bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigallocatechin gallate (EGCG) inhibits lipopolysaccharide‐induced inflammation in RAW 264.7 macrophage cells via modulating nuclear factor kappa‐light‐chain enhancer of activated B cells (NF‐κB) signaling pathway
Authors: Hossen Imam , Kaiqi Zhang , Hua Wu , Junsong Xiao , Mingquan Huang , Yanping Cao
Published: May 2023

Epigallocatechin‐3‐gallate (EGCG) is a major bioactive compound in tea polyphenol extract. After ingestion, EGCG reaches the intestine and may commence anti‐inflammation in the intestinal organ. Thus, in this paper, the anti‐inflammatory effect of EGCG was studied using lipopolysaccharide (LPS)‐induced inflammation in RAW 264.7 cells. LPS induction instigated morphological deformation extensively which was normalized by EGCG. In LPS‐induced macrophage cells, EGCG was found to lower cellular nitric oxide (32% of LPS group) and intercellular ROS level (45.4% of LPS group). It also suppressed the expression of IL‐1β (LPS 132.6 ± 14.6, EGCG 10.67 ± 3.65), IL‐6 (LPS 2994.44 ± 178.5, EGCG 408.33 ± 52.34), TNF‐α (LPS 27.11 ± 2.84, EGCG 1.22 ± 0.03), and iNOS (LPS 40.45 ± 11.17, EGCG 10.24 ± 0.89). The GO function analysis identified that these differential genes involved 24 biological processes, 18 molecular functions, and 19 cellular component‐related processes. KEGG pathway enrichment analysis revealed that LPS significantly affects NF‐κB, TNF, and TLR signaling pathways. Western blotting revealed that EGCG diminished P‐IκB/IκB ratio by 75% and p‐p65/p65 by 50% compared to the LPS group. Finally, Arg‐1 and CD‐206 mRNA expression were determined by RT‐PCR, which was consistent with the RNA‐Seq result. These findings indicate that EGCG exerts an anti‐inflammatory effect by reducing NO and ROS production, suppressing TLR4 protein expression, and inhibiting IκB and p65 phosphorylation.
Spatial–temporal patterns of brain disconnectome in Alzheimer's disease
Authors: Liang Li , Zhou Pengzheng , Ye Chenfei , Yang Qi , Ma Ting
Published: May 2023

Mounting evidences have shown that progression of white matter hyperintensities (WMHs) with vascular origin might cause cognitive dysfunction symptoms through their effects on brain networks. However, the vulnerability of specific neural connection related to WMHs in Alzheimer's disease (AD) still remains unclear. In this study, we established an atlas‐guided computational framework based on brain disconnectome to assess the spatial–temporal patterns of WMH‐related structural disconnectivity within a longitudinal investigation. Alzheimer's Disease Neuroimaging Initiative (ADNI) database was adopted with 91, 90 and 44 subjects including in cognitive normal aging, stable and progressive mild cognitive impairment (MCI), respectively. The parcel‐wise disconnectome was computed by indirect mapping of individual WMHs onto population‐averaged tractography atlas. By performing chi‐square test, we discovered a spatial–temporal pattern of brain disconnectome along AD evolution. When applied such pattern as predictor, our models achieved highest mean accuracy of 0.82, mean sensitivity of 0.86, mean specificity of 0.82 and mean area under the receiver operating characteristic curve (AUC) of 0.91 for predicting conversion from MCI to dementia, which outperformed methods utilizing lesion volume as predictors. Our analysis suggests that brain WMH‐related structural disconnectome contributes to AD evolution mainly through attacking connections between: (1) parahippocampal gyrus and superior frontal gyrus, orbital gyrus, and lateral occipital cortex; and (2) hippocampus and cingulate gyrus, which are also vulnerable to Aβ and tau confirmed by other researches. All the results further indicate that a synergistic relationship exists between multiple contributors of AD as they attack similar brain connectivity at the prodromal stage of disease.
PCSK9 promotes T helper 1 and T helper 17 cell differentiation by activating the nuclear factor‐κB pathway in ankylosing spondylitis
Authors: Cai Jianfei , Jiang Yinghui , Chen Fucai , Wu Shubin , Ren Hongjun , Wang Pingping , Wang Jiayong , Liu Wei
Published: May 2023

Objective

Our previous study reveals that proprotein convertase subtilisin/kexin type 9 (PCSK9) is positively related to inflammatory markers, T helper (Th)‐17 cells, and treatment response in ankylosing spondylitis (AS) patients. Subsequently, this study aimed to explore the effect of PCSK9 on Th cell differentiation and its potential molecular mechanism in AS.

Methods

Serum PCSK9 was determined by enzyme‐linked immunosorbent assay in 20 AS patients and 20 healthy controls (HCs). Then naïve CD4+ T cells were isolated from AS patients and infected with PCSK9 overexpression or knockdown adenovirus followed by polarization assay. Afterward, PMA (an NF‐κB activator) was administrated.

Results

PCSK9 was increased in AS patients compared to HCs (p < .001), and it was positively related to Th1 cells (p = .050) and Th17 cells (p = .039) in AS patients. PCSK9 overexpression increased the CD4+IFN‐γ+ cells (p < .05), CD4+IL‐17A+ cells (p < .01), IFN‐γ (p < .01), and IL‐17A (p < .01), while it exhibited no effect on CD4+IL‐4+cells or IL‐4 (both p > .05); its knockdown displayed the opposite function on them. Moreover, PCSK9 overexpression upregulated the p‐NF‐κB p65/NF‐κB p65 (p < .01), while it had no effect on p‐ERK/ERK or p‐JNK/JNK (both p > .05); its knockdown decreased p‐NF‐κB p65/NF‐κB p65 (p < .01) and p‐JNK/JNK (p < .05). Then, PMA upregulates p‐NF‐κB p65/NF‐κB p65 (p < .001) and increased CD4+IFN‐γ+ cells, CD4+IL‐17A+ cells, IFN‐γ, and IL‐17A (all p < .01), also it alleviated the effect of PCSK9 knockdown on NF‐κB inhibition and Th cell differentiation (all p < .01).

Conclusion

PCSK9 enhances Th1 and Th17 cell differentiation in an NF‐κB‐dependent manner in AS, while further validation is necessary.
Contaminated meal intake (Aeromonas hydrophila) does not elicit hormonal or immune modulation in bullfrogs (Lithobates catesbeianus)
Authors: Figueiredo Aymam Cobo de , Christie Monteiro Titon Stefanny , Lima Alan Siqueira , Floreste Felipe Rangel , Neto Patrício Getúlio Garcia , Gomes Fernando Ribeiro
Published: May 2023

The gastrointestinal tract (GIT) is colonized by resident microbiota but contact with foreign microbiota during feeding can impair GIT functions. During meal digestion, several vertebrates modulate the systemic immune function and immunoregulatory hormones concentration. However, in ectothermic animals, it is not known if this hormonal and immune modulation during the postprandial period is affected by the presence of pathogenic microbiota in the food. This study aimed to investigate the effects of contaminated meal ingestion on hormonal and innate immune responses in bullfrogs (Lithobates catesbeianus). Bullfrogs were divided into three treatments: fed three times with sterilized fish feed (control group), fed twice with sterilized fish feed and once with fish feed containing live bacteria (Aeromonas hydrophila, 109 UFC/mL), and fed three times with fish feed containing live bacteria. Blood and GIT tissues were collected 24 h after treatments to measure plasma and tissue corticosterone levels, NL ratio, and plasma bacterial killing ability. The ingestion of contaminated meal did not affect the hormonal and immune parameters. In conclusion, ingestion of contaminated food was not capable of intensifying the hypothalamic–pituitary–interrenal axis activation and the consequent hormonal and immune responses observed after feeding in bullfrogs. However, our results suggest that the ingestion of three contaminated meals tended to decrease stomach corticosterone levels (nonstatistically significant), possibly contributing to preventing the transmigration of the bacteria to organs outside the GIT.
Concordance between electronic health record‐recorded race/ethnicity and parental report in hospitalized children
Authors: Hoang Kim , Gold Jessica , Powell Carmin , Lee Henry C. , Floyd Baraka , Schroeder Alan , Chadwick Whitney
Published: May 2023

Background

Electronic health records (EHRs) have become an important repository for patient race and ethnicity. Misclassification could negatively affect efforts to monitor and reduce health disparities and structural discrimination.

Objective

We assessed the concordance of parental reports of race/ethnicity for their hospitalized children with EHR‐documented demographics. We also aimed to describe parents' preferences on how race/ethnicity should be captured in the hospital's EHR.

Designs, Settings, and Participants

From December 2021 to May 2022, we conducted a single‐center cross‐sectional survey of parents of hospitalized children asking to describe their child's race/ethnicity and compared these responses to the race/ethnicity documented in the EHR.

Main Outcome and Measures

Concordance was analyzed with a kappa statistic (κ). Additionally, we queried respondents about their awareness of and preferences for race/ethnicity documentation.

Results

Of the 275 participants surveyed (79% response rate), there was 69% agreement (κ = 0.56) for race and 80% agreement (κ = 0.63) for ethnicity between parent report and EHR documentation. Sixty‐eight parents (21%) felt that the designated categories poorly represent their child's race/ethnicity. Twenty‐two (8%) were uncomfortable with their child's race/ethnicity being displayed on the hospital's EHR. Eighty‐nine (32%) preferred a more comprehensive list of race/ethnicity categories.

Conclusions

Nonconcordance between EHR‐recorded race/ethnicity and parental report exists in the EHR for our hospitalized patients, which has implications for describing patient populations and for understanding racial and ethnic disparities. Current EHR categories may be limited in their ability to capture the complexity of these constructs. Future efforts should focus on ensuring that demographic information in the EHR is accurately collected and appropriately reflects families' preferences.
Applications of curcumin loaded nanoemulsions in photoinactivation of Aspergillus niger spores
Authors: Arboleda‐Murillo J. Alejandro , Cañon‐Ibarra Andres F. , Sanchez Leidy T. , Pinzon Magda I. , Villa Cristian C.
Published: May 2023

Background

Aspergillus niger is one of the most common fungal contaminants of food products, leading to several economic losses on fruit, vegetables and other food products during storage. Over the years, several new techniques have been developed to control fungal growth, including photodynamic inactivation, in which excitation of a photosensitizer in the right wavelength leads to ROS production and microbial death.

Results

On this paper, curcumin was used as a natural photosentitizer against A. niger spores. Nanoemulsions were used in order to encapsulated curcumin and increase its water solubility. Results showed that spores inhibition could reach up to 80% after 3 min of irradiation while values for un‐encapsulated curcumin were around 30%.

Conclusion

Results presented show that nanoemulsions could be use to enhance the photoinactivation properties of curcumin, against fungal spores from A. niger. This type of process can be use for food decontamination and preservation.
Green dispersive solid‐phase microextraction of melamine using crosslinked beta‐cyclodextrin with citric acid followed by high‐performance liquid chromatography
Authors: Nasrollahi Seyedeh Sara , Yamini Yadollah
Published: May 2023

In this research, a green approach for dispersive solid phase microextraction was introduced for the extraction and determination of melamine in various matrices such as infant formula and hot water in a melamine bowl. In this way, a natural polar polymer called ß‐cyclodextrin has been cross‐linked with citric acid to create a water‐insoluble adsorbent. The extraction was carried out by dispersion of the sorbent into the sample solution. The effective parameters on the extraction efficiency of the melamine, including ion strength, extraction time, sample volume, amount of absorbent, pH, type of desorption solvent, desorption time, and desorption solvent volume were optimized by one variable at a time approach. Under the optimal conditions, the method showed a good linear dynamic range for melamine in the range of 1–1000 μg/L with a coefficient of determination of 0.9985. The obtained limit of detection was 0.3 μg/L. The intra‐day and inter‐day relative standard deviations (n = 3) were 3.1% and 3.2% respectively. Lastly, this technique was applied to extract and determine the analyte in a melamine bowl and infant formula with acceptable and satisfactory results.
A Novel Method for Thyroarytenoid Myofiber Culture
Authors: Gartling Gary , Nakamura Ryosuke , Bing Renjie , Branski Ryan C.
Published: May 2023

Objectives/Hypothesis

Myofiber culture has been employed to investigate muscle physiology in vitro and is well‐established in the rodent hind limb. Thyroarytenoid (TA) myofiber culture has not been described, providing an opportunity to employ this method to investigate distinct TA myofiber functions. The purpose of this study was to assess the feasibility of a TA myofiber culture model.

Study Design

In vitro.

Methods

TA muscles from five Sprague Dawley rats were independently isolated and digested for 90 min. A smooth‐tip, wide‐bored pipette dissociated TA myofibers from cartilage, and the fibers were distributed on collagen‐coated dishes and incubated at 37°C, 5% CO2 for 2 h. Myofiber specificity was determined via immunolabeling for desmin and myosin heavy chain (MHC). Myofibers viability was assessed over 7 days via esterase assay. Additional myofibers were immunolabeled for satellite cell marker Pax‐7. Glucocorticoid (GC) receptor (GR) was immunolabeled following GC treatment.

Results

The harvest technique yielded ~120 myofibers per larynx. By day 7, ~60% of the fibers remained attached and were calcein AM‐positive/ethidium homodimer‐negative, indicating viability. Myofibers were positive for desmin and MHC, indicating muscle specificity. Cells surrounding myofibers were positive for Pax‐7, indicating the presence of myogenic satellite cells. Myofibers also responded to GC treatment as determined by GR nuclear translocation.

Conclusion

TA myofibers remained viable in culture for at least 7 days with a predictable response to exogenous stimuli. This technique provides novel investigative opportunities regarding TA structure and function.

Level of Evidence

N/A Laryngoscope, 133:3109–3115, 2023
Reactive‐transport model for the production, transport, and consumption of sulfide in a spent nuclear fuel deep geological repository in crystalline rock
Authors: Hung Chi‐Che , Briggs Scott , Yu Yun‐Chen , Wu Yuan‐Chieh , King Fraser
Published: May 2023

A 1‐D reactive‐transport model has been developed to describe the production and transport of sulfide in a deep geological repository in crystalline rock and the subsequent corrosion of the copper canister. The model accounts for various processes, including: (i) the microbial reduction of sulfate by organotrophic and lithotrophic sulfate‐reducing bacteria, (ii) the supply of sulfate from both the ground water and from the dissolution of gypsum present as an accessory mineral in the bentonite buffer, (iii) diffusive transport of reactants and products, and (iv) sequestration of a fraction of the microbially produced sulfide by precipitation as mackinawite. The results of a base case simulation and of sensitivity analyses indicate that the extent of uniform corrosion is approximately 0.2 mm after 1 million years and that the maximum flux of sulfide to the canister surface is below the threshold for localized corrosion or stress corrosion cracking.
Investigating the effect of bentonite compaction density and environmental conditions on the corrosion of copper materials
Authors: Tully Claire S. , Binns Wilfred J. , Zagidulin Dmitrij , Noël James J.
Published: May 2023

The proposed long‐term management plan for used nuclear fuel is to isolate it within a multiple‐barrier system underground in a deep geological repository (DGR). In the Canadian design, used fuel bundles will be sealed in copper‐coated carbon steel used fuel containers, encased in blocks of bentonite clay, emplaced approximately 500–800 m below ground, and surrounded by a bentonite gapfill material. A laboratory experimental campaign has been undertaken to demonstrate the integrity of the multiple‐barrier system. DGR‐relevant copper materials were embedded in bentonite clay, compacted to various densities, and sealed into a hermetic pressure vessel pressurized with demineralized water. Experiments explored the influence of bentonite compaction in the range of 1100–1600 kg/m3 on copper corrosion over durations of 1–18 months. Postexposure analysis of the copper coupons showed nonhomogeneous corrosion, with corrosion products composed of Cu2O, with some Cu2S. The average corrosion rates decreased as a function of time and increasing bentonite compaction density. In general, we observed that higher bentonite compaction density suppressed the corrosion of embedded copper.
Influence of corrosion fatigue on the fatigue strength of an AlSi10MgMn high‐pressure die‐casting alloy with regard to the surface condition
Authors: Schönowitz Markus , Maier Bernd , Grün Florian , Bauer‐Troßmann Kathrin
Published: May 2023

This study investigates the influence of corrosion fatigue on the fatigue strength of an AlSi10MgMn high‐pressure die‐casting alloy with regard to the surface condition. Two different surface conditions are compared. First, an unmachined surface condition with a rough surface () and second a machined and polished surface condition with a smooth, polished surface () are tested. The specimens are loaded with a cyclic bending moment at a constant stress ratio of R = 0 till failure. A 5 wt% NaCl solution enables the corrosion fatigue tests. Corrosion fatigue leads to a significant reduction of the endurable stresses along the whole load spectrum independent from the surface condition. The applied corrosive solution prevents the formation of a pronounced long‐life fatigue strength limit within the tested load cycle range. Hence, the reduction of the endurable stresses increases with the increasing number of load cycles, reaching approximately 37% at load cycles. No significant influence of the surface condition, independent of the environment (air, 5 wt% NaCl), on the fatigue behaviour is found.
Understanding the Degradation Mechanisms of Conducting Polymer Supercapacitors
Authors: Chang Xueying , Yang Zhiyin , Huang Ailun , Katsuyama Yuto , Lin Cheng‐Wei , El‐Kady Maher F. , Wang Chenxiang , Kaner Richard B.
Published: May 2023

Conducting polymers like polyaniline (PANI) are promising pseudocapacitive electrode materials, yet experience instability in cycling performance. Since polymers often degrade into oligomers, short chain length anilines have been developed to improve the cycling stability of PANI‐based supercapacitors. However, the capacitance degradation mechanisms of aniline oligomer‐based materials have not been systematically investigated and are little understood. Herein, two composite electrodes based on aniline trimers (AT) and carbon nanotubes (CNTs) are studied as model systems and evaluated at both pre‐cycling and post‐cycling states through physicochemical and electrochemical characterizations. The favorable effect of covalent bonding between AT and CNTs is confirmed to enhance cycling stability by preventing the detachment of aniline trimer and preserving the electrode microstructure throughout the charge/discharge cycling process. In addition, higher porosity has a positive effect on electron/ion transfer and the adaptation to volumetric changes, resulting in higher conductivity and extended cycle life. This work provides insights into the mechanism of enhanced cycling stability of aniline oligomers, indicating design features for aniline oligomer electrode materials to improve their electrochemical performance.
A two‐stage genome‐wide association study identified four potential early‐onset nonsmall cell lung cancer risk loci based on 26,652 participants in Chinese population
Authors: Fan Jingyi , Hong Tongtong , Zhao Xiaoyu , Liang Shuang , Zhu Meng , Jiang Yue , Jin Guangfu , Hu Zhibin , Ma Hongxia , Dai Juncheng , Shen Hongbing
Published: May 2023

Early‐onset lung cancer is rare with an increasing incidence rate. Although several genetic variants have been identified for it with candidate gene approaches, no genome‐wide association study (GWAS) has been reported. In this study, a two‐stage strategy was adopted: firstly we performed a GWAS to identify variants associated with early‐onset nonsmall‐cell lung cancer (NSCLC) risk using 2556 cases (age ≤ 50 years) and 13,327 controls by logistic regression model. To further discriminate younger cases from older ones, we took a case–case analysis for the promising variants with above early‐onset cases and 10,769 cases (age > 50 years) by Cox regression model. After combining these results, we identified four early‐onset NSCLC susceptibility loci at 5p15.33 (rs2853677, odds ratio [OR] = 1.48, 95% confidence interval [CI]: 1.36–1.60, Pcase‐control = 3.58 × 10−21; hazard ratio [HR] = 1.10, 95% CI: 1.04–1.16, Pcase–case = 6.77 × 10−4), 5p15.1 (rs2055817, OR = 1.24, 95% CI: 1.15–1.35, Pcase–control = 1.39 × 10−7; HR = 1.08, 95% CI: 1.02–1.14, Pcase–case = 6.90 × 10−3), 6q24.2 (rs9403497, OR = 1.24, 95% CI: 1.15–1.35, Pcase–control = 1.61 × 10−7; HR = 1.11, 95% CI: 1.05–1.17, Pcase–case = 3.60 × 10−4) and 12q14.3 (rs4762093, OR = 1.31, 95% CI: 1.18–1.45, Pcase–control = 1.90 × 10−7; HR = 1.10, 95% CI: 1.03–1.18, Pcase–case = 7.49 × 10−3). Except for 5p15.33, other loci were found to be associated with NSCLC risk for the first time. All of them had stronger effects in younger patients than in older ones. These results provide a promising overview for early‐onset NSCLC genetics.
Homologous recombination repair gene mutations in colorectal cancer favors treatment of immune checkpoint inhibitors
Authors: Lin Yan , Luo Shanshan , Luo Min , Lu Xuerou , Li Qian , Xie Mingzhi , Huang Yu , Liao Xiaoli , Zhang Yumei , Li Yongqiang , Liang Rong
Published: May 2023

Immune checkpoint inhibitor (ICI) therapy is insensitive for Colorectal cancer (CRC) patients with microsatellite stable (MSS). Genomic data of three CRC cohort, n = 35), and the Cancer Genome Atlas (TCGA CRC cohort, n = 377), were analyzed. A cohort treated with ICIs from Memorial Sloan Kettering Cancer Center (MSKCC CRC cohort, n = 110) and two cases from the local hospital were characterized the impact of the HRR mutation on prognosis of CRC. Homologous recombination repair (HRR) gene mutations were more common in CN and HL cohorts (27.85%; 48.57%) than in TCGA CRC cohort (15.92%), especially in the MSS populations, the frequencies of HRR mutation were higher in CN and HL cohort (27.45%, 51.72%) than in TCGA cohort (6.85%). HRR mutations were associated with high tumor mutational burden (TMB‐H). Although HRR mutation uncorrelated with an improved overall survival in the MSKCC CRC cohort (p = 0.97), HRR mutated patients had a significantly improved OS compared to the HRR wildtype population particularly in MSS subgroups (p = 0.0407) under ICI treatment. It probably contributed by a higher neoantigen and increased CD4+ T cell infiltration which found in the TCGA MSS HRR mutated CRC cohort. The similar phenomenon on cases was observed that MSS metastatic CRC patient with HRR mutation seemed more sensitive to ICI after multi‐line chemotherapy in clinical practice than HRR wildtype. This finding suggests the feasibility of HRR mutation as an immunotherapy response predictor in MSS CRC, which highlights a potential therapeutic approach for these patients.
Broadside scanning comb‐line leaky‐wave antenna with gain enhancement and reduced cross‐polarization
Authors: Ahmad Ayaz , Mukherjee Jayanta
Published: May 2023

In this work, a comb‐line leaky‐wave antenna with a pair of wide stubs is proposed with enhanced gain and reduced cross‐polarization. To ensure broadside scanning, three sections of transmission lines are used in the stub with the longitudinal offset. The stubs are placed half‐wavelength apart on both sides of the delay line to achieve high gain and a low‐cross polarization level. The antenna provides 46.8% impedance bandwidth with |S11| below −10 dB. The maximum measured gain and total efficiency are 18.5 dBi and 85%, respectively. The optimized broadside frequency of the leaky‐wave antenna is 10.2 GHz.
Detailed Monte‐Carlo characterization of a Faraday cup for proton therapy
Authors: Ehwald Julian , Togno Michele , Lomax Antony John , Weber Damien Charles , Safai Sairos , Winterhalter Carla
Published: May 2023

Background

Experiments with ultra‐high dose rates in proton therapy are of increasing interest for potential treatment benefits. The Faraday Cup (FC) is an important detector for the dosimetry of such ultra‐high dose rate beams. So far, there is no consensus on the optimal design of a FC, or on the influence of beam properties and magnetic fields on shielding of the FC from secondary charged particles.

Purpose

To perform detailed Monte Carlo simulations of a Faraday cup to identify and quantify all the charge contributions from primary protons and secondary particles that modify the efficiency of the FC response as a function of a magnetic field employed to improve the detector's reading.

Methods

In this paper, a Monte Carlo (MC) approach was used to investigate the Paul Scherrer Institute (PSI) FC and quantify contributions of charged particles to its signal for beam energies of 70, 150, and 228 MeV and magnetic fields between 0 and 25 mT. Finally, we compared our MC simulations to measurements of the response of the PSI FC.

Results

For maximum magnetic fields, the efficiency (signal of the FC normalized to charged delivered by protons) of the PSI FC varied between 99.97% and 100.22% for the lowest and highest beam energy. We have shown that this beam energy‐dependence is mainly caused by contributions of secondary charged particles, which cannot be fully suppressed by the magnetic field. Additionally, it has been demonstrated that these contributions persist, making the FC efficiency beam energy dependent for fields up to 250 mT, posing inevitable limits on the accuracy of FC measurements if not corrected. In particular, we have identified a so far unreported loss of electrons via the outer surfaces of the absorber block and show the energy distributions of secondary electrons ejected from the vacuum window (VW) (up to several hundred keV), together with electrons ejected from the absorber block (up to several MeV). Even though, in general, simulations and measurements were well in agreement, the limitation of the current MC calculations to produce secondary electrons below 990 eV posed a limit in the efficiency simulations in the absence of a magnetic field as compared to the experimental data.

Conclusion

TOPAS‐based MC simulations allowed to identify various and previously unreported contributions to the FC signal, which are likely to be present in other FC designs. Estimating the beam energy dependence of the PSI FC for additional beam energies could allow for the implementation of an energy‐dependent correction factor to the signal. Dose estimates, based on accurate measurements of the number of delivered protons, provided a valid instrument to challenge the dose determined by reference ionization chambers, not only at ultra‐high dose rates but also at conventional dose rates.
Time‐domain scaled boundary perfectly matched layer for elastic wave propagation
Authors: Zhang Guoliang , Zhao Mi , Du Xiuli , Zhang Junqi
Published: May 2023

A novel artificial boundary method called the scaled boundary perfectly matched layer (SBPML) is proposed for the transient analysis of elastic wave propagation in unbounded domains. This method constructs a generalized perfectly matched layer (PML) around the finite interior subdomain based on a coordinate transformation inspired by the scaled boundary finite element method (SBFEM). It can model the infinite exterior subdomains of heterogeneous materials, featuring both parallel and radial straight‐line physical surfaces and interfaces. In addition, generally‐shaped (even nonconvex‐shape) artificial boundaries can be used to provide high flexibility in choosing the geometry of the finite interior subdomain. Two coordinate mapping technologies, namely the modified scaled boundary coordinate transformation from the SBFEM and the complex coordinate stretching from the PML, are successively utilized to construct the proposed method. By introducing the integral of stress as an auxiliary variable, the resulting SBPML subdomain is represented in the time domain using a mixed displacement‐stress unsplit‐field formulation. This has the added benefit of allowing for easy incorporation into standard dynamic finite element methods. The performance of the SBPML is demonstrated through several numerical examples, including P‐SV and SH wave propagation problems occurring in unbounded domains with complex geometries and heterogeneous material properties. The numerical results are evaluated in comparison to both reference solution and existing artificial boundary methods, ultimately demonstrating the flexibility, robustness, accuracy, and stability of the proposed approach.
A mass‐ and energy‐preserving numerical scheme for solving coupled Gross–Pitaevskii equations in high dimensions
Authors: Liu Jianfeng , Tang Qinglin , Wang Tingchun
Published: May 2023

This article is concerned with numerical study of a coupled system of Gross–Pitaevskii equations which describes the spin‐orbit‐coupled Bose–Einstein condensates. Due to the fact that this system possesses the total mass and energy conservation property and often appears in high dimensions, it brings a significant burden in designing and analyzing a suitable numerical scheme for solving the coupled Gross–Pitaevskii equations (CGPEs). In this article, an implicit finite difference scheme is proposed to solve the CGPEs, which is proved to be uniquely solvable, mass‐ and energy‐conservative in the discrete sense. In particular, it is proved in a rigorous way that, without any grid‐ratio restriction, the scheme is stable and convergent at the rate of with time step and mesh size in the maximum norm, while previous works often require certain restriction on the grid ratio and only give the error estimates in the discrete norm or norm which could not imply the maximum error estimate. Numerical results are carried out to underline the error estimate and conservation laws, and investigate several dynamics of the CGPEs.
Combining Transoral Nasopharyngeal Brush and Plasma Epstein‐Barr Virus DNA in Detecting Locally Recurrent Nasopharyngeal Carcinoma
Authors: Lai Ronald , Yeung David Chun Man , Yeung Zenon Wing Chi , Hui Thomas Sin Chun , Lam Wai Kei Jacky , Chan Kwan Chee Allen , Ng Cherrie Wing Kei , To Zion Wing Hei , Cho Ryan Hung Wai , Chan Catherine Po Ling , Lai Calvin Chee Fung , Leung Natalie Moon Wah , Wong Eddy Wai Yeung , Chung Joseph Chun Kit , Tsang Raymond King Yin , Li Kenneth Wing Sum , Chow James Chung Hang , Cheung Ken Ka Man , Chan Jason Y.K.
Published: May 2023

Objective

To evaluate the sensitivities and specificities of Epstein‐Barr virus (EBV) DNA in the detection of locally recurrent or persistent nasopharyngeal carcinoma (NPC) through nasopharyngeal (NP) brush biopsy and plasma, respectively, and whether a combination of both would be superior to the individual tests.

Study Design

A case‐control study was conducted from September 2016 to June 2022.

Setting

A multicentre study at 3 tertiary referral centers in Hong Kong was conducted by the Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong.

Methods

Twenty‐seven patients with biopsy‐confirmed locally recurrent NPC were recruited as study subjects. Magnetic resonance imaging was performed to rule out regional recurrence. The control group consisted of 58 patients with a prior history of NPC who were now disease‐free based on endoscopic and imaging findings. Patients underwent both the transoral NP brush (NP Screen®) and blood for plasma Epstein‐Barr DNA levels.

Results

The sensitivity and specificity of the combined modalities were 84.62% and 85.19%, respectively. The positive predictive value was 73.33% and the negative predictive value was 92.0%.

Conclusion

The combination of NP brush biopsy and plasma EBV DNA is potentially an additional surveillance modality in detecting the local recurrence of NPC. Further study with a larger sample size would be required to validate the cutoff values.
A super‐stretched self‐healing silicone elastomer based on high molecular weight polydimethylsiloxanes through intermolecular quadruple hydrogen bonding
Authors: Lang Yue , Zheng Wei , Wang Wenpin , Li Zhibo
Published: May 2023

Supramolecular silicone elastomer is a promising material for sustainable development. Here, quadruple hydrogen bonded ureidopyrimidinone (UPy) units were grafted onto high molecular weight polydimethylsiloxanes (PDMS), providing a novel supramolecular silicone elastomer. The high molecular weight PDMS precursor was prepared through a cyclic trimeric phosphazene base catalyzed ring‐opening polymerization of Octamethylcyclotetrasiloxane (D4) and tetravinyltetramethylcyclotetrasiloxane (V4) with a well‐controlled vinyl content. Its side chains were modified by hydroxyl groups via a thiol‐ene reaction. Then UPy units were further grafted on the side chain of high molecular weight PDMS by the isocyanate‐hydroxy reaction. The mechanical and self‐healing properties of the elastomer can be controlled by adjusting the molecular weight of PDMS and the amount of UPy units. The obtained PDMS elastomers displayed excellent stretchability (elongation at break of 1513%), good self‐healing efficiency (76% at 60°C for 2 h), and high resilience (elastic recovery of 93% under 300% strain cyclic stretching).
Multiscale deep learning framework captures systemic immune features in lymph nodes predictive of triple negative breast cancer outcome in large‐scale studies
Authors: Verghese Gregory , Li Mengyuan , Liu Fangfang , Lohan Amit , Kurian Nikhil Cherian , Meena Swati , Gazinska Patrycja , Shah Aekta , Oozeer Aasiyah , Chan Terry , Opdam Mark , Linn Sabine , Gillett Cheryl , Alberts Elena , Hardiman Thomas , Jones Samantha , Thavaraj Selvam , Jones J Louise , Salgado Roberto , Pinder Sarah E , Rane Swapnil , Sethi Amit , Grigoriadis Anita
Published: May 2023

The suggestion that the systemic immune response in lymph nodes (LNs) conveys prognostic value for triple‐negative breast cancer (TNBC) patients has not previously been investigated in large cohorts. We used a deep learning (DL) framework to quantify morphological features in haematoxylin and eosin‐stained LNs on digitised whole slide images. From 345 breast cancer patients, 5,228 axillary LNs, cancer‐free and involved, were assessed. Generalisable multiscale DL frameworks were developed to capture and quantify germinal centres (GCs) and sinuses. Cox regression proportional hazard models tested the association between smuLymphNet‐captured GC and sinus quantifications and distant metastasis‐free survival (DMFS). smuLymphNet achieved a Dice coefficient of 0.86 and 0.74 for capturing GCs and sinuses, respectively, and was comparable to an interpathologist Dice coefficient of 0.66 (GC) and 0.60 (sinus). smuLymphNet‐captured sinuses were increased in LNs harbouring GCs (p < 0.001). smuLymphNet‐captured GCs retained clinical relevance in LN‐positive TNBC patients whose cancer‐free LNs had on average ≥2 GCs, had longer DMFS (hazard ratio [HR] = 0.28, p = 0.02) and extended GCs' prognostic value to LN‐negative TNBC patients (HR = 0.14, p = 0.002). Enlarged smuLymphNet‐captured sinuses in involved LNs were associated with superior DMFS in LN‐positive TNBC patients in a cohort from Guy's Hospital (multivariate HR = 0.39, p = 0.039) and with distant recurrence‐free survival in 95 LN‐positive TNBC patients of the Dutch‐N4plus trial (HR = 0.44, p = 0.024). Heuristic scoring of subcapsular sinuses in LNs of LN‐positive Tianjin TNBC patients (n = 85) cross‐validated the association of enlarged sinuses with shorter DMFS (involved LNs: HR = 0.33, p = 0.029 and cancer‐free LNs: HR = 0.21 p = 0.01). Morphological LN features reflective of cancer‐associated responses are robustly quantifiable by smuLymphNet. Our findings further strengthen the value of assessment of LN properties beyond the detection of metastatic deposits for prognostication of TNBC patients. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Quality assessment of traditional Chinese medicine using quality biomarkers: Compound DanShen dripping pills as an example
Authors: Shen Qian , Wu Yu , Li Zhen , Wu Xin , Wang Yu , Chen Yuanxing , Zhuang Pengwei , Guo Hong , Zhang Yanjun
Published: May 2023

Background

The quality control of traditional Chinese medicine (TCM) is one of the main topics in TCM modernisation research. To date, the overwhelming majority of research has focused on chemical ingredients in the quality control of TCM. However, detecting a single or multiple chemical components cannot fully demonstrate the specificity and correlation between quality and efficacy.

Purpose

To solve the problem that the association between quality control and efficacy is lacking.

The present study was designed to establish a methodology for quality control based on quality biomarkers (Q‐biomarkers) and the vasodilatation efficacy of compound DanShen dripping pills (CDDP) as a case.

Methods

Guided by the basic principles of Q‐biomarkers, the compounds in TCM were determined by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry. Predicted targets were screened through network pharmacology. The potential Q‐biomarkers were further screened through proteomics and partial least squares regression analysis. The protein–protein interaction network that combines both predicted targets and potential Q‐biomarkers was constructed to screen Q‐biomarkers.

Results

There were 32 components and 79 predictive targets for CDDP. Proteomic results indicated that the expression of 23 differential proteins changed as pharmacodynamic and componential changes. CPSF6, RILP11, TMEM209, COQ7, VPS18, PPPP1CA, NF2, and ARFRP1 highly correlated with vasodilation. Protein interaction network analysis showed that NF2 and PPPP1CA were closely related to predicted proteins. Thus, NF2 and PPPP1CA could be considered as Q‐biomarkers of CDDP.

Conclusion

Our preliminary study suggested the feasibility of the Q‐biomarkers theory in the quality of TCM. The concept of Q‐biomarkers provided a powerful method to strengthen the link between clinical efficacy and the quality of TCM. In conclusion, a novel, more scientific, and standard quality control method was established in this study.
Non‐invasive prenatal testing (NIPT) in twin pregnancies affected by early single fetal demise: A systematic review of NIPT and vanishing twins
Authors: van Eekhout Jacintha C. A. , Bekker Mireille N. , Bax Caroline J. , Galjaard Robert‐Jan H.
Published: May 2023

The screening performance of non‐invasive prenatal testing (NIPT) in vanishing twin (VT) pregnancies is relatively unknown. To close this knowledge gap, we conducted a systematic review of the available literature. Studies describing the test performance of NIPT for trisomy 21, 18, 13, sex chromosomes and additional findings in pregnancies with a VT were retrieved from a literature search with a publication date until October 4, 2022. The methodological quality of the studies was assessed with the quality assessment tool for diagnostic accuracy studies‐2 (QUADAS‐2). The screen positive rate of the pooled data and the pooled positive predictive value (PPV) were calculated using a random effects model. Seven studies, with cohort sizes ranging from 5 to 767, were included. The screen positive rate of the pooled data for trisomy 21 was 35/1592 (2.2%), with a PPV of 20% (confirmation in 7/35 cases [95% CI 9.8%–36%]). For trisomy 18, the screen positive rate was 13/1592 (0.91%) and the pooled PPV 25% [95% CI 1.3%–90%]. The screen positive rate for trisomy 13 was 7/1592 (0.44%) and confirmed in 0/7 cases (pooled PPV 0% [95% CI 0%–100%]). The screen positive rate for additional findings was 23/767 (2.9%), of which none could be confirmed. No discordant negative results were reported. There is insufficient data to fully evaluate NIPT performance in pregnancies with a VT. However, existing studies suggest that NIPT can successfully detect common autosomal aneuploidies in pregnancies affected by a VT but with a higher false positive rate. Further studies are needed to determine the optimal timing of NIPT in VT pregnancies.
Proton radiation hardness of GaInAsP alloys for space solar cell applications
Authors: Pellegrino C. , Schön J. , Lang R. , Dimroth F. , Zimmermann C. G. , Lackner D.
Published: May 2023

Recent technology development in space mission design has raised a demand for space solar cells with a higher level of radiation tolerance as compared with state‐of‐the‐art, commercially available products. Therefore, new material systems are being investigated. Recently, we highlighted the superior radiation tolerance of GaInAsP solar cells to 1 MeV electron irradiation as compared with standard GaAs solar cells. A high InP fraction within this semiconductor compound was found to foster the regeneration rate of electron‐induced defects when the solar cells were annealed at 60°C under AM0 illumination, which are typical space‐operating conditions. In light of considering this material system in future radiation‐hard designs, the degradation of GaInAsP solar cells subjected to proton irradiation also needs to be investigated. Here, we report on the degradation and regeneration of GaInAsP solar cells lattice‐matched to InP substrates after 1 MeV proton irradiation. A detailed description of the radiation damage is achieved by solar cell numerical modeling combined with deep‐level transient spectroscopy analysis. The irradiation‐induced defects are quantified, and their evolution during annealing is monitored. The results are compared with the degradation data of similar solar cells obtained after 1 MeV electron irradiation. A slower regeneration rate of the proton‐induced defects is found in comparison with the electron‐induced defects. This difference is ultimately attributed to a different topology of the radiation damage caused by proton irradiation.
Hepatocyte nuclear factor 4α multiple isoforms, their functions, and their interactomes
Authors: Herrera‐Pulido Jehison Alirio , Boisvert Francois‐Michel , Boudreau Francois
Published: May 2023

Hepatocyte nuclear factor 4‐alpha (HNF4α) is a master regulator gene belonging to the nuclear receptor superfamily and is involved in regulating a wide range of critical biological processes in different organs. Structurally, the HNF4A locus is organized into two independent promoters and is subjected to alternative splicing to produce twelve distinct isoforms. However, little is known about the biological impact of each isoform and the mechanisms by which they regulate transcription. Proteomic analyses have led to the identification of proteins that interact with specific HNF4α isoforms. The identification and validation of these interactions and their roles in the co‐regulation of targeted gene expression are essential to better understand the role of this transcription factor in different biological processes and pathologies. This review addresses the discoveries of different HNF4α isoforms and the main functions of the P1 and P2 isoform subgroups. It also provides information on the most recent focus areas in research on the nature and function of proteins associated with each of the isoforms in some biological contexts.
Airway clearance after highly effective CFTR modulators: Normalizing life and reducing treatment burden
Authors: Goetz Danielle M. , Frederick Carla K. , Perez Geovanny , Borowitz Drucy
Published: May 2023

Objectives

Airway clearance therapy (ACT) is an important component of therapy for cystic fibrosis (CF) but is associated with significant treatment burden. Highly effective CFTR modulator therapy (HEMT) has improved pulmonary function for many people with CF (pwCF). We sought to understand changes in attitudes and practices about ACT in the post‐HEMT era.

Study Design

Surveys of CF community members and CF care team members.

Methodology

Separate surveys were created for the CF community and CF care providers to evaluate attitudes towards ACT and exercise in the post‐HEMT era. We solicited answers from pwCF via the CF Foundation's Community Voice and from CF care providers via CF Foundation listservs. Surveys were available between July 20 and August 3, 2021.

Results

Surveys were completed by 153 community members (parents of children and pwCF) and 192 CF care providers. Belief that exercise can substitute partially for ACT was endorsed similarly by community members (59%) and providers (68%). After starting HEMT, 36% of parents of children and 51% of adults did fewer ACT treatments including 13% who stopped ACT. Adults reported altering their ACT regimen more than parents of children, though the sample size was limited. Half of providers had changed their ACT recommendations for those on HEMT. Fifty‐three percent of respondents had discussed changing ACT with their care team (36% of parents, 58% of pwCF).

Conclusions

Providers should be aware that ACT management changes may have been undertaken by pwCF who have pulmonary benefits of HEMT. Treatment burden should be considered in co‐management decisions regarding ACT and exercise.
Defect‐Dependent Optoelectronic Properties at a Molecular p‐dopant/Monolayer WS2 Interface
Authors: Ma Jie , Amsalem Patrick , Schultz Thorsten , Xu Xiaomin , Koch Norbert
Published: May 2023

Combining transition metal dichalcogenides (TMDCs) and molecular semiconductors is an attractive route for forming van der Waals heterostructures with optoelectronic properties not found in either component. Herein, the strong p‐type molecular dopant, 1,3,4,5,7,8‐hexafluoro‐tetracyano naphthoquinodimethane (F6TCNNQ), is utilized to form a van der Waals interface with a WS2 monolayer chemical vapor deposition grown on sapphire, which is characterized with angle‐resolved photoelectron and UV‐visible absorption spectroscopy. The interface formed by F6TCNNQ and the as‐grown WS2 monolayer (ML‐WS2) shows no sign of strong interaction or charge transfer. In contrast, defects formed by annealing of ML‐WS2 at 1000 K (d‐ML‐WS2) induce strong n‐type doping of the TMDC. Subsequent F6TCNNQ adsorption on d‐ML‐WS2 is then accompanied by pronounced charge transfer resulting in the formation of interface F6TCNNQ anions and an interface optical transition at 1.5 eV, possibly attributed to an interlayer excitonic state. It is shown in the results that the presence of defects within TMDC monolayers can substantially modify not only the TMDC electronic properties, but also the ground and excited states of their interface with organic molecular dopants. This demonstrates an additional degree of freedom for designing tailored (opto‐)electronic properties based on the combination of TMDCs and molecular semiconductors.