Published: May 2020

COVID‐19 is undoubtedly placing a considerable toll on parents, according to the American Psychological Association's (APA's) annual Stress in America report, with many saying that working from home while coordinating their children's online learning is causing a significant amount of stress. To better understand how individuals are coping with the extreme stress of this crisis, the APA has adapted its annual stress poll into a monthly analysis of stressors and stress levels, officials stated.
Walgreens pharmacists complete first phase of MH training
Authors: Canady Valerie A.
Published: May 2020

Observing an increasing need for mental health resources, particularly since the start of the COVID‐19 pandemic, Walgreens officials announced May 20 the chain's completion of the first phase of training in Mental Health First Aid, administered by the National Council for Behavioral Health. The program is targeted for all the company's health outcomes pharmacists.
‘Dear Colleague’ letter urges behavioral telehealth expansion
Authors: Canady Valerie A.
Published: May 2020

Citing concerns about mental health and addiction during these “tumultuous times,” members of Congress last month wrote a letter to congressional leaders urging for the expansion of behavioral telehealth services in any upcoming COVID‐19 response package.
Global well‐posedness and existence of uniform attractor for magnetohydrodynamic equations
Authors: Ai Chengfei , Tan Zhong , Zhou Jianfeng
Published: May 2020

We study the global well‐posedness and existence of uniform attractor for magnetohydrodynamic (MHD) equations. The hydrodynamic system consists of the Navier–Stokes equations for the fluid velocity and pressure coupled with a reduced from of the Maxwell equations for the magnetic field. The fluid velocity is assumed to satisfy a no‐slip boundary condition, while the magnetic field is subject to a time‐dependent Dirichlet boundary condition. We first establish the global existence of weak and strong solutions to Equations (1.1)‐(1.4). And at this stage, we further derive the existence of a uniform attractor for Equations (1.1)‐(1.4).
On p–Laplacian boundary value problems involving Caputo–Katugampula fractional derivatives
Authors: Matar Mohammed M. , Lubbad Asma A. , Alzabut Jehad
Published: May 2020

In this paper, we study the existence and uniqueness of solutions for a p–Laplacian boundary value problem defined by semilinear fractional system that involves Caputo–Katugampola fractional derivatives. Our main results rely on the implementation of the Banach and Schauder fixed point theorems. An example is introduced to expose the applicability of the theoretical findings.
Calculation of passive intermodulation product on nonlinear area source using reciprocity principle
Authors: Chen Qianwen , Chen Xiong
Published: May 2020

A compact passive intermodulation calculation method for the nonlinear source with noticeable size is proposed and demonstrated. By approximating the transmission factors of linear carrier and nonlinear passive intermodulation to be the non‐dimensional ratios between the current and power based on the reciprocal calculation principle, the PIM synthetize on a nonlinear source with notable size can ignore the complicated microwave characteristic analysis, while just need the accumulation of each PIM product of each nonlinear cell, which significantly simplifies the calculation process for the passive intermodulation product on a practical microwave device. The study proposed a compact solution to solve PIM product from the nonlinear source with big scale, which can be extended to the PIM analysis of practical microwave device with unevenly distributed PIM product.
28 GHz metal cavity‐backed twin arc slot antenna for high efficiency and thermal management
Authors: Kim Hyunjin , Nam Sangwook
Published: May 2020

This article presents a metal cavity‐backed antenna array with high gain and high radiation efficiency. The proposed antenna can be used for the purpose of thermal management. A 28 GHz linear polarized antenna is implemented on a low cost substrate with an aluminum structure that functions as a heat sink. Each antenna element is connected to integrated circuits with a stripline embedded in the printed circuit board. Each element is fed by a slot‐coupled feeding structure and radiated through twin arc slots fabricated in circular metal cavity. The simulated antenna efficiency is over 80% including feeding structures. The simulated and measured radiation patterns show 17.2 dBi of peak gain. From the thermal simulation, temperature reduction can be expected.
Nonlinear augmented finite element method for arbitrary cracking in large deformation plates and shells
Authors: Wang Liang , Ma Xueshi , Yang Qingda , Karkkainen Ryan L.
Published: May 2020

This article presents a nonlinear augmented finite element method (N‐AFEM) for the analysis of arbitrary crack initiation and propagation in large deformation plates and shells. The FE formulations for plate/shell elements and a shell‐like cohesive zone element, both with explicit consideration of geometric nonlinearity, have been derived in detail. The geometrically nonlinear shell‐like cohesive element has the essential feature of 3D but with crack displacements directly extracted from midplane shell element nodes, which enables an accurate description of crack propagation in shells and plates under large deformation. Furthermore, a novel augmentation process that can explicitly account for the discontinuous displacement fields of cracked elements without the need of extra nodes or nodal DoFs has been develop based on a nonlinear Newton‐Raphson method. The numerical performance of the N‐AFEM in modeling a number of benchmark shell/plate fracture problems demonstrates that the method is efficient, accurate, and robust.
Exploring a near‐surface subsidence over a rehabilitated underground mine through ambient seismic noise tomography in combination with other geophysical methods
Authors: Cárdenas‐Soto Martín , Escobedo‐Zenil David , Tejero‐Andrade Andrés , Nava‐Flores Muricio , Vidal‐García Martín Carlos , Natarajan Thulasiraman
Published: May 2020

An unexpected surface subsidence in Mexico City on 19 May 2015 prompted a detailed geophysical investigation of the three‐dimensional structure of a collapsed‐soil mine located in a section of the Chapultepec Park in the vicinity of an artificial lake. As revealed from past geological explorations, the subsoil at the site consists of volcano‐sedimentary materials that were quarried in the mid‐20th century; subsequently, during the construction of the park, most of those mines had been only partially rehabilitated, with a potential risk of land subsidence. Near‐surface imaging techniques based on ambient seismic noise as well as microgravimetry, electrical resistivity tomography, shallow seismic refraction methods were evaluated for their applicability to characterize the structure of the collapsed mine. Tomography images computed using ambient‐noise array data characterized the extent of the underground mine showing high‐velocity anomaly, while results from microgravimetry and electrical resistivity tomography analyses indicated the structure through weak contrasts in gravity and resistivity anomalies. Additionally, electrical resistivity tomography results also illustrated the saturated nature of the subsoil. While different methods exhibit different capabilities to constrain such a small spatial feature, the present study highlighted the scope of an integrated approach in confirming the existence of potential voids as well as to estimate soil‐subsidence hazard. In terms of operational convenience and rapid performance, the ambient noise tomography method proved to be a relatively efficient and economical reconnaissance tool for identifying 3D velocity contrasts in an urban environment.
Performance of different optimal charging schemes in a solar charging station using dynamic programming
Authors: Hajidavalloo Mohammad R. , Shirazi Farzad A. , Mahjoob Mohammad J.
Published: May 2020

Electric Vehicles (EVs) are gradually replacing conventional vehicles as they are environmentally friendly and cause less pollution problems. Unregulated charging has severe impacts on the distribution grid and may incur EV owners higher charging costs. Therefore, controlled charging infrastructures to supply the charging needs of large numbers of EVs are of vital importance. In this article, an optimal control scenario is presented to formulate the charge scheduling problem of EVs in a solar charging station (CS). Two different objective functions are considered. The first objective function holds for minimizing the total charging cost of EVs. In this case, the benefits of Vehicle‐to‐Grid (V2G) are investigated by comparing the charging costs of EVs with and without this capability. The total EV charging costs and grid benefits are also investigated in the second objective function which holds for minimizing the extracted power from the grid. A modified version of Dynamic Programming is used to solve the large state‐space model defined for the optimal control problem with extremely shorter computation time and minimal loss of optimality. Extensive simulations are done in two representative summer and winter climates to determine the role of solar energy in the CS performance. The results show that in the cost minimization algorithms, significant savings for EV owners and a smooth load shape for the grid are achieved. For the minimized power from the grid algorithm, a total near Photovoltaic (PV)‐curve charging power is obtained to exploit the PV power as much as possible to minimize the impacts on the
grid.
Approaches to studying the genomic architecture of complex birth defects
Authors: Taiwo Toluwani E. , Cao Xuanye , Cabrera Robert M. , Lei Yunping , Finnell Richard H.
Published: May 2020

Every year nearly 6 percent of children worldwide are born with a serious congenital malformation, resulting in death or lifelong disability. In the United States, birth defects remain one of the leading causes of infant mortality. Among the common structural congenital defects are conditions known as neural tube defects (NTDs). These are a class of malformation of the brain and spinal cord where the neural tube fails to close during the neurulation. Although NTDs remain among the most pervasive and debilitating of all human developmental anomalies, there is insufficient understanding of their etiology. Previous studies have proposed that complex birth defects like NTDs are likely omnigenic, involving interconnected gene regulatory networks with associated signals throughout the genome. Advances in technologies have allowed researchers to more critically investigate regulatory gene networks in ever increasing detail, informing our understanding of the genetic basis of NTDs. Employing a systematic analysis of these complex birth defects using massively parallel DNA sequencing with stringent bioinformatic algorithms, it is possible to approach a greater level of understanding of the genomic architecture underlying NTDs. Herein, we present a brief overview of different approaches undertaken in our laboratory to dissect out the genetics of susceptibility to NTDs. This involves the use of mouse models to identify candidate genes, as well as large scale whole genome/whole exome (WGS/WES) studies to interrogate the genomic landscape of NTDs. The goal of this research is to elucidate the gene‐environment interactions contributing to NTDs, thus encouraging global research efforts in their prevention.
A Comprehensive Analysis of Symmetric Arginine Dimethylation in Colorectal Cancer Tissues Using Immunoaffinity Enrichment and Mass Spectrometry
Authors: Lim Yongchul , Park Yae Eun , Ha Sujin , Lee Ji Eun , Kim Hee Cheol
Published: May 2020

Protein arginine methyltransferase 5 (PRMT5) is a major enzyme responsible for generating monomethyl and symmetric dimethyl arginine in proteins. PRMT5 is essential for cell viability and development, and its overexpression is observed in a variety of cancers. In the present study, it is found that levels of PRMT5 protein and symmetric arginine dimethylation in colorectal cancer (CRC) tissues are increased compared to those in adjacent noncancerous tissues. Using immunoaffinity enrichment of methylated peptides combined with high‐resolution mass spectrometry, a total of 147 symmetric dimethyl‐arginine (SDMA) sites in 94 proteins are identified, many of which are RNA binding proteins and enzymes. Quantitative analysis comparing CRC and normal tissues reveals significant increase in the symmetric dimethylation of 70 arginine sites in 46 proteins and a decrease in that of four arginine sites in four proteins. Among the 94 proteins identified in this study, it is confirmed that KH‐type splicing regulatory protein is a target of PRMT5 and highly expressed in CRC tissues compared to noncancerous tissues. This study is the first comprehensive analysis of symmetric arginine dimethylation using clinical samples and extends the number of known in vivo SDMA sites. The data obtained are available via ProteomeXchange with the identifier PXD015653.
Quantitative Proteomics Reveals the Effects of Resveratrol on High‐Altitude Polycythemia Treatment
Authors: Deng Bingnan , Liu Weili , Pu Lingling , Wang Xinxing , Duan Ruifeng , Wang Tianhui , Wang Zirou , Du Lianqun , Gao Zhixian , Chen Zhaoli
Published: May 2020

High‐altitude polycythemia (HAPC) is a common plateau chronic disease in which red blood cells are compensatory hyperproliferative due to high altitude hypoxic environment. HAPC severely affects the physical and mental health of populations on the plateau. However, the pathogenesis and treatment of HAPC has been rarely investigated. Here, the hypoxia‐induced HAPC model of rat is established, in which hemoglobin concentration significantly increases and platelets clearly decrease. The effect of resveratrol upon hypoxia enables HAPC remission and makes hemoglobin and platelet tend to a normal level. Furthermore, quantitative proteomics is applied to investigate the plasma proteome variation and the underlying molecular regulation during HAPC occurrence and treatment with resveratrol. Hypoxia promotes erythrocyte developing and differentiating and disrupts cytoskeleton organization. Notably, the resveratrol administration reverses the proteome change pattern due to hypoxia and contributes to plateau adaption. Quantitative verification of differentially expressed proteins confirms the roles of resveratrol in HAPC. Resveratrol is expected to be useful for HAPC treatment.
Real‐Time Reconstruction of Arbitrary Slices for Quantitative and In Situ 3D Characterization of Nanoparticles
Authors: Vanrompay Hans , Buurlage Jan‐Willem , Pelt Daniël M. , Kumar Vished , Zhuo Xiaolu , Liz‐Marzán Luis M. , Bals Sara , Batenburg K. Joost
Published: May 2020

A detailed 3D investigation of nanoparticles at a local scale is of great importance to connect their structure and composition to their properties. Electron tomography has therefore become an important tool for the 3D characterization of nanomaterials. 3D investigations typically comprise multiple steps, including acquisition, reconstruction, and analysis/quantification. Usually, the latter two steps are performed offline, at a dedicated workstation. This sequential workflow prevents on‐the‐fly control of experimental parameters to improve the quality of the 3D reconstruction, to select a relevant nanoparticle for further characterization, or to steer an in situ tomography experiment. Here, an efficient approach to overcome these limitations is presented, based on the real‐time reconstruction of arbitrary 2D reconstructed slices through a 3D object. Implementation of this method may lead to generalized implementation of electron tomography for routine nanoparticle characterization in 3D.
Enhancing Interfacial Properties of Mg2Si‐Based Thermoelectric Joint with Mg2SiNi3 Compound as Electrodes
Authors: Chen Shaoping , Chen Yanzuo , Ohno Saneyuki , Xu Libin , Fan Wenhao , Xue Lin , Ferhat Marhoun , Wu Yucheng
Published: May 2020

The phase component and its evolution during aging at the joint between thermoelectric (TE) materials and electrodes are of much importance to the quality and the performance of the TE devices. While the figure of merit zT of TE materials determines the maximum efficiency of TE devices, undesired side reactions causing the growing interfacial resistance or mechanical failures between TEs and metal electrodes limit the actual performance of devices. Herein, the candidate electrode materials (Mg2Ni and Mg2SiNi3) for Mg2Si are explored, which is one of the cost‐effective and environmentally friendly TE materials exhibiting high zT. The electrodes are directly bonded to Mg2Si by field‐activated pressure‐Assisted sintering (FAPAS) in one‐step process. The interfaces of fabricated joints with different sintering times are monitored by electron microscopy, followed by the measurement of shear strength and the contact resistances. Outperforming strength (28.29 MPa) and contact resistance (63 μΩ cm2) are observed with Mg2SiNi3 at the joint bonded for 30 min. A long‐term stability test on Mg2SiNi3/Mg2Si joint reveals a minute increase in the contact resistance as well as sufficient mechanical stability, suggesting that Mg2SiNi3 is a great candidate of the electrode materials for Mg2Si.
Fluorescence quantum yields of matrices used in ultraviolet matrix‐assisted laser desorption/ionization
Authors: Lin Hou‐Yu , Song Botao Farren , Ni Chi‐Kung
Published: May 2020

Rationale

Ultraviolet matrix‐assisted laser desorption/ionization (MALDI) is among the most popular soft ionization methods in mass spectrometry. Several theoretical models have been proposed to explain the primary ion generation in MALDI. These models require knowledge of various matrix molecular parameters for simulation. One such parameter is the fluorescence quantum yield. However, the fluorescence quantum yield reported in previous studies remains controversial.

Methods

In this study, we used a commercial and a homemade integrating sphere to measure the absorption and fluorescence quantum yields of several commonly used matrices, including 2,3‐dihydroxybenzoic acid, 2,4‐dihydroxybenzoic acid (2,4‐DHB), 2,5‐dihydroxybenzoic acid (2,5‐DHB), 2,6‐dihydroxybenzoic acid, 3,4‐dihydroxybenzoic acid, 3,5‐dihydroxybenzoic acid, α‐cyano‐4‐hydroxycinnamic acid, 2,4,6‐trihydroxyacetophenone, and ferulic acid.

Results

The fluorescence quantum yields of these matrices were determined to be low (<0.08) at low laser fluences and decreased as the laser fluence increased. The fluorescence quantum yields at the typical laser fluence for MALDI are below 0.04 (2,4‐DHB and 2,5‐DHB) and 0.01 (the other matrices). Shot‐to‐shot fluctuations of fluorescence intensity and absorption are not directly related to the fluctuation of ions. Possible mechanisms for the decrease in the fluorescence quantum yield as the laser fluence increased were discussed.

Conclusions

The fluorescence quantum yields of these commonly used matrices are much lower than those reported in previous studies. Although fluorescence quantum yield is an important parameter and it is crucial to obtain an accurate value for theoretical models in simulations, the use of fluorescence quantum yield alone is not a sufficient parameter to justify these models.
Comparison of operative time between robotic and laparoscopic myomectomy for removal of numerous myomas
Authors: Won Seyeon , Lee Nara , Kim Miseon , Kim Mi Kyoung , Kim Mi‐La , Jung Yong Wook , Yun Bo Seong , Seong Seok Ju
Published: May 2020

Background

We hypothesized that the total operative time of robot myomectomy (RM) is shorter than that of laparoscopic myomectomy (LM) in cases where numerous myomas are removed, due to the faster suturing time of the robotic system. To verify this, we compared the surgical outcomes of RM vs LM for the number of myomas removed.

Methods

The medical records of 144 women underwent LM and 121 women underwent RM by a single surgeon were reviewed.

Results

The operative time did not statistically differ between the groups, even when the number of removed myomas was more than 12 (200.6 ± 48.2 vs 196.0 ± 48.4 minutes, P = .791). Note that in our logistic regression analysis, the operation type was excluded from the independent risk factors prolonging operative time.

Conclusion

RM showed a similar operative time relative to LM regardless of the number of myomas removed (numerous or not).
Tissue-specific angiogenic and invasive properties of human neonatal thymus and bone MSCs: Role of SLIT3-ROBO1
Authors: Wang Shuyun , Huang Shan , Johnson Sean , Rosin Vadim , Lee Jeffrey , Colomb Eric , Witt Russell , Jaworski Alexander , Weiss Stephen J. , Si Ming-Sing
Published: May 2020

Although mesenchymal stem/stromal cells (MSCs) are being explored in numerous clinical trials as proangiogenic and proregenerative agents, the influence of tissue origin on the therapeutic qualities of these cells is poorly understood. Complicating the functional comparison of different types of MSCs are the confounding effects of donor age, genetic background, and health status of the donor. Leveraging a clinical setting where MSCs can be simultaneously isolated from discarded but healthy bone and thymus tissues from the same neonatal patients, thereby controlling for these confounding factors, we performed an in vitro and in vivo paired comparison of these cells. We found that both neonatal thymus (nt)MSCs and neonatal bone (nb)MSCs expressed different pericytic surface marker profiles. Further, ntMSCs were more potent in promoting angiogenesis in vitro and in vivo and they were also more motile and efficient at invading ECM in vitro. These functional differences were in part mediated by an increased ntMSC expression of SLIT3, a factor known to activate endothelial cells. Further, we discovered that SLIT3 stimulated MSC motility and fibrin gel invasion via ROBO1 in an autocrine fashion. Consistent with our findings in human MSCs, we found that SLIT3 and ROBO1 were expressed in the perivascular cells of the neonatal murine thymus gland and that global SLIT3 or ROBO1 deficiency resulted in decreased neonatal murine thymus gland vascular density. In conclusion, ntMSCs possess increased proangiogenic and invasive behaviors, which are in part mediated by the paracrine and autocrine effects of SLIT3.

Significance statement Mesenchymal stromal cells (MSCs), due to their ubiquity, can be isolated from various tissues and are being evaluated for their therapeutic effects. Despite their advanced clinical evaluation, the tissue-specific pro-regenerative properties of MSCs are poorly understood. Using a unique clinical situation that permits simultaneous isolation of thymus- and bone-derived MSCs from the same patient, a paired comparison was performed, which allowed to control for donor age, health status, and individual variability. It was found that neonatal thymus MSCs possess more proangiogenic, motile, and invasive behavior and that this is in part due to increased signaling from the SLIT3-ROBO1 axis. In sum, human MSCs likely have important tissue-specific regenerative characteristics and MSC SLIT3 expression may be an informative biomarker for regenerative and therapeutic potency.
Programmable NIR‐II Photothermal‐Enhanced Starvation‐Primed Chemodynamic Therapy using Glucose Oxidase‐Functionalized Ancient Pigment Nanosheets
Authors: Yang Chen , Younis Muhammad Rizwan , Zhang Jing , Qu Junle , Lin Jing , Huang Peng
Published: May 2020

Chemodynamic therapy (CDT) has attracted considerable attention recently, but the poor reaction kinetics restrict its practical utility in clinic. Herein, glucose oxidase (GOx) functionalized ancient pigment nanosheets (SrCuSi4O10, SC) for programmable near‐infrared II (NIR‐II) photothermal‐enhanced starvation primed CDT is developed. The SC nanosheets (SC NSs) are readily exfoliated from SC bulk suspension in water and subsequently functionalized with GOx to form the nanocatalyst (denoted as SC@G NSs). Upon laser irradiation, the photothermal effect of SC NSs can enhance the catalytic activity of GOx for NIR‐II photothermal‐enhanced starvation therapy, which effectively eliminates intratumoral glucose and produces abundant hydrogen peroxide (H2O2). Importantly, the high photothermal‐conversion efficiency (46.3%) of SC@G NSs in second biological window permits photothermal therapy of deep‐seated tumors under the guidance of NIR‐II photoacoustic imaging. Moreover, the acidity amplification due to gluconic acid generation will in turn accelerate the degradation of SC NSs, facilitating the release of strontium (Sr) and copper (Cu) ions. Both the elevated H2O2 and the released ions will prime the Cu2+/Sr2+‐H2O2 reaction for enhanced CDT. Thus, a programmable NIR‐II photothermal‐enhanced starvation primed CDT is established to combat cancer with minimal side effects.
A Biomimetic Nanogenerator of Reactive Nitrogen Species Based on Battlefield Transfer Strategy for Enhanced Immunotherapy
Authors: Feng Qianhua , Li Yuzhen , Wang Ning , Hao Yutong , Chang Junbiao , Wang Zeying , Zhang Xueli , Zhang Zhenzhong , Wang Lei
Published: May 2020

Currently, cell membrane is always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular activity seems more meaningful. Inspired by the specific killing mechanism of deoxy‐hemoglobin (Hb) dependent drug (RRx‐001) in hypoxic red blood cells (RBC), this work aims to develop an inner and outer RBC‐biomimetic antitumor nanoplatform that replicates both membrane surface properties and intracellularly certain therapeutic mechanisms of RRx‐001 in hypoxic RBC. Herein, RRx‐001 and Hb are introduced into RBC membrane camouflaged TiO2 nanoparticles. Upon arrival at hypoxic tumor microenvironment (TME), the biomimetic nanoplatform (R@HTR) is activated and triggers a series of reactions to generate reactive nitrogen species (RNS). More importantly, the potent antitumor immunity and immunomodulatory function of RNS in TME are demonstrated. Such an idea would transfer the battlefield of RRx‐001 from hypoxic RBC to hypoxic TME, enhancing its combat capability. As a proof of concept, this biomimetic nanoreactor of RNS exhibits efficient tumor regression and metastasis prevention. The battlefield transfer strategy would not only present meaningful insights for immunotherapy, but also realize substantial breakthroughs in biomimetic nanotechnology.
Dispersibility and Photochemical Stability of Delaminated MXene Flakes in Water
Authors: Shen Shuyi , Ke Tao , Rajavel Krishnamoorthy , Yang Kun , Lin Daohui
Published: May 2020

The environmental stability of 2D MXene flakes must be systematically studied before their further application. Herein, the colloidal dispersibility and photochemical stability of delaminated Ti3C2Tx MXene flakes modified with hydrazine (HMH) and KOH and with water as the control (HMH‐Ti3C2, KOH‐Ti3C2, and H2O‐Ti3C2, respectively) are experimentally and theoretically studied. Modification greatly increases the dispersibility of Ti3C2Tx flakes. Their critical coagulation concentrations are 28.7, 106, and 49.1 mm NaCl, and their Hamaker constants are 23.7 × 10−21, 19.1 × 10−21, and 37.7 × 10−21 J, respectively; the colloidal interaction follows the classical Derjaguin–Landau–Verwey–Overbeek theory. HMH‐Ti3C2 and KOH‐Ti3C2 exhibit higher photochemical stability, as indicated by their stronger resistance to oxidation under UV and visible light irradiation. Changes in their physicochemical properties and the generation of reactive oxygen species (ROS) are assayed. Spin‐polarized density functional theory calculations and molecular dynamics simulations are used to determine the mechanisms underlying the differences in the photochemical stability of Ti3C2Tx flakes. K+ ions protect the flakes from oxidation by acting as a middle layer to reduce the coupling between Ti3+ and ROS, while HMH provides stronger protection by absorbing photoelectrons or reacting with ROS. These findings provide new insight into the environmental transformation and design of functional MXenes.
Transdermal theranostics
Authors: Than Aung , Zan Ping , Chen Peng
Published: May 2020

Skin offers an easily accessible site for drug administration as well as for health signal monitoring, with non‐invasiveness or minimal‐invasiveness, convenience, and good patient compliance. Transdermal theranostics promises for personalized, home‐based, and long‐term management of chronic diseases, and is expected to change the landscape of healthcare profoundly. In this article, we review the recent advances in transdermal drug delivery, diagnosis based on sweat and skin interstitial fluid, and wearable devices. The advantages, limitations, and commercialization of these emerging techniques are comparatively discussed.
Exact quark-mass dependence of the Higgs-gluon form factor at three loops in QCD
Authors: Czakon Michał , Niggetiedt Marco
Published: May 2020

Abstract

We determine the three-loop form factor parameterising the amplitude for the production of an off-shell Higgs boson in gluon fusion in QCD with a single massive quark. The result is obtained via a numerical solution of a system of differential equation for the occurring master integrals. The solution is also used to determine the high-energy and threshold expansions of the form factor. Our findings may be used for the evaluation of virtual corrections generated by top-quark and b-quark loops in Higgs boson hadroproduction cross sections at next-to-next-to-leading order.
Multidisciplinary multi-objective design optimization of an active morphing wing section
Authors: Dexl Florian , Hauffe Andreas , Wolf Klaus
Published: May 2020

Design and optimization of morphing wings are of current research interest as they promise increasing efficiency and flexibility of future aircraft. A challenging task is to find structural layouts of morphing wings that enable aerodynamically optimized shape changes without defining the target shape a priori. The current paper addresses this task and presents a method that combines the optimization of the active structure of a wing section, parameterized by Lindenmayer cellular systems, with an aerodynamic evaluation. Neither the structural layout nor the target shape has to be defined a priori. This aim is achieved by a multidisciplinary optimization using evolutionary algorithms with aerodynamic and structural objectives. The developed method allows to optimize the topology of the internal structure, the placement of linear contraction, and expansion actuators as well as the setting of their actuation degree concurrently. It is shown that the present approach allows to find optimized internal layouts containing active structural elements for morphing wing sections.
Apps und ihre Anwendungsgebiete in der Rheumatologie
Authors: Krusche M. , Ruffer N. , Grahammer M. , Knitza J.
Published: May 2020

Mit der steigenden Verwendung von Smartphones einhergehend, nimmt auch die Nutzung von mobilen Applikationen (Apps) rapide zu. Im medizinischen Kontext könnten chronisch kranke Patienten von dem Einsatz dauerhaft profitieren. Verstärkt wird diese Entwicklung durch das Digitale-Versorgung-Gesetz (DVG), wonach Patienten ab Q4/2020 einen Rechtsanspruch auf bestimmte Apps, sog. digitale Gesundheitsanwendungen (DiGAs), haben, die von den gesetzlichen Krankenkassen erstattet werden. Besonders im Bereich der Rheumatologie bieten sich für das Management chronischer Erkrankungen und ihrer Komorbiditäten verschiedene Anknüpfungspunkte. Nicht nur unter rheumatologischen Patienten ist das Interesse an App-Angeboten groß, sondern auch unter deutschen Rheumatologen zeigt sich eine steigende Bereitschaft, Apps im Berufsalltag anzuwenden und Patienten zu empfehlen. Dieser Artikel will einen Überblick über die Entwicklung der App-Landschaft in der deutschsprachigen Rheumatologie vermitteln.