bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of various fused heterocyclic rings from thiazolopyridine and their pharmacological and antimicrobial evaluations
Authors: Mahmoud Naglaa F. H. , Balamon Mina G.
Published: June 2020

Various fused‐heterocyclic‐derivatives containing thiazolopyridine moieties has been synthesized by allowing 5‐aminothiazolo[3,2‐a]pyridine derivative 1 to undergo annulations reactions with different reagents under different‐reaction conditions. The biological assessment of compounds 2, 11, 14, 15, and 19 showed remarkable antimicrobial activities. In addition, selected derivatives of the products were screened for their anticancer activities against two tumor cell lines using MTT assay and the results showed that some of these compounds have potent cytotoxic effect, as concluded from their IC50 values. Meanwhile, compounds 3a, 7 have exhibited very strong potency as anticancer candidates. Thiazolopyridine structures have been confirmed as a useful lead compounds for the development of new anticancer agents. Molecular docking showed that,‐some of the synthesized compounds more suitable inhibitor against‐ALR2 with farther alteration in future.
Efficient one‐pot synthesis of novel 6′,9′‐dihydro‐2H,7′H‐spiro[pyrimidine‐5,8′‐[1,3]dioxolo[4,5‐f]quinoline]‐2,4,6(1H,3H)‐trione derivatives under mild and “green” reaction conditions
Authors: Ebrahimi Seyed Esmaeil Sadat , Nozari Nasrin , Bahadorikhalili Saeed , Yahya‐Meymandi Azadeh , Foroumadi Alireza , Larijani Bagher , Biglar Mahmood , Mahdavi Mohammad
Published: June 2020

In this paper, an efficient method is introduced for the synthesis of 7′,9′‐disubstituted 6′,9′‐dihydro‐2H,7′H‐spiro[pyrimidine‐5,8′‐[1,3]dioxolo[4,5‐f]quinoline]‐2,4,6(1H,3H)‐trione derivatives under mild and “green” reaction conditions. The method is based on one‐pot multicomponent reaction of an aldehyde, barbituric acid, and benzo[d][1,3]dioxol‐5‐amine in ethanol as a green and environmentally friendly solvent. The reaction has given the products in the highest isolated yield in the presence of acetic acid as catalyst under reflux conditions. Various aldehydes, bearing electron‐donating or ‐withdrawing functionalities have been used under the optimized conditions and successfully gave the desired products (13 examples) in high isolated yields.
Detection of GM1‐gangliosidosis in newborn dried blood spots by enzyme activity and biomarker assays using tandem mass spectrometry
Authors: Su Peiling , Khaledi Hamid , Waggoner Christine , Gelb Michael H.
Published: June 2020

GM1‐gangliosidosis is a rare autosomal recessive lysosomal storage disease caused by deficiency of β‐galactosidase (GLB1). Newborn screening (NBS) may be warranted in the near future given the initiation of a number of gene therapy clinical trials. Here, we report a tandem mass spectrometry (MS/MS) enzymatic assay of GLB1 using dried blood spots (DBS), and the demonstration that GLB1 activities in newborn DBS from seven GM1‐gangliosidosis patients are well below those measured in random newborn DBS. MS/MS analysis of two glycan biomarkers, dp5 and A2G2, shows high elevation in newborn DBS from GM1‐gangliosidosis compared to the levels in the nonaffected reference range.
Zonisamide promotes survival of human‐induced pluripotent stem cell‐derived dopaminergic neurons in the striatum of female rats
Authors: Miyawaki Yoshifumi , Samata Bumpei , Kikuchi Tetsuhiro , Nishimura Kaneyasu , Takahashi Jun
Published: June 2020

The transplantation of dopaminergic (DA) progenitors derived from pluripotent stem cells improves the behavior of Parkinson's disease model animals. However, the survival of DA progenitors is low, and the final yield of DA neurons is only approximately 0.3%–2% the number of transplanted cells. Zonisamide (ZNS) increases the number of survived DA neurons upon the transplantation of mouse‐induced pluripotent stem (iPS) cell‐derived DA progenitors in the rat striatum. In this study, we induced DA progenitors from human iPS cells and transplanted them into the striatum of female rats with daily administration of ZNS. The number of survived DA neurons was evaluated 1 and 4 months after transplantation by immunohistochemistry, which revealed that the number of survived DA neurons was significantly increased with the administration of ZNS. To assess the mechanism of action of ZNS, we performed a gene expression analysis to compare the gene expression profiles in striatum treated with or without ZNS. The analysis revealed that the expression of SLIT‐and NTRK‐like protein 6 (SLITRK6) was upregulated in rat striatum treated with ZNS. In conclusion, ZNS promotes the survival of DA neurons after the transplantation of human‐iPS cell‐derived DA progenitors in the rat striatum. SLITRK6 is suggested to be involved in this supportive effect of ZNS by modulating the environment of the host brain.
WRF‐based dynamical downscaling of ERA5 reanalysis data for High Mountain Asia: Towards a new version of the High Asia Refined analysis
Authors: Wang Xun , Tolksdorf Vanessa , Otto Marco , Scherer Dieter
Published: June 2020

The High Asia Refined analysis (HAR) is a regional atmospheric data set generated by dynamical downscaling of the Final operational global analysis (FNL) using the Weather Research and Forecasting (WRF) model. It has been successfully and widely utilized. A new version (HAR v2) with longer temporal coverage and extended domains is currently under development. ERA5 reanalysis data is used as forcing data. This study aims to find the optimal set‐up for the production of the HAR v2 to provide similar or even better accuracy as the HAR. First, we conducted a sensitivity study, in which different cumulus, microphysics, planetary boundary layer, and land surface model schemes were compared and validated against in situ observations. The technique for order preference by similarity to the ideal solution (TOPSIS) method was applied to identify the best schemes. Snow depth in ERA5 is overestimated in High Mountain Asia (HMA) and causes a cold bias in the WRF output. Therefore, we used Japanese 55‐year Reanalysis (JRA‐55) to correct snow depth initialized from ERA5 based on the linear scaling approach. After applying the best schemes identified by the TOPSIS method and correcting the initial snow depth, the model performance improves. Finally, we applied the improved set‐up for the HAR v2 and computed a one‐year run for 2011. Compared to the HAR, the HAR v2 has a better representation of air temperature at 2 m. It produces slightly higher precipitation amounts, but the spatial distribution of seasonal mean precipitation is closer to observations.
Socioeconomic risk of droughts under a 2.0°C warmer climate: Assessment of population and GDP exposures to droughts in China
Authors: Liu Yujie , Chen Jie
Published: June 2020

Socioeconomic development and natural ecosystems of China are strongly affected by droughts. The socioeconomic risk of droughts in China should be quantified under climate change. This study assessed drought impacts on population and gross domestic product (GDP) under the 2.0°C‐warmer climate scenario, by implementing multiple general circulation model (GCM) simulations under the representative concentration pathway (RCP). Using the standardized precipitation evapotranspiration index (SPEI), we calculated drought frequencies in the base period (1986–2005) and 2.0°C‐warmer climate (2040–2059 in RCP4.5). Then, population and GDP exposures were evaluated by combining the drought frequency with population and GDP simulations under a shared socioeconomic pathway (SSP). Droughts were likely to occur more frequently under the 2°C‐warmer climate, especially for inland areas of northern China (i.e., Xinjiang, Xizang, Qinghai, Ningxia, Shaanxi, Gansu provinces), consisting mainly of mild and moderate droughts. Population exposure to drought was projected at 4.94 ± 0.36 × 109 person‐months, around 2% increase over the base period value. GDP exposure would increase significantly to 2.08 ± 0.15 × 1014 PPP $‐months, approximately 14‐fold over the base period. Probability analysis showed nearly 50% of the grid cells of China's entire territory undergoing more than an 11‐fold increase in GDP exposure. Our findings indicated the climate and GDP effects were primary contributors, respectively, to the changed population and GDP exposures to drought. Population and GDP exposures were distributed unequally across the country, having a large impact in the east where both population and economic activity are highly agglomerated. Our results reveal an urgent need to design and implement effective adaptation measures to overcome droughts, especially in eastern China.
The impacts of late spring soil moisture in the Tibetan Plateau on summer precipitation in eastern China
Authors: Yuan Yuan , Lai Xin , Gong Yuanfa , Chen Jinlei
Published: June 2020

The Community Land Model version 4.5(CLM4.5), driven by the atmospheric forcing dataset CRUNCEP, was used to simulate the spatial and temporal characteristics of soil moisture across the Tibetan Plateau from 1981 to 2016. Compared with station data and two reanalysis products (i.e., the ERA‐Interim and GLDAS‐CLM), it is found that CLM4.5 can well reproduce the spatial and temporal variations of soil moisture in the Tibetan Plateau. This study reveals the relationship between soil moisture on the Tibetan Plateau in May and summer precipitation in eastern China and the physical mechanism for the impact of soil moisture on summer precipitation. Singular value decomposition (SVD)analysis shows that the surface soil moisture in the south‐central Tibetan Plateau was positively related to the summer precipitation in South China and negatively related to that in the middle and lower reaches of the Yangtze River and Northeast China. The soil moisture in the western Tibetan Plateau was the opposite of that in the south‐central region. The wetter the surface soil moisture in the south‐central Tibetan Plateau in May was, the lower the surface temperature, sensible heat flux and net longwave radiation flux, and the higher the latent heat flux and net shortwave radiation flux and leading to weaker surface heating. In contrast, lower surface soil moisture in the western Tibetan Plateau led to stronger surface heating. This led to a weaker western Pacific subtropical high and a more northerly rain belt. The weather in South China was controlled by large cyclonic circulations forming convergences and updrafts that led to more rainfall in South China. The precipitation in the middle and lower reaches of the Yangtze River and Northeast China was less under the control of the anomalous anticyclone than that in South China, and vice versa.
Fluorinated indium‐gallium‐zinc oxide thin‐film transistor with reduced vulnerability to hydrogen‐induced degradation
Authors: Wang Sisi , Li Jiapeng , Shi Runxiao , Xia Zhihe , Lu Lei , Kwok Hoi Sing , Wong Man
Published: June 2020

Thin‐film transistors (TFTs) based on amorphous indium‐gallium‐zinc oxide channels with or without fluorination were fabricated. The sensitivity of their electrical characteristics to hydrogen exposure was compared. It is shown that TFTs built with fluorinated channels exhibit significantly improved intrinsic resistance against hydrogen‐induced degradation; hence, they are potentially better suited for integration with hydrogen‐containing devices such as photo‐diodes based on amorphous hydrogenated silicon and TFTs based on low‐temperature polycrystalline silicon. The observed improvement correlates well with a reduced population of oxygen‐related defects and reduced hydrogen incorporation in the fluorinated channels.
Correlation between ion impurity in thermally activated delayed fluorescence organic light‐emitting diode materials and device lifetime
Authors: Inoue Masaru , Oyabu Noriaki , Kaneko Yoshiyuki , Kim Jun‐Yun , Yang Joong‐Hwan
Published: June 2020

We propose a measurement method of ion impurity amounts of thermally activated delayed fluorescence (TADF) green dopant powders in a solution by applying a triangle voltage waveform and measuring a small displacement current that has been developed for screening and optimization of materials for thin‐film transistor‐liquid crystal displays (TFT‐LCDs). We found that there is a strong correlation between ion impurity and organic light‐emitting diode (OLED) lifetime, and we confirmed that the TADF green dopant, having a large number of ion impurity, has short OLED lifetime.
Negative‐pressure wound therapy does not reduce superficial SSI in pancreatectomy and hepatectomy procedures
Authors: O'Neill Conor H. , Martin Robert C. G.
Published: June 2020

Introduction

Surgical site infections (SSIs) lead to increased morbidity and cost. Negative‐pressure wound therapy (NPWT) removes wound exudate and improves local blood flow, but its effect on SSI is unproven following hepatectomy and pancreatectomy. The aim of this trial was to evaluate the effect of NPWT on SSI in this population.

Methods

Patients were randomized to incisional NPWT or sterile island dressing following surgery. SSI predictive factors were recorded as well as patient comorbidities. Wound complications and type of SSI were recorded prospectively.

Results

Forty patients received the standardized perioperative bundle. Twenty patients received sterile island: 11 hepatic and 9 pancreatic resections; 20 patients received NPWT: 11 hepatic and 9 pancreatic resections; 23 patients were male; mean age 60.8 years (SD ±10.3); mean BMI 31.7 (SD ±7.0). There were three incisional wound infections: two with sterile island, one with NPWT; six organ space infections: four sterile island and two NPWT. There were no significant differences in SSI rates between groups (P = .57).

Conclusion

NPWT does not improve SSI rates over simple sterile dressing following hepatectomy or pancreatectomy. Improvements in SSI must be directed toward organ‐space infections, which are unaffected by NPWT.
Gauging the efficacy of neoadjuvant endocrine therapy in breast cancer patients with known axillary disease
Authors: Hammond Jacob B. , Parnall Taylor H. , Scott Derek W. , Kosiorek Heidi E. , Pockaj Barbara A. , Ernst Brenda J. , Northfelt Donald W. , McCullough Ann E. , Ocal Idris Tolgay , Cronin Patricia A.
Published: June 2020

Background and Objectives

Neoadjuvant endocrine therapy (NET) for ER+ breast cancer can downstage primary tumors. We evaluated NET efficacy in node‐positive patients.

Methods

Node‐positive patients undergoing NET for ER+ breast cancer from 2012 to 2019 were reviewed. Primary endpoints included rates of axillary lymphadenectomy (ALND), pathologic complete response (pCR), and final nodal staging.

Results

Thirty‐nine patients were included. Before NET, all were clinically node‐positive (cN1 = 36, 94%; cN2 = 2, 5%; cN3 = 1, 3%; Stage II = 23, 59%, Stage III = 16, 41%). After NET, nine (23%) had clinically persistent axillary disease necessitating ALND. The remaining 30 (77%) underwent sentinel lymph node biopsy (SLNB). Of these, 25 (83%) were SLNB+ on frozen section, undergoing immediate ALND. Five patients were negative on frozen section: one had a confirmed axillary pCR, and four had residual nodal disease on permanent pathology. One underwent delayed ALND, and for the remaining three patients, decision was made to forgo ALND. Final overall axillary staging was: N0 (pCR) = 1, 3%, pN1mic = 1, 3%, pN1 = 20, 51%, pN2 = 12, 30%, pN3 = 5, 13%; Stage II = 16, 41%, Stage III = 23, 59%.

Conclusions

While NET is reported to downstage primary tumors, downstaging of the axilla was unsuccessful in the majority of patients.
Expandable distal femur megaprosthesis: A European Musculoskeletal Oncology Society study on 299 cases
Authors: Staals Eric Lodewijk , Sambri Andrea , Campanacci Domenico Andrea , Muratori Francesco , Leithner Andreas , Gilg Magdalena Maria , Gortzak Yair , Van De Sande Michiel , Dierselhuis Edwin , Mascard Eric , Windhager Reinhard , Funovics Philipp , Schinhan Martina , Vyrva Oleg , Sys Gwen , Bolshakov Nikolay , Aston Will , Gikas Panagiotas , Schubert Thomas , Jeys Lee , Abudu Adesegun , Manfrini Marco , Donati Davide Maria
Published: June 2020

Background and Objectives

Expandable distal femur prostheses have become more popular over the last decades, but scientific data is limited.

Methods

A retrospective study was performed, including cases treated between 1986 and 2019 in 15 European referral centers for bone sarcomas.

Results

A total of 299 cases were included. Average follow‐up was 80 months (range, 8‐287 months). Mean patient age was 10 years. Most (80%) of the implants were noninvasive growers and a fixed hinge knee was used more often (64%) than a rotating hinge. Most prosthetic designs showed good (>80%) implant survival at 10 years, but repeat surgery was required for 63% of the patients. The most frequent reason for revision procedure was the completion of lengthening potential. Noninvasive expandable implants showed less risk of infection compared to invasive growers (11.8% vs 22.9% at 10 years). No difference in aseptic loosening was found between cemented and uncemented stems.

Conclusions

This study shows the increasing popularity of expandable distal femur prostheses, with overall good results for function and implant survival. However, repeat surgery is frequently required, especially in patients under the age of 10 years old. Infection is less frequent in noninvasive growers compared to implants that require invasive lengthening procedures.
Brain metabolomics study for the protective effects of Rhodiola crenulata extract on Alzheimer's disease by HPLC coupled with Fourier transform‐ion cyclotron resonance mass spectrometry
Authors: Li Xintong , Wang Yanan , Su Mingming , Chu Xiaowen , Li Siqi , Yue Yiqiang , Zhang Xiaoxue , Wang Jiahong , Han Fei
Published: June 2020

In order to investigate the protective effects of Rhodiola crenulata extract on Alzheimer's disease, a brain metabolomics study in rats was conducted by high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry. Rat model was constructed by bilateral hippocampal injection of amyloid‐β peptide and immunohistochemistry was performed to evaluate the pharmacological effect of Rhodiola crenulata extract. Multivariate statistical analysis was used to discover potential biomarkers in rat brain and related metabolic pathways analysis was conducted to elucidate the action mechanism of Rhodiola crenulata extract. As a result, a total of 19 metabolites contributing to Alzheimer's disease progress were identified and nine of them were restored to the normal levels after drug administration. Pathway analysis revealed that the protective effects of Rhodiola crenulata extract are related to the regulation of glutathione metabolism and arachidonic acid metabolism in rat brain. In conclusion, this work demonstrates that the developed metabolomics method is useful to investigate the protective effects of Rhodiola crenulata extract against Alzheimer's disease. These outcomes may further provide reliable evidence to illuminate the intervention mechanism of other traditional Chinese medicines on Alzheimer's disease.
Analysis and evaluation of nucleosides, nucleobases, and amino acids in safflower from different regions based on ultra high performance liquid chromatography coupled with triple‐quadrupole linear ion‐trap tandem mass spectrometry
Authors: Pu Zong‐Jin , Yue Shi‐Jun , Yan Hui , Tang Yu‐Ping , Chen Yan‐Yan , Tan Ya‐Jie , Shi Xu‐Qin , Zhu Zhen‐Hua , Tao Hui‐Juan , Chen Jia‐Qian , Zhou Gui‐Sheng , Huang Sheng‐Liang , Peng Guo‐Ping , Su Shu‐Lan , Duan Jin‐Ao
Published: June 2020

Safflower has both medicinal and edible values but research on its nutrient composition is still lacking. This study was established for the quantitative determination of 28 nucleosides, nucleobases, and amino acids based on the ultra‐performance liquid chromatography coupled with triple‐quadrupole linear ion‐trap tandem mass spectrometry. Analysis of 30 batches of safflower from different producing areas indicated that the contents of l‐proline, l‐asparagine, l(+)‐arginine, l‐serine, l‐histidine, uracil, guanosine, and uridine was high in safflower. Principle component analysis and cluster analysis found that samples from different regions could be distinguished well, and samples from the same area could be clustered into one class, different geographical environments may cause the differences of nucleosides, nucleobases, and amino acids in safflower. The analysis of principal component analysis, cluster analysis, and counter propagation artificial neural network show similar results. Then the content of nucleosides, nucleobases, and essential amino acids were compared, and found that the content in safflower from Gansu was higher than those from other regions, and there was a little difference between the samples from Xinjiang, Sichuan, and Yunnan. This research revealed the composition of nucleosides, nucleobases, and amino acids in safflower, and provided a theoretical basis for utilization of safflower.
Two‐dimensional liquid chromatography analysis of all‐trans‐, 9‐cis‐, and 13‐cis‐astaxanthin in raw extracts from Phaffia rhodozyma
Authors: Du Xiping , Wang Chun , Wu Ling , Li Zhipeng , Sadiq Faizan Ahmed , Jiang Zedong , Chen Feng , Ni Hui , Li Qingbiao
Published: June 2020

An effective two‐dimensional liquid chromatography method has been established for the analysis of all‐trans‐astaxanthin and its geometric isomers from Phaffia rhodozyma employing a C18 column at the first dimension and a C30 column in the second dimension, connected by a 10‐port valve using the photo‐diode array detector. The regression equation of astaxanthin calibration curve was established, and the precision and accuracy values were found to be in the range of 0.32–1.14% and 98.21–106.13%, respectively. By using two‐dimensional liquid chromatography, it was found that day light, ultrasonic treatment, and heat treatment have significant influence on the content of all‐trans‐astaxanthin in the extract from P. rhodozyma due to the transformation of all‐trans‐astaxanthin to cis‐astaxanthin. The day light and ultrasonic treatments more likely transform all‐trans‐astaxanthin to 9‐cis‐astaxanthin, and the thermal treatment transforms all‐trans‐astaxanthin to 13‐cis‐astaxanthin. These results indicate that the two‐dimensional liquid chromatography method can facilitate monitoring astaxanthin isomerization in the raw extract from P. rhodozyma. In addition, the study will provide a general reference for monitoring other medicals and bioactive chemicals with geometric isomers.
Hydrophobic deep eutectic solvent as a green extractant for high‐performance liquid chromatographic determination of tetracyclines in water samples
Authors: Di Xin , Zhao Xiaojun , Guo Xiaoli
Published: June 2020

A green extractant, hydrophobic deep eutectic solvent was first introduced for extraction of tetracycline, oxytetracycline, and chlortetracycline from environmental water samples prior to high‐performance liquid chromatography determination. Deep eutectic solvents consist of methyltrioctylammonium chloride and various medium‐chain alcohols/acids, and are easy in preparation, low cost and toxicity, desirably biodegradable, and biocompatible. The overall time required for sample preparation was 6 min and the volume of organic solvent used for extraction was only 400 µL. Under the optimized extraction condition, the present method yielded low limit of detection (0.5–2.0 ng/mL), acceptable precision (relative standard deviations < 9.7%), good linearity from 2.0 to 500 ng/mL (r2 ≥ 0.9991). This optimized procedure was applied for determination of tetracyclines in different water samples with desirable spiked recovery ranged from 77.5 to 87.6%. There is, therefore, a great potential to further expand application of the method for investigation of other ultra‐trace analyte(s) in environmental matrixes.
Herbivores stimulate respiration from labile and recalcitrant soil carbon pools in grasslands of Yellowstone National Park
Authors: Chen Ji , Frank Douglas A.
Published: June 2020

Quantifying the effects of grazing on soil organic carbon (SOC) decomposition is of crucial importance for understanding soil C dynamics. However, less attention has been paid to the pool‐specific SOC decomposition and the underlying factors associated with each C pool, representing critical knowledge gaps on soil C dynamics. In this study, we applied a state‐of‐the‐art Bayesian data assimilation technique to re‐analyze previous soil incubation data to examine how herbivores influenced the fraction and cumulative respiration of labile and recalcitrant soil C pools from seven edaphically diverse sites in Yellowstone National Park, whereas those variables were not explored in the earlier study. Our results showed that grazing significantly increased cumulative respiration from both labile and recalcitrant C pools. Greater cumulative respiration from the labile C pool was related to grazers increasing labile C pool fractions, while higher cumulative respiration from the recalcitrant C pool was associated with grazers accelerating the decomposition rate of the recalcitrant C pool. Cumulative respiration from both labile and recalcitrant C pools was positively correlated with shoot biomass, soil gravimetric moisture, and soil C and nitrogen content. Our results underscore how knowledge of pool‐specific SOC decomposition can provide a better mechanistic understanding of soil C dynamics along topo‐edaphic gradients in grazed grassland.
Analysis of lubricating performance for involute spur gear under vibration
Authors: Jian Guangxiao , Wang Youqiang , Zhang Ping , Xie Yinong , Zhao Jingjing
Published: June 2020

In order to investigate the dynamic characteristics of an oil film under vibration, the dynamic model of an involute gear system was established based on the dynamics theory. The vibration and lubrication characteristics of the gear system were analysed in detail. Furthermore, based on the numerical solution of lubrication, a model of oil film stiffness was established. The dynamic characteristics of the oil film were verified by calculating the oil film stiffness. It was found that both oil film pressure and thickness manifested certain dynamic characteristics under vibration. Moreover, the intensities of oscillation amplitude and frequency were different under different loads and rotating speeds. The oil film stiffness gradually decreased and increased, respectively, with the increasing rotating speed and load. Therefore, for a heavy‐duty high‐speed gear system, the coupling effect of vibration and lubrication should be considered.
Haploinsufficiency of the Primary Familial Brain Calcification Gene SLC20A2 Mediated by Disruption of a Regulatory Element
Authors: Cassinari Kévin , Rovelet‐Lecrux Anne , Tury Sandrine , Quenez Olivier , Richard Anne‐Claire , Charbonnier Camille , Olaso Robert , Boland Anne , Deleuze Jean‐François , Besancenot Jean‐François , Delpont Benoit , Pouliquen Dorothée , Lecoquierre François , Chambon Pascal , Thauvin‐Robinet Christel , Campion Dominique , Frebourg Thierry , Battini Jean‐Luc , Nicolas Gaël
Published: June 2020

Objective

Primary familial brain calcification (PFBC) is a rare cerebral microvascular calcifying disorder with diverse neuropsychiatric expression. Five genes were reported as PFBC causative when carrying pathogenic variants. Haploinsufficiency of SLC20A2, which encodes an inorganic phosphate importer, is a major cause of autosomal‐dominant PFBC. However, PFBC remains genetically unexplained in a proportion of patients, suggesting the existence of additional genes or cryptic mutations. We analyzed exome sequencing data of 71 unrelated, genetically unexplained PFBC patients with the aim to detect copy number variations that may disrupt the expression of core PFBC‐causing genes.

Methods

After the identification of a deletion upstream of SLC20A2, we assessed its consequences on gene function by reverse transcriptase droplet digital polymerase chain reaction (RT‐ddPCR), an ex vivo inorganic phosphate uptake assay, and introduced the deletion of a putative SLC20A2 enhancer mapping to this region in human embryonic kidney 293 (HEK293) cells by clustered regularly interspaced short palindromic repeats (CRISPR) ‐ CRISPR‐associated protein 9 (Cas9).

Results

The 8p11.21 deletion, segregating with PFBC in a family, mapped 35 kb upstream of SLC20A2. The deletion carriers/normal controls ratio of relative SLC20A2 mRNA levels was 60.2% (P < 0.001). This was comparable with that of patients carrying an SLC20A2 premature stop codon (63.4%; P < 0.001). The proband exhibited a 39.3% decrease of inorganic phosphate uptake in blood (P = 0.015). In HEK293 cells, we observed a 39.8% decrease in relative SLC20A2 mRNA levels after normalization on DNA copy number (P < 0.001).

Discussion

We identified a deletion of an enhancer of SLC20A2 expression, with carriers showing haploinsufficiency in similar ranges to loss‐of‐function alleles, and we observed reduced mRNA levels after deleting this element in a cellular model. We propose a 3‐step strategy to identify and easily assess the effect of such events. © 2020 International Parkinson and Movement Disorder Society
Solvability for p‐Laplacian generalized fractional coupled systems with two‐sided memory effects
Authors: Ren Jing , Zhai Chengbo
Published: June 2020

This paper determines the solvability of multipoint boundary value problems for p‐Laplacian generalized fractional differential systems with Riesz–Caputo derivative, which exhibits two‐sided nonlocal memory effects. An equivalent integral form for the generalized fractional differential system is deduced by transformation. First, we obtain the existence of solutions on the basis of the upper–lower solutions method, in which an explicit iterative approach for approximating the solution is established. Second, we deal with a special case of our fractional differential system; in order to obtain novel results, an abstract sum‐type operator equation A(x,x)+Bx+e=x on ordered Banach space is discussed. Without requiring the existence of upper–lower solutions or compactness conditions, we get several unique results of solutions for this operator equation, which provide new inspiration for the study of boundary value problems. Then, we apply these abstract results to get the uniqueness of solutions for our differential system.
Partial inverse nodal problems for differential pencils on a star‐shaped graph
Authors: Wang Yu Ping , Shieh Chung‐Tsun , Wei Xianbiao
Published: June 2020

In this paper, the authors study partial inverse nodal problems for differential pencils on a star‐shaped graph. We firstly show that the potential on each edge can be uniquely determined by twin‐dense nodal subsets on some interior intervals under certain conditions. Without any nodal information on some potential on the fixed edge, we may add some spectral information to guarantee these uniqueness theorems. We still consider the case of arbitrary intervals having the internal vertex. In particular, we pose and solve a new partial inverse nodal problem for differential pencils on the star‐shaped graph from the Weyl m‐function and the theory concerning densities of zeros of entire functions.
Prenatal High‐Salt Diet–Induced Metabolic Disorders via Decreasing Peroxisome Proliferator–Activated Receptor Gamma Coactivator 1α in Adult Male Rat Offspring
Authors: Liu Yanping , Yang Chunli , Feng Xueqin , Qi Linglu , Guo Jun , Zhu Dan , Thai Phung N. , Zhang Yingying , Zhang Pengjie , Sun Miao , Lv Juanxiu , Zhang Lubo , Xu Zhice , Lu Xiyuan
Published: June 2020

Scope

Although prenatal high‐salt (HS) intake leads to physiological complications in the offspring, little is known regarding its effects on the offspring's glucose metabolism. Therefore, the objectives of this study are to determine the consequences of prenatal HS diet on the offspring's metabolism and to test a potential therapy.

Methods and Results

Pregnant rats are fed either a normal‐salt (1% NaCl) or high‐salt (8% NaCl) diet during the whole pregnancy. Experiments are conducted in five‐month‐old male offspring. It is found that the prenatal HS diet reduced the glucose tolerance and insulin sensitivity of the offspring. Additionally, there is down‐regulation of peroxisome proliferator‐activated receptor gamma coactivator 1 alpha (Ppargc1a/PPARGC1A) at the transcript and protein level, which leads to decreased mitochondrial biogenesis and oxidative respiration in skeletal muscle. Moreover, the down‐regulation of Ppargc1a is accompanied by decreases in the expression of glucose transporter type 4 (Glut4). With endurance exercise training, these changes are mitigated, which ultimately resulted in improved insulin resistance.

Conclusion

These findings suggest that prenatal HS intake induces metabolic disorders via the decreased expression of Ppargc1a in the skeletal muscle of adult offspring, providing novel information concerning the mechanisms and early prevention of metabolic diseases of fetal origins.
Compact long‐term evolution antenna for automotive mobile communications
Authors: Liu Guifeng , Du Biao , He Yingran , Wu Yang
Published: June 2020

This letter presents a compact long‐term evolution antenna, which is capable of covering 698 to 960 MHz and 1710 to 2690 MHz bands simultaneously for automotive mobile communications. Taking performance and aesthetic appeal into account, the antenna is placed in a shark fin plastic shell, which is mounted on the roof of the vehicle. The proposed antenna is mainly composed of a feeding monopole, a grounded strip, a parasitic strip, and a parasitic patch. The lower band is covered by the quarter‐wavelength resonant modes of the feeding monopole and grounded strip. The higher band is originally generated by the high order modes of the feeding monopole and grounded strip, and further widened by the quarter wavelength resonant modes of two parasitic structures. The utilization of some miniaturization techniques, such as parasitic radiating elements, loading substrate, and meandering radiating elements, enables the proposed antenna to achieve a compact structure. Therefore, the proposed antenna only occupies a compact volume of 29 mm × 15 mm × 57 mm. It is worth noting that the proposed antenna achieves two widebands without additional matching network. Besides, the proposed antenna has omnidirectional radiation patterns in the azimuthal plane for the working bands.
A full duplex ultrawideband over free‐space optics architecture based on polarization multiplexing and wavelength reuse
Authors: Mirza Jawad , Ghafoor Salman , Hussain Ashiq
Published: June 2020

This article demonstrates the integration of fiber optics with free space optics for the transmission of ultrawideband signals at a data rate of 2 Gbps. The fiber‐based components enable all‐optical generation of ultrawideband signals. The free space optical link allows bandwidth flexibility along with reduced installation costs. The proposed architecture employs polarization multiplexing and carrier reuse in order to make the radio access units simple and cost‐efficient. The free space optical link is modeled using the log‐normal (LN) channel model. Bit‐error‐rate (BER) measurements demonstrate that the proposed link is suitable for the transmission of high throughput ultrawideband signals.
A modern review of the uncertainties in volumetric imaging of respiratory‐induced target motion in lung radiotherapy
Authors: Vergalasova Irina , Cai Jing
Published: June 2020

Radiotherapy has become a critical component for the treatment of all stages and types of lung cancer, often times being the primary gateway to a cure. However, given that radiation can cause harmful side effects depending on how much surrounding healthy tissue is exposed, treatment of the lung can be particularly challenging due to the presence of moving targets. Careful implementation of every step in the radiotherapy process is absolutely integral for attaining optimal clinical outcomes. With the advent and now widespread use of stereotactic body radiation therapy (SBRT), where extremely large doses are delivered, accurate, and precise dose targeting is especially vital to achieve an optimal risk to benefit ratio. This has largely become possible due to the rapid development of image‐guided technology. Although imaging is critical to the success of radiotherapy, it can often be plagued with uncertainties due to respiratory‐induced target motion. There has and continues to be an immense research effort aimed at acknowledging and addressing these uncertainties to further our abilities to more precisely target radiation treatment. Thus, the goal of this article is to provide a detailed review of the prevailing uncertainties that remain to be investigated across the different imaging modalities, as well as to highlight the more modern solutions to imaging motion and their role in addressing the current challenges.
Early embryo‐maternal communication in the oviduct: A review
Authors: Kölle Sabine , Hughes Barbara , Steele Heather
Published: June 2020

An intact embryo‐maternal communication is critical for the establishment of a successful pregnancy. To date, a huge number of studies have been performed describing the complex process of embryo‐maternal signaling within the uterus. However, recent studies indicate that the early embryo communicates with the oviductal cells shortly after fertilizationand that this is important for the successful establishment of pregnancy. Only if the early embryo is capable to signal the mother within a precise timeframe and to garner a response, will the embryo be able to survive and reach the uterus. This review will give an overview of all the experimental designs which have investigated embryo‐maternal interaction in the oviduct. In addition to that, it will provide a comprehensive analysis of the findings to date elucidating the morphological and molecular changes in the oviduct which are induced by the presence of the early embryo highlighting how the tubal responses affect embryo development and survival.
Advancing machine learning for MR image reconstruction with an open competition: Overview of the 2019 fastMRI challenge
Authors: Knoll Florian , Murrell Tullie , Sriram Anuroop , Yakubova Nafissa , Zbontar Jure , Rabbat Michael , Defazio Aaron , Muckley Matthew J. , Sodickson Daniel K. , Zitnick C. Lawrence , Recht Michael P.
Published: June 2020

Purpose

To advance research in the field of machine learning for MR image reconstruction with an open challenge.

Methods

We provided participants with a dataset of raw k‐space data from 1,594 consecutive clinical exams of the knee. The goal of the challenge was to reconstruct images from these data. In order to strike a balance between realistic data and a shallow learning curve for those not already familiar with MR image reconstruction, we ran multiple tracks for multi‐coil and single‐coil data. We performed a two‐stage evaluation based on quantitative image metrics followed by evaluation by a panel of radiologists. The challenge ran from June to December of 2019.

Results

We received a total of 33 challenge submissions. All participants chose to submit results from supervised machine learning approaches.

Conclusions

The challenge led to new developments in machine learning for image reconstruction, provided insight into the current state of the art in the field, and highlighted remaining hurdles for clinical adoption.
A nonlocal lattice particle model for J2 plasticity
Authors: Wei Haoyang , Chen Hailong , Liu Yongming
Published: June 2020

In virtue of their intrinsic integro‐differential formulation of underlying physical behavior of materials, discontinuous computational methods are more beneficial over continuum‐mechanics‐based approaches for materials failure modeling and simulation. However, application of most discontinuous methods is limited to elastic/brittle materials, which is partially due to their formulations are based on force and displacement rather than stress and strain measures as are the cases for continuous approaches. In this article, we formulate a nonlocal maximum distortion energy criterion in the framework of a lattice particle model for modeling of elastoplastic materials. Similar to the maximum distortion energy criterion in continuum mechanics, the basic idea is to decompose the energy of a discrete material point into dilatational and distortional components, and plastic yielding of bonds associated with this material point is assumed to occur only when the distortional component reaches a critical value. However, the formulated yield criterion is nonlocal since the energy of a material point depends on the deformation of all the bonds associated with this material point. Formulation of equivalent strain hardening rules for the nonlocal yield model was also developed. Compared to theoretical and numerical solutions of several benchmark problems, the proposed formulation can accurately predict both the stress‐strain curves and the deformation fields under monotonic loading and cyclic loading with different strain hardening cases.
Multifidelity adaptive kriging metamodel based on discretization error bounds
Authors: Mell L. , Rey V. , Schoefs F.
Published: June 2020

This article presents an approach to build a multifidelity kriging metamodel from finite element computations on different meshes for stuctural reliability assessment. The proposed method takes advantage of the computation of bounds on the discretization error, which enables to guarantee the state (safe or failure) of each computation of the performance function. An algorithm to build the metamodel from the different levels of fidelity and estimate the failure probability is provided. Illustrations are presented on a two dimensional mechanical crack opening problem. Bounds on the failure probability are also post‐processed.
Spirituality among family caregivers of cancer patients: The Spiritual Perspective Scale
Authors: La In Seo , Johantgen Meg , Storr Carla L. , Cagle John G. , Zhu Shijun , Ross Alyson
Published: June 2020

Spirituality is a critical resource for family caregivers of patients with cancer. However, studies on spirituality are hampered because measures of spirituality lack consistency and have not been validated in cancer caregivers. This study examined the validity of the Spiritual Perspective Scale (SPS) among cancer caregivers and explored whether measurement bias may influence differences in spirituality across caregiver and patient characteristics. In this secondary analysis, 124 caregivers of cancer patients were used to evaluate the validity of the 10‐item SPS. A multiple indicators multiple causes model was applied to explore differences in the association between a latent spirituality factor and characteristics of caregivers and patients. Overall reliability of the SPS was adequate (Cronbach's α = .95). The SPS scores were predictive of higher meaning and purpose (r = .32, p = .004) and lower depression (r = −.22, p = .046) at 3‐month follow‐up. Construct validity of the SPS with a single‐factor structure was supported in cancer caregivers. Adjusting for a direct effect of race did not alter the pattern of results, and caregivers who were older, female, ethnic minorities, less‐educated, affiliated with a religion, and who provided care to another individual in addition to the patient had greater levels of spirituality. This study provides evidence for psychometric validation of the SPS in cancer caregivers. Understanding differences in caregivers’ spirituality by using the SPS with psychometrically acceptable properties and minimal measurement bias deserves more attention to optimize spirituality assessment and support in cancer caregiving.
Tensile properties of glass fiber‐reinforced polyester composites at extreme cold temperatures
Authors: Ahmed Saad R. , Khanna Sanjeev
Published: June 2020

Glass fiber‐reinforced polymers are widely used in structural systems as load‐bearing elements at both high and low temperatures. This investigation presents the evaluation of glass fiber‐reinforced unsaturated polyester under quasi‐static tension loading at extremely cold temperatures. This work includes the preparation of polyester resin sheets and E‐glass fiber cloth reinforced polyester composite to determine the tensile properties and failure modes over a range of high to very cold temperatures over 60°C to −80°C. The results show that fiber reinforced polyester has higher strength at all temperatures compared to the unreinforced polyester matrix. The reinforced specimens exhibit a more uniform brittle trend at temperatures below room temperature (RT) and a reasonable ductility at and above RT. Tensile properties of the unreinforced material were found to degrade above RT. The composite has the highest strength at the lowest temperature of −80°C. Both monolithic and reinforced polyester are brittle in nature at temperatures below RT, though reinforced composites show slight ductility.
Immune checkpoint inhibitors and diabetes
Authors: Campbell Nicola , Poole Ruth
Published: June 2020

In the first in this new series of articles on diabetes and cancer, Dr Nicola Campbell and Dr Ruth Poole focus on diabetes and checkpoint inhibitors which are becoming the most frequently used immunotherapies in the treatment of cancer.

The increased immune activity from this treatment can result in the development of type 1 diabetes, as discussed here.
FreeStyle Libre and diabetes distress: a pilot analysis in a real‐life secondary care clinic setting
Authors: Whitehouse Phoebe , Kadis Tara , Jayagopal Vijay
Published: June 2020

The use of flash glucose monitoring has been shown to reduce hypoglycaemic episodes and improve diabetes control, but there is little evidence regarding its psychological impact. Here, a pilot evaluation is presented which assesses whether or not the use of FreeStyle Libre impacted on patient anxiety scores.
Development of hierarchical surface roughness on porous poly (vinylidene fluoride) membrane for membrane distillation process
Authors: Rabiei Sima , Mousavi Seyed Mahmoud , Paterson Anthony H.J.
Published: June 2020

The surface hydrophobicity of a poly (vinylidene fluoride) membrane was increased through the phase separation of polycarbonate (PC) solution on the membrane surface. A variety of characterization techniques including surface contact angle measurement, scanning electron microscopy, liquid entry pressure measurement, atomic force microscopy, porosity measurement, pore size measurement, and attenuated total reflectance‐Fourier transform infrared spectroscopy were performed to investigate the membrane surface modification. According to the results, the formation of PC deposits on the membrane surface provided hierarchical structures consisting of micro and nanoscale roughness which enhanced the surface hydrophobicity. Direct contact membrane distillation (DCMD) experiments, in which an aqueous solution of sodium chloride (3.5 wt%) resembling the seawater was used as feed, were carried out to assess the performance of membranes. This surface modification technique led to the improved pore wetting resistance of the coated membrane in DCMD application. This novel method is believed to have a great potential to apply on a wide variety of membranes for MD application.