bluuebunny/crossref_metadata_2025 huggingface dataset:
Fluorinated or brominated meta‐diamides as the new scaffolds for the treatment of rice bacterial leaf blight
Authors: Guo Shengxin , He Feng , Zhang Wei , Wang Ya , Yu Lijiao , Wu Jian
Published: February 2023

Rice is the main calorie source and stable food for half of the global population worldwide, while the rice bacterial leaf blight has been one of the main challenges to rice yields and quality. Herein, we revealed the novel scaffolds, fluorinated or brominated meta‐diamides (F1–F44), for treating the rice bacterial leaf bright for the first time. The major findings are as follows: (i) based on the different methods, fluorinated meta‐diamides and brominated meta‐diamides were obtained, respectively, and the latter has rarely been reported; (ii) fluorinated meta‐diamide F17 showed a protection activity of 51.3% and a curative activity of 48.7% against the rice bacterial leaf blight caused by the bacteria Xanthomonas oryzae pv. oryzae (Xoo), which were better than those of used bactericides. Scanning electron microscopy suggested that F17 may deform and rupture Xoo; and (iii) the majority of brominated meta‐diamides were more active than corresponding fluorinated meta‐diamides, which revealed the antibacterial activity of brominated meta‐diamides for the first time. The present work is expected to provide new ideas for meta‐diamides for treating rice bacterial leaf blight.
Parallel simulations for fast‐moving landslides: Space‐time mesh adaptation and sharp tracking of the wetting front
Authors: Gatti Federico , Fois Marco , de Falco Carlo , Perotto Simona , Formaggia Luca
Published: February 2023

We propose a highly scalable solver for a two‐dimensional depth‐integrated fluid dynamic model in order to simulate flow‐like landslides, such as debris or mud flows. The governing equations are discretized on quadtree meshes by means of a two‐step second‐order Taylor–Galerkin scheme, enriched by a suitable flux correction in order to avoid spurious oscillations, in particular near discontinuities and close to the wetting‐drying interface. A mesh adaptation procedure based on a gradient‐recovery a posteriori error estimator allows us to efficiently deal with a discretization of the domain customized to the phenomenon under investigation. Moreover, we resort to an adaptive scheme also in time to prevent filtering out the landslide dynamics, and to an interface tracking algorithm to avoid an excessive refinement in noninterfacial regions while preserving details along the wetting‐drying front. Finally, after verifying the performance of the proposed numerical method on idealized settings, we carry out a scalability analysis of the code both on idealized and real scenarios, to check the efficiency of the overall implementation.
A model for transforming egocentric views into goal‐directed behavior
Authors: LaChance Patrick A. , Taube Jeffrey S.
Published: February 2023

Neurons in the rat postrhinal cortex (POR) respond to the egocentric (observer‐centered) bearing and distance of the boundaries, or geometric center, of an enclosed space. Understanding of the precise geometric and sensory properties of the environment that generate these signals is limited. Here we model how this signal may relate to visual perception of motion parallax along environmental boundaries. A behavioral extension of this tuning is the known ‘centering response’, in which animals follow a spatial gradient function based on boundary parallax to guide behavior toward the center of a corridor or enclosure. Adding an allocentric head direction signal to this representation can translate the gradient across two‐dimensional space and provide a new gradient for directing behavior to any location. We propose a model for how this signal may support goal‐directed navigation via projections to the dorsomedial striatum. The result is a straightforward code for navigational variables derived from visual geometric properties of the surrounding environment, which may be used to map space and transform incoming sensory information into an appropriate motor output.
Identification of target proteins for breast cancer genetic risk loci and blood risk biomarkers in a large study by integrating genomic and proteomic data
Authors: Jia Guochong , Yang Yaohua , Ping Jie , Xu Shuai , Liu Lili , Guo Xingyi , Tao Ran , Long Jirong , Zheng Wei
Published: February 2023

Genome‐wide association studies (GWAS) have identified around 200 loci associated with breast cancer risk. However, protein targets for these loci remain largely unknown. Identifying protein targets and biomarkers can improve the understanding of cancer biology and etiology and identify high‐risk individuals for cancer prevention. In this study, we investigated genetically predicted levels of 1142 circulating proteins with breast cancer risk in 133 384 cases and 113 789 controls of European ancestry included in the Breast Cancer Association Consortium (BCAC). We identified 22 blood protein biomarkers associated with the risk of overall breast cancer at a false discovery rate (FDR) <0.05, including nine proteins encoded by genes located at least 500 kb away from previously reported risk variants for breast cancer. Analyses focusing on 124 encoding genes located at GWAS‐identified breast cancer risk loci found 20 proteins associated with overall breast cancer risk and one protein associated with triple‐negative breast cancer risk at FDR <0.05. Adjustment for the GWAS‐identified risk variants significantly attenuated the association for 13 of these proteins, suggesting that these proteins may be the targets of these GWAS‐identified risk loci. The identified proteins are involved in various biological processes, including glutathione conjugation, STAT5 signaling and NF‐κB signaling pathways. Our study identified novel protein targets and risk biomarkers for breast cancer risk.
Diepoxybutane induces the p53‐dependent transactivation of the CCL4 gene that mediates apoptosis in exposed human lymphoblasts
Authors: Ewunkem Akamu J. , Deve Maya , Harrison Scott H. , Muganda Perpetua M.
Published: February 2023

Diepoxybutane (DEB) is the most toxic metabolite of the environmental chemical 1,3‐butadiene. We previously demonstrated the occurrence of DEB‐induced p53‐mediated apoptosis in human lymphoblasts. The p53 protein functions as a master transcriptional regulator in orchestrating the genomic response to a variety of stress signals. Transcriptomic analysis indicated that C‐C chemokine ligand 4 (CCL4) gene expression was elevated in a p53‐dependent manner in DEB‐exposed p53‐proficient TK6 cells, but not in DEB‐exposed p53‐deficient NH32 cells. Thus, the objective of this study was to determine whether the CCL4 gene is a transcriptional target of p53 and deduce its role in DEB‐induced apoptosis in human lymphoblasts. Endogenous and exogenous wild‐type p53 transactivated the activity of the CCL4 promoter in DEB‐exposed lymphoblasts, but mutant p53 activity on this promoter was reduced by ∼80% under the same experimental conditions. Knockdown of the upregulated CCL4 mRNA levels in p53‐proficient TK6 cells inhibited DEB‐induced apoptosis by ∼45%–50%. Collectively, these observations demonstrate for the first time that the CCL4 gene is upregulated by wild‐type p53 at the transcriptional level, and this upregulation mediates apoptosis in DEB‐exposed human lymphoblasts.
Mechanistic insights into the role of vitamin D and computational identification of potential lead compounds for Parkinson's disease
Authors: John Marshal Jayaraj , Kuriakose Beena Briget , Alhazmi Amani Hamed , Muthusamy Karthikeyan
Published: February 2023

Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects dopaminergic neurons in the midbrain. A recent study suggests that Orphan Nuclear Receptor 1 (NURR1) impairment may contribute to PD pathogenesis. Our study found three potent agonists for NURR1 protein based on structural and ligand‐based screening methods. The pharmacophore is comprised of a hydrogen bond donor, a hydrophobic group, and two aromatic rings (DHRR). The Pharmacophore screening method screened 3142 compounds, of which 3 were screened using structure‐based screening. An analysis of the molecules using Molecular Mechanics‐Generalized Born Surface Area (binding free energy) revealed a range of −46.77 to −59.06 Kcal/mol. After that, chemical reactivity was investigated by density functional theory, and molecular dynamics simulation was performed (protein‐ligand stability). Based on the computational studies, Lifechemical_16901310, Maybridge_2815310, and NPACT_392450 are promising agonists with respect to NURR1. To confirm the potency of the identified compounds, further validation and experiments must be conducted.
ADSCs‐exo attenuates hepatic ischemia–reperfusion injury after hepatectomy by inhibiting endoplasmic reticulum stress and inflammation
Authors: Zhang Qianzhen , Piao Chenxi , Xu Jiayuan , Wang Yue , Liu Tao , Ma Haiyang , Wang Hongbin
Published: February 2023

Hepatic ischemia–reperfusion (I/R) injury commonly occurs during liver surgery. Exosomes from adipose‐derived stem cells (ADSCs‐exo) induce a hepatoprotective effect during hepatic I/R injury. This study aimed to investigate the possible mechanism by which ADSCs‐exo attenuates hepatic I/R injury in rats. Rats were randomly divided into four groups: Sham, I30R + PH, ADSCs, and ADSCs‐exo groups. Liver tissues were collected immediately after 24 h of reperfusion for further analyses. The content of inflammatory factors in liver tissue was detected using enzyme‐linked immunosorbent assay. The pathological changes in liver tissue were analyzed using HE staining. Transmission electron microscopy was used to visualize the ultrastructural changes of hepatocytes. Real‐time quantitative polymerase chain reaction (RT‐qPCR) and western blot analysis were used to detect the expression of endoplasmic reticulum stress (ERS)‐related genes and proteins. Liver histomorphology and hepatocyte ultrastructure changes improved after ADSCs‐exo treatment. Moreover, ADSCs‐exo treatment significantly downregulated tumor necrosis factor‐α, interleukin‐1β (IL‐1β), and IL‐6 levels while upregulating IL‐10 levels. Western blot analysis suggested that the protein expressions of GRP78, p‐PERK, p‐eIF2α, p‐IRE1α, XBP1s, ATF‐6, ATF‐4, CHOP, p‐JNK, cleaved‐Caspase‐3, cleaved Caspase‐9, and cleaved Caspase‐12 significantly decreased after ADSCs‐exo treatment. RT‐qPCR results demonstrated that mRNA expression of GRP78, IRE1α, XBP1, ATF‐6, ATF‐4, CHOP, JNK, Caspase‐3, Caspase‐9, and Caspase‐12 markedly reduced after ADSCs‐exo treatment. In conclusion, ADSCs‐exo protects against hepatic I/R injury after hepatectomy by inhibiting ERS and inflammation. Therefore, ADSCs‐exo can be considered as a viable option for the treatment of hepatic I/R injury.
The miR‐181 family: Wide‐ranging pathophysiological effects on cell fate and function
Authors: Bell‐Hensley Austin , Das Samarjit , McAlinden Audrey
Published: February 2023

MicroRNAs (miRNAs) are epigenetic regulators that can target and inhibit translation of multiple mRNAs within a given cell type. As such, a number of different pathways and networks may be modulated as a result. In fact, miRNAs are known to regulate many cellular processes including differentiation, proliferation, inflammation, and metabolism. This review focuses on the miR‐181 family and provides information from the published literature on the role of miR‐181 homologs in regulating a range of activities in different cell types and tissues. Of note, we have not included details on miR‐181 expression and function in the context of cancer since this is a broad topic area requiring independent review. Instead, we have focused on describing the function and mechanism of miR‐181 family members on differentiation toward a number of cell lineages in various non‐neoplastic conditions (e.g., immune/hematopoietic cells, osteoblasts, osteoclasts, chondrocytes, adipocytes). We have also provided information on how modulation of miR‐181 homologs can have positive effects on disease states such as cardiac abnormalities, pulmonary arterial hypertension, thrombosis, osteoarthritis, and vascular inflammation. In this context, we have used some examples of FDA‐approved drugs that modulate miR‐181 expression. We conclude by discussing some common mechanisms by which miR‐181 homologs appear to regulate a number of different cellular processes and how targeting specific miR‐181 family members may lead to attractive therapeutic approaches to treat a number of human disease or repair conditions, including those associated with the aging process.
Implementation and function of interdisciplinary rounds: An observational multisite hospital study from project ACHIEVE
Authors: Vundi Nikita , Clouser Jessica M. , Adu Akosua K. , Li Jing
Published: February 2023

Background

Interdisciplinary rounds (IDR) are increasingly employed by hospitals; however, there is no formal definition, structure, or framework.

Objective

The purpose of this observational study was to document the heterogeneity of IDRs and assess the different characteristics associated with IDR functions.

Designs, Settings, and Participants

Observation of IDR occurred at 27 hospitals that were purposively selected to ensure a mix of the following criteria: geographic region, provider type, for‐profit status, population (e.g., urban, rural), and teaching status. Hospitals identified general medical floors covered by hospitalists for IDR observations.

Intervention

The study team conducted hospital site visits to observe the implementation of IDR. A checklist was developed to record IDR structure and processes, content, and outcomes. Data from two content expert observers were reconciled, and a consensus was attained.

Main Outcome and Measures

The study measures include two IDR functions: topics discussed during IDR (changes in medical treatment, responsibilities and shared understanding of goals and expectations, anticipation of discharge date and needs, anticipating follow‐up care and service needs), and effective communication.

Results

Hospitals varied significantly in IDR implementation. 51.9% included the “core” team (i.e., a physician, nurse, pharmacist, and case manager/social worker), though all included a case manager or social worker. Most (81.5%) occurred before noon. Content chiefly focused on medical care (74.1 to 92.6%) with patient responsibilities and preferences being less frequently discussed (25.9 to 40.7%). Bivariate analyses revealed that afternoon rounds were more likely to include dischargeȐrelated topics, such as patient/caregiver preferences (100% vs. 27.3%, p = .003) and follow‐up needs (100% vs. 36.4%, p = .010).When IDR occurred at bedside, financial resources were more often assessed (100% vs. 34.8%, p = .015) and patient's ability to obtain medication was more often anticipated (75% vs. 21.7%, p = .031).
Application of Multiparameter Quantitative Magnetic Resonance Imaging in the Evaluation of Graves' Ophthalmopathy
Authors: Li Zhangfang , Luo Yaosheng , Feng Xiaoting , Zhang Qing , Zhong Qiang , Weng Chanyan , Chen Zhi , Shen Jie
Published: February 2023

Background

Assessment of the activity of Graves' ophthalmopathy (GO) is difficult. Existing methods need improvement.

Purpose

Investigate the application of multiparametric magnetic resonance imaging (MRI) in GO.

Study Type

Retrospective.

Population

A total of 235 GO patients (age: 38.8 ± 13.4 years; 90 male; 96 active patients).

Field Strength/Sequence

Short‐tau inversion recovery (STIR) fast spin echo, multiecho spin echo T2 mapping and 3D T1‐weighted fast field echo sequences at 3.0 T.

Assessment

Two physicians assessed the mean and maximum signal intensity ratio of extraocular muscles to white matter (SIR), T2 relaxation time (T2RT), extraocular muscle area (EMA), fat fraction (FF), retrobulbar fat volume (RFV), and extraocular muscle volume (EMV). Clinical activity score (CAS) ≧ 3 was in active stage.

Statistical Tests

The optimal cut‐off point of diagnostic efficacy was selected using receiver operating characteristic (ROC) curve analysis and evaluated using area under the curve (AUC), compared using Student's t test, analysis of variance or Kruskal–Wallis H test. The correlation used Pearson correlation analysis. The discriminant equation used a binary logistic regression analysis. P < 0.05 was considered statistically significant.

Results

The SIRmean, SIRmax, T2RTmean, T2RTmax, EMA, and EMV in active GO patients were significantly higher than those in inactive and were positively correlated with CAS (r = 0.276, 0.228, 0.438, 0.388, 0.502, and 0333, respectively). The FFmax of active patients was significantly lower than that of inactive patients and was negatively correlated with CAS (r = −0.44). Logistic regression analysis indicated that T2RTmean was independently associated with GO active periods and had good diagnostic performance (area under ROC curve = 0.736, sensitivity 70.7%, specificity 69.3%). T2RTmean ≧ 74.295 could be a diagnostic cut‐off for judging GO activity (sensitivity 55.3%).

Conclusion

SIR, T2RT, EMV, and FF can quantitatively assess the activity and severity of GO and can potentially provide a basis for clinical judgment and selection of treatment options.

Evidence Level

4.

Technical Efficacy

Stage 2.
Short handling times allow for active prey selection in suspension feeding copepods
Authors: Ryderheim Fredrik , Thygesen Uffe H. , Kiørboe Thomas
Published: February 2023

The time it takes copepods to handle prey can vary depending on the properties of the prey, but it is still largely unknown how handling times may affect copepod feeding efficiency. We compiled data on prey‐handling times derived from video observations in 10 species of calanoid and cyclopoid copepods consuming a large variety of prey. Prey‐handling times vary by five orders of magnitude, and the largest fraction of this variation is explained by relative prey size: larger prey takes longer to handle. When normalized by prey volume (volume of prey handled per unit time), however, larger prey are handled more efficiently than smaller prey. Within this overarching pattern there are distinct differences among species. Thus, large species handle a certain prey size much faster than small species. However, when further normalizing by predator size, the data for all species (except Mesocyclops spp.) collapse on a common relationship. Handling times are generally not limiting maximum consumption rates, and less so for large prey. This allows room for prey selectivity, and indeed copepods are known to be highly selective feeders. Our data predict that copepods can afford to be more selective when feeding on larger than on smaller prey and when consumption is not limited by prey encounter rate, and this is consistent with observations of copepod feeding behavior. We argue that the fast handling times allow copepods to optimize their diet through prey selectivity, and that this is one key to the evolutionary success of pelagic copepods.
Nonlinear Photonic Waveguides: A Versatile Platform for Terahertz Radiation Generation (a Review)
Authors: Carnio Brett N. , Moutanabbir Oussama , Elezzabi Abdulhakem Y.
Published: February 2023

Continued development in the areas of communication, security, medicine, and safety is calling for terahertz‐wave technologies to evolve beyond laboratory research and into the realm of real‐world applications. Due to the compatibility of waveguides with on‐chip fabrication techniques and their ability to realize a small footprint, such structures provide a unique opportunity to achieve terahertz radiation generation in an on‐chip arrangement, ideal for practical applications requiring terahertz electric fields. This review considers waveguiding arrangements that produce terahertz radiation using the nonlinear frequency‐conversion techniques of optical rectification and difference frequency generation. The investigated terahertz radiation waveguiding sources are categorized into three different classes: those that confine and guide both the excitation electric fields and the generated terahertz radiation, those that confine and guide the excitation electric fields but not the generated terahertz radiation, and those that confine and guide the generated terahertz radiation but not the excitation electric fields. Various types of waveguides are surveyed from each category, including dielectric waveguides, metallic waveguides, photonic crystal waveguides, poled waveguides, and multiple waveguides embedded within one another. This review provides a detailed overview of state‐of‐the‐art terahertz radiation waveguide sources, with the intent of aiding in the continuing development of such sources.
High‐Performance Electro‐Optic Modulator on Silicon Nitride Platform with Heterogeneous Integration of Lithium Niobate
Authors: Ruan Ziliang , Chen Kaixuan , Wang Zong , Fan Xuancong , Gan Ranfeng , Qi Lu , Xie Yiwei , Guo Changjian , Yang Zhonghua , Cui Naidi , Liu Liu
Published: February 2023

Silicon nitride (SiN) emerges as an important platform for ultralow loss photonic integrations with complementary metal‐oxide‐semiconductor compatibility. However, active devices, such as modulators, are difficult to realize on pure SiN due to the lack of any electro‐optic (EO) properties of the material. Here, an SiN and lithium niobate (LN) heterogenous integration platform supporting high‐performance EO modulators on SiN waveguide circuits is introduced. An efficient evanescent coupling structure is realized for low‐loss light transitions between the SiN waveguide and the LN ridge waveguide with a measured mode transition loss of only 0.4 dB. Based on this heterogeneous platform, an EO Mach–Zender interference modulator on SiN is built with unprecedented loss, efficiency, and bandwidth performances. A half‐wave voltage of 4.3 V with a modulation bandwidth of 37 GHz and an overall insertion loss of 1 dB is measured for a 7‐mm long device. Data transmission up to 128 Gb s−1 with a bit‐error‐rate of <2.4 × 10‐4 is also demonstrated.
Performance Enhancement of Cadmium‐Free Quantum‐Dot Light‐Emitting Diodes via Cl‐Passivated Zn1−x−ySnxMgyO Nanoparticles as Electron Transport Layers
Authors: Zhao Jinxing , Wang Lijin , Lv Peiwen , Wang Fenghe , Li Xu , Chen Song , Qian Lei , Tang Aiwei
Published: February 2023

Although cadmium (Cd)‐based nanocrystals have enabled high‐performance quantum‐dot light‐emitting diodes (QLEDs), their mass production is likely to be affected by environmental protection policies. Among all the potential Cd‐free candidates, Cu‐In‐Zn‐S (CIZS) nanocrystals (NCs) have attracted particular interests. Still, the performance of the corresponding LED is currently limited by imbalanced charge injection and luminescence quenching, which are both related to the ZnO‐based electron transporting layer (ETL). This work demonstrates that ZnO nanoparticles (NPs) doped with Sn, Mg (Zn1−x−ySnxMgyO), and passivated with Cl are promising to resolve the above issues. All‐solution‐processed QLEDs based on Cd‐free CIZS NCs are fabricated by using Zn0.9Sn0.1O NPs as the ETL, and the peak external quantum efficiency (EQEmax) was nearly twice that of ZnO (EQEmax = 1.74%). The main reason is that the incorporation of Sn can reduce the conductivity of ZnO by an order of magnitude. Combining the advantages of Zn0.9Sn0.1O, Zn0.8Sn0.1Mg0.1O@Cl NPs are designed by the co‐doping of Mg and Cl passivation. The EQEmax and current efficiency based on Zn0.8Sn0.1Mg0.1O and Zn0.8Sn0.1Mg0.1O@Cl as ETLs are further increased to 4.84%, 14.00 cd A−1 and 5.53%, 15.99 cd A−1, respectively. The positive effects of Mg ions can remarkably optimize energy level structure to balance charge injection, while Cl can further passivate defects. The findings offer a new guideline for developing Cd‐free light‐emitting diodes.
Faster Multispectral Imager Based on Thin Liquid Crystal Modulator and 3D Neural Network Lattice
Authors: Pasha Doron , Abuleil Marwan J. , August Isaac Y. , Abdulhalim Ibrahim
Published: February 2023

Computational spectral imaging using reconstruction methods such as compressed sensing and deep learning is becoming popular. Despite the great progress, for multispectral imaging, only few expectations are realized due to various constraints. Here, a new method is proposed for multispectral sensing based on use of the following: (i) dual spectral modules, one defining the working spectral bands while the other as spectral modulator, and (ii) distributed 3D neural network algorithm. The method shows fast and accurate sensing, avoids a complicated calibration process, and can directly access any wavelength at any point. Experimental demonstration is presented using thin liquid crystal cells showing high peak signal‐to‐noise ratio.
Monte Carlo simulation of shielding designs for a cabinet form factor preclinical MV‐energy photon FLASH radiotherapy system
Authors: Rosenstrom Andrew , Santana‐Leitner Mario , Rokni Sayed H. , Shumail Muhammad , Tantawi Sami , Dewji Shaheen , Loo Billy W.
Published: February 2023

Purpose

A preclinical MV‐energy photon FLASH radiotherapy system is being designed at Stanford and SLAC National Accelerator Laboratory. Because of the higher energy and dose rate compared to conventional kV‐energy photon laboratory‐scale irradiators, adequate shielding in a stand‐alone cabinet form factor is more challenging to achieve. We present a Monte Carlo simulation of multilayered shielding for a compact self‐shielding system without the need for a radiation therapy vault.

Methods

A multilayered shielding approach using multiple alternating layers of high‐Z and low‐Z materials is applied to the self‐shielded cabinet to effectively mitigate the secondary radiation produced and to allow the device to be housed in a Controlled Radiation Area outside of a radiation vault. The multilayered shielding approach takes advantage of the properties of high‐Z and low‐Z radiation shielding materials such as density, cross‐section, atomic number of the shielding elements, and products of radiation interactions within each layer. The Monte Carlo radiation transport code, FLUKA, is used to simulate the total effective dose produced by the operation.

Results

The multilayered shielding designs proposed and simulated produced effective dose rates significantly lower than monolayer designs with the same total material thickness at the regulatory boundary; this is accomplished through the manipulation of the locations where secondary radiation is produced and reactions due to material properties such as neutron back reflection in hydrogen. Borated polyethylene at 5 wt% significantly increased the shielding performance as compared to regular polyethylene, with the magnitude of the reduction depending upon the order of the shielding material.

Conclusions

The multilayered shielding provides a path for shielding preclinical FLASH systems that deliver MV‐energy bremsstrahlung photons. This approach promises to be more efficient with respect to the shielding material mass and space claim as compared to shielded vaults typically required for clinical radiation therapy with MV photons.
Radiation hematologic toxicity prediction for locally advanced rectal cancer using dosimetric and radiomics features
Authors: Yue Haizhen , Geng Jianhao , Gong Liqing , Li Yongheng , Windsor Gabrielle , Liu Jiacheng , Pu Yichen , Du Yi , Wang Ruoxi , Wu Hao , Jiao Zhicheng , Bai Harrison , Jing Bin
Published: February 2023

Background

Hematologic toxicity (HT) is a common adverse tissue reaction during radiotherapy for rectal cancer patients, which may lead to various negative effects such as reduced therapeutic effect, prolonged treatment period and increased treatment cost. Therefore, predicting the occurrence of HT before radiotherapy is necessary but still challenging.

Purpose

This study proposes a hybrid machine learning model to predict the symptomatic radiation HT in rectal cancer patients using the combined demographic, clinical, dosimetric, and Radiomics features, and ascertains the most effective regions of interest (ROI) in CT images and predictive feature sets.

Methods

A discovery dataset of 240 rectal cancer patients, including 145 patients with HT symptoms and a validation dataset of 96 patients (63 patients with HT) with different dose prescription were retrospectively enrolled. Eight ROIs were contoured on patient CT images to derive Radiomics features, which were then, respectively, combined with the demographic, clinical, and dosimetric features to classify patients with HT symptoms. Moreover, the survival analysis was performed on risky patients with HT in order to understand the HT progression.

Results

The classification models in ROIs of bone marrow and femoral head exhibited relatively high accuracies (accuracy = 0.765 and 0.725) in the discovery dataset as well as comparable performances in the validation dataset (accuracy = 0.758 and 0.714). When combining the two ROIs together, the model performance was the best in both discovery and validation datasets (accuracy = 0.843 and 0.802). In the survival analysis test, only the bone marrow ROI achieved statistically significant performance in accessing risky HT (C‐index = 0.658, P = 0.03). Most of the discriminative features were Radiomics features, and only gender and the mean dose in Irradvolume was involved in HT.

Conclusion

The results reflect that the Radiomics features of bone marrow are significantly correlated with HT occurrence and progression in rectal cancer. The proposed Radiomics‐based model may help the early detection of radiotherapy induced HT in rectal cancer patients and thus improve the clinical outcome in future.
Efficient optimization of chemical exchange saturation transfer MRI at 7 T using universal pulses and virtual observation points
Authors: Delebarre Thaddée , Gras Vincent , Mauconduit Franck , Vignaud Alexandre , Boulant Nicolas , Ciobanu Luisa
Published: February 2023

Purpose

To optimize the homogeneity of the presaturation module in a Chemical Exchange Saturation Transfer (CEST) acquisition at 7 T using parallel transmission (pTx).

Theory and Methods

An optimized pTx‐CEST presaturation scheme based on precomputed universal pulses was designed. The optimization was performed by minimizing the L2‐norm between the effective and a given target while imposing energy constraints under virtual observation points (VOPs) supervision. The proposed method was evaluated through simulations and experimentally, both in vitro, on a realistic human head phantom, and in vivo, on healthy volunteers. The results were compared with circular polarization (CP) presaturation and other pTx approaches previously proposed. All experiments were conducted on a 7 T MRI scanner using a commercial 8Tx/32Rx head coil.

Results

The simulations show that the proposed pTx strategy boosted with VOPs is superior to the CP mode and existent pTx approaches. While the best results are obtained with subject specific pulses, the gain provided by the use of VOPs renders the universal pulses superior to tailored pulses optimized under vendor provided Specific Absorption Rate (SAR) management. In the phantom, the glucose map was significantly more homogeneous than with CP (root mean square error [RMSE] 17% vs. 30%). The efficiency of the method for in vivo hydroxyl, glutamate and rNOE weighted CEST acquisitions was also demonstrated.

Conclusion

The use of a pTx presaturation scheme based on universal pulses optimized under VOP SAR management is significantly benefiting CEST imaging at high magnetic field.
Combination of passive and active methods towards site characterization of accelerometer stations in Greece
Authors: Papadopoulos George , Fikos Ilias , Garcia‐Jerez Antonio , Theodoulidis Nikos , Vargemezis George
Published: February 2023

The strong correlation between earthquake damage and the local geological conditions in an area has long been established, and site characterization studies are common practice for realistic estimation of seismic hazard and mitigation of the respective seismic risk. Estimation of the time‐averaged S‐waves velocity of the topmost 30 m (VS30) is recognized as a basic proxy for site characterization and has been incorporated in several building codes. In our work, we examine the inversion of single‐station ambient noise horizontal to vertical spectral ratio (HVSR) curves to estimate the local one‐dimensional (1D) VS(Z) structure. The inversion is performed based on the diffuse field assumption, which allows for the inversion of HVSR, including the contributions of both body and surface waves. Although ambient noise data acquisition is immensely cost‐effective, HVSR curve inversion is subject to the solution non‐uniqueness issue, offering ambiguous results. To provide a possible solution for this matter, additional near‐surface geophysical methods such as the multichannel analysis of surface waves and the electrical resistivity tomography (ERT) were applied to derive information on the shallow subsurface structure. The acquired 1D seismic velocity profile was implemented as initial model in the HVSR inversion to constrain the velocities of the upper meters. Additionally, the inferred stratigraphy from the ERT electrical profile was utilized to constrain the thicknesses of the layers. Tests were conducted with and without a priori information from complementary techniques to explore how the HVSR inversion procedure is facilitated. The proposed methodology was applied at the locations of six accelerometers in the city of Thessaloniki, northern Greece, under different geological conditions. The reliability of the inverted VS(Z) models was checked by performing 1D numerical simulations of ambient noise waveforms generated by distributed sources and by direct comparison between synthetic ambient noise HVSR and single‐station earthquake HVSR curves.
Initial development and validation of the School Anxiety Inventory–College Version (SAI‐CV)
Authors: Beckmann Emily A. , Jastrowski Mano Kristen E.
Published: February 2023

To develop the School Anxiety Inventory–College Version (SAI‐CV)—a measure of school anxiety specifically tailored for college students—and provide initial reliability and validity evidence. College undergraduates (N = 1004) from a large Midwestern University. Participants completed the SAI‐CV as well as measures of test anxiety, fear of negative evaluation, and college self‐efficacy. SAI‐CV total and subscale scores indicated excellent internal consistency reliability (Cronbach's α = .94–.97). Confirmatory factor analysis supported a three‐factor model for each domain: school situations (academic failure, social evaluation, peer aggression) and anxiety symptoms (cognitive, behavioral, physiological). The SAI‐CV also exhibited strong evidence of convergent and discriminant validity. Findings support strong initial psychometric evidence of the SAI‐CV. Given that school anxiety is a prevalent and debilitating health concern among college students, future efforts should establish the clinical utility of the SAI‐CV and development of targeted interventions.
Cyclic and linear germylenes as ligands: DFT study
Authors: Rahmati Somayeh , Ayoubi‐Chianeh Mojgan
Published: February 2023

Following our previous surveys on group 14 divalents, we report new series ofN‐heterocyclic germylenes (NHGe) and their analogs that are regarded as cyclic (1C–10C) and linear (1L–10L) forms. Their thermodynamic and structural parameters are compared and contrasted, at the B3LYP/6‐311++G** level of theory. The complexation of these NHGe with Cu metal is investigated. Various analyses such as the atoms in molecules (AIM), natural bond orbital (NBO), non‐covalent interaction (NCI), and ultraviolet‐visible (UV‐Vis) are performed to determine the strength of our germylenes to act as ligands. The results indicate that there are strong interactions between the metal‐ligand bonds with a high contribution of ‐back donation. Every linear germylene demonstrates a higher ability ofσ‐donation andπ‐acceptation. Our scrutinized germylenes turn out as remarkable ligands to the Cu that can be applied in several types of catalysis.
Built environment factors predictive of early rapid lung function decline in cystic fibrosis
Authors: Gecili Emrah , Brokamp Cole , Rasnick Erika , Afonso Pedro M. , Andrinopoulou Eleni‐Rosalina , Dexheimer Judith W. , Clancy John P. , Keogh Ruth H. , Ni Yizhao , Palipana Anushka , Pestian Teresa , Vancil Andrew , Zhou Grace C. , Su Weiji , Siracusa Christopher , Ryan Patrick , Szczesniak Rhonda D.
Published: February 2023

Background

The extent to which environmental exposures and community characteristics of the built environment collectively predict rapid lung function decline, during adolescence and early adulthood in cystic fibrosis (CF), has not been examined.

Objective

To identify built environment characteristics predictive of rapid CF lung function decline.

Methods

We performed a retrospective, single‐center, longitudinal cohort study (n = 173 individuals with CF aged 6–20 years, 2012–2017). We used a stochastic model to predict lung function, measured as forced expiratory volume in 1 s (FEV1) of % predicted. Traditional demographic/clinical characteristics were evaluated as predictors. Built environmental predictors included exposure to elemental carbon attributable to traffic sources (ECAT), neighborhood material deprivation (poverty, education, housing, and healthcare access), greenspace near the home, and residential drivetime to the CF center.

Measurements and Main Results

The final model, which included ECAT, material deprivation index, and greenspace, alongside traditional demographic/clinical predictors, significantly improved fit and prediction, compared with only demographic/clinical predictors (Likelihood Ratio Test statistic: 26.78, p < 0.0001; the difference in Akaike Information Criterion: 15). An increase of 0.1 μg/m3 of ECAT was associated with 0.104% predicted/yr (95% confidence interval: 0.024, 0.183) more rapid decline. Although not statistically significant, material deprivation was similarly associated (0.1‐unit increase corresponded to additional decline of 0.103% predicted/year [−0.113, 0.319]). High‐risk regional areas of rapid decline and age‐related heterogeneity were identified from prediction mapping.

Conclusion

Traffic‐related air pollution exposure is an important predictor of rapid pulmonary decline that, coupled with community‐level material deprivation and routinely collected demographic/clinical characteristics, enhance CF prognostication and enable personalized environmental health interventions.
NKp46‐specific single domain antibodies enable facile engineering of various potent NK cell engager formats
Authors: Lipinski Britta , Arras Paul , Pekar Lukas , Klewinghaus Daniel , Boje Ammelie Svea , Krah Simon , Zimmermann Jasmin , Klausz Katja , Peipp Matthias , Siegmund Vanessa , Evers Andreas , Zielonka Stefan
Published: February 2023

Herein, we describe the generation of potent NK cell engagers (NKCEs) based on single domain antibodies (sdAbs) specific for NKp46 harboring the humanized Fab version of Cetuximab for tumor targeting. After immunization of camelids, a plethora of different VHH domains were retrieved by yeast surface display. Upon reformatting into Fc effector‐silenced NKCEs targeting NKp46 and EGFR in a strictly monovalent fashion, the resulting bispecific antibodies elicited potent NK cell‐mediated killing of EGFR‐overexpressing tumor cells with potencies (EC50killing) in the picomolar range. This was further augmented via co‐engagement of Fcγ receptor IIIa (FcγRIIIa). Importantly, NKp46‐specific sdAbs enabled the construction of various NKCE formats with different geometries and valencies which displayed favorable biophysical and biochemical properties without further optimization. By this means, killing capacities were further improved significantly. Hence, NKp46‐specific sdAbs are versatile building blocks for the construction of different NKCE formats.
Functional, pathogenic, and pharmacological roles of protein folding intermediates
Authors: Biasini Emiliano , Faccioli Pietro
Published: February 2023

Protein expression and function in eukaryotic cells are tightly harmonized processes modulated by the combination of different layers of regulation, including transcription, processing, stability, and translation of messenger RNA, as well as assembly, maturation, sorting, recycling, and degradation of polypeptides. Integrating all these pathways and the protein quality control machinery, deputed to avoid the production and accumulation of aberrantly folded proteins, determines protein homeostasis. Over the last decade, the combined development of accurate time‐resolved experimental techniques and efficient computer simulations has opened the possibility of investigating biological mechanisms at atomic resolution with physics‐based models. A meaningful example is the reconstruction of protein folding pathways at atomic resolution, which has enabled the characterization of the folding kinetics of biologically relevant globular proteins consisting of a few hundred amino acids. Combining these innovative computational technologies with rigorous experimental approaches reveals the existence of non‐native metastable states transiently appearing along the folding process of such proteins. Here, we review the primary evidence indicating that these protein folding intermediates could play roles in disparate biological processes, from the posttranslational regulation of protein expression to disease‐relevant protein misfolding mechanisms. Finally, we discuss how the information encoded into protein folding pathways could be exploited to design an entirely new generation of pharmacological agents capable of promoting the selective degradation of protein targets.
CRISPR/Cas9‐mediated knockout of NlCYP6CS1 gene reveals its role in detoxification of insecticides in Nilaparvata lugens (Hemiptera: Delphacidae)
Authors: Zhang Yan‐Chao , Gao Yang , Ye Wen‐Nan , Peng Yu‐Xuan , Zhu Kun Yan , Gao Cong‐Fen
Published: February 2023

BACKGROUND

The brown planthopper (Nilaparvata lugens) is one of the major rice insect pests in Asia. Recently, high levels of insecticide resistance have been frequently reported and cytochrome P450 monooxygenase (P450)‐mediated metabolic detoxification is a common resistance mechanism in N. lugens. However, there has been no persuasive genetic method to prove the role of P450s in insecticide resistance in N. lugens.

RESULTS

Here, CRISPR/Cas9 system was used to disrupt the P450 gene NlCYP6CS1 to elucidate its role in insecticide resistance in field populations of N. lugens. We successfully constructed a homozygous strain (Nl6CS1‐KO) with a 5‐bp deletion and 1‐bp insertion mutation of NlCYP6CS1. Compared with a background resistant strain (Nl‐R), the susceptibility of knockout strain Nl6CS1‐KO to imidacloprid, nitenpyram, thiamethoxam, dinotefuran, and pymetrozine was increased by 2.3‐, 3.4‐, 7.0‐, 4.2‐ and 3.9‐fold, respectively, but not significantly changed to triflumezopyrim, chlorpyrifos and buprofezin. Life table analysis demonstrated that the Nl6CS1‐KO strain resembled the Nl‐R strain in terms of egg and nymph developmental duration and adult lifespan, but differed from the Nl‐R strain in the survival rate of eggs and nymphs, reproduction, and body weight.

CONCLUSIONS

Our study demonstrates the effect of functional deletion of NlCYP6CS1 on multiple insecticide resistance in N. lugens. For the first time, we applied CRISPR/Cas9 system to reveal the mechanism of insecticide resistance in N. lugens, which may shed light on similar studies in other hemipteran insects. © 2023 Society of Chemical Industry.
Unveiling the Origin of Co3O4Quantum Dots for Photocatalytic Overall Water Splitting
Authors: Guo Xu , Liu Xing , Wang Menglong , Yan Junqing , Chen Yubin , Liu Shengzhong
Published: February 2023

Spinel cobalt oxide displays excellent photocatalytic performance, especially in solar driven water oxidation. However, the process of water reduction to hydrogen is considered as the Achilles’ heel of solar water splitting over Co3O4owing to its low conduction band. Enhancement of the water splitting efficiency using Co3O4requires deeper insights of the carrier dynamics during water splitting process. Herein, the carrier dynamic kinetics of colloidal Co3O4quantum dots‐Pt hetero‐junctions is studied, which mimics the hydrogen reduction process during water splitting. It is showed that the quantum confinement effect induced by the small QD size raised the conduction band edge position of Co3O4QDs, so that the ligand‐to‐metal charge transfer from 2p state of oxygen to 3d state of Co2+occurs, which is necessary for overall water splitting and cannot be achieved in Co3O4bulk crystals. The findings in this work provide insights of the photocatalytic mechanism of Co3O4catalysts and benefit rational design of Co3O4‐based photocatalytic systems.
A Review of Phosphorus Structures as CO2 Reduction Photocatalysts
Authors: Zhai Rui , Zhang Lihui , Gu Mengyue , Zhao Xuewen , Zhang Bo , Cheng Yonghong , Zhang Jinying
Published: February 2023

Effective photocatalytic carbon dioxide (CO2) reduction into high‐value‐added chemicals is promising to mitigate current energy crisis and global warming issues. Finding effective photocatalysts is crucial for photocatalytic CO2 reduction. Currently, metal‐based semiconductors for photocatalytic CO2 reduction have been well reviewed, while review of nonmetal‐based semiconductors is almost limited to carbon nitrides. Phosphorus is a promising nonmetal photocatalysts with various allotropes and tunable band gaps, which has been demonstrated to be promising non‐metallic photocatalysts. However, no systematic review about phosphorus structures for photocatalytic CO2 reduction reactions has been reported. Herein, the progresses of phosphorus structures as photocatalysts for CO2 reduction are reviewed. The fundamentals of photocatalytic CO2 reduction, corresponding properties of phosphorus allotropes, photocatalysts with phosphorus doping or phosphorus‐containing ligands, research progress of phosphorus allotropes as photocatalysts for CO2 reduction have been reviewed in this paper. The future research and perspective of phosphorus structures for photocatalytic CO2 reduction are also presented.
Advanced two‐dimensional materials toward polysulfides regulation of metal–sulfur batteries
Authors: Fan Haining , Luo Wenbin , Dou Shixue , Zheng Zijian
Published: February 2023

Metal–sulfur battery, which provides considerable high energy density at a low cost, is an appealing energy‐storage technology for future long‐range electric vehicles and large‐scale power grids. One major challenge of metal–sulfur batteries is their long‐term cycling stability, which is significantly deteriorated by the generation of various soluble polysulfide intermediates and the shuttling of these intermediates through the separator. Furthermore, the intrinsically sluggish reaction kinetics associated with the poor conductivity of sulfur/sulfides family causes a large polarization in cycle behavior, which further deteriorates the electrode rechargeability. To solve these problems, the research communities have spent a great amount of effort on designing smart cathodes to delicately tailor the physiochemical interaction between the sulfur hosts and polysulfides. Here, we summarize the key progress in the development of two‐dimensional (2D) host materials showing advantageous tunability of their physiochemical properties through coordination control methods such as defect engineering, heteroatom doping, heterostructure, and phase and interface engineering. Accordingly, we discuss the mechanisms of polysulfide anchoring and catalyzing upon specific coordination environment in conjunction with possible structure–property relationships and theoretical analysis. This review will provide prospective fundamental guidance for future sulfur host design and beyond.