bluuebunny/crossref_metadata_2025 huggingface dataset:
HMGB1 protein promotes glomerular mesangial matrix deposition via TLR2 in lupus nephritis
Authors: Feng Xiaojuan , Yang Ran , Tian Yuexin , Miao Xinyan , Guo Huifang , Gao Fan , Yang Lin , Zhao Song , Zhang Wei , Liu Jinxi , Li Hongbo , Tian Yu , Zhao Lu , Wang Shuo , Liu Wei , Wang Kexin , Li Yuzhe , Wang Ziwei , Liu Qingjuan , Wang Chunlin , Liu Shuxia
Published: October 2019

Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus. Patients with LN mostly die of sclerosing glomerulonephritis and renal failure. The inhibition of glomerular mesangial matrix deposition is an efficient method to restrict the progress of renal injury. By recognizing and binding extracellular and intracellular ligands, Toll‐like receptor 2 (TLR2) contributes to the pathogenesis of most immune diseases. However, the relationship between TLR2 and LN is still unknown. Our previous studies confirmed that high‐mobility group box 1 (HMGB1), an important ligand of TLR2, promotes the progression of LN by inducing the proliferation of glomerular mesangial cells. However, whether or not HMGB1 participates in the pathogenesis of glomerular mesangial matrix deposition in LN remains unknown. In this study, we observed the upregulated expression of TLR2 in the glomeruli of LN patients and MRL/lpr mice. The inhibition of either TLR2 or HMGB1 inhibited the release of fibronectin and the activation of the MyD88/NF‐κB pathway in mesangial cells cultured with LN plasma. In addition, both TLR2‐ and HMGB1‐deficient mice showed reduced 24 hr urine protein levels and improved glomerular histological changes and sclerosis levels. These results indicate that TLR2 regulates glomerular mesangial matrix deposition in LN through the activation of the MyD88/NF‐κB pathway by binding to HMGB1.
Tracking muscle wasting and disease activity in facioscapulohumeral muscular dystrophy by qualitative longitudinal imaging
Authors: Monforte Mauro , Laschena Francesco , Ottaviani Pierfrancesco , Bagnato Maria Rosaria , Pichiecchio Anna , Tasca Giorgio , Ricci Enzo
Published: October 2019

Background

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most frequent late‐onset muscular dystrophies, characterized by progressive fatty replacement and degeneration involving single muscles in an asynchronous manner. With clinical trials at the horizon in this disease, the knowledge of its natural history is of paramount importance to understand the impact of new therapies. The aim of this study was to assess disease progression in FSHD using qualitative muscle magnetic resonance imaging, with a focus on the evolution of hyperintense lesions identified on short‐tau inversion recovery (STIR+) sequences, hypothesized to be markers of active muscle injury.

Methods

One hundred genetically confirmed consecutive FSHD patients underwent lower limb muscle magnetic resonance imaging at baseline and after 365 ± 60 days in this prospective longitudinal study. T1 weighted (T1w) and STIR sequences were used to assess fatty replacement using a semiquantitative visual score and muscle oedema. The baseline and follow‐up scans of each patient were also evaluated by unblinded direct comparison to detect the changes not captured by the scoring system.

Results

Forty‐nine patients showed progression on T1w sequences after 1 year, and 30 patients showed at least one new STIR+ lesion. Increased fat deposition at follow‐up was observed in 13.9% STIR+ and in only 0.21% STIR‐ muscles at baseline (P < 0.001). Overall, 89.9% of the muscles that showed increased fatty replacement were STIR+ at baseline and 7.8% were STIR+ at 12 months. A higher number of STIR+ muscles at baseline was associated with radiological worsening (odds ratio 1.17, 95% confidence interval 1.06–1.30, P = 0.003).

Conclusions

Our study confirms that STIR+ lesions represent prognostic biomarkers in FSHD and contributes to delineate its radiological natural history, providing useful information for clinical trial design. Given the peculiar muscle‐by‐muscle involvement in FSHD, MRI represents an invaluable tool to explore the modalities and rate of disease progression.
Macrophage ACKRobatics: An atypical Cxcr3 keeps macrophages in check
Authors: Viswanathan Gopinath , Tobin David M.
Published: October 2019

Discussion on an unusual role for a cxcr3 receptor, in which it antagonizes a paralogous receptor to limit macrophage migration.
Intraoperative Phase Contrast MRI Analysis of Cerebrospinal Fluid Velocities During Posterior Fossa Decompression for Chiari I Malformation
Authors: Delavari Nader , Wang Anthony C. , Bapuraj Jayapalli Rajiv , Londy Frank , Muraszko Karin M. , Garton Hugh J.L. , Maher Cormac O.
Published: October 2019

Background

Cerebrospinal fluid (CSF) velocity at the craniovertebral junction (CVJ) is known to be altered in patients with Chiari I malformation (CMI), and normalization of CSF velocities is associated with symptom resolution. However, preoperative and intraoperative prediction methods have thus far failed to identify patients in whom CSF velocities can be normalized with posterior fossa decompression (PFD) without duraplasty. Phase contrast MRI (PC‐MRI) may assist not only in diagnosis of CMI but also in guiding the intraoperative decision to perform duraplasty during PFD.

Purpose

To use intraoperative MRI data to quantify changes in CSF hydrodynamics at the CVJ during each step of PFD with duraplasty (PFDD) in 12 consecutive patients.

Study Type

Retrospective case series with all patients imaged before, during and after decompression, and all data analyzed postprocedure.

Population/Subjects

Pediatric patients, mean age 14 years (range 4‐18), undergoing PFD for CMI.

Field Strength/Sequence

Intraoperative studies involved a dedicated 1.5T Siemens MRI imager. PC‐MRI scans were in the axial plane at the CVJ.

Assessment

Two observers assessed measurements.

Statistical Test

The equality of matched pairs of observations was tested using the Wilcoxon matched‐pairs signed‐ranks test.

Results

Data analyses of the PC‐MRI demonstrated a marked and immediate increase in CSF velocity at the posterior CVJ during PFDD. Mean cranially‐directed velocities increased by a mean of 1.049cm/s (P = 0.028) from preincision to postoperative measurement. There was a mean 0.45 cm/s (P = 0.022) increase in mean cranial velocity from preincision to bone decompression scans, and a mean 0.48 cm/s (P = 0.018) increase in mean velocity from preincision to duraplasty.

Data Conclusion

In all subjects, significant increases in the mean and peak velocities of cranially‐ and caudally‐directed velocities were observed from preincision to post‐PFDD scans at the posterior CVJ.

Level of Evidence: 2

Technical Efficacy: Stage 4

J. Magn. Reson. Imaging 2020;51:1463–1470.
Seronegative hepatitis C virus infection in Polish blood donors—Virological characteristics of index donations and follow‐up observations
Authors: Grabarczyk Piotr , Kubicka‐Russel Dorota , Kopacz Aneta , Liszewski Grzegorz , Sulkowska Ewa , Zwolińska Paulina , Madaliński Kazimierz , Marek Maciej , Szabelewska Małgorzata , Świątek Ewa , Laskus Tomasz , Radkowski Marek
Published: October 2019

Nucleic acid testing (NAT) was implemented in Poland in 1999 for screening of plasma for fractionation and for all blood donors in 2002. To analyze seronegative NAT‐positive samples representing hepatitis C virus (HCV) window‐period (WP) in the years 2000 to 2016 and to determine infection outcome. We analyzed results of 17 502 739 donations screened in minipools (6‐48) or individually. Index samples underwent viral load (VL) quantification, genotyping and Ag, and anti‐HCV re‐testing using chemiluminescence (CMIA), electrochemiluminescence (ECLIA), and fourth‐generation enzyme‐linked immunosorbent assay (IV EIA) assays. HCV‐seronegative infections were identified in 126 donations (7.2/mln donations; 95% confidential intervals, 6.0‐8.6). Frequency of NAT yields was decreasing over time. Of the initial 126 seronegative index cases 106 were retested: 32.1% were reactive in IV EIA, 11.3% in ECLIA, and 1.9% in CMIA. The lowest VL correlated with absent anti‐HCV and HCV Ag, while VL was highest when the antigen was detectable and then it decreased when anti‐HCV appeared at a level detectable by sensitive third generation tests while retesting. The proportion of genotype 1 was 38.9% in samples positive only for HCV RNA and 71.4% in samples that were anti‐HCV reactive in re‐testing. In parallel, genotype 3 frequency was 50% in the former group and 21% in the latter. NAT is an effective measure to limit HCV transmission by transfusion and IV EIA seems to have higher clinical sensitivity than ECLIA. Samples representing likely successive phases of early HCV infection were characterized by different genotype distribution probably due to very early elimination of genotype 3.
Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women
Authors: Zhao Junwei , Zhu Jiacheng , Guo Junhan , Zhu Tailin , Zhong Jixing , Liu Min , Ruan Yetian , Liao Shujie , Li Fang
Published: October 2019

Human papillomavirus (HPV)16 gene mutation is usually associated with persistent HPV infection and cervical intraepithelial neoplasia (CIN). However, the functional implications of HPV16 mutations remain poorly understood.145 LCR/E6/E7 of the HPV16 isolates were amplified and sequenced, and HPV16 integration status was detected. In total, 89 SNPs (68 in the LCR, 13 in E6, 8 in E7) were discovered, 11 of which were nonsynonymous mutations (8 in E6, 3 in E7). The H85Y and E120D variants in E6 were significantly reduced in the high‐grade squamous intraepithelial lesion (HSIL) group compared to the <HSIL group (P = .046 and .005), conversely the N29S in E7(P = .01). Amino acid substitutions (D32N/E, E36Q, H85Y, and E120D in E6 and N29H/S and R77C in E7) were predicted to have an effect on conserved structural and functional residues, and five amino acid substitutions (H85Y, E36Q, I34L, and D32E in E6; R77C in E7) would potentially change the secondary structure. “6329G>T,” a potential binding site for TATA‐binding protein, is the most common in LCR variants. A4 (Asian) was associated with an increased risk of HSIL compared to A1–3(P = .009). The H85/E120 in E6 and N29 in HPV16 E7 might play a critical role in carcinogenesis by disrupting p53 and Rb degradation due to affecting their interaction, respectively. In a word, the findings in this study provide preventative and therapeutic interventions of HPV16 ‐related cervical lesions/cancer.
Improved trafficking and expression of luminopsins for more efficient optical and pharmacological control of neuronal activity
Authors: Zhang James Y. , Tung Jack K. , Wang Zuhui , Yu Shan Ping , Gross Robert E. , Wei Ling , Berglund Ken
Published: October 2019

Luminopsins (LMOs) are chimeric proteins consisting of a luciferase fused to an opsin that provide control of neuronal activity, allowing for less cumbersome and less invasive optogenetic manipulation. It was previously shown that both an external light source and the luciferase substrate, coelenterazine (CTZ), could modulate activity of LMO‐expressing neurons, although the magnitudes of the photoresponses remained subpar. In this study, we created an enhanced iteration of the excitatory luminopsin LMO3, termed eLMO3, that has improved membrane targeting due to the insertion of a Golgi trafficking signal sequence. In cortical neurons in culture, the expression of eLMO3 resulted in significant reductions in the formation of intracellular aggregates, as well as in a significant increase in total photocurrents. Furthermore, we corroborated the findings with injections of adeno‐associated viral vectors into the deep layers of the somatosensory cortex (the barrel cortex) of male mice. We observed greatly reduced numbers of intracellular puncta in eLMO3‐expressing cortical neurons compared to those expressing the original LMO3. Finally, we quantified CTZ‐driven behavior, namely whisker‐touching behavior, in male mice with LMO3 expression in the barrel cortex. After CTZ administration, mice with eLMO3 displayed significantly longer whisker responses than mice with LMO3. In summary, we have engineered the superior LMO by resolving membrane trafficking defects, and we demonstrated improved membrane targeting, greater photocurrents, and greater functional responses to stimulate with CTZ.
Remote ischemic preconditioning and its role in the prevention of new onset atrial fibrillation post‐cardiac surgery. A meta‐analysis of randomized control trials
Authors: Kumar Ashish , Singh Harpreet , Shariff Mariam
Published: October 2019

Background

The denouement of remote ischemic preconditioning on new onset atrial fibrillation (NOAF) post‐cardiac surgery is not well‐established. An updated meta‐analysis of randomized control trials was performed by comparing remote ischemic preconditioning with controls and the outcome of interest was NOAF.

Methods

The systemic review was performed in accordance with the PRISMA (Preferred reporting items for systemic review) and AHA (American Heart Association) guidelines. PubMed database was searched to include relevant randomized control trials from inception to July 2019. We used Mantel‐Haenzsel method with random error model to calculate risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed using the I2 test> 50% or χ2 P < .05. Publication bias was visually assessed using a funnel plot.

Results

Twelve randomized control trials were included in the final analysis. Remote ischemic preconditioning did not alter the risk of NOAF post‐cardiac surgery [RR: 0.95, CI: 0.83‐1.09, P = .48, I2 = 37%, χ2 P = .09].

Conclusion

In conclusion, the present meta‐analysis failed to provide any evidence for the beneficial effect of remote ischemic preconditioning in the prevention of NOAF.
Recent progress of enantioseparation under scale production (2014–2019)
Authors: Wu Datong , Pan Fei , Tan Wensheng , Gao Li , Tao Yongxin , Kong Yong
Published: October 2019

Very different from enantiorecognition at an analytical level, preparative enantioseparation at scale production has to confront many problems. In recent years, various separation techniques have been developed with much progress including high‐performance liquid chromatography, liquid–liquid extraction, membrane separation, enantioselective solid‐phase absorption, and enantioselective precipitation. Among them, in order to achieve high enantiomerical purity of the enantiomers after separation, two approaches are commonly carried out. One is that continuous separation is necessary when one‐step separation cannot have satisfactory efficiency. Another is that most of the research groups focus on the construction of novel chiral environment with much more rigid structures of the selectors. Combined with these two aspects, we mainly introduce current topics, trends, strategies related to enantioseparation under large scale.
Analyses of reaction rate data for the simple hydrolysis of acetic anhydride in the acetonitrile/water and acetone/water cosolvent systems using recently developed thermodynamic rate equations
Authors: Wiseman F. L. , Scott D. W. , Tamine J. , O'Connell R. , Smarra A. , Olowoyo S.
Published: October 2019

This article presents reaction rate data for the simple hydrolysis of acetic anhydride in the acetonitrile/water and acetone/water cosolvent systems and regression analyses using recently developed thermodynamic rate equations that contain electrostatic and solvent‐solute terms. The isomole fraction plots for these reaction systems are linear, and previous theoretical work has shown that the electrostatic term is negligible for such systems. On the other hand, the reaction rates are dependent upon the cosolvent mole fraction, indicating that the solvent‐solute term, which is modeled empirically, is significant. The results of the analyses provide the foundation for a paradigm shift away from the emphasis on electrostatic effects to more tenable explanations of kinetic behavior in solvent systems.
Active rehabilitation of Amazonian sand mines converges soils, plant communities and environmental status to their predisturbance levels
Authors: Gastauer Markus , Caldeira Cecílio F. , Ramos Silvio J. , Silva Delmo F. , Siqueira José Oswaldo
Published: October 2019

The continuous monitoring of mineland rehabilitation is paramount for identifying deviations from desired trajectories and providing assessments for environmental agencies. In this study, we analyzed soil texture and chemical properties, vegetation development and soil respiration along rehabilitation chronosequences including nonrehabilitated areas, areas at different rehabilitation stages and reference sites covered by native forests in three sand mines in the Carajás National Forest, eastern Amazonia, Brazil, to estimate their rehabilitation status. For nine environmental variables related to ecological processes, vegetation structure, and community diversity, we computed response ratios in relation to predisturbance levels found in native reference sites and integrated them into an index of rehabilitation status using a multivariate approach. Our analyses showed that the soil chemical properties and tree community composition of the rehabilitated minelands converged over time to those of native ecosystems. All environmental indicators and the overall rehabilitation status increased with rehabilitation time, indicating that rehabilitation interventions set the rehabilitation trajectory on a desired path. Although most indicators did not achieve predisturbance levels, we conclude that rehabilitation activities can effectively reduce the environmental impacts of sand extraction in Amazonia over short time periods, thereby contributing to the recovery of ecosystem services and the protection of biodiversity.
Topological Photonic Integrated Circuits Based on Valley Kink States
Authors: Ma Jingwen , Xi Xiang , Sun Xiankai
Published: October 2019

Valley pseudospin, a new degree of freedom in photonic lattices, provides an intriguing way to manipulate photons and enhance the robustness of optical networks. Here, topological waveguiding, refracting, resonating, and routing of valley‐polarized photons in integrated circuits are experimentally demonstrated. Specifically, it is shown that at the domain wall between photonic crystals of different topological valley phases, there exists a topologically protected valley kink state that is backscattering‐free at sharp bends and terminals. These valley kink states are further harnessed for constructing high‐Q topological photonic crystal cavities with tortuously shaped cavity geometries. A novel optical routing scheme at an intersection of multiple valley kink states is also demonstrated, where light splits counterintuitively due to the valley pseudospin of photons. These results can not only lead to robust optical communication and signal processing, but also open the door for fundamental research of topological photonics in areas such as lasing, quantum photon‐pair generation, and optomechanics.
The role of numeracy and information load in the tourist decision‐making process
Authors: Castañeda José‐Alberto , Rodríguez‐Molina Miguel‐Ángel , Frías‐Jamilena Dolores‐María , García‐Retamero Rocío
Published: October 2019

The aim of the present study is to merge two strands of research that have evolved in tandem (a) the consequences of numeracy; and (b) the effect of information load on the consumer decision‐making process. The study analyses the interaction effect between these two factors on decision accuracy and on a set of cognitive and affective variables of the decision‐making process (namely, confusion, calibration, and emotion). We measured participants' numeracy and used an experimental design to manipulate the information load. The results showed that the effect of numeracy on decision accuracy was entirely mediated by cognitive and affective processes involved in decision‐making. In particular, numeracy was found to have a negative relationship with the level of confusion, calibration, and emotions experienced during the decision‐making process. The results also showed that information load interacted with numeracy, such that individuals with high numeracy maintained lower levels of emotion when placed under conditions of low information load. However, under these same conditions, individuals with low numeracy maintained positive emotions. The findings help to identify approaches that can contribute to reducing the negative effects of low numeracy among consumers, in a context where the online channel predominates (the tourism sector).
Parkinson's Disease: Glucocerebrosidase 1 Mutation Severity Is Associated with CSF Alpha‐Synuclein Profiles
Authors: Lerche Stefanie , Wurster Isabel , Roeben Benjamin , Zimmermann Milan , Riebenbauer Benjamin , Deuschle Christian , Hauser Ann‐Kathrin , Schulte Claudia , Berg Daniela , Maetzler Walter , Waniek Katharina , Lachmann Ingolf , Liepelt‐Scarfone Inga , Gasser Thomas , Brockmann Kathrin
Published: October 2019

Background

Mutations in the gene glucocerebrosidase (GBA1) are specifically associated with alpha‐synucleinopathies, namely, Parkinson's disease (PD) and dementia with Lewy bodies. As disease‐modifying treatment options such as alpha‐synuclein lowering compounds are under way, patient stratification according to alpha‐synuclein‐specific enrichment strategies, possibly reflected by cerebrospinal fluid (CSF) profiles, is a much needed prerequisite.

Objective

Are GBA1 mutations associated with a CSF alpha‐synuclein profile in PD?

Methods

Screening of the GBA1 gene and analysis of CSF levels of total alpha‐synuclein were performed in 80 PDGBA, 80 PDGBA_wildtype and 39 healthy controls cross‐sectionally. Subgroup analyses based on mutation severity was done for PDGBA.

Results

Patients carrying severe GBA1 mutations showed (1) an earlier age at onset, (2) more pronounced cognitive decline and higher prevalence of rapid eye movement sleep behavior disorder, and (3) reduced CSF levels of total alpha‐synuclein.

Conclusion

The effects of GBA1 mutations on CSF alpha‐synuclein profiles and phenotypical characteristics seem dependent on GBA1 mutation severity. © 2019 International Parkinson and Movement Disorder Society
Technical Note: A dose calculation framework for dynamic electron arc radiotherapy (DEAR) using VirtuaLinac Monte Carlo simulation tool
Authors: Wang Xiaorong , Sawkey Daren , Wu Qiuwen
Published: October 2019

Purpose

Dynamic electron arc radiotherapy (DEAR) is a novel dynamic technique that achieves highly conformal dose through simultaneous couch and gantry motion during delivery. The purpose of this study is to develop a framework integrating a Monte Carlo dose engine (VirtuaLinac) to a treatment planning system (TPS, Eclipse) for DEAR. A quality assurance (QA) procedure is also developed.

Methods and materials

The interfaces include the following: computed tomography image export and conversion for VirtuaLinac; VirtuaLinac computation tasks management through application programming interface (API); and dose matrix processing and evaluation. The framework was validated with both static beam and DEAR plan with a 3 × 3 cm2 cutout for both 6 and 9 MeV electrons. Verification plans for DEAR were created on flat phantom and a hybrid dose calculation technique was developed which convolves precalculated small field kernel with the beam trajectory, and the resulting dose was compared with the full VirtuaLinac calculation and film measurement.

Results

Excellent agreement between VirtuaLinac and eMC was observed with three‐dimensional γ pass rate of 98% at 1%/1 mm criteria for both 6 and 9 MeV electrons. Film measurement shows two‐dimensional (2D) γ passing rate of 99.8 % (6 MeV) and 97.1% (9 MeV) at 2%/2 mm criteria. For DEAR plans the comparison of VirtuaLinac and measurement shows the 2D γ passing rates of 94% at 2%/2 mm for 6 MeV. The dose distributions from hybrid method in phantom are identical to the full VirtuaLinac simulations, but can be done instantly.

Conclusions

A framework has been developed for DEAR dose calculation using VirtuaLinac Monte Carlo dose engine. The VirtuaLinac calculated dose was validated against measurement. A feasible and practical DEAR QA method has been developed for dose measurement in phantom. The hybrid dose calculation technique is efficient and suitable for DEAR QA purpose.
Deep learning modeling using normal mammograms for predicting breast cancer risk
Authors: Arefan Dooman , Mohamed Aly A. , Berg Wendie A. , Zuley Margarita L. , Sumkin Jules H. , Wu Shandong
Published: October 2019

Purpose

To investigate two deep learning‐based modeling schemes for predicting short‐term risk of developing breast cancer using prior normal screening digital mammograms in a case‐control setting.

Methods

We conducted a retrospective Institutional Review Board‐approved study on a case‐control cohort of 226 patients (including 113 women diagnosed with breast cancer and 113 controls) who underwent general population breast cancer screening. For each patient, a prior normal (i.e., with negative or benign findings) digital mammogram examination [including mediolateral oblique (MLO) view and craniocaudal (CC) view two images] was collected. Thus, a total of 452 normal images (226 MLO view images and 226 CC view images) of this case‐control cohort were analyzed to predict the outcome, i.e., developing breast cancer (cancer cases) or remaining breast cancer‐free (controls) within the follow‐up period. We implemented an end‐to‐end deep learning model and a GoogLeNet‐LDA model and compared their effects in several experimental settings using two mammographic view images and inputting two different subregions of the images to the models. The proposed models were also compared to logistic regression modeling of mammographic breast density. Area under the receiver operating characteristic curve (AUC) was used as the model performance metric.

Results

The highest AUC was 0.73 [95% Confidence Interval (CI): 0.68–0.78; GoogLeNet‐LDA model on CC view] when using the whole‐breast and was 0.72 (95% CI: 0.67–0.76; GoogLeNet‐LDA model on MLO + CC view) when using the dense tissue, respectively, as the model input. The GoogleNet‐LDA model significantly (all P < 0.05) outperformed the end‐to‐end GoogLeNet model in all experiments. CC view was consistently more predictive than MLO view in both deep learning models, regardless of the input subregions. Both models exhibited superior performance than the percent breast density (AUC = 0.54; 95% CI: 0.49–0.59).

Conclusions

The proposed deep learning modeling approach can predict short‐term breast cancer risk using normal screening mammogram images. Larger studies are needed to further reveal the promise of deep learning in enhancing imaging‐based breast cancer risk assessment.
Quantitative 3D myocardial perfusion with an efficient arterial input function
Authors: Mendes Jason Kraig , Adluru Ganesh , Likhite Devavrat , Fair Merlin J. , Gatehouse Peter D. , Tian Ye , Pedgaonkar Apoorva , Wilson Brent , DiBella Edward V. R.
Published: October 2019

Purpose

The purpose of this study was to further develop and combine several innovative sequence designs to achieve quantitative 3D myocardial perfusion. These developments include an optimized 3D stack‐of‐stars readout (150 ms per beat), efficient acquisition of a 2D arterial input function, tailored saturation pulse design, and potential whole heart coverage during quantitative stress perfusion.

Theory and Methods

All studies were performed free‐breathing on a Prisma 3T MRI scanner. Phantom validation was used to verify sequence accuracy. A total of 21 subjects (3 patients with known disease) were scanned, 12 with a rest only protocol and 9 with both stress (regadenoson) and rest protocols. First pass quantitative perfusion was performed with gadoteridol (0.075 mmol/kg).

Results

Implementation and quantitative perfusion results are shown for healthy subjects and subjects with known coronary disease. Average rest perfusion for the 15 included healthy subjects was 0.79 ± 0.19 mL/g/min, the average stress perfusion for 6 healthy subject studies was 2.44 ± 0.61 mL/g/min, and the average global myocardial perfusion reserve ratio for 6 healthy subjects was 3.10 ± 0.24. Perfusion deficits for 3 patients with ischemia are shown. Average resting heart rate was 59 ± 7 bpm and the average stress heart rate was 81 ± 10 bpm.

Conclusion

This work demonstrates that a quantitative 3D myocardial perfusion sequence with the acquisition of a 2D arterial input function is feasible at high stress heart rates such as during stress. T1 values and gadolinium concentrations of the sequence match the reference standard well in a phantom, and myocardial rest and stress perfusion and myocardial perfusion reserve values are consistent with those published in literature.
Should you be friendly but not friends with employees?
Authors: Hodges Dawn Z.
Published: October 2019

Not long ago, a friend and former colleague was hired as a dean of arts and sciences. Because there were three new deans, the human resources director met with them. She told them to be friendly with employees, but not friends.
Chemical grafting of salicylaldehyde onto carbon fiber for enhancing interfacial strength of silicone resin composites
Authors: Liu Jingxiang , Liu Huilin , Wu Guangshun
Published: October 2019

Chemical grafting of salicylaldehyde onto the surface of carbon fibers (CFs) via the bridging 3‐aminopropyltriethoxysilane was reported to improve interfacial properties of composites. Surface microstructures, compositions, wettability, and surface energy of CFs before and after modification were studied. Single‐fiber tensile strength (TS) was also determined to evaluate the damage degree brought by using the grafting strategy to the fiber intrinsic strength. The interfacial shear strength of composites was characterized to confirm interfacial compatibility and adhesion between CFs and matrix resin. Antihydrothermal aging experiments were also carried out to evaluate their environmental stability. As a result, the introduced salicylaldehyde molecules could increase polar functional groups, roughness, and interfacial wettability of CFs, and thus enhance interfacial strength as well as the hydrothermal aging resistance of the resulting composites significantly. Such sharp improvements could be due to the increases of interfacial compatibility, mechanical interlocking, and chemical bonding at the interfacial region via the formation of salicylaldehyde‐modified interface. Meanwhile, the modification procedure does not decrease fiber TS.
Validation of fetal DNA fraction estimation and its application in noninvasive prenatal testing for aneuploidy detection in multiple pregnancies
Authors: Chen Min , Jiang Fuman , Guo Yulai , Yan Huanchen , Wang Jiayan , Zhang Longmei , Zeng XiaoJing , Li Sheng , Li Yufan , Li Nan , Zhang Chunsheng , Zhu Wentao , Du Bole , Wang Yang , Lan Zhiheng , Luo Xingcheng , Luo Fei , Chen Dunjin
Published: October 2019

Objective

To analyze the fetal fraction, fetal sex, and chromosomal aneuploidy in multiple pregnancies using noninvasive prenatal testing (NIPT).

Method

A total of 362 pregnant women including 203 singleton pregnancies, 69 twins, and 90 higher‐order multiple pregnancies were recruited. Fetal fractions estimated by size ratio‐based and Y chromosome‐based approaches in singleton pregnancies with male fetus were used as source data to establish the model. The model was then applied to multiple pregnancies for fetal fraction estimation. By comparing the fetal fractions estimated by size ratio to those estimated by Y chromosome or autosomal chromosomes, fetal sex and chromosomal aneuploidy can be analyzed.

Results

The size ratio‐based approach has been well established in estimating fetal fractions for twin and higher‐order multiple pregnancies. Fetal fraction had a positive correlation with gestational age in twin and triplet pregnancies. Fetal sex was determined with accuracies of 98.6% (95% CI, 92.19%‐99.96%) in twins and 97.6% (95% CI, 91.76%‐99.71%) in triplet pregnancies. Four trisomy 21, one trisomy 18, and one trisomy 13 cases were detected by NIPT. Two trisomy 21 singleton pregnancies and one trisomy 21 twin pregnancy were confirmed by karyotyping.

Conclusion

Fetal sex and chromosomal aneuploidy in multiple pregnancies can be determined using NIPT.
Simulation‐based fetal shunting training
Authors: Phithakwatchara Nisarat , Nawapun Katika , Viboonchart Sommai , Jaingam Suparat , Wataganara Tuangsit
Published: October 2019

Objectives

To develop a simulation model and assess the learning curve of fetal shunting.

Methods

Three staff and three trainees performed fetal shunting on a model using the fetal bladder stent. The model was evaluated according to various sources of validity evidence. The number of procedures to reach competency was determined by the learning curve‐cumulative summation (LC‐CUSUM) and CUSUM analysis. The learning and control phases were defined as the periods before and after passing the level of competency, respectively.

Results

The model was validated to be constructive in the educational process. A total of 600 procedures were carried out with an overall success rate of 94.2% and no significant difference between staff and trainees. The average number of procedures to reach competency was 47. Total procedural time decreased after passing the level of competency. Although the trainees required a longer procedural time in the learning phase than the staff did, there was no significant between‐group difference in the control phase.

Conclusions

Using this model, the estimated number of procedures to achieve competency was 47, as substantiated by the increased procedural success and reduced procedural time in the control phase. Training on this simulation model may improve technical performance.
Return to the countryside: The return intentions of highly educated young people in the Akmola province of northern Kazakhstan
Authors: Buchenrieder Gertrud , Dufhues Thomas , Möllers Judith , Runschke David , Sagyndykova Galiya
Published: October 2019

The rural out‐migration of young people leads to problems such as “brain drain” and the overageing of the rural population. The purpose of this paper is to study return migration motives among students originating from rural areas. The case study relates to the province of Akmola, northern Kazakhstan. Based on data collected from college and university students (n = 357), a binary logistic regression model is used to identify rural return motives. Noneconomic and economic motives are equally important in forming a return intention. Our findings do not suggest that particularly underperforming students intend to return. As expected, compared with those in major cities, students who study in a regional town intend to return more often. We also found a large difference in return intentions along ethnic lines. Students of non‐Kazakh decent are much more likely to return than ethnic Kazakhs, and the two ethnic groups have quite distinct motives indicating signs of ethnic discrimination against non‐Kazakhs in the job market.
Predicting Paclitaxel Disposition in Humans With Whole‐Body Physiologically‐Based Pharmacokinetic Modeling
Authors: Fu Qiang , Sun Xinxin , Lustburg Maryam B. , Sparreboom Alex , Hu Shuiying
Published: October 2019

Paclitaxel is a commonly used drug in the treatment of multiple solid tumors, including cancers of the breast, lung, and ovaries. Despite the established exposure–pharmacodynamic relationships for paclitaxel, treatment is associated with wide interindividual pharmacokinetic variability that leads to unpredictability of the agent's clinical activity and toxicity. We hypothesized that physiologically‐based modeling approaches could be employed to predict the human pharmacokinetics of paclitaxel following administration of the approved Cremophor‐based formulation (Taxol). The model was developed from tissue distribution studies performed in mice and applied to plasma concentration‐time data obtained in adult cancer patients receiving Taxol at the approved dose and schedule (175 mg/m2 by a 3‐hour intravenous infusion), taking into account interspecies differences in physiological parameters. The final model adequately captured the observed concentrations in patients and allowed prediction of paclitaxel distribution profiles in multiple target organs and can be applied to further refine the chemotherapeutic treatment with a clinically important agent.
Electrical Contact Formation in Micro Four‐Point Probe Measurements
Authors: Folkersma Steven , Bogdanowicz Janusz , Petersen Dirch H. , Hansen Ole , Henrichsen Henrik H. , Nielsen Peter F. , Shiv Lior , Vandervorst Wilfried
Published: October 2019

Herein, the electrical contact formation between the electrodes of the micro four‐point technique and a semiconducting sample is described. It is shown that the contact is formed in two stages: a voltage‐induced electrical contact formation, followed by a current‐induced decrease in contact resistance. Moreover, a method is proposed allowing for precise control of the final contact resistance. Finally, it is demonstrated that the contacting process is similar on 1D fin structures, where the demonstrated control of the electrical contact is needed while measuring on nanometer‐wide fins in arrays with a pitch smaller than the electrode contact size.
Retracted: Bilobalide alleviates tumor necrosis factor‐alpha‐induced pancreatic beta‐cell MIN6 apoptosis and dysfunction through upregulation of miR‐153
Authors: Hao Yan , Wang Weiwei , Wu Dong , Liu Kai , Sun Yihan
Published: October 2019

Type 1 diabetes mellitus (T1DM) is a systemic disease and one classical type of total DM. Bilobalide (BB) is constituted of EGb 761. Our purpose was identifying the role of BB in TIDM in the current study. MIN6 cells were treated by TNF‐α; then, viability, apoptosis, and insulin secretion were assessed by performing Cell Counting Kit‐8 assay, flow cytometry, glucose‐stimulated insulin secretion assay, and western blot. The effects of BB were assessed to identify its function. Further, the above mentioned parameters were reassessed when silencing miR‐153. TNF‐α declined viability and insulin secretion as well as raised apoptosis and inducible nitric oxide synthase (iNOS) expression in MIN6 cells. BB alleviated the apoptosis and dysfunction induced by TNF‐α. MiR‐153 expression was elevated by BB when induced by TNF‐α. Increase of viability and insulin secretion as well as decline of apoptosis and iNOS induced by BB treatment was alleviated by silencing miR‐153. The rates of p/t‐p70S6K, p/t‐mammalian target of rapamycin (mTOR) and p/t‐adenosine monophosphate‐activated protein kinase (AMPK) were raised by BB and suppressed by silencing miR‐153 under TNF‐α induced condition. BB raised viability and insulin secretion, declined apoptosis and iNOS expression by up‐regulating miR‐153. Furthermore, BB activated AMPK/mTOR pathway by up‐regulating miR‐153.
Time‐of‐flight secondary ion tandem mass spectrometry depth profiling of organic light‐emitting diode devices for elucidating the degradation process
Authors: Iida Shin‐ichi , Murakami Tetsushi , Kurosawa Yu , Suzuri Yoshiyuki , Fisher Gregory L. , Miyayama Takuya
Published: October 2019

Rationale

Organic light‐emitting diode (OLED) products based on display applications have become popular in the past 10 years, and new products are being commercialized with rapid frequency. Despite the many advantages of OLEDs, these devices still have a problem concerning lifetime. To gain an understanding of the degradation process, the authors have investigated the molecular information for deteriorated OLED devices using time‐of‐flight secondary ion mass spectrometry (TOF‐SIMS).

Methods

TOF‐SIMS depth profiling is an indispensable method for evaluating OLED devices. However, the depth profiles of OLEDs are generally difficult due to the mass interference among organic compounds, including degradation products. In this study, the tandem mass spectrometry (MS/MS) depth profiling method was used to characterize OLED devices.

Results

After degradation, defects comprised of small hydrocarbons were observed. Within the defect area, the diffusion of all OLED compounds was also observed. It is supposed that the source of the small hydrocarbons derives from decomposition of the OLED compounds and/or contaminants at the ITO interface.

Conclusions

The true compound distributions have been determined using MS/MS depth profiling methods. The results suggest that luminance decay is mainly due to the decomposition and diffusion of OLED compounds, and that OLED decomposition may be accelerated by adventitious hydrocarbons present at the ITO surface.
High‐resolution mass spectrometry for future space missions: Comparative analysis of complex organic matter with LAb‐CosmOrbitrap and laser desorption/ionization Fourier transform ion cyclotron resonance
Authors: Selliez Laura , Maillard Julien , Cherville Barnabe , Gautier Thomas , Thirkell Laurent , Gaubicher Bertrand , Schmitz‐Afonso Isabelle , Afonso Carlos , Briois Christelle , Carrasco Nathalie
Published: October 2019

Rationale

Mass spectrometers are regularly boarded on spacecraft for the exploration of the Solar System. A better understanding of the origin, distribution and evolution of organic matter and its relationships with inorganic matter in different extra‐terrestrial environments requires the development of innovative space tools, described as Ultra‐High‐Resolution Mass Spectrometry (UHRMS) instruments.

Methods

Analyses of a complex organic material simulating extraterrestrial matter (Titan's tholins) are performed with a homemade space‐designed Orbitrap™ equipped with a laser ablation ionization source at 266 nm: the LAb‐CosmOrbitrap. Mass spectra are obtained using only one laser shot and transient duration of 838 ms. A comparison is made on the same sample with a laboratory benchmark mass spectrometer: a Fourier Transform Ion Cyclotron Resonance equipped with a laser desorption ionization source at 355 nm (LDI‐FTICR) allowing accumulation of 20,000 laser shots.

Results

Mass spectra and attributions of molecular formulae based on the peaks detected by both techniques show significant similarities. Detection and identification of the same species are validated. The formation of clusters ions with the LAb‐CosmOrbitrap is also presented. This specific feature brings informative and unusual indirect detections about the chemical compounds constituting Titan's tholins. In particular, the detection of HCN confirms previous results obtained with laboratory Electrospray Ionization (ESI)‐UHRMS studies about the understanding of polymeric patterns for the formation of tholins.

Conclusions

The capabilities of the LAb‐CosmOrbitrap to decipher complex organic mixtures using single laser shot and a short transient are highlighted. In agreement with results provided by a commercial FTICR instrument in the laboratory, we demonstrate in this work the relevance of a space laser‐CosmOrbitrap instrument for future planetary exploration.
New noise‐to‐state stability and instability criteria for random nonlinear systems
Authors: Yao Liqiang , Zhang Weihai
Published: October 2019

This paper investigates the noise‐to‐state stability and instability criteria for random nonlinear affine systems. Firstly, some new noise‐to‐state stability theorems, which weaken the sufficient conditions in the existing stability criteria on random nonlinear systems, are given by means of the uniformly asymptotically stable function. Secondly, the noise‐to‐state instability definitions are introduced and the sufficient conditions of noise‐to‐state instability are provided based on a new established lemma and the uniformly asymptotically stable function. Finally, some examples show the feasibility of theoretical findings.
Syntheses and Biological Importance of Herboxidiene/GEX1A
Authors: Thirupathi Barla , Zilla Mahesh Kumar
Published: October 2019

The importance of exceptionally potent bioactivities, scarcity of natural abundance and interesting structural features of herboxidiene/GEX1A attracted great interest from synthetic, medicinal chemists. In this review we discussed chemical syntheses and biological significances of herboxidiene/GEX1A. Aim of this review to gather valuable insights by various research groups into one place, to accelerate and design an efficient synthetic methods and surplus biological studies of herboxidiene/GEX1A. Existing reports are useful for design and develop new medications, reports includes: herbicidal activity, lowering of plasma cholesterol, anti‐tumor activity in numerous cell lines, pre‐mRNA splicing‐modulatory action, activity against Niemann‐Pick disease type C (NPC), and focuses on total syntheses of herboxidiene/GEX1A (Figure 1).
Numerical and Experimental Analysis of Copper Electroforming on an Aluminum Substrate as a Rotating Cone Electrode Cell
Authors: Memannavaz Hossein , Pebdeni Hamid H. , Liaghat Gholmhossein , Rahmati Sadegh , Najafi Mohammad , Fazeli Hamid
Published: October 2019

In this paper, the advantages of numerical simulation to improve the process of copper electroforming are demonstrated. In this regard, the finite element model of copper electroforming for a rotating cone electrode was first prepared and then, the effect of the key parameters, such as applied current density, solution conductivity, electrode spacing, and anode height, on the uniformity of the thickness was investigated. The model combines tertiary current distribution with Bulter–Volmer electrode kinetics and computational fluid dynamics at the turbulent condition. In order to validate the model, a cone‐shaped shell was produced by electroforming method in the laboratory. The obtained results illustrate that the tertiary current distribution model on the rotating cone cell cathode is accurate and efficient for the electroforming process simulation and it can be used for parametric studies. Moreover, the effect of the current density on the morphology and properties of the electroformed layer was investigated.
Developing a simple method to enhance the generation of cone and rod photoreceptors in pluripotent stem cell-derived retinal organoids
Authors: Zerti Darin , Dorgau Birthe , Felemban Majed , Ghareeb Ali E. , Yu Min , Ding Yuchun , Krasnogor Natalio , Lako Majlinda
Published: October 2019

Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases such as Stargardt's disease, age-related macular degeneration, and retinitis pigmentosa. The final impact of all retinal dystrophies is the loss of photoreceptors; hence, there is a pressing need for research into replacement. Seminal work has shown that a simple three-dimensional culture system enables differentiation of human pluripotent stem cells to retinal organoids containing large numbers of photoreceptors developing alongside retinal neurons and Müller glia cells in a laminated structure that resembles the native retina. Despite these promising developments, current protocols show different efficiencies across pluripotent stem cells and result in retinal organoids with a mixture of photoreceptor cells at varying maturation states, along with nonphotoreceptor cell types. In this study, we investigated the impact of stage-specific addition of retinoic acid (RA), 9-cis-retinal, 11-cis-retinal, levodopa (l-DOPA), triiodothyronine (T3), and γ-secretase inhibitor ((2S)-N-[(3,5-Difluorophenyl)acetyl]-l-alanyl-2-phenyl]glycine1,1-dimethylethyl ester2L [DAPT]) in the generation of cone and rod photoreceptors. Our results indicate that addition of RA + T3 during days 90 to 120 of differentiation enhanced the generation of rod and S-cone photoreceptor formation, while the combined addition of DAPT from days 28 to 42 with RA during days 30 to 120 of differentiation led to enhanced generation of L/M-cones at the expense of rods. l-DOPA when added together with RA during days 90 to 120 of differentiation also promoted the emergence of S-cones at the expense of rod photoreceptors. Collectively, these data represent an advance in our ability to direct generation of rod and cone photoreceptors in vitro.