bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in hysterectomy‐corrected uterine cancer mortality rates during 2002 to 2015: mortality of nonendometrioid cancer on the rise?
Authors: Gustafson Line W. , Booth Berit B. , Kahlert Johnny , Ørtoft Gitte , Mejlgaard Else , Clarke Megan A. , Wentzensen Nicolas , Rositch Anne F. , Hammer Anne
Published: July 2020

Corpus uteri cancer is the most common gynecological malignancy in most developed countries. The disease is typically diagnosed at an early stage, is of endometrioid histologic subtype, and has a fairly good prognosis. Here, we describe hysterectomy‐corrected mortality rates of corpus uteri cancer, overall and stratified by age, stage and histologic subtype. Using data from nationwide Danish registries, we calculated uncorrected and hysterectomy‐corrected age‐standardized mortality rates of corpus uteri cancer among women ≥35 years during 2002 to 2015. Individual‐level hysterectomy status was obtained from national registries; hysterectomy‐corrected mortality rates were calculated by subtracting posthysterectomy person‐years from the denominator, unless hysterectomy was performed due to corpus uteri cancer. Correction for hysterectomy resulted in a 25.5% higher mortality rate (12.3/100000 person‐years vs 9.8/100000 person‐years). Mortality rates were highest in women aged 70+, irrespective of year of death, histologic subtype and stage. A significant decline was observed in overall hysterectomy‐corrected mortality rates from 2002 to 2015, particularly among women aged 70+. Mortality rates of endometrioid cancer declined significantly over time (annual percent change [APC]: −2.32, 95% CI −3.9, −0.7, P = .01), whereas rates of nonendometrioid cancer increased (APC: 5.90, 95% CI: 3.0, 8.9, P < .001). With respect to stage, mortality rates increased significantly over time for FIGOI‐IIa (APC: 6.18 [95% CI: 1.9, 10.7] P = .01) but remained unchanged for FIGO IIb‐IV. In conclusion, increasing mortality rates of nonendometrioid cancer paralleled the previously observed rise in incidence rates of this histologic subtype. Given the poor prognosis of nonendometrioid cancer, more studies are needed to clarify the underlying reason for these findings.
A chemical conjugation of JQ‐1 and a TLR7 agonist induces tumoricidal effects in a murine model of melanoma via enhanced immunomodulation
Authors: Wang Xiaodong , Yu Bingying , Cao Birong , Zhou Ji , Deng Yongqiang , Wang Zhulin , Jin Guangyi
Published: July 2020

In recent years, inhibitors of the BET bromodomain proteins, such as BRD4 inhibitors, have demonstrated robust antitumor activity. JQ‐1, a representative small molecular BRD4 inhibitor, is also effective to block PD‐1/PD‐L1 signaling by significantly decreasing the PD‐L1 expression on tumor cells. However, toxicity of BRD4 inhibitors on lymphoid and hematopoietic tissues limits their clinical usage. In this research, we designed and studied an immunogenic BRD4 inhibitor, SZU‐119, by coupling JQ‐1 with a TLR7 agonist, SZU‐101. In vitro, SZU‐119 stimulated the production of cytokines in mouse BMDCs and spleen lymphocytes, and inhibited the expression of PD‐L1 in mouse B16 tumor cells. In vivo, SZU‐119 suppressed the B16 tumor growth at both injected and uninjected sites, and prolonged the survival time of mice. SZU‐119 elevated the number of total CD8+ and IFN‐γ+ CD8+ T cells in spleens, with greater CTL cytotoxicity to B16 tumor cells. It was also observed that the infiltration of CD8+ T cells was increased in tumors at both local and distant sites, and the PD‐L1 expression was decreased in tumor cells at the primary site. In conclusion, we have demonstrated that SZU‐119 activated the innate immune cells, kept efficacy of PD‐L1 blockade and abrogated immune toxicity, showing more potent antitumor effects than the simple mixture of SZU‐101 and JQ‐1 in a mouse melanoma model. Our work provides new insights for the development of anti‐melanoma drugs that concurrently target innate and adaptive immunity.
Use of cancer data for cancer control in the Eastern Mediterranean Region: Results of a survey among population‐based cancer registries
Authors: Znaor Ariana , Fouad Heba , Majnoni d'Intignano Fosca , Hammerich Asmus , Slama Slim , Pourghazian Nasim , Eser Sultan , Piñeros Petersen Marion , Bray Freddie
Published: July 2020

Data from population‐based cancer registries (PBCR) are critical for planning, monitoring and evaluation of cancer control programs, but are frequently underutilized by key stakeholders. As part of the ongoing partnership of the International Agency for Research on Cancer (IARC) and the WHO Eastern Mediterranean Regional Office (EMRO) in cancer surveillance, we designed a cancer registry survey to assess the level of involvement of PBCR in national cancer control planning across the region. A questionnaire on registry characteristics, their contribution to cancer control and perceived barriers, was sent to 14 countries with operational PBCR. We obtained replies from Bahrain, Egypt, Iraq, Iran, Jordan, Kuwait, Lebanon, Morocco, Oman, Qatar, Saudi Arabia, Tunisia and the United Arab Emirates. We found a high participation of PBCR in cancer control planning (all registries involved, 46% routinely) and the evaluation of screening (92% registries involved, 46% routinely), but a much lower level of participation in palliative care and rehabilitation activities. Specified barriers included poor governance, a lack of awareness by policy makers, insufficient resources and a limited availability of data electronically, including mortality data. Appropriate planning to ensure the sustainability of PBCR (including the employment of permanent staff), increasing training, building research capacity and ensuring an efficient provision of high‐quality data to policymakers, were among the proposed solutions. The results of our study reinforce the need for further tailoring of activities in support of cancer registration and enhanced networking among stakeholders, toward improving quality and use of cancer registry data for cancer control in the EMR.
Synchronisation of policy related uncertainty, financial stress and economic activity in the United States
Authors: Tiwari Aviral Kumar , Nasir Muhammad Ali , Shahbaz Muhammad
Published: July 2020

This study analyses the synchronisation of economic activity, financial stress and uncertainty in the United States by employing a wavelet‐based approach of cohesion. Being innovative in the choice of the methodological framework as well as underlying factors of interest, we employed the monthly data on the policy‐related uncertainty indexes, Chicago Fed National Activity Index (CFNAI) and Kansas City Federal Reserve Financial Stress Index (KCFSI). Our key empirical findings suggest that the co‐movements of policy uncertainty, financial stress and economic activity are frequencies as well as time‐dependent. The uncertainty indices are found to be synchronised at lower and intermediate frequencies for all of the pairs. In the nexus between uncertainty and economic activity, financial stress plays a crucial role. Co‐movement of the policy uncertainty is observed to be more pronounced during the crisis periods though at different frequencies which indicated the usefulness of the proposed framework to analyse the implications of contemporaneous policy uncertainty and financial stress for the real economy. Concomitantly this informs the policy efforts to address the financial and economic instabilities which may arise as a consequence of financial stress and policy uncertainty.
Production of a novel poly(ɛ‐caprolactone)‐methylcellulose electrospun wound dressing by incorporating bioactive glass and Manuka honey
Authors: Schuhladen Katharina , Raghu Swathi N. V. , Liverani Liliana , Neščáková Zuzana , Boccaccini Aldo R.
Published: July 2020

Wound dressings produced by electrospinning exhibit a fibrous structure close to the one of the extracellular matrix of the skin. In this article, electrospinning was used to fabricate fiber mats based on the well‐known biopolymers poly(ɛ‐caprolactone) (PCL) and methylcellulose (MC) using benign solvents. The blend fiber mats were cross‐linked using Manuka honey and additionally used as a biodegradable platform to deliver bioactive glass particles. It was hypothesized that a dual therapeutic effect can be achieved by combining Manuka honey and bioactive glass. Morphological and chemical examinations confirmed the successful production of submicrometric PCL‐MC fiber mats containing Manuka honey and bioactive glass particles. The multifunctional fiber mats exhibited improved wettability and suitable mechanical properties (ultimate tensile strength of 3–5 MPa). By performing dissolution tests using simulated body fluid, the improved bioactivity of the fiber mats by the addition of bioactive glass was confirmed. Additionally, cell biology tests using human dermal fibroblasts and human keratinocytes‐like HaCaT cells showed the potential of the fabricated composite fiber mats to be used as wound dressing, specially due to the ability to support wound closure influenced by the presence of bioactive glass. Moreover, based on the results of the antibacterial tests, it is apparent that an optimization of the electrospun fiber mats is required to develop suitable wound dressing for the treatment of infected wounds.
MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG‐E8, and induces polarization via TLR4‐dependent pathway
Authors: Li Kangxin , Chen Guiming , Luo Haihua , Li Jianhang , Liu Aihua , Yang Chen , Wang Juan , Xu Jia , Gao Shenghan , Chen Peng , Jiang Yong
Published: July 2020

Myeloid‐related protein 8/14 (MRP8/14) participates in various inflammatory responses, however, its effect on macrophage efferocytosis remains unclear. Here, we demonstrate that MRP8/14 significantly inhibits the efferocytosis of apoptotic thymocytes by mouse bone marrow‐derived macrophages (BMDMs), which later proves to be associated with the receptor for advanced glycation end products (RAGE) or for reducing the expression of growth arrest‐specific protein 6 and milk fat globule epidermal growth factor 8, independent of RAGE. Furthermore, MRP8/14 promotes polarization of BMDMs from the M2‐ to M1‐like phenotype by upregulating expression of M1‐related surface receptor proteins and signature M1‐marker genes and by downregulating signature M2‐marker gene expression, which depends on Toll‐like receptor 4 and p38 mitogen‐activated protein kinase/nuclear factor κB pathways. Thus, we report a significant inhibitory effect of MRP8/14 on macrophage efferocytosis and MRP8/14‐mediated phenotypic polarization, which may be helpful in developing novel therapeutic strategies leading to inflammation resolution.
Recent advances of the function of sphingosine 1‐phosphate (S1P) receptor S1P3
Authors: Fan Xuehui , Liu Lili , Shi Yue , Guo Fanghan , He Xiao , Zhao Xiuli , Zhong Di , Li Guozhong
Published: July 2020

Known as a variety of sphingolipid metabolites capable of performing various biological activities, sphingosine 1‐phosphate (S1P) is commonly found in platelets, red blood cells, neutrophils, lymph fluid, and blood, as well as other cells and body fluids. S1P comprises five receptors, namely, S1P1–S1P5, with the distribution of S1P receptors exhibiting tissue selectivity to some degree. S1P1, S1P2, and S1P3 are extensively expressed in a wide variety of different tissues. The expression of S1P4 is restricted to lymphoid and hematopoietic tissues, while S1P5 is primarily expressed in the nervous system. S1P3 plays an essential role in the pathophysiological processes related to inflammation, cell proliferation, cell migration, tumor invasion and metastasis, ischemia‐reperfusion, tissue fibrosis, and vascular tone. In this paper, the relevant mechanism in the role of S1P3 is summarized.
Early‐life stress affects behavioral and neurochemical parameters differently in male and female juvenile Wistar rats
Authors: Noschang C. , Krolow R. , Arcego D. M. , Marcolin M. , Ferreira A. G. , da Cunha A. A. , Wyse A. T. S. , Dalmaz C.
Published: July 2020

Neonatal handling is an early life stressor that leads to behavioral and neurochemical changes in adult rats in a sex‐specific manner and possibly affects earlier stages of development. Here, we investigated the effects of neonatal handling (days 1–10 after birth) on juvenile rats focusing on biochemical parameters and olfactory memory after weaning. Male neonatal handled rats performed more crossings on the hole‐board task, increased Na+/K+‐ATPase activity in the olfactory bulb, and decreased acetylcholinesterase activity in the hippocampus versus non‐handled males. Female neonatal handled animals increased the number of rearing and nose‐pokes on the hole‐board task, decreased glutathione peroxidase activity, and total thiol content in the hippocampus versus non‐handled females. This study reinforces that early life stress affects behavioral and neurochemical parameters in a sex‐specific manner even before the puberty onset.
Synthesis and antitumor activity of some nitrogen heterocycles bearing pyrimidine moiety
Authors: Ahmed Marwa H. , El‐Hashash Maher A. , Marzouk Magda I. , El‐Naggar Abeer M.
Published: July 2020

Synthesis of novel pyrimidine derivatives 4‐16 was accomplished by heterocyclization of polarized system, for example, Chalcone. Claisen‐Schmidt condensation of 2‐acetyl naphthalene with 4‐(N, N‐dimethylaminobenzaldehyde) afforded chalcone 3, which was utilized for synthesis various pyrimidine derivatives by treatment with urea, thiourea, and guandine hydrochloride in ethanolic sodium hydroxide solution. The reactivity of the synthesized pyrimidine derivatives towards different nucleophilic and electrophilic reagent were examined. The constructions of the newly synthesized pyrimidine derivatives were elucidated from their spectral and elemental analysis. All the synthesized compounds were tested in vitro for their anticancer activities against HePG‐2 and MCF‐7 cell lines. Some of them posses a wide range of pharmacological activity. Finally, a molecular docking study was conducted to reveal the probable interaction with the dihydrofolate reductase (DHFR) active site.
Sucrose replacement: a sensory profile and time‐intensity analysis of a tamarind functional beverage with artificial and natural non‐nutritive sweeteners
Authors: Sousa Lima Rafael , Cazelatto de Medeiros Alessandra , André Bolini Helena Maria
Published: July 2020

BACKGROUND

Tamarind pulp contains polyphenolic compounds that exert antioxidant and anti‐inflammatory effects with a positive impact on human health. The elaboration of a tamarind‐based functional beverage, without the addition of sucrose, can be an alternative to traditional caloric beverages. This study aimed to evaluate the sensory profile and time intensity of a functional tamarind beverage containing artificial and natural non‐nutritive sweeteners.

RESULTS

The results of the acceptance test, check‐all‐that‐apply, and time‐intensity tests showed that there were no statistically significant differences between the means of samples sweetened with sucralose and samples sweetened with sucrose for attributes relating to appearance, aroma, flavor, or texture, or for overall impression. Samples with natural sweeteners had lower means for overall product impression and a lower percentage of purchase intention. The perception of astringency, bitter taste, and bitter aftertaste may be linked to the lower global impression of the product. The descriptors ‘tamarind flavor’ and ‘refreshment sensation’ were higher in products that were more liked. The sample sweetened with stevia showed higher levels of sweetness, bitterness, and longer sweet stimulus duration in the time‐intensity test.

CONCLUSION

The sample sweetened with sucralose was the best alternative to sucrose in the functional tamarind beverage. The analyzed sweeteners did not show changes in the perception of the natural characteristics of the fruit used, such as tamarind flavor, refreshment sensation, and astringency. However, the attributes related to sweet and bitter aftertaste experienced in samples with natural sweeteners may have influenced the reduction in the intention to purchase the product. © 2020 Society of Chemical Industry
Chlorogenic acid ameliorates obesity by preventing energy balance shift in high‐fat diet induced obese mice
Authors: He Xiaoyun , Zheng Shujuan , Sheng Yao , Miao Tong , Xu Jia , Xu Wentao , Huang Kunlun , Zhao Changhui
Published: July 2020

BACKGROUND

Chlorogenic acid is a type of phenolic acid found in many plants. Chlorogenic acid has an anti‐obesity effect with an unclear mechanism. The present study aimed to investigate the regulatory effect of chlorogenic acid on energy balance in high‐fat diet (HFD) induced obese C57BL/6J mice administrated 100 mg kg–1 chlorogenic acid for 13 weeks.

RESULTS

The consumption of chlorogenic acid ameliorated HFD induced obesity. Chlorogenic acid did not change the physical activity but significantly decreased food intake and increased body temperature, thermal dissipation and brown adipose tissue activity. Moreover, chlorogenic acid improved glucose tolerance but had a moderate impact on other blood indices. Additionally, chlorogenic acid failed to restore the microbiota change associated with HFD induced obesity, but modified the gut bacterial composition in a unique way.

CONCLUSION

Supplementation with chlorogenic acid can improve HFD induced obesity and associated glucose intolerance mainly via regulating food intake and energy expenditure. © 2020 Society of Chemical Industry
Continuing surgical care in cancer patients during the nationwide lockdown in the COVID‐19 pandemic—Perioperative outcomes from a tertiary care cancer center in India
Authors: Pai Esha , Chopra Saumya , Mandloi Deepak , Upadhyay Arvind K. , Prem Amar , Pandey Durgatosh
Published: July 2020

Background

The coronavirus disease‐2019 (COVID‐19) pandemic has disrupted management of non‐COVID‐19 illnesses, including cancer. For many solid organ cancers, surgical intervention is imperative. We present our experience with major operations during a nationwide lockdown.

Method

This was an observational study of 184 patients, analyzing their perioperative outcomes and categorizing morbidity according to Clavien‐Dindo Classification. Strict screening required symptomatic patients to be referred to COVID centers and their operations postponed. Continuous and categorical variables were expressed as medians with range and frequencies and percentages, respectively. A two‐sided α < .05 was statistically significant.

Results

During the lockdown, we initiated a graded response over four phases: (I) 24 March to 14 April (18 procedures); (II) 15 April to 3 May (26 procedures); (III) 4 to 17 May (41 procedures); and (IV) 18 to 31 May (99 procedures). The rates of major perioperative morbidity were 10.9% and mortality 1.6%. Over the four phases, the major morbidity rates were 11.1%, 15.4%, 9.8%, and 13.1%. On multivariate analysis, an emergency procedure was the only significant factor associated with morbidity. During the study period, no hospital staff became symptomatic for COVID‐19.

Conclusion

In a region with milder impact of COVID‐19, treatment of cancer patients need not be deferred. Our study showed that with appropriate precautions, asymptomatic patients may undergo operations without increased morbidity to them and hospital staff.
Soil aggregation accounts for the mineral soil organic carbon and nitrogen accrual in broadleaved forests as compared to that of coniferous forests in Northeast China: Cross‐sites and multiple species comparisons
Authors: Wei Chenhui , Wang Qiong , Ren Manli , Pei Zhongxue , Lu Jiali , Wang Huimei , Wang Wenjie
Published: July 2020

Differences in soil organic carbon (SOC) and total nitrogen (TN) between broadleaved and coniferous forests are not well‐defined, hindering the evaluation of the influence of forest‐type on land degradation and development. For these two foresttypes, we determined differences in soil aggregation, SOC, and TN by comparing 202 plots at six sites with 14 common afforestation tree species. Bulk soil was separated to macroaggregates (0.25–2 mm), microaggregates (0.053–0.25 mm), and silt and clay fractions (<0.053 mm). Inter‐site variations were excluded by MANOVA (multiple analysis of variance) and MANCOVA (multiple analysis of covariance). Broadleaved forests exhibited 30–50% higher SOC and TN in bulk soils than that of coniferous forests, and aggregates contributed to 75–77% of the SOC and TN accrual. The high accrual was a result of SOC and TN concentration increases in aggregates (30–50%), macroaggregates fraction increases (50%, with a 14% decrease in the non‐aggregate fractions), aggregates diameter increases (one‐third), and non‐significant differences in C/N. Uncertainty tests showed a low bias (4.2%), and the accrual of SOC and TN in broadleaved forests were larger at sites with less clay and at higher altitude and more precipitation and afforested with more fraxinus and less poplar. Our results highlight that SOC and TN accrual in broadleaved forests is mainly due to the stronger aggregates protection, which should be fully considered during precise land evaluation and species selection for afforestation. Future studies identifying the mechanisms underlying these changes should consider interactions among leaf functional traits, aggregation‐disaggregation processes, and microbial rhizosphere deposition.
Effects of carbon‐based materials and redmuds on metal(loid) immobilization and growth of Salix dasyclados Wimm. on a former mine Technosol contaminated by arsenic and lead
Authors: Lebrun Manhattan , Van Poucke Reinhart , Miard Florie , Scippa Gabriella S. , Bourgerie Sylvain , Morabito Domenico , Tack Filip M. G.
Published: July 2020

Metal(loid) soil contamination is a widespread issue and its remediation a priority. Phytoremediation involves the use of plants to stabilize/extract metal(loid)s and prevent spreading of contaminants. Salicaceae are fast growing trees that can tolerate and accumulate metal(loid)s. Amendments may be needed to facilitate plant growth on the contaminated substrate. Biochar, the solid product of pyrolysis, can ameliorate soil properties and reduce metal(loid) bioavailability but showed low affinity toward arsenic. Redmud, a waste product, can immobilize arsenic and other metal(loid)s and improve soil conditions. To evaluate the potential of those amendments to immobilize metal(loid)s and facilitate the establishment of a cover vegetation with willow (Salix dasyclados Wimm.), a pot experiment was conducted using several carbon‐based materials (biochar and activated carbon) and redmuds. Two carbon‐based materials and two redmuds were selected for the pot experiment based on characteristics and sorption tests. A former mining soil was amended with these products and Salix dasyclados cuttings were planted. Biochar and one redmud improved growth of Salix dasyclados Wimm. Redmud, which is cheaper than biochar, performed equally well as the biochar at a lower application rate. It can therefore be concluded that the application of redmud, associated to Salix dasyclados, could be an option for the phytoremediation of an As and Pb contaminated soil. However, these results need to be evaluated on a bigger scale to assess the gain brought by the combination of redmud and Salix dasyclados on the contaminated area.
Accelerated Polypeptide Synthesis via N‐Carboxyanhydride Ring Opening Polymerization in Continuous Flow
Authors: Vrijsen Jeroen Hendrik , Rasines Mazo Alicia , Junkers Tanja , Qiao Greg Guanghua
Published: July 2020

In nature, polypeptide‐based materials are ubiquitous, yet their synthetic production is hampered by high cost, limited scalability, and often stringent reaction conditions. Herein an elegant approach is presented for N‐carboxyanhydride ring opening polymerization (NCA ROP) of Nε‐benzyloxycarbonyl‐l‐lysine (ZLL) and γ‐benzyl‐l‐glutamate (BLG) NCA in continuous flow. The polymerization is initiated by primary amine initiators using N,N‐dimethylformamide (DMF) as solvent. Carrying out the reaction in a silicon microflow reactor speeds up the rate of ROP (92% conversion in 40 min in flow as opposed to 6 h in batch) due to highly efficient permeation of CO2 through the reactor tubing. The polymerization strategy provides a facile, scale‐up friendly alternative to traditional batch mode polymerization and has the capability of streamlining NCA ROP.
Effect of Branch Point Distribution on the Radius of Gyration in Batch Free‐Radical Polymerization with Chain Transfer to Polymer
Authors: Tobita Hidetaka
Published: July 2020

Free‐radical polymerization is irreversible, and the primary chains formed earlier are expected to possess larger branching density compared with those formed later, leading to a branching density distribution (BDD) among primary chains. In addition to the BDD, the primary chain length distribution (CLD) may change during polymerization. For a primary CLD with a shift toward smaller chain length during polymerization, the expected g‐ratio for a given number k of branch points can be approximated reasonably well with that for the random branched polymers having the accumulated primary CLD. On the other hand, when the primary CLD moves toward larger chain length during polymerization, the expected g‐ratio may become smaller than the corresponding random branched polymers, due to an “unnatural” combination in the length of backbone and branch chains. The compactness of branched architecture could be controlled through the consideration of the maximum end‐to‐end path length.
Well‐posedness of a stochastic phase‐field problem with multiplicative noises
Authors: El Kettani Perla
Published: July 2020

In this paper, we prove the existence and uniqueness of the solution of a stochastic phase‐field problem with multiplicative noises. Phase‐field models are typically used to describe melting and solidification processes. We consider here the case of multiplicative noises induced by a Q‐Brownian motion.
Stability analysis of fractional order neutral‐type systems considering time varying delays, nonlinear perturbations, and input saturation
Authors: Aghayan Zahra Sadat , Alfi Alireza , Tenreiro Machado J. A.
Published: July 2020

This article investigates the robust stability of fractional order neutral‐type systems involving nonlinear perturbations and time varying delays in the presence of input saturation. Design criteria, expressed in terms of linear matrix inequalities, are derived with the aid of the Lyapunov Krasovskii functional for the state feedback controller. Based on the cone complementarity linearization method, an optimization problem is also formulated for finding the controller gains subject to maximizing the domain of attraction. The main results are confirmed by numerical simulations.
Dosimetry modeling of focused kV x‐ray radiotherapy for wet age‐related macular degeneration
Authors: Yan Huagang , Sun Weiyuan , Mruthyunjaya Prithvi , Beadle Beth , Yu Weihong , Kanwal Bushra , MacDonald Carolyn A. , Liu Wu
Published: July 2020

Purpose

Wet (neovascular) age‐related macular degeneration (AMD) is the leading cause of blindness in the United States. The mainstay treatment requires monthly intravitreal injection of anti‐vascular endothelial growth factor (anti‐VEGF) drugs, associated with multiple visits, high cost, and the risk of procedural injury and infection. Anti‐VEGF drugs inhibit the formation of neovasculature but do not directly attack it. Radiotherapy can destroy neovasculature and potentially also inhibit wet‐AMD associated inflammation and fibrosis not addressed by VEGF inhibitors. However, the current collimation‐based radiotherapy device uses fixed 4 mm beams, which are prone to overtreat or undertreat the choroidal neovascularization (CNV) lesions because of their various sizes and shapes. This simulation study evaluates personalized conformal treatment with focused kV radiation using cutting‐edge polycapillary x‐ray optics.

Methods

Simulation of the polycapillary optics was achieved via Monte Carlo (MC)‐based three‐dimensional (3D) geometric ray tracing. Phase‐space files modeling the focused photons were generated. The method was previously verified by phantom measurements. The ultrasmall ~0.2 mm beam focal spot perpendicular to the beam direction enables spatially fractionated grid therapy, which has been shown to preferentially damage abnormal neovascular blood vessels vs normal ones. Geant4‐based MC simulations of scanning while rotating beam delivery were performed to conformally treat three clinical cases of large, medium, and small CNV lesions with regular and grid deliveries. Dose delivery uncertainties due to positioning errors were analyzed, including ±0.75 mm displacement in the three orthogonal directions and ±5° vertical/horizontal rotation of the eyeball.

Results

The simulated CNV treatments by 60‐kVp focused x‐ray beams show highly conformal delivery of dose to the lesion plus margin (0.75 mm) with sharp dose fall‐offs and controllable spatial modulation patterns. The 90%–10% isodose penumbra is <0.5 mm. With a prescription dose of 16 Gy to the lesions, the critical structure doses are well below the tolerance. The average CNV dose varies within 10% (mostly within 4%) due to 0.75‐mm linear displacements and 5‐degree gaze angle rotation of the eyeball.

Conclusion

Focused kV technique allows personalized treatment of CNV lesions and reduces unwanted radiation to adjacent healthy tissue. The simulated dose distribution is superior to currently available techniques.
Deep learning using a biophysical model for robust and accelerated reconstruction of quantitative, artifact‐free and denoised images
Authors: Torop Max , Kothapalli Satya V. V. N. , Sun Yu , Liu Jiaming , Kahali Sayan , Yablonskiy Dmitriy A. , Kamilov Ulugbek S.
Published: July 2020

Purpose

To introduce a novel deep learning method for Robust and Accelerated Reconstruction (RoAR) of quantitative and B0‐inhomogeneity‐corrected

maps from multi‐gradient recalled echo (mGRE) MRI data.

Methods

RoAR trains a convolutional neural network (CNN) to generate quantitative

maps free from field inhomogeneity artifacts by adopting a self‐supervised learning strategy given (a) mGRE magnitude images, (b) the biophysical model describing mGRE signal decay, and (c) preliminary‐evaluated F‐function accounting for contribution of macroscopic B0 field inhomogeneities. Importantly, no ground‐truth

images are required and F‐function is only needed during RoAR training but not application.

Results

We show that RoAR preserves all features of

maps while offering significant improvements over existing methods in computation speed (seconds vs. hours) and reduced sensitivity to noise. Even for data with SNR = 5 RoAR produced

maps with accuracy of 22% while voxel‐wise analysis accuracy was 47%. For SNR = 10 the RoAR accuracy increased to 17% vs. 24% for direct voxel‐wise analysis.

Conclusions

RoAR is trained to recognize the macroscopic magnetic field inhomogeneities directly from the input magnitude‐only mGRE data and eliminate their effect on

measurements. RoAR training is based on the biophysical model and does not require ground‐truth

maps. Since RoAR utilizes signal information not just from individual voxels but also accounts for spatial patterns of the signals in the images, it reduces the sensitivity of

maps to the noise in the data. These features plus high computational speed provide significant benefits for the potential usage of RoAR in clinical settings.
Lippmann‐Schwinger solvers for the computational homogenization of materials with pores
Authors: Schneider Matti
Published: July 2020

We show that under suitable hypotheses on the nonporous material law and a geometric regularity condition on the pore space, Moulinec‐Suquet's basic solution scheme converges linearly. We also discuss for which derived solvers a (super)linear convergence behavior may be obtained, and for which such results do not hold, in general. The key technical argument relies on a specific subspace on which the homogenization problem is nondegenerate, and which is preserved by iterations of the basic scheme. Our line of argument is based in the nondiscretized setting, and we draw conclusions on the convergence behavior for discretized solution schemes in FFT‐based computational homogenization. Also, we see how the geometry of the pores' interface enters the convergence estimates. We provide computational experiments underlining our claims.
Preparation of polycarbonate/poly(lactic acid) with improved printability and processability for fused deposition modeling
Authors: Geng Yi , He Hui , Liu Hao , Jing Huaishuai
Published: July 2020

Fused deposition modeling (FDM) is the most widely used 3D‐printing technology due to its simplicity to operate and low cost. However, many engineering plastics such as polycarbonate (PC) with better properties cannot be applied in common FDM printer because of their poor processability and printability. Poly(lactic acid) (PLA) as the most common printing material has the disadvantages of insufficient heat resistance and poor toughness, which limits the application of PLA‐based FDM product in more potential fields. To develop new material available for FDM, PC/PLA blend was prepared by polymer blending and achieved essential printability for FDM. Ethylene‐butyl acrylate‐glycidyl methacrylate terpolymer (PTW) was introduced to PC/PLA blend as warpage modifier and also had a good toughening effect. Thus, PC/PLA/PTW blend had been prepared as FDM filament with excellent comprehensive properties. The phase morphology of PLA changed from independent dispersed phase to semi‐continuous phase with increasing PLA content. Different from the injection molding samples, the morphology of FDM‐printed samples indicated that the PLA phase oriented in the same direction due to the tensile orientation of the filaments caused by nozzle scanning. Five printing modes were designed to study the effect of printing direction on mechanical properties and failure modes. It was proved that the adhesion between the filaments was weaker than the strength of filament itself and easily caused adjacent filament exfoliation, ultimately resulting in the failure. The work provided some referential conclusions contributing to optimization of printing strategy.
Poly(azomethine ether)‐derived carbon nanofibers for self‐standing and binder‐free supercapacitor electrode material applications
Authors: Choi Young Chul , Kim Min Su , Ryu Kyoung Moon , Lee Sang Hoon , Jeong Young Gyu
Published: July 2020

We report the microstructure and electrochemical performance of poly(azomethine ether) (PAME)‐derived carbon nanofibers (CNFs), which were fabricated by a facile two‐step process of electrospinning and carbonization, as self‐standing and binder‐free supercapacitor electrode materials. The SEM images showed that the average diameter decreased noticeably from ~293.9 nm of as‐spun nanofibers to ~150.3 nm of CNFs after the carbonization at 1000°C. The EDS, XPS, Raman, and XRD analyses demonstrated that PAME‐derived CNFs have a nitrogen self‐doped graphitic structure. Accordingly, PAME‐derived CNFs were characterized to have relatively high electrical conductivity of ~3.1 S/cm and excellent wettability to water. The cyclic voltammetry and galvanostatic charge/discharge tests revealed that PAME‐derived CNFs have a high specific capacitance of 298 F/g at 0.3 A/g, energy density of 3.3 to 13.9 Wh/kg, power density of 37.5 to 250.0 W/kg, and capacity retention of ~94% after 1000 cycles.
First‐trimester screening based on cell‐free DNA vs combined screening: A randomized clinical trial on women's experience
Authors: Migliorini Sonia , Saccone Gabriele , Silvestro Fiora , Massaro Giulia , Arduino Bruno , D'Alessandro Pietro , Petti Maria Teresa , Paino Jessica Anna Cinzia , Guida Maurizio , Locci Mariavittoria , Zullo Fulvio
Published: July 2020

Objective

To compare women's experience of first‐trimester combined screening (FTCS), with women's experience of an approach that uses the combination of a detailed early anatomy scan and cell‐free DNA (cfDNA) analysis.

Methods

This was single‐center, open label, parallel group, randomized clinical trial. Pregnant women were randomized at the time of their first prenatal visit to either a policy of first‐trimester risk assessment based on FTCS, or to a policy of first‐trimester risk assessment based on ultrasound findings and cfDNA. FTCS included ultrasound evaluation with crown‐rump length, nuchal translucency (NT) measurement, and a detailed ultrasound scan, along with biochemistry (PAPP‐A and free beta hCG). In this group, invasive diagnostic testing was offered to patients with risk >1 in 100, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Women randomized in the intervention group received an approach of first‐trimester risk assessment based on ultrasound findings and cfDNA. cfDNA analysis included a simultaneous microarray‐based assay of non‐polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. In the intervention group, invasive diagnostic testing was offered to patients with abnormal cfDNA screening results, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Participants received pre‐test and post‐test questionnaires regarding to measure reassurance, satisfaction, and anxiety. The primary outcome was the post‐test reassurance, defined as mean score of reassurance post‐test questionnaire. The effect of the assigned screening test on the mean of each outcome was quantified as mean difference (MD) with 95% confidence interval (CI).

Results

Forty women with singleton gestations were enrolled in the trial. Mean score for reassurance was significantly higher in the cfDNA group compared to the FTCS group in the pre‐test questionnaire (MD 0.80 points, 95% CI 0.27 to 1.33) and in the post‐test questionnaire (MD 16.50 points, 95% CI 2.18 to 30.82). Women randomized to the cfDNA group had higher satisfaction and lower mean anxiety score as assessed in the STAI pre‐test questionnaire.

Conclusions

First‐trimester risk assessment for fetal aneuploidy with a combination of a detailed ultrasound examination and cfDNA is associated with better maternal reassurance and better maternal satisfaction compared to the standard first‐trimester combined screening with nuchal translucency, and biochemistry.

Trial registration

Clinicaltrials.gov NCT04077060.
Image‐based root phenotyping links root architecture to micronutrient concentration in cassava
Authors: Busener Natalie , Kengkanna Jitrana , Saengwilai Patompong Johns , Bucksch Alexander
Published: July 2020

Societal Impact Statement

Micronutrient deficiency or “hidden hunger” is estimated to affect two billion people worldwide and increasing the micronutrient concentration of food could play an important role in tackling this global challenge. Using a combination of imaging techniques and atomic absorption spectroscopy, we describe a link between root phenotype and micronutrient concentration in cassava, which could enable new phenotypic selection strategies for breeding. This approach could be used with existing breeding infrastructure to enhance the micronutrient concentration of cassava and hence, benefit the health of people, particularly in low‐income countries where cassava is consumed as a staple crop.

Cassava storage roots are a staple food in low‐income countries of South‐East Asia and sub‐Saharan Africa, where growth stunting is prevalent as a consequence of micronutrient deficiencies. We aim to link phenotypes of field‐grown cassava roots to micronutrient concentration in the edible storage roots as a simple way to improve phenotypic selection for nutritional value in cassava.

We used existing and newly developed imaging techniques to quantify root phenotypes of the cassava root architecture over time and used flame atomic absorption spectroscopy to measure micronutrient concentration in storage roots. Both together allow the association of root phenotypes with micronutrient concentration in mature cassava roots.

We show that early and late bulking genotypes in cassava exhibit distinct foraging behaviors that are associated with micronutrient concentration in the edible storage root. Our observations suggest that late bulking cassava is a key to provide sufficient micronutrients in the edible storage root.

The association between root phenotype and micronutrient concentration with imaging techniques allows phenotypic selection for enhanced micronutrient concentration. Therefore, implementing image‐based phenotyping into cassava breeding programs in sub‐Saharan Africa and South‐East Asia could be an essential element to resolve micronutrient deficiencies that puts individuals at a higher risk of growth stunting.
Review of the Wedge Test and Single Curve Initiation Principle Applied to Aluminized High Explosives
Authors: Elia Thomas , Chuzeville Vincent , Baudin Gérard , Genetier Marc , Lefrançois Alexandre , Osmont Antoine , Boulanger Rémi
Published: July 2020

The experiments have a key role in the initiation and transition studies of solid high explosives. Detonic has forced scientist to improve their experimental approach by designing relevant set‐up and developing accurate metrological devices. For example, the wedge or pop‐plot test was developed in the 50’s and remains a legacy experiment in the characterization of high explosive. However, for 70 years, it has been widely improved, because of the accurate measurements need. This paper aims to review the main improvements performed on the pop‐plot test and analyze a series of results acquired on melt‐cast and cast‐cured high explosives. We first describe the current set‐up with its new metrological devices. Then, we discuss the results and limitations of this test.
A humanized antibody inhibitor for cathepsin L
Authors: Shi Xiaojing , Zhang Yong
Published: July 2020

Cathepsin L (CTSL) is a cysteine protease involved in a variety of physiological and pathological processes. Potent inhibitors against CTSL have long been sought for drug development. Due to insufficient specificity and suboptimal pharmacological properties for current CTSL inhibitors, novel agents are still required for selectively blocking CTSL activity. Here we generated a humanized antibody inhibitor of CTSL by genetically fusing the inhibitory propeptide of procathepsin L to the N‐terminus of the light chain of a humanized antibody. The resulting antibody fusion could be stably expressed and displays highly potent inhibition activity and specificity toward CTSL. This work demonstrates a new approach for the rapid generation of antibody inhibitors of CTSL. It can possibly be extended to create inhibitory antibodies targeting other cathepsin proteases, providing novel research and therapeutic tools.
Tight junction protein claudin‐1 is downregulated by TGF‐β1 via MEK signaling in benign prostatic epithelial cells
Authors: Wang Ke , Pascal Laura E. , Li Feng , Chen Wei , Dhir Rajiv , Balasubramani Goundappa K. , DeFranco Donald B. , Yoshimura Naoki , He Dalin , Wang Zhou
Published: July 2020

Background

Benign prostatic hyperplasia (BPH) is arguably the most common disease in aging men. Although the etiology is not well understood, chronic prostatic inflammation is thought to play an important role in BPH initiation and progression. Our recent studies suggest that the prostatic epithelial barrier is compromised in glandular BPH tissues. The proinflammatory cytokine transforming growth factor beta 1 (TGF‐β1) impacts tight junction formation, enhances epithelial barrier permeability, and suppresses claudin‐1 messenger RNA expression in prostatic epithelial cells. However, the role of claudin‐1 in the prostatic epithelial barrier and its regulation by TGF‐β1 in prostatic epithelial cells are not clear.

Methods

The expression of claudin‐1 was analyzed in 22 clinical BPH specimens by immunohistochemistry. Human benign prostate epithelial cell lines BPH‐1 and BHPrE1 were treated with TGF‐β1 and transfected with small interfering RNAs specific to claudin‐1. Epithelial monolayer permeability changes in the treated cells were measured using trans‐epithelial electrical resistance (TEER). The expression of claudin‐1, E‐cadherin, N‐cadherin, snail, slug, and activation of mitogen‐activated proteins kinases (MAPKs) and AKT was assessed following TGF‐β1 treatment using Western blot analysis.

Results

Claudin‐1 expression was decreased in glandular BPH tissue compared with adjacent normal prostatic tissue in patient specimens. TGF‐β1 treatment or claudin‐1 knockdown in prostatic epithelial cell lines increased monolayer permeability. TGF‐β1 decreased levels of claudin‐1 and increased levels of snail and slug as well as increased phosphorylation of the MAPK extracellular signal‐regulated kinase‐1/2 (ERK‐1/2) in both BPH‐1 and BHPrE1 cells. Overexpression of snail or slug had no effect on claudin‐1 expression. In contrast, PD98059 and U0126, inhibitors of the upstream activator of ERK‐1/2 (ie, MEK‐1/2) restored claudin‐1 expression level as well as the epithelial barrier.

Conclusion

Our findings suggest that downregulation of claudin‐1 by TGF‐β1 acting through the noncanonical MEK‐1/2/ERK‐1/2 pathway triggers increased prostatic epithelial monolayer permeability in vitro. These findings also suggest that elevated TGF‐β1 may contribute to claudin‐1 downregulation and compromised epithelial barrier in clinical BPH specimens.
Residue interaction dynamics in Vaucheria aureochrome1 light‐oxygen‐voltage: Bridging theory and experiments
Authors: Deb Anwesha , Grewal Rajdeep Kaur , Roy Soumen , Mitra Devrani
Published: July 2020

Allosteric communication is the basis of signaling and information transfer. Collective interactions between amino acid residues, which are spatially distributed in the three dimensional structure of a protein molecule, form the basis of allosteric network. While the construction of residue interaction graphs (RIG) is based on static crystal structures of proteins, it is important to extract information on protein dynamics to understand allostery. Therefore, quantitative analysis of RIG based on the framework of differential network (DN), is immensely helpful in identifying key amino acid residue interactions within such communication pathways. While the simultaneous availability of protein structures from two different states is essential for DN, there are additional challenges. Crystallographic artifacts like nonbiological dimeric arrangements within the crystal lattice automatically influence the construction and eventually the interpretation of RIG. Therefore, experimental validation of predictions from the analyses of RIG is naturally scarce in the literature. Herein, we study the photo sensor domain of the signaling photoreceptor transcription factor, aureochrome1, to understand light‐driven signaling. We perform direct experiments to verify the predictions from RIG using the machinery of DN. However, the agreement leaves scope for improvement. We then discuss the notion of quaternary structure alignment to obtain a biologically meaningful dimer. Thence, we reconstruct the RIG and reanalyze the modified structure. Results of these reanalyses render far superior agreement with experiments. Therefore, this notion of addressing crystallographic biases provides a fresh yet general approach for reconciliation of theory and experiments. It is applicable beyond the present case to all signaling proteins in general.