bluuebunny/crossref_metadata_2025 huggingface dataset:
Peptide Amphiphiles as Biodegradable Adjuvants for Efficient Retroviral Gene Delivery
Authors: Kaygisiz Kübra , Rauch‐Wirth Lena , Iscen Aysenur , Hartenfels Jan , Kremer Kurt , Münch Jan , Synatschke Christopher V. , Weil Tanja
Published: November 2023

Retroviral gene delivery is the key technique for in vitro and ex vivo gene therapy. However, inefficient virion‐cell attachment resulting in low gene transduction efficacy remains a major challenge in clinical applications. Adjuvants for ex vivo therapy settings need to increase transduction efficiency while being easily removed or degraded post‐transduction to prevent the risk of venous embolism after infusing the transduced cells back to the bloodstream of patients, yet no such peptide system have been reported thus far. In this study, peptide amphiphiles (PAs) with a hydrophobic fatty acid and a hydrophilic peptide moiety that reveal enhanced viral transduction efficiency are introduced. The PAs form β‐sheet‐rich fibrils that assemble into positively charged aggregates, promoting virus adhesion to the cell membrane. The block‐type amphiphilic sequence arrangement in the PAs ensures efficient cell‐virus interaction and biodegradability. Good biodegradability is observed for fibrils forming small aggregates and it is shown that via molecular dynamics simulations, the fibril‐fibril interactions of PAs are governed by fibril surface hydrophobicity. These findings establish PAs as additives in retroviral gene transfer, rivalling commercially available transduction enhancers in efficiency and degradability with promising translational options in clinical gene therapy applications.
Micro‐Vessels‐Like 3D Scaffolds for Studying the Proton Radiobiology of Glioblastoma‐Endothelial Cells Co‐Culture Models
Authors: Akolawala Qais , Keuning Floor , Rovituso Marta , van Burik Wouter , van der Wal Ernst , Versteeg Henri H. , Rondon Araci M. R. , Accardo Angelo
Published: November 2023

Glioblastoma (GBM) is a devastating cancer of the brain with an extremely poor prognosis. While X‐ray radiotherapy and chemotherapy remain the current standard, proton beam therapy is an appealing alternative as protons can damage cancer cells while sparing the surrounding healthy tissue. However, the effects of protons on in vitro GBM models at the cellular level, especially when co‐cultured with endothelial cells, the building blocks of brain micro‐vessels, are still unexplored. In this work, novel 3D‐engineered scaffolds inspired by the geometry of brain microvasculature are designed, where GBM cells cluster and proliferate. The architectures are fabricated by two‐photon polymerization (2PP), pre‐cultured with endothelial cells (HUVECs), and then cultured with a human GBM cell line (U251). The micro‐vessel structures enable GBM in vivo‐like morphologies, and the results show a higher DNA double‐strand breakage in GBM monoculture samples when compared to the U251/HUVECs co‐culture, with cells in 2D featuring a larger number of DNA damage foci when compared to cells in 3D. The discrepancy in terms of proton radiation response indicates a difference in the radioresistance of the GBM cells mediated by the presence of HUVECs and the possible induction of stemness features that contribute to radioresistance and improved DNA repair.
Grain Engineering of Sb2S3 Thin Films to Enable Efficient Planar Solar Cells with High Open‐Circuit Voltage
Authors: Liu Xinnian , Cai Zhiyuan , Wan Lei , Xiao Peng , Che Bo , Yang Junjie , Niu Haihong , Wang Huan , Zhu Jun , Huang Yi‐Teng , Zhu Huimin , Zelewski Szymon J. , Chen Tao , Hoye Robert L. Z. , Zhou Ru
Published: November 2023

Sb2S3 is a promising environmentally friendly semiconductor for high performance solar cells. But, like many other polycrystalline materials, Sb2S3 is limited by nonradiative recombination and carrier scattering by grain boundaries (GBs). This work shows how the GB density in Sb2S3 films can be significantly reduced from 1068 ± 40 to 327 ± 23 nm µm−2 by incorporating an appropriate amount of Ce3+ into the precursor solution for Sb2S3 deposition. Through extensive characterization of structural, morphological, and optoelectronic properties, complemented with computations, it is revealed that a critical factor is the formation of an ultrathin Ce2S3 layer at the CdS/Sb2S3 interface, which can reduce the interfacial energy and increase the adhesion work between Sb2S3 and the substrate to encourage heterogeneous nucleation of Sb2S3, as well as promote lateral grain growth. Through reductions in nonradiative recombination at GBs and/or the CdS/Sb2S3 heterointerface, as well as improved charge‐carrier transport properties at the heterojunction, this work achieves high performance Sb2S3 solar cells with a power conversion efficiency reaching 7.66%. An impressive open‐circuit voltage (VOC) of 796 mV is achieved, which is the highest reported thus far for Sb2S3 solar cells. This work provides a strategy to simultaneously regulate the nucleation and growth of Sb2S3 absorber films for enhanced device performance.
Metal‐Phenolic Network with Pd Nanoparticle Nodes Synergizes Oxidase‐Like and Photothermal Properties to Eradicate Oral Polymicrobial Biofilm‐Associated Infections
Authors: Chen Lei , Peng Mengna , Li Huaping , Zhou Jianan , He Wei , Hu Rongdang , Ye Fangfu , Li Yuanfeng , Shi Linqi , Liu Yong
Published: November 2023

Designing an effective treatment strategy to combat oral diseases caused by complex polymicrobial biofilms remains a great challenge. Herein, a series of metal‐phenolic network with Pd nanoparticle nodes using polyphenols as stabilizers and reducing agents is constructed. Among them, sulfonated lignin‐Pd (SLS‐Pd) with ultrafine size palladium nanoparticles and broadband near infrared absorption exhibit excellent oxidase‐like activity and stable photothermal effect. In vitro experiments demonstrate that the superoxide radical generated by SLS‐Pd oxidase‐like activity exhibits selective antibacterial effects, while its photothermal effect induced hyperthermia exhibits potent antifungal properties. This difference is further elucidated by RNA‐sequencing analysis and all‐atom simulation. Moreover, the SLS‐Pd‐mediated synergistic antimicrobial system exhibits remarkable efficacy in combating various biofilms and polymicrobial biofilms. By establishing a root canal model and an oropharyngeal candidiasis model, the feasibility of the synergistic antimicrobial system in treating oral biofilm‐related infections is further validated. This system provides a promising therapeutic approach for polymicrobial biofilm‐associated infections in the oral cavity.
Identifying the Quantitative Relationship Between the Molecular Structure and the Horizontal Transition Dipole Orientation of TADF Emitters
Authors: Shi Yiming , Shi Haochen , Zhang Yu , Zang Xiaoyan , Zhao Ziming , Zhao Suling , Qiao Bo , Liang Zhiqin , Xu Zheng , Wang Lijuan , Song Dandan
Published: November 2023

Realizing the horizontal orientation of molecular transition dipole moment (TDM) can greatly improve the out‐coupling efficiency and the resultant external quantum efficiency (EQE) of organic light‐emitting diodes (OLEDs). Herein, key parameters governing the horizontal TDM have been continuously explored. However, quantitatively identifying the key parameters from the molecular structure viewpoint is rather challenging due to the complexity of the influencing parameters. Here, by training the machine learning (ML) models using the experimental results, the quantitative relationship between the molecular structure and the horizontal TDM ratio (ϴ) of thermally activated delayed fluorescent (TADF) emitters in the host‐guest films is identified. The molecular structure is represented by either quantum chemistry‐calculated structural descriptors or topological/physical/chemical molecular descriptors. Key descriptors are ranked and can be used for guiding molecular structure design. Moreover, the accuracy of ML models is double‐verified by comparing the predicted results with experimental ϴ values and the trend of experimental EQE based on a group of materials. Using compressed sensing technology, the low‐dimension material space is also visually constructed based on key descriptors, and the results are consistent with those of the ML models.
Light‐Induced Nanoscale Deformation in Azobenzene Thin Film Triggers Rapid Intracellular Ca2+ Increase via Mechanosensitive Cation Channels
Authors: Peussa Heidi , Fedele Chiara , Tran Huy , Marttinen Mikael , Fadjukov Julia , Mäntylä Elina , Priimägi Arri , Nymark Soile , Ihalainen Teemu O.
Published: November 2023

Epithelial cells are in continuous dynamic biochemical and physical interaction with their extracellular environment. Ultimately, this interplay guides fundamental physiological processes. In these interactions, cells generate fast local and global transients of Ca2+ ions, which act as key intracellular messengers. However, the mechanical triggers initiating these responses have remained unclear. Light‐responsive materials offer intriguing possibilities to dynamically modify the physical niche of the cells. Here, a light‐sensitive azobenzene‐based glassy material that can be micropatterned with visible light to undergo spatiotemporally controlled deformations is used. Real‐time monitoring of consequential rapid intracellular Ca2+ signals reveals that the mechanosensitive cation channel Piezo1 has a major role in generating the Ca2+ transients after nanoscale mechanical deformation of the cell culture substrate. Furthermore, the studies indicate that Piezo1 preferably responds to shear deformation at the cell‐material interphase rather than to absolute topographical change of the substrate. Finally, the experimentally verified computational model suggests that Na+ entering alongside Ca2+ through the mechanosensitive cation channels modulates the duration of Ca2+ transients, influencing differently the directly stimulated cells and their neighbors. This highlights the complexity of mechanical signaling in multicellular systems. These results give mechanistic understanding on how cells respond to rapid nanoscale material dynamics and deformations.
Clinically Translatable Solid‐State Dye for NIR‐II Imaging of Medical Devices
Authors: Li Deling , Shi Hui , Qi Qingrong , Chang Baisong , Jiang Yuanwen , Qian Kun , Guan Xiudong , Kang Peng , Ma Ning , Zhang Yuan , Zhang Zeyu , Shi Xiaojing , Qu Chunrong , Wu Yilei , Chen Weiyu , Chen Hao , Li Baowang , Chen Liangpeng , Li Ziyang , Ma Shunchang , Xu Lingyun , Zhang Yanrong , Tian Jie , Hu Zhenhua , Jia Wang , Cheng Zhen
Published: November 2023

Medical devices are commonly implanted underneath the skin, but how to real‐time noninvasively monitor their migration, integrity, and biodegradation in human body is still a formidable challenge. Here, the study demonstrates that benzyl violet 4B (BV‐4B), a main component in the FDA‐approved surgical suture, is found to produce fluorescence signal in the first near‐infrared window (NIR‐I, 700–900 nm) in polar solutions, whereas BV‐4B self‐assembles into highly crystalline aggregates upon a formation of ultrasmall nanodots and can emit strong fluorescence in the second near‐infrared window (NIR‐II, 1000–1700 nm) with a dramatic bathochromic shift in the absorption spectrum of ≈200 nm. Intriguingly, BV‐4B‐involved suture knots underneath the skin can be facilely monitored during the whole degradation process in vivo, and the rupture of the customized BV‐4B‐coated silicone catheter is noninvasively diagnosed by NIR‐II imaging. Furthermore, BV‐4B suspended in embolization glue achieves hybrid fluorescence‐guided surgery (hybrid FGS) for arteriovenous malformation. As a proof‐of‐concept study, the solid‐state BV‐4B is successfully used for NIR‐II imaging of surgical sutures in operations of patients. Overall, as a clinically translatable solid‐state dye, BV‐4B can be applied for in vivo monitoring the fate of medical devices by NIR‐II imaging.
Hierarchically Porous and Minimally Stacked Graphene Cathodes for High‐Performance Lithium–Oxygen Batteries
Authors: Yu Wei , Shen Zhaohan , Yoshii Takeharu , Iwamura Shinichiroh , Ono Manai , Matsuda Shoichi , Aoki Makoto , Kondo Toshihiro , Mukai Shin R. , Nakanishi Shuji , Nishihara Hirotomo
Published: November 2023

Although lithium–oxygen batteries have attracted attention due to their extremely high energy densities, rational design, and critical evaluation of high‐energy‐density cathode for practical Li–O2 batteries is still urgently needed. Herein, the multiscale, angstrom‐to‐millimeter, precisely controllable synthesis of binder‐free cathodes with minimally stacked graphene free from edge sites is demonstrated. The proposed Li–O2 battery, based on a hierarchically porous cathode with a practical mass loading of >4.0 mg cm−2, simultaneously exhibits an unprecedented specific areal (>30.0 mAh cm−2), mass (>6300 mAh g−1), and volumetric (>480 mAh cm−3) capacities. The battery displays the optimal energy density of 793 Wh kg−1 critically normalized to the total mass of all active materials including electrolytes and even discharge products Li2O2. Comprehensive in situ characterizations demonstrate a unique discharge mechanism in hierarchical pores which contributes to competitive battery performance. Superior rate performance in a current density range of 0.1 to 0.8 mA cm−2 and long‐cycle stability (>260 cycles) at a current density of 0.4 mA cm−2, outperforming state‐of‐the‐art carbon cathodes. This study yields insight into next‐generation carbon cathodes, not only for use in practical Li–O2 batteries, but also in other metal–gas batteries with high energy densities.
Reference evapotranspiration prediction using machine learning models: An empirical study from minimal climate data
Authors: Shaloo  , Kumar Bipin , Bisht Himani , Rajput Jitendra , Mishra Anil Kumar , TM Kiran Kumara , Brahmanand Pothula Srinivasa
Published: November 2023

The scarcity of climatic data is the biggest challenge for developing countries, and the development of models for reference evapotranspiration (ET0) estimation with limited datasets is crucial. Therefore, the current investigation assessed the efficacy of four machine learning (ML) models, namely, linear regression (LR), support vector machine (SVM), random forest (RF), and neural networks (NN), to predict ET0 based on minimal climate data in comparison with the standard FAO‐56 Penman‐Monteith (PM) method. The data on daily climate parameters were collected for the period 2000−2021, including maximum and minimum temperatures (Tmax and Tmin), mean relative humidity (RH), wind speed (WS), and sunshine hours (SSH). The performance of the developed models considering different input combinations was evaluated by using several statistical performance measures. The results showed that the SVM model performed better than the other ML models during training (R2 = 0.985; mean absolute error [MAE] = 0.170 mm/day; mean square error [MSE] = 0.052 mm/day; root mean square error [RMSE] = 0.229 mm/day; mean absolute percentage error [MAPE] = 5.72%) and testing stages (R2 = 0.985; MAE = 0.168 mm/day; MSE = 0.050 mm/day; RMSE = 0.224 mm/day; MAPE = 5.91%) under full dataset scenario. The best performance of the models to estimate was with Tmax, RH, Ws, SSH, and Tmin. The results of the current study are substantial as it offers an approach to estimate ET0 in semi‐arid data‐scarce region.
Rapid Polyolefin Hydrogenolysis by a Single‐Site Organo‐Tantalum Catalyst on a Super‐Acidic Support: Structure and Mechanism
Authors: Lai Qingheng , Mason Alexander H. , Agarwal Amol , Edenfield Wilson C. , Zhang Xinrui , Kobayashi Takeshi , Kratish Yosi , Marks Tobin J.
Published: November 2023

The novel electrophilic organo‐tantalum catalyst AlS/TaNpx (1) (Np=neopentyl) is prepared by chemisorption of the alkylidene Np3Ta=CHtBu onto highly Brønsted acidic sulfated alumina (AlS). The proposed catalyst structure is supported by EXAFS, XANES, ICP, DRIFTS, elemental analysis, and SSNMR measurements and is in good agreement with DFT analysis. Catalyst 1 is highly effective for the hydrogenolysis of diverse linear and branched hydrocarbons, ranging from C2 to polyolefins. To the best of our knowledge, 1 exhibits one of the highest polyolefin hydrogenolysis activities (9,800 (CH2 units) ⋅ mol(Ta)−1 ⋅ h−1 at 200 °C/17 atm H2) reported to date in the peer‐reviewed literature. Unlike the AlS/ZrNp2 analog, the Ta catalyst is more thermally stable and offers multiple potential C−C bond activation pathways. For hydrogenolysis, AlS/TaNpx is effective for a wide variety of pre‐ and post‐consumer polyolefin plastics and is not significantly deactivated by standard polyolefin additives at typical industrial concentrations.
Atomically Dispersed Iron Regulating Electronic Structure of Iron Atom Clusters for Electrocatalytic H2O2 Production and Biomass Upgrading
Authors: Xu Hui , Zhang Shengbo , Zhang Xinyuan , Xu Min , Han Miaomiao , Zheng Li Rong , Zhang Yunxia , Wang Guozhong , Zhang Haimin , Zhao Huijun
Published: November 2023

The integration of highly active single atoms (SAs) and atom clusters (ACs) into an electrocatalyst is critically important for high‐efficiency two‐electron oxygen reduction reaction (2e− ORR) to hydrogen peroxide (H2O2). Here we report a tandem impregnation‐pyrolysis‐etching strategy to fabricate the oxygen‐coordinated Fe SAs and ACs anchored on bacterial cellulose‐derived carbon (BCC) (FeSAs/ACs‐BCC). As the electrocatalyst, FeSAs/ACs‐BCC exhibits superior electrocatalytic activity and selectivity toward 2e− ORR, affording an onset potential of 0.78 V (vs. RHE) and a high H2O2 selectivity of 96.5 % in 0.1 M KOH. In a flow cell reactor, the FeSAs/ACs‐BCC also achieves high‐efficiency H2O2 production with a yield rate of 12.51±0.18 mol gcat−1 h−1 and a faradaic efficiency of 89.4 %±1.3 % at 150 mA cm−2. Additionally, the feasibility of coupling the produced H2O2 and electro‐Fenton process for the valorization of ethylene glycol was explored in detail. The theoretical calculations uncover that the oxygen‐coordinated Fe SAs effectively regulate the electronic structure of Fe ACs which are the 2e− ORR active sites, resulting in the optimal binding strength of *OOH intermediate for high‐efficiency H2O2 production.
Chiral Gold Nanorods with Five‐Fold Rotational Symmetry and Orientation‐Dependent Chiroptical Properties of Their Monomers and Dimers
Authors: Zhang Lingling , Chen Yilin , Zheng Jiapeng , Lewis George R. , Xia Xinyue , Ringe Emilie , Zhang Wei , Wang Jianfang
Published: November 2023

Chiral plasmonic nanoparticles have attracted much attention because of their strong chiroptical responses and broad scientific applications. However, the types of chiral plasmonic nanoparticles have remained limited. Herein we report on a new type of chiral nanoparticle, chiral Au nanorod (NR) with five‐fold rotational symmetry, which is synthesized using chiral molecules. Three different types of Au seeds (Au elongated nanodecahedrons, nanodecahedrons, and nanobipyramids) are used to study the growth behaviors. Different synthesis parameters, including the chiral molecules, surfactant, reductant, seeds, and Au precursor, are systematically varied to optimize the chiroptical responses of the chiral Au NRs. The chiral scattering measurements on the individual chiral Au NRs and their dimers are performed. Intriguingly, the chiroptical signals of the individual chiral Au NRs and their end‐to‐end dimers are similar, while those of the side‐by‐side dimers are largely reduced. Theoretical calculations and numerical simulations reveal that the different chiroptical responses of the chiral NR dimers are originated from the coupling effect between the plasmon resonance modes. Our study enriches chiral plasmonic nanoparticles and provides valuable insight for the design of plasmonic nanostructures with desired chiroptical properties.
Production of Biobased Ethylbenzene by Cascade Biocatalysis with an Engineered Photodecarboxylase
Authors: Qin Zhaoyang , Zhou Yi , Li Zhi , Höhne Matthias , Bornscheuer Uwe T. , Wu Shuke
Published: November 2023

Production of commodity chemicals, such as benzene, toluene, ethylbenzene, and xylenes (BTEX), from renewable resources is key for a sustainable society. Biocatalysis enables one‐pot multistep transformation of bioresources under mild conditions, yet it is often limited to biochemicals. Herein, we developed a non‐natural three‐enzyme cascade for one‐pot conversion of biobased l‐phenylalanine into ethylbenzene. The key rate‐limiting photodecarboxylase was subjected to structure‐guided semirational engineering, and a triple mutant CvFAP(Y466T/P460A/G462I) was obtained with a 6.3‐fold higher productivity. With this improved photodecarboxylase, an optimized two‐cell sequential process was developed to convert l‐phenylalanine into ethylbenzene with 82 % conversion. The cascade reaction was integrated with fermentation to achieve the one‐pot bioproduction of ethylbenzene from biobased glycerol, demonstrating the potential of cascade biocatalysis plus enzyme engineering for the production of biobased commodity chemicals.
Hydrogel‐Based Macroscopic Click Chemistry
Authors: Li Qingyun , Hu Ziqing , Ji Xiaofan
Published: November 2023

The click reaction has found good utility across various fields due to the characteristics of high efficiency, atom economy, simple and mild reaction conditions. Click chemistry is usually utilized for connecting components of microscopic level, while it is still unable for joining macroscopic building blocks. Materials consisting of macroscopic building blocks realize the flexible fabrication of three‐dimensional structures at macroscopic level, exerting significance on parallel manufactures. In this work, we reported macroscopic click chemistry utilizing hydrogel as macroscopic building blocks. Hydrogels G1 and G2 were prepared by incorporating M1 (N,N′‐dimethyl‐1,2‐ethanediamine) and P1 (alkyne functionalized polyethylene glycol) respectively, where polymer chains formed through diffusion‐induced amino‐yne click reaction entangled different hydrogel networks together. Additionally, chain‐like aggregates and complicated 3D structures such as tetrahedron and quadrangular pyramid were constructed based on the adhesion of the hydrogel blocks. The approach enables us to find more possibilities in the delicate designation of 3D aggregations as well as large‐scale manufacturing.
Furan fatty acid amounts and their occurrence in triacylglycerols of white asparagus (Asparagus officinalis) from the German market
Authors: Müller Franziska , Bauer Vanessa , Vetter Walter
Published: November 2023

Vegetables including asparagus contain a wide range of fatty acids, mainly stored in triacylglycerols. One class of interesting minor fatty acids is the family of furan fatty acids (FuFAs) because of their antioxidant properties. Since FuFAs have not been studied previously in asparagus (Asparagus officinalis L.), we developed and applied a simplified method for their analysis in 20 fresh and three preserved samples. Four FuFAs were detected with clear dominance of the dimethyl‐substituted FuFAs (D‐FuFAs) 11D5 and 9D5 as well as small amounts of the monomethyl‐substituted FuFAs (M‐FuFAs) 11M5 and 9M5. The total amounts of FuFAs in fresh white asparagus ranged from 1.4 to 4.6 mg/100 g dry weight (mean 3.0 mg/100 g dry weight). Subsequent LC‐Q‐Orbitrap‐HRMS measurements enabled the detection of 22 different FuFA‐containing TAGs. These were predominantly found together with one or two polyunsaturated fatty acid.
Multi‐interactions driven continuous removal of organic dyes from water by lignocellulosic‐based fibers
Authors: Chen Guangyan , Li Chao , Song Dandan , Zhang Yu , Gan Guangdong , Xie Yi , Hu Zai‐Yin
Published: November 2023

Water polluted by organic dyes is normally present in industrial production, which seriously threatens environmental safety. Research on dye adsorption has recently been related to nanomaterials due to their large specific surface area. However, there are still some problems associated with their preparation, application, and recovery. In this study, we developed the one‐step synthesis of lignocellulosic‐Fe(OH)3 hybrid fibers by in situ growth of Fe(OH)3 nanoparticles on lignocellulosic, which could be used as effective adsorbents for dye removal. The formed Fe(OH)3 nanoparticles were dispersed homogeneously on the surface of lignocellulosic. The as‐prepared hybrid fibers featured a large absorption capacity for methylene blue, up to 150.9 mg/g. In a fixed‐bed column separation process, dye pollutants were successfully removed from the water even at a high speed of 5.0 mL/min, with the separation efficiency higher than 99.99%. Remarkably, 1.0 g of lignocellulosic‐Fe(OH)3 was capable of separating over 1200 mL of dye solution continuously and thoroughly. Notably, the underlying adsorption mechanism analyses suggested that multi‐interactions of hydrogen bonds, π–π interactions, and coordinate bonds contribute to the adsorption ability of lignocellulosic‐Fe(OH)3.
Liquid biopsy detects genomic drivers in NSCLC without EGFR mutations by single‐plex testing: WJOG13620L
Authors: Uemura Takehiro , Kenmotsu Hirotsugu , Hazama Daisuke , Teraoka Shunsuke , Kobe Hiroshi , Azuma Koichi , Yamaguchi Teppei , Masuda Takeshi , Yokoyama Toshihide , Otsubo Kohei , Haratani Koji , Hayakawa Daisuke , Oki Masahide , Takemoto Shinnosuke , Ozaki Tomohiro , Akashi Yusaku , Hata Akito , Hashimoto Hiroya , Yamamoto Nobuyuki , Nakagawa Kazuhiko
Published: November 2023

Background

Actionable tumor genomic alterations, primarily EGFR mutations, occur in nearly 70% of Japanese advanced nonsquamous non‐small cell lung cancer (NSCLC) patients. Standard assessment of tumor tissue includes rapid testing for EGFR mutations, ALK fusions and ROS1 fusions. We conducted a prospective observational study (WJOG13620L) of follow‐on next‐generation sequencing of circulating tumor DNA (ctDNA) in patients without driver alterations after EGFR testing.

Methods

Patients with untreated advanced (Stage IIIB–IV or relapsed) nonsquamous NSCLC without EGFR mutations according to single‐plex testing of tumor tissue, were enrolled into this study. Patients with other known driver mutations or who underwent comprehensive genomic profiling were excluded. Plasma was analyzed by Guardant360, and the primary endpoint was the proportion of patients with pathogenic gene alterations in at least one of nine genes.

Results

Among the 72 patients enrolled, ALK and ROS1 fusions were tested in 86.1% and 65.2%, respectively. Alterations in pre‐defined genes were detected in 21 patients (29.2%; 95% confidence interval: 19.0–41.1, p < 0.001 [one‐sided null hypothesis proportion of 10%]), including RET fusion (n = 1) and mutations in KRAS (n = 11), EGFR (n = 5), ERBB2 (n = 3), and BRAF (n = 1). Median time from sample submission to results was 8 days (range, 5–17 days).

Conclusion

Rapid follow‐on comprehensive testing of ctDNA should be considered prior to first‐line treatment for patients with advanced nonsquamous NSCLC when no alterations are detected after single‐plex tissue testing.
Plasma exchange for treatment of a therapy‐related thrombotic microangiopathy in a patient with advanced hepatocellular carcinoma—A case report
Authors: Stortz Marco , Shmanko Kateryna , Kraus Daniel , Gairing Simon , Boedecker‐Lips Simone , Förster Friederich , Weinmann Arndt , Weinmann‐Menke Julia
Published: November 2023

Key Clinical Message

Thrombotic microangiopathies are a side effect of anti‐VEGF therapies, which are often limited to the kidneys but can also occur systemically and be life‐threatening. Screening for increasing proteinuria is essential.

We present the case of a 65‐year‐old male patient with a multifocal HCC, Barcelona clinic liver cancer (BCLC) classification B at the time of diagnosis. The HCC was treated with nine sessions of transarterial chemoembolization (TACE), and after a progress, the therapy was switched to a combination of atezolizumab and bevacizumab. Five months after therapy change, he presented with an acute kidney injury. The histopathology of the renal biopsy showed findings of a thrombotic microangiopathy (TMA), which we treated with 12 sessions of therapeutic plasma exchange in combination with steroids, resulting in a decreased TMA activity and later in a remission of the TMA. This case suggests the importance of monitoring the kidney function and proteinuria in patients under anti‐vascular endothelial growth factor (VEGF) therapy and shows a rare differential diagnosis for a worsening of kidney function in these patients. Furthermore, it shows that therapeutic plasma exchange might be a valuable therapeutic option for patients with TMA due to anti‐VEGF therapy.
Hemolacria secondary to major depressive disorder and generalized anxiety disorder: A case report
Authors: Razeghian Jahromi Leila , Ghaderian Jahromi Mehdi , Ghavipisheh Mahsa , Ahrari Iman
Published: November 2023

Key Clinical Message

Hemolacria can occur on the basis of a psychiatric disorder without an organic cause. However, this should be a diagnosis of exclusion. Treatment of the underlying psychiatric illness may relieve this condition.

A 24‐year‐old man presented with the chief complaint of bloody tears, which began 4 months earlier after commencing mandatory military service. He had no underlying diseases, and all work‐ups returned normal, though a microscopic examination confirmed red blood cells. He was diagnosed with hemolacria secondary to generalized anxiety disorder and major depressive disorder, responding to propranolol and sertraline. Hemolacria was totally cured after 6 months of treating the underlying psychiatric illness.
Hauser‐Kraus Annulation Initiated Multi‐Cascade Reactions for Facile Access to Functionalized and Fused Oxazepines, Carbazoles and Phenanthridinediones
Authors: Sankara Chenikkayala Siva , Namboothiri Irishi N. N.
Published: November 2023

The Hauser‐Kraus (H−K) annulation of N‐unsubstituted 3‐olefinic oxindoles with 3‐nucleophilic phthalides triggers a cascade of ring expansion and ring contraction reactions through several regioselective steps in one pot. While oxazepines were isolated in the presence of stoichiometric amounts of base at room temperature, carbazoles and phenanthridinediones were the products in the presence of excess base and microwave irradiation. Mechanistic studies guided by stepwise reactions and control experiments revealed that the isolable oxazepine intermediate, formed via ring expansion of the H−K adduct, is the key precursor to carbazole and phenanthridinedione via decarboxylative regioselective cyclizations.
The effect of NaCl and HPAM solution concentration on HPAM gel structure degradation by ultrasonic waves
Authors: Hasiri Mojtaba , Maaref Sepideh , Kantzas Apostolos
Published: November 2023

The present study evaluated the impact of ultrasonic waves on the degradation of partially hydrolyzed polyacrylamide (HPAM) gel structures, focusing on the effects of sonication time, NaCl concentration, and HPAM solution concentration. Results showed that both sonication time and salinity levels play a crucial role in the degradation of HPAM gel, with an increase in sonication time leading to a decrease in the remaining gel and the presence of NaCl in the solution decreasing the residual time required for degradation. The results also revealed that higher levels of salinity expedite the degradation of the gel. In addition, the study discovered that a rise in polymer solution concentration usually results in a reduction in gel degradation. The research suggests there might be an ideal combination of polymer solution and NaCl concentration for achieving the greatest decrease in the degradation rate. For 2‐min sonication, as the salinity of the HPAM solution, with a concentration of up to 5000 ppm, increases, the accumulated energy remains relatively constant. However, when the polymer solution concentration is increased, the accumulated energy becomes more sensitive to changes in salinity. The results of this study provide valuable insight into the interplay between polymer solution concentration, salt concentration, and the energy required for gel degradation, which can be applied in various fields including the oil and gas industry, petroleum processing, and environmental remediation.
An integrated intervention programme for couples facing colorectal cancer: A randomized controlled trial
Authors: Wang Zhiming , Chen Meizhen , Cao Qian , Gong Jiali , Zhao Jie , Lin Chunyan , Luo Huamin , Wu Xinyu , Chen Ying , Li Qiuping
Published: November 2023

Background

Under the guidance of a preliminary Live with Love Conceptual Framework, a Caring for Couples Coping with Colorectal Cancer (4Cs: CRC) programme was designed specifically for colorectal cancer couples. The objectives of this study included examining the efficacy of the programme for couples adapting to colorectal cancer and comparing the effects of different intervention delivery modes (online, face‐to‐face and blended) on couple outcomes.

Methods

A four‐arm randomized controlled trial was conducted among Chinese colorectal cancer couples. Couples were randomly assigned to an online intervention, a face‐to‐face intervention, a blended intervention or a control group. Self‐efficacy, dyadic coping, communication and dyadic outcomes (physical and mental health, negative and positive emotions and marital satisfaction) were evaluated at baseline and 6 weeks later. Analysis of variance (ANOVA) and repeated measures ANOVA were employed to assess between‐group differences and within‐group effects in the four groups, respectively.

Results

A total of 179 couples completed the 6‐week study and post‐study assessments. The intervention showed generally medium‐to‐large effects across multiple measured outcomes, including self‐efficacy, dyadic coping, communication, mental health, negative emotions and positive emotions for both patients and spouse caregivers. Additionally, interventions delivered through different modes produced equally significant effects on couple outcomes.

Conclusions

The integrated intervention programme is effective in improving cancer adaptation in colorectal cancer couples. Long‐term follow‐up and a mix of quantitative and qualitative assessments are crucial for further evaluation of the programme.

Trial registration

Retroactive registration is under review.
Virtual Patient Simulation Using Copula Modeling
Authors: Zwep Laura B. , Guo Tingjie , Nagler Thomas , Knibbe Catherijne A.J. , Meulman Jacqueline J. , van Hasselt J. G. Coen
Published: November 2023

Virtual patient simulation is increasingly performed to support model‐based optimization of clinical trial designs or individualized dosing strategies. Quantitative pharmacological models typically incorporate individual‐level patient characteristics, or covariates, which enable the generation of virtual patient cohorts. The individual‐level patient characteristics, or covariates, used as input for such simulations should accurately reflect the values seen in real patient populations. Current methods often make unrealistic assumptions about the correlation between patient's covariates or require direct access to actual data sets with individual‐level patient data, which may often be limited by data sharing limitations. We propose and evaluate the use of copulas to address current shortcomings in simulation of patient‐associated covariates for virtual patient simulations for model‐based dose and trial optimization in clinical pharmacology. Copulas are multivariate distribution functions that can capture joint distributions, including the correlation, of covariate sets. We compare the performance of copulas to alternative simulation strategies, and we demonstrate their utility in several case studies. Our work demonstrates that copulas can reproduce realistic patient characteristics, both in terms of individual covariates and the dependence structure between different covariates, outperforming alternative methods, in particular when aiming to reproduce high‐dimensional covariate sets. In conclusion, copulas represent a versatile and generalizable approach for virtual patient simulation which preserve relationships between covariates, and offer an open science strategy to facilitate re‐use of patient data sets.
Maize yield and dry milling grain quality trade‐offs in Argentinean flint germplasm
Authors: Abdala Lucas J. , Alvarez Prado Santiago , Donadio Pablo , Borrás Lucas
Published: November 2023

Trade‐offs between yield and grain quality for dry milling are common in maize (Zea mays L.), but the magnitude of these correlations can differ depending on the specific quality trait. We aimed to quantify the relationship between yield and grain traits known to affect dry milling, with a focus on describing the genetic control of the traits that show no negative yield effects. For this, we tested commercial hybrids differing in grain hardness and a recombinant inbred line (RIL) population with their derived hybrids. Commercial hybrids showed that grain hardness (test weight, flotation index, and vitreousness) were all negatively correlated to yield, while screen retention, a key trait for the milling industry, showed no correlation with yield. Also, while all grain quality traits in the RIL and derived hybrid populations showed high heritability (>0.77), results showed that adequate hybrid test weight (>76 kg hL−1) and flotation index (<25%) did not depend on its midparental performance. High hybrid vitreousness was only achieved when both parental inbreds had high vitreousness. Hybrid screen retention was accurately predicted by an environmentally consistent quantitative trait locus and by inbred genetic and phenotypic information (p < 0.001). This suggests a strong genetic control that can be exploited without yield penalties. Our study shows that the trade‐off between yield and grain quality is trait dependent, and highlights that only some traits measured in inbreds can help predict derived hybrid performance for dry milling.
Peroxygenase‐Catalysed Sulfoxidations in Non‐Aqueous Media
Authors: Li Huanhuan , Shen Qianqian , Zhou Xiaoying , Duan Peigao , Hollmann Frank , Huang Yawen , Zhang Wuyuan
Published: November 2023

Chiral sulfoxides are valuable building blocks in asymmetric synthesis. However, the biocatalytic synthesis of chiral sulfoxides is still challenged by low product titres. Herein, we report the use of peroxygenase as a catalyst for asymmetric sulfoxidation under non‐aqueous conditions. Upon covalent immobilisation, the peroxygenase showed stability and activity under neat reaction conditions. A large variety of sulfides was converted into chiral sulfoxides in very high product concentration with moderate to satisfactory optical purity (e. g. 626 mM of (R)‐methyl phenyl sulfoxide in approx. 89 % ee in 48 h). Further polishing of the ee value via cascading methionine reductase A (MsrA) gave>99 % ee of the sulfoxide. The robustness of the enzymes and high product titer is superior to the state‐of‐the‐art methodologies. Gram‐scale synthesis has been demonstrated. Overall, we demonstrated a practical and facile catalytic method to synthesize chiral sulfoxides.
Marginal value analysis reveals shifting importance of migration habitat for waterfowl under a changing climate
Authors: Burner Ryan C. , Golas Benjamin D. , Aagaard Kevin J. , Lonsdorf Eric V. , Thogmartin Wayne E.
Published: November 2023

Migratory waterfowl are an important resource for consumptive and non‐consumptive users alike and provide tremendous economic value in North America. These birds rely on a complex matrix of public and private land for forage and roosting during migration and wintering periods, and substantial conservation effort focuses on increasing the amount and quality of target habitat. Yet, the value of habitat is a function not only of a site's resources but also of its geographic position and weather. To quantify this value, we used a continental‐scale energetics‐based model of daily dabbling duck movement to assess the marginal value of lands across the contiguous United States during the non‐breeding period (September to May). We examined effects of eliminating each habitat node (32 × 32 km) in both a particularly cold and a particularly warm winter, asking which nodes had the largest effect on survival. The marginal value of habitat nodes for migrating dabbling ducks was a function of forage and roosting habitat but, more importantly, of geography (especially latitude and region). Irrespective of weather, nodes in the Southeast, central East Coast, and California made the largest positive contributions to survival. Conversely, nodes in the Midwest, Northeast, Florida, and the Pacific Northwest had consistent negative effects. Effects (positive and negative) of more northerly nodes occurred in late fall or early spring when climate was often severe and was most variable. Importance and effects of many nodes varied considerably between a cold and a warm winter. Much of the Midwest and central Great Plains benefited duck survival in a warm winter, and projected future warming may improve the value of lands in these regions, including many National Wildlife Refuges, for migrating dabbling ducks. Our results highlight the geographic variability in habitat value, as well as shifts that may occur in these values due to climate change.
Belowground competition and niche partitioning between the Babassu palm and Urochloa grass in eastern Amazonian pastures
Authors: de Alencar Pageú André Brenner , de Deus Ribeiro Lima Odenilson , Diniz Daniel Cutrim , da Silva Luciana Sousa , Detert Maria Elisabeth , Gehring Christoph
Published: November 2023

Much of deforested Amazonia is dominated by pastures planted with exotic Urochloa (syn Brachiaria) grass, containing interspersed, ruderal Babassu palm (Attalea speciosa). This two‐species system offers the opportunity to investigate how two very competitive species interact. We investigated three monospecific Urochloa pastures containing dispersed Babassu palm clusters in the eastern periphery of Amazonia. We mapped 0‐ to 50‐cm Babassu and Urochloa root profiles at three distances representing contrasting relative dominance: “within clusters” (0.4–0.6 m from adult palm, Babassu‐dominated), “close” (2.5–4.0 m), and “far” (>8.0–10.0 m, Urochloa‐dominated). Total Babassu root share count was 76.0% within Babassu clusters, as opposed to Urochloa root share count (80.0%) far from clusters, confirming our experimental dominance gradient. Babassu and Urochloa root diameter composition differed strongly, whereas 44.6% of all Babassu roots were mid‐diameter or coarse; 83.0% of all Urochloa roots were fine graminoid. Vertical root profiles likewise differed: Babassu coarse and mid‐diameter roots concentrated within clusters at 20–50 cm depth, well protected against disturbance, though Babassu mid‐diameter roots did extend up to 10 m, indicating active foraging at long distances. By contrast, Urochloa mid‐diameter and coarse roots concentrated in the topsoil (70.4% in top 20 cm). Notably, 45.0% of all Urochloa fine roots but only 29.3% of deeper rooting Babassu concentrated in the top 0–10 cm. Both Urochloa mid‐diameter (R = 0.49) and fine roots (R = 0.40) correlated positively with Urochloa aboveground biomass. Fine‐root fine‐scale variability was high, with high‐density hotspots of both species in the topsoil. Babassu vertical root profiles were unaffected by the degree of interspecific competitive confrontation, whereas Urochloa fine roots were significantly shallower within than outside of Babassu clusters. Though differing Babassu and Urochloa vertical root profiles do support the notion of niche expansion caused by Babassu clusters within the vast Urochloa pastures throughout Amazonia, we also find a strong horizontal and vertical niche overlap with no indication of fine‐scale root segregation, indicating direct competition between both species, possibly in a dynamic state of “mutual invasability.” In practical terms, our findings call for the diversification of Amazonian pastures beyond this two‐species system in order to increase productivity and ecological efficiency.
The competitive exclusion–tolerance rule explains habitat partitioning among co‐occurring species of burying beetles
Authors: Burke Kevin W. , Groulx Adam F. , Martin Paul R.
Published: November 2023

Habitat partitioning among co‐occurring, ecologically similar species is widespread in nature and thought to be an important mechanism for coexistence. The factors that cause habitat partitioning, however, are unknown for most species. We experimentally tested among three alternative hypotheses to explain habitat partitioning among two species of co‐occurring burying beetle (Nicrophorus) that occupy forest (Nicrophorus orbicollis) and wetland (Nicrophorus hebes) habitats. Captive experiments revealed that the larger N. orbicollis (forest) was consistently dominant to N. hebes (wetland) in competitive interactions for carcasses that they require for reproduction. Transplant enclosure experiments in nature revealed that N. hebes had poor reproductive success whenever the dominant N. orbicollis was present. In the absence of N. orbicollis, N. hebes performed as well, or better, in forest versus its typical wetland habitat. In contrast, N. orbicollis performed poorly in wetlands regardless of the presence of N. hebes. These results support the competitive exclusion–tolerance rule where the competitively dominant N. orbicollis excludes the subordinate N. hebes from otherwise suitable or preferable forest habitat, while the subordinate N. hebes is uniquely able to tolerate the challenges of breeding in wetlands. Transplant experiments further showed that carcass burial depth—an important trait thought to enhance the competitive ability of the dominant N. orbicollis—is costly in wetland habitats. In the presence of N. hebes, N. orbicollis buried carcasses deeper; deeper burial is thought to provide a competitive advantage in forests but further compromised the reproductive success of N. orbicollis in wetlands. Overall, results provide evidence that the competitive exclusion–tolerance rule underlies habitat partitioning among ecologically similar species and that the traits important for competitive dominance in relatively benign environments are costly in more challenging environments, consistent with a trade‐off.