bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexible Molecular Electrochromic Devices Run by Low‐Cost Commercial Cells
Authors: Parashar Ranjeev Kumar , Kandpal Suchita , Bandyopadhyay Prasanta , Sadhukhan Mainak , Kumar Rajesh , Mondal Prakash Chandra
Published: April 2023

The present era has seen tremendous demands for low‐cost electrochromic materials for visible‐region multicolor display technology, paper‐based, flexible, and wearable electronic devices, smart windows, and optoelectronic applications. Towards this goal, the authors report large‐scale, high‐yield and robust polyelectrochromic devices fabricated on rigid to flexible ITO substrates comprising novel anthracene containing viologen, (1,1″‐bis(anthracen‐9‐ylmethyl)‐[4,4″‐bipyridine]‐1,1'‐diium bromide, abbreviated as AnV2+), and polythiophene (P3HT). Interestingly, the devices show three states of reversible visible color in response to the applied bias, sub‐second to second switching time (0.7 s/1.6 s), high coloration efficiency (484 cm2/C), and longer cycling stability up to 9,000 s (3,000 switching cycles). Introduction of the anthracene moieties to viologen inhibits the formation of an undesired dimer of cation radicals in response to the applied bias, otherwise the device's color‐switching would be hampered when the bias polarity is reversed. The fabricated electrochromic devices are tested with commercially available low‐cost cells to perform—a unique approach toward practical applications. The computational study facilitates the understanding of experimental results. Alternating current (AC)‐based electrical impedance spectroscopy reveals that P3HT facilitates enhanced charge transfer to AnV2+. This work shows CMOS compatibility and can pave the way for developing cost‐effective flexible and wearable electrochromic devices.
Application of n‐Polysilicon Rear Emitter for High‐Efficiency p‐TOPCon Solar Cells
Authors: Khokhar Muhammad Quddamah , Yousuf Hasnain , Fan Xinyi , Han Seungyong , Kim Youngkuk , Dhungel Suresh Kumar , Yi Junsin
Published: April 2023

This study entails the examination of tunnel oxide passivated contact on p‐type silicon wafers (p‐TOPCon) passivated with n‐polysilicon for a solar cell by using Quokka‐3, a numerical simulation program. The effects of the thickness, bulk lifetime, resistivity, and selectivity of charge carriers due to the polysilicon passivated contact are investigated. Through such n‐polysilicon passivated contact, the back‐emitter solar cells engender higher internal power owing to enhanced surface passivation. This further reduces the shading loss due to front metallization; however, the reduced minority carrier lifetime of the p‐type Czochralski (Cz) wafer restricts the possibilities for high efficiency. Subsequently, the minority charge carrier lifetime of the p‐type wafer conceivably becomes an obstacle to realizing TOPCon solar cells with a high conversion efficiency. This study demonstrates that a configuration suitable for the industrial manufacturing of high‐efficiency solar cells is a crystalline silicon solar cell on a p‐type wafer through a rear‐emitter n‐polysilicon passivated contact. A roadmap toward 24.87% of the p‐TOPCon solar cells through the n‐type polysilicon passivated contact is also devised.
Role of FLCN Phosphorylation in Insulin‐Mediated mTORC1 Activation and Tumorigenesis
Authors: Wang Guoyan , Chen Lei , Lei Xinjian , Qin Senlin , Geng Huijun , Zheng Yining , Xia Chao , Yao Junhu , Meng Tong , Deng Lu
Published: April 2023

The amino acid‐stimulated Rag GTPase pathway is one of the main pathways that regulate mechanistic target of rapamycin complex 1 (mTORC1) activation and function, but little is known about the effects of growth factors on Rag GTPase‐mediated mTORC1 activation. Here, a highly conserved insulin‐responsive phosphorylation site on folliculin (FLCN), Ser62, that is phosphorylates by AKT1 is identified and characterized. mTORC2‐AKT1 is localized on lysosomes, and RagD‐specific recruitment of mTORC2‐AKT1 on lysosomes is identified as an essential step in insulin‐AKT1‐mediated FLCN phosphorylation. Additionally, FLCN phosphorylation inhibits the activity of RagC GTPase and is essential for insulin‐induced mTORC1 activation. Functionally, phosphorylated FLCN promotes cell viability and induces autophagy, and also regulates in vivo tumor growth in an mTORC1‐dependent manner. Its expression is also positively correlated with mTORC1 activity in colon cancer, clear cell renal cell carcinoma, and chordoma. These results indicate that FLCN is an important intermediate for cross‐talk between the amino acid and growth factor pathways. Further, FLCN phosphorylation may be a promising therapeutic target for diseases characterized by mTORC1 dysregulation.
Uncovering Tumor‐Promoting Roles of Activin A in Pancreatic Ductal Adenocarcinoma
Authors: Yu Seok‐Yeong , Luan Yi , Tang Siyuan , Abazarikia Amirhossein , Dong Rosemary , Caffrey Thomas C. , Hollingsworth Michael A. , Oupicky David , Kim So‐Youn
Published: April 2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with high incidence rates of metastasis and cachexia. High circulating activin A, a homodimer of inhibin βA subunits that are encoded by INHBA gene, predicts poor survival among PDAC patients. However, it still raises the question of whether activin A suppression renders favorable PDAC outcomes. Here, the authors demonstrate that activin A is abundantly detected in tumor and stromal cells on PDAC tissue microarray and mouse PDAC sections. In orthotopic male mice, activin A suppression, which is acquired by tumor‐targeted Inhba siRNA using cholesterol‐modified polymeric nanoparticles, retards tumor growth/metastasis and cachexia and improves survival when compared to scramble siRNA‐treated group. Histologically, activin A suppression coincides with decreased expression of proliferation marker Ki67 but increased accumulation of α‐SMAhigh fibroblasts and cytotoxic T cells in the tumors. In vitro data demonstrate that activin A promotes KPC cell proliferation and induces the downregulation of α‐SMA and upregulation of IL‐6 in pancreatic stellate cells (PSC) in the SMAD3‐dependent mechanism. Moreover, conditioned media from activin A‐stimulated PSC promoted KPC cell growth. Collectively, our data provide a mechanistic basis for tumor‐promoting roles of activin A and support therapeutic potentials of tumor activin A suppression for PDAC.
The Combination of R848 with Sorafenib Enhances Antitumor Effects by Reprogramming the Tumor Immune Microenvironment and Facilitating Vascular Normalization in Hepatocellular Carcinoma
Authors: He Yuchao , Zhan Linlin , Shi Jian , Xiao Manyu , Zuo Ran , Wang Chengmeng , Liu Zhiyong , Gong Wenchen , Chen Liwei , Luo Yi , Zhang Shaojun , Wang Youwei , Chen Lu , Guo Hua
Published: April 2023

Novel promising strategies for combination with sorafenib are urgently needed to enhance its clinical benefit and overcome toxicity in hepatocellular carcinoma (HCC). the molecular and immunomodulatory antitumor effects of sorafenib alone and in combination with the new immunotherapeutic agent R848 are presented. Syngeneic HCC mouse model is presented to explore the antitumor effect and safety of three sorafenib doses alone, R848 alone, or their combination in vivo. R848 significantly enhances the sorafenib antitumor activity at a low subclinical dose with no obvious toxic side effects. Furthermore, the combination therapy reprograms the tumor immune microenvironment by increasing antitumor macrophages and neutrophils and preventing immunosuppressive signaling. Combination treatment promotes classical M1 macrophage‐to‐FTH1high M1 macrophage transition. The close interaction between neutrophils/classical M1 macrophages and dendritic cells promotes tumor antigen presentation to T cells, inducing cytotoxic CD8+ T cell‐mediated antitumor immunity. Additionally, low‐dose sorafenib, alone or combined with R848, normalizes the tumor vasculature, generating a positive feedback loop to support the antitumor immune environment. Therefore, the combination therapy reprograms the HCC immune microenvironment and normalizes the vasculature, improving the therapeutic benefit of low‐dose sorafenib and minimizing toxicity, suggesting a promising novel immunotherapy (R848) and targeted therapy (tyrosine kinase inhibitors) combination strategy for HCC treatment.
Singlet Fission‐Based High‐Resolution X‐Ray Imaging Scintillation Screens
Authors: Wang Jian‐Xin , Yin Jun , Gutiérrez‐Arzaluz Luis , Thomas Simil , Shao Wenyi , Alshareef Husam N. , Eddaoudi Mohamed , Bakr Osman M. , Mohammed Omar F.
Published: April 2023

X‐ray imaging technology is critical to numerous different walks of daily life, ranging from medical radiography and security screening all the way to high‐energy physics. Although several organic chromophores are fabricated and tested as X‐ray imaging scintillators, they generally show poor scintillation performance due to their weak X‐ray absorption cross‐section and inefficient exciton utilization efficiency. Here, a singlet fission‐based high‐performance organic X‐ray imaging scintillator with near unity exciton utilization efficiency is presented. Interestingly, it is found that the X‐ray sensitivity and imaging resolution of the singlet fission‐based scintillator are dramatically improved by an efficient energy transfer from a thermally activated delayed fluorescence (TADF) sensitizer, in which both singlet and triplet excitons can be efficiently harnessed. The fabricated singlet fission‐based scintillator exhibits a high X‐ray imaging resolution of 27.5 line pairs per millimeter (lp mm−1), which exceeds that of most commercial scintillators, demonstrating its high potential use in medical radiography and security inspection.
CES1‐Triggered Liver‐Specific Cargo Release of CRISPR/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration
Authors: Zhao Yunfei , Li Yun , Wang Fan , Gan Xuelan , Zheng Tianye , Chen Mengyue , Wei Li , Chen Jun , Yu Chao
Published: April 2023

The broad application of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing tools is hindered by challenges in the efficient delivery of its two components into specific cells and intracytoplasmic release. Herein, a novel copolymer for delivery of Cas9‐mRNA/ single‐guide RNA (Cas9‐mRNA/sgRNA) in vitro and vivo, using carboxylesterase‐responsive cationic triadic copolymeric nanoparticles targeted proprotein convertase subtilisin/kexin type 9 (PCSK9) for hyperlipidemia amelioration is reported. A dimethyl biguanide derivative is designed and synthesized to form cationic block, and copolymerization onto prepolymer with propyl methacrylate, to fabricate a triadic copolymer mPEG‐b‐P(Met/n‐PMA). The copolymer can self‐assemble with Cas9‐mRNA/sgRNA, indicating the excellent potential of nanoparticles to form a delivery carrier. This vehicle can efficiently release RNA in response to the hepatocytes carboxylesterase for genome editing. It was demonstrated that the mPEG‐b‐P(Met/n‐PMA)/Cas9 mRNA/sgRNA nanoparticles effectively accumulated in hepatocytes, lead to the inhibition of PCSK9, and lowered the levels of Low‐density lipoprotein cholesterol and total cholesterol in mouse serum down 20% of nontreatment. Interestingly, the nanoparticles even enable multiple functions in the regulation of blood glucose and weight. This study establishes a novel method to achieve complex CRISPR components stable loading, safe delivery, and fixed‐point release, which expand the application of CRISPR delivery systems.
Engineering Extracellular Vesicles as Delivery Systems in Therapeutic Applications
Authors: Wang Liwei , Wang Di , Ye Zhaoming , Xu Jianbin
Published: April 2023

Extracellular vesicles (EVs) are transport vesicles secreted by living cells and released into the extracellular environment. Recent studies have shown that EVs serve as “messengers” in intercellular and inter‐organismal communication, in both normal and pathological processes. EVs, as natural nanocarriers, can deliver bioactivators in therapy with their endogenous transport properties. This review article describes the engineering EVs of sources, isolation method, cargo loading, boosting approach, and adjustable targeting of EVs. Furthermore, the review summarizes the recent progress made in EV‐based delivery systems applications, including cancer, cardiovascular diseases, liver, kidney, nervous system diseases, and COVID‐19 and emphasizes the obstacles and challenges of EV‐based therapies and possible strategies.
Ultrahigh Energy Storage Density in Superparaelectric‐Like Hf0.2Zr0.8O2Electrostatic Supercapacitors
Authors: Chen Haiyan , Liu Lei , Yan Zhongna , Yuan Xi , Luo Hang , Zhang Dou
Published: April 2023

Electrostatic capacitors attract great interest in energy storage fields due to their advantages of high power‐density, fast charge/discharge speed, and great reliability. Intensive efforts have been placed on the development of high‐energy‐density of capacitors. Herein, a novel supercapacitor with Hf0.2Zr0.8O2/xAl2O3/Hf0.2Zr0.8O2(HAHx) is designed to improve the breakdown strength (Eb) through optimizing Al2O3(AO) film thickness. Low‐temperature annealing is first proposed to enhance the polarization difference (Pm−Pr) due to the formation of dispersed polar nanoregions, which is called “superparaelectric‐like” similar to previous super‐paraelectric behavior of perovskite structures. As results, both largeEbandPm−Prvalues are obtained, leading to an ultrahigh energy storage density of 87.66 J cm−3with a high efficiency of 68.6%, as well as a reliable endurance of 107cycles. This work provides a feasible pathway to improve both the polarization difference and breakdown strength of HfO2‐based films by the combination of insulation insertion layer and low‐temperature annealing. The proposed strategy can contribute to the realization of high‐performance electrostatic supercapacitors with excellent microsystem compatibility.
Autophagy‐Activated Self‐reporting Photosensitizer Promoting Cell Mortality in Cancer Starvation Therapy
Authors: Zhang Ruoyao , Zhang Chen , Chen Chao , Tian Minggang , Chau Joe H. C. , Li Zhao , Yang Yuanzhan , Li Xiaoqiong , Tang Ben Zhong
Published: April 2023

Cancer starvation therapy have received continuous attention as an efficient method to fight against wide‐spectrum cancer. However, during cancer starvation therapy, the protective autophagy promotes cancer cells survival, compromising the therapeutic effect. Herein, a novel strategy by combination of autophagy‐activated fluorescent photosensitizers (PSs) and cancer starvation therapy to realize the controllable and efficient ablation of tumor is conceived. Two dual‐emissive self‐reporting aggregation‐induced emission luminogens (AIEgens), TPAQ and TPAP, with autophagy‐activated reactive oxygen species (ROS) generation are prepared to fight against the protective autophagy in cancer starvation therapy. When protective autophagy occurs, a portion of TPAQ and TPAP will translocate from lipid droplets to acidic lysosomes with significant redshift in fluorescence emission and enhanced ROS generation ability. The accumulation of ROS induced by TPAQ‐H and TPAP‐H causes lysosomal membrane permeabilization (LMP), which further results in cell apoptosis and promotes cell death. In addition, TPAQ and TPAP can enable the real‐time self‐reporting to cell autophagy and cell death process by observing the change of red‐emissive fluorescence signals. Particularly, the efficient ablation of tumor via the combination of cancer starvation therapy and photodynamic therapy (PDT) induced by TPAQ has been successfully confirmed in 3D tumor spheroid chip, suggesting the validation of this strategy.
A United Triboelectrification Mechanism for Contacts between All Types of Materials
Authors: Wang Haobin , Huang Shuyi , Kuang Haoze , Zhang Chi , Liu Yulu , Zhang Kaihang , Cai Xinyu , Wang Xiaozhi , Luo Jikui , Wang Zhong Lin
Published: April 2023

Triboelectrification for contacts between three types of materials—metals, polymers, and semiconductors—are investigated. The results show that triboelectrification is a charge exchange process between the surfaces of two friction materials, and its output is the synergetic effects of the electrostatic induction (ESI) and dynamic junction modulation (DJM). There are four current/voltage peaks in output of triboelectrification: two of them are attributed to the ESI effect and determined by the surface state densities and electron affinity difference of the materials, while the other two are associated with the DJM effect and determined by the charging exchange between the surface states and the depletion region. However, metals and polymers have no‐modulation of depletion region due to their high conductivity and insulating nature, respectively, thus only two peaks induced by the ESI effect are observable no matter what types of metals and polymers are in pair for contacting. Semiconductors have a depletion region, there will be two more output current/voltage peaks induced by the junction modulation when a semiconductor is in contact with any type of materials. The observations reveal a universal triboelectrification mechanism for contacts between materials, and provide an intuitive guidance for the development of high‐performance triboelectric nanogenerators.
The impact of dementia on rehabilitation outcomes following hip fracture
Authors: Loh Yee Leng , Wicks John , Alexander Tara
Published: April 2023

Objective

To compare clinical outcomes between patients for whom their participation in inpatient rehabilitation was and was not impacted by dementia through matching patients reporting dementia (dementia group) with those not reporting dementia (non‐dementia group).

Methods

Prospectively collected data held by the Australasian Rehabilitation Outcome Centre (AROC) were analyzed for patients aged 65 years or older receiving inpatient rehabilitation in public hospitals in Australia following a hip fracture and discharged between July 1, 2014, and June 30, 2019. Patients reported as having dementia impacting their rehabilitation program were matched to patients not reporting dementia based on age, admission motor Functional Independence Measure (FIM) score, and accommodation prior to rehabilitation. The matched cohorts were compared in relation to clinical outcomes (motor and cognitive FIM improvement, FIM efficiency, length of stay, and discharge destination) following participation in hospital‐based rehabilitation using univariate analysis.

Results

Patients with dementia had significantly lower cognitive FIM scores on commencing rehabilitation (17.6 and 26.9, respectively, P < 0.001) and their median length of stay was 2 days shorter than those without dementia (21 and 23 days, respectively, P < 0.001). Relative change in FIM score and FIM efficiency (per week) were lower in the dementia group [relative FIM score change of dementia vs non‐dementia, respectively, 26.2% vs. 44.0% (P < 0.001) and FIM efficiency, 6.5 vs. 8.9 (P < 0.001)]. Discharge destination between the two groups was statistically different, with 35.7% of patients with dementia being discharged to residential aged care facilities (RACFs) compared to 21.7% of those without dementia (P < 0.001). More patients with dementia had carers in their private residence in the post‐rehabilitation phase, 82.2% vs. 57.6% (P < 0.001).

Conclusion

Patients with dementia who sustain a fractured hip benefit from inpatient rehabilitation, although their clinical outcomes are not as good as those without dementia. FIM change and FIM efficiency were lower in the dementia group. Length of stay in the hospital for patients with dementia was shorter due to earlier recognition for the need for placement in either an RACF or at home with carer support. The need for placement in an RACF or carer support in a private residence was significantly greater in the dementia group.
Performance and analysis of key factors on the design of melt crystallization‐based separation process
Authors: Jia Shengzhe , Yu Liuyang , Gao Zhenguo , Wu Songgu , Tang Weiwei , Wang Jingkang , Gong Junbo
Published: April 2023

This study combines theoretical models with experiments to analyze the impurity migration mechanism and obtain the key factors of separation optimization for the design of layer melt crystallization. The fractal slice model was used to explore pore structure formation and calculate the heat properties of the crystal layer. It was found that the fractal characteristics approached the features of Euclidean geometry with increasing porosity, and the thermal conductivity showed a linear decrease with the porosity. Three kinetic models were established based on the temperature difference to reveal quantitative correlations with the degree of supercooling (or superheating). The effects of the pore structure, kinetic behavior, and sweating intensity on the separation process are highlighted. Finally, this work analyzed the important roles of kinetic factors and impurity migration distribution, where a qualitative analysis revealed that the kinetic effect was important in impurity migration in the sweating process.
Pd nanoparticles supported on magnetic CoTiMgLDH with enhanced catalytic activity in Suzuki cross‐coupling and reductive degradation of dyes
Authors: Choudhary Anu , Sharma Vrinda , Sharma Surbhi , Sharma Nitika , Paul Satya
Published: April 2023

With an aim to combine the catalytic properties of Pd nanoparticles (NPs) with the excellent characteristics of porous layered double hydroxides (LDH), in the present study, four different catalysts (Pd/Fe3O4‐CoTiMgAlLDH, Pd/Fe3O4‐CoTiMgLDH, Pd/Fe3O4‐CoTiAlLDH and Pd/Fe3O4‐CoTiLDH) were synthesized by supporting Pd NPs onto four different Fe3O4‐LDH supports, which were synthesized by varying the metals in LDH. The catalytic activity of these catalysts was studied for Suzuki coupling and reductive degradation of dyes. Pd/Fe3O4‐CoTiMgLDH outperformed the other catalysts in both reactions. The synthesized catalysts were examined via different characterization techniques like X‐ray diffraction (XRD), Brunauer–Emmett–Teller analysis (BET), X‐ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), high resolution transmission electron microscopy (HR‐TEM), field emission scanning electron microscopy (FE‐SEM), energy dispersive X‐ray (EDX), energy dispersive X‐ray mapping (SEM–EDX mapping), inductively coupled plasma atomic emission spectroscopy (ICP‐AES) and vibrating sample magnetometry (VSM). On the basis of results obtained from XPS and the experimental data, Fe3O4‐CoTiMgLDH was found to be the support of choice as it not only stabilized the Pd0 NPs but also increased the electron density on the anchored Pd0 species, which enhanced the catalytic activity of Pd/Fe3O4‐CoTiMgLDH for studied organic transformations.
Thermal oxidation of model molecules to reveal vegetable oil polymerization studied by NMR spectroscopy and self‐diffusion
Authors: Barani Mara , Bonetti Rino , Parker Wallace O.
Published: April 2023

Oxidative polymerization of plant oils and lipids is poorly understood yet widely encountered. Oils and fats are renewable resources providing biofuels and polymers. Oil oxidation is accelerated at high temperatures, typically above 110°C, where triacylglycerides are converted into toxic compounds and viscous deleterious polymers. Polymerization of mono‐unsaturated oil (210°C, 3 h, open to air) was investigated by comparing four similar sized molecules with different functional groups: oleic acid, methyl oleate, trans‐7‐tetradecene, and stearic acid. Non‐volatile products identified by NMR spectroscopy are minor ketones for saturated fatty acid (stearic acid), epoxides for acyl chains without acid groups (methyl oleate, tetradecane) and copious oligomerization, through ester cross‐links, for acyl chains with acid, and olefinic groups (oleic acid). Long range CH coupling clearly shows ester (not ether) cross‐links, contradicting long‐held beliefs. Chain fragmentation also occurs for heated oleic acid as revealed by formation of a species with a methylene group bonded to oxygen of an ester, CH2OC(O). Large size (slow diffusion) of the first oligomer (trimer) formed from oleic acid, used to represent hydrolyzed vegetable oil, was evidenced by DOSY (diffusion‐ordered spectroscopy). Combined NMR results show oligomers found in heated oleic acid are fatty acid estolides. Model oil reactions demonstrate why olefin and carboxylic acid groups are required for polymerization.
Anatomy and computed tomography of the nasal cavity, nasal conchae, and paranasal sinuses of the endangered Patagonian huemul deer (Hippocamelus bisulcus)
Authors: Núñez‐Cook Samuel , Vidal‐Mugica Fernando , Salinas Paulo
Published: April 2023

This study explores for the first time the shape, volume, and configuration of nasal cavity structures of the endangered Patagonian huemul deer via computed tomography (CT). Three‐dimensional (3D) reconstructions derived from data sets obtained from five Patagonian huemul deer skulls were analyzed. Using semiautomatic segmentation, 3D models were created of all the sinus compartments and nasal conchae. Volumetric measurements were taken of seven sinus compartments. The Patagonian huemul deer has a wide, large nasal cavity, with an osseous nasal aperture typical of cervids and a choana with characteristics that differentiate it from the pudu and roe deer. It also has six nasal meatuses and three nasal conchae, with the ventral nasal concha having the greatest volume and surface, which given its extension ensures a greater ability to humidify and heat the air. Further analysis showed the complex system of paranasal sinuses to be characterized by a rostroventral and interconnected group, where communication with the nasal cavity is common through the nasomaxillary opening, and a caudodorsal group that communicates with the nasal cavity through openings in the nasal meatuses. Our study of the endangered Patagonian huemul deer documents an intricate, and in some nasal cavity structures, unique morphological construction which may predispose it to higher rates of sinonasal afflictions due largely to its nasal complex anatomy, thus affecting its high cultural value.
Transparent Superhydrophobic Coatings of Silica Nanoparticles Using Functionalized Polyurethanes
Authors: Sheyara R. T. Birla , Ramar Periyamuthu , Satheeshkumar Muthu , Kumar B. V. N. Phani , Samanta Debasis
Published: April 2023

Superhydrophobic coatings are essential to prepare water‐repellent surfaces, self‐cleaning materials, etc. Silica nano‐materials are often immobilized to different surfaces for imparting super‐hydrophobicity. Direct coating of silica‐nanoparticles is often challenging since it can easily be peeled off under different environments. Herein, we reported the use of properly functionalized polyurethanes to facilitate the strong binding of silica‐nanoparticles to surfaces. The alkyne terminal polyurethane was synthesized by step‐growth polymerization while click‐reactions facilitated to post‐functionalization using phenyl moiety and were characterized by 1H, 13C nuclear magnetic resonance (NMR) spectroscopies, and 1H spin‐lattice relaxation times (T1s). Upon functionalization, the glass transition temperature (Tg) increased due to enhanced interchain interactions. Moreover, additives like di(propyleneglycol)dibenzoate showed a substantial plasticizing effect to compensate for the increase in Tg, an important parameter for low‐temperature applications. NMR signatures the spatial interactions between various protons of grafted silica‐nanoparticles and phenyl triazole functionalized polyurethanes, thus indicating the usefulness of polyurethanes to bind silica‐nanoparticles. After coating functionalized silica‐nanoparticles to leather using functionalized polyurethanes, a contact angle value of more than 157° was observed with retention of grain patterns of leather due to transparency. We anticipate the results to help design varieties of materials with superhydrophobicity where the structural integrity of the surfaces is retained.
Infrared detectors for first generation extremely large telescope instruments and their characterization program
Authors: Bezawada Naidu , George Elizabeth , Ives Derek , Alvarez Domingo , Serra Benoit , Mehrgan Leander , Müller Eric , Haug Marcus , Leveratto Serban , Pfuhl Oliver , Guzman Ronald , Guidolin Ivan , Jost Andreas , Popovic Dan , Moins Christophe , Klein Barbara , Conzelmann Ralf , Accardo Matteo , Brinkmann Martin
Published: April 2023

The detectors for the three first generation extremely large telescope (ELT) instruments MICADO (Multi‐AO Imaging Camera for Deep Observations), HARMONI (A High Angular Resolution Monolithic Optical and Near‐infrared Integral Field Spectrograph), and METIS (A Mid‐infrared ELT Imager and Spectrograph) cover from the optical to longwave infrared wavelengths. MICADO and HARMONI detector focal planes require 17  H4RG (Hawaii‐4RG) near‐infrared whilst the METIS focal planes consist of 5  SWIR (shortwave infrared) detectors and one longwave infrared detector. Procurement of the optical and SWIR detectors has been completed, whilst the H4RGs and long wavelength detectors are still in progress. A custom cryogenic facility for infrared array testing (FIAT) has been designed and developed at European Southern Observatory (ESO) over the last few years in order to characterize the infrared detectors for ELT and future Very Large Telescope instruments. FIAT is currently being commissioned in our labs with an H4RG engineering detector. FIAT will be used to characterize the science H4RG‐15 detectors for MICADO and HARMONI, the two first‐light instruments of the ELT while the existing Mosaic Test Facility (MTF) will be used for characterizing the SWIR detectors for METIS. This paper presents an overview of the detector systems for the three instruments, their engineering challenges, and the requirements for the detectors' performance and their characterization program. The paper will also describe a test setup for H4RG detectors including a new preamplifier design with options to operate the detector in different modes and it will also report on the test results from the engineering H4RG detector, as part of the commissioning of FIAT and discuss detector performance and related detector issues.
Develop adult extrapolation to pediatrics and pediatric dose optimization based on the physiological pharmacokinetic model of azithromycin
Authors: Liang Luhua , Li Wentao , Zhang Zhihao , Li Dingyuan , Pu Sijing , Xiang Rongwu , Zhai Fei
Published: April 2023

Physiologically‐based pharmacokinetic (PBPK) models are more frequently used for supporting pediatric dose selection in small‐molecule drugs. Through literature research, drug parameters of azithromycin and clinical data from different studies were obtained. Through parameter optimization of the absorption and dissolution process, the adult intravenous model was extended to the adult oral model. The adult intravenous and oral PBPK models are precise to meet the AAFE<2 standard, and the pharmacokinetic parameters of the predicted values of the model are all within the mean standard deviation of the clinical observations. The values of plasma protein unbound fraction, renal clearance, and gastric juice pH between adults and pediatrics were changed by using the age‐dependent pediatric organ maturity formula, and the adult model was extrapolated to the pediatric model. The final developed pediatric PBPK model was used to evaluate optimal dosing for children of different developmental ages. The relationship between the frist dose and age was as follows: 8.8 mg/kg/day from 0.5 to 2 years old, 9.2 mg/kg/day from 3 to 6 years old, 9.4 mg/kg/day from 7 to 12 years old, and 8.2 mg/kg/day from 13 to 18 years old, taken in half for 2–5 days. Simultaneously, the simulated exposures achieved with the dosing regimen proposed were comparable to adult plasma exposures for treatment of community‐acquired pneumonia. A reasonable azithromycin pharmacokinetic–pharmacodynamic model for adults and pediatrics has been established, which can be demonstrated by the use of literature pediatric data to develop pediatric PBPK models, expanding the scope of this powerful modeling tool.
In‐depth analysis of patterns in selection of different physiologically based pharmacokinetic modeling tools: Part I – Applications and rationale behind the use of open source‐code software
Authors: Rajput Arham Jamaal , Aldibani Hamza Khaled Abdelmajed , Rostami‐Hodjegan Amin
Published: April 2023

PBPK applications published in the literature support a greater adoption of non‐open source‐code (NOSC) software as opposed to open source‐code (OSC) alternatives. However, a significant number of PBPK modelers are still using OSC software, understanding the rationale for the use of this modality is important and may help those embarking on PBPK modeling. No previous analysis of PBPK modeling trends has included the rationale of the modeler. An in‐depth analysis of PBPK applications of OSC software is warranted to determine the true impact of OSC software on the rise of PBPK. Publications focusing on PBPK modeling applications, which used OSC software, were identified by systematically searching the scientific literature for original articles. A total of 171 articles were extracted from the narrowed subset. The rise in the use of OSC software for PBPK applications was greater than the general discipline of pharmacokinetics (9 vs. 4), but less than the overall growth of the PBPK area (9 vs. 43). Our report demonstrates conclusively that the surge in PBPK usage is primarily attributable to the availability and implementations of NOSC software. Modelers preferred not to share the reasons for their selection of certain modeling software and no ‘explicit’ rationale was given to support the use of OSC analysed by this study. As the preference for NOSC versus OSC software tools in the PBPK area continues to be divided, initiatives to add the rationale in using one form over another to every future PBPK modeling report will be a welcomed and informative addition.
Rapid synthesis of BaMoO4:Eu3+ red phosphors using microwave irradiation
Authors: Li Zhao , Cheng Ju‐long , Wang Ya‐nan , Wu Kun‐yao , Cao Jing
Published: April 2023

This study synthesized BaMoO4:Eu3+ red phosphors using the microwave method. In addition, the phase composition, morphology, and luminescence properties of the red phosphors were characterized using X‐ray diffraction, field‐scanning electron microscopy, and photoluminescence spectroscopy. The results revealed that doping red phosphors with different concentrations of Eu3+ does not change the crystal structure of the matrix material. The BaMoO4:Eu3+ phosphors exhibited micron‐scale irregular polyhedra, which could be excited by ultraviolet light with a wavelength of 395 nm to induce red‐light emission. The optimal dosage of Eu3+ was 0.08, and the chromaticity coordinates of BaMoO4:0.08Eu3+ phosphors were (0.5869, 0.3099). White light‐emitting diode (w‐LED) devices manufactured by using a combination of BaMoO4:0.08Eu3+ phosphor and commercially available phosphors exhibited good white‐light emission under the excitation of an ultraviolet chip. The BaMoO4:0.08Eu3+ red phosphors that rapidly synthesized under the microwave field are expected to be used in w‐LED devices.
Social media as a learning tool in anatomy education from the perspective of medical and dental students
Authors: Ortadeveci Abdullah , Ozden Hilmi
Published: April 2023

The traditional approach to anatomy teaching is still the most common. Recently, there has been a demand for methods that make students more active and open to communication and cooperation, and are well integrated with technology. Our aim in this study was to determine the social media usage characteristics and anatomy learning experiences of medical and dentistry students, and their expectations about learning via social media. A questionnaire was prepared and distributed to faculties of Medicine and Dentistry in 10 different universities in Türkiye via Google forms. The questionnaire was voluntarily answered by 762 students. Frequency, exploratory factor and confirmatory factor analyses were applied to the data acquired, and a structural equation modeling (SEM) approach was used. The results showed that 54.3% of the students spent more than 90 min/day on social media; 96.5% of the participants preferred to follow anatomical content pages on social media (acpSM) administered by an academic. They stated that the instant responses from acpSM's admin had a positive effect on motivation to learning (4.08 ± 0.89, mean ± SD, on 5‐point Likert‐type scale). The SEM revealed a statistically significant correlation between the students' learning motivation and the sufficiency and suitability of acpSM content (p < 0.010). Thus, medical and dental students are eager to learn anatomy via social media. However, they found acpSM to be insufficient in quality and quantity and wanted future content to be administered by academics. An acpSM optimized for content sufficiency and suitability increased students' learning motivation.
Particle implantation combined with chemotherapy for rhabdomyosarcoma of the head and neck: A 8‐year long‐term follow‐up case report
Authors: He Sidou , Tian Shuhang , Xu Na , Zhang Jianguo , Duan Chao , Ma Xiaoli
Published: April 2023

Rhabdomyosarcomas (RMSs) are highly malignant soft‐tissue sarcomas. Head and neck RMSs often pose unique challenges to treatment because of their closeness to important structures. We here report a rare case of a 1‐year‐old boy with a 1‐month history of right eye swelling and an eye mass. Biopsy of deep tumors in the maxillofacial region supports embryonal RMS. Postoperative positron emission computed tomography showed a 5.0 cm × 4.8 cm × 4.2 cm malignant tumor in the right maxillary region. In accordance with the international RMS study group guideline, the child was diagnosed with IIIa and TNM stage T2bN1M1 embryonal RMS. The child was treated with a combination of chemotherapy and 125I seed implantation radiotherapy and eventually achieved partial remission. This case report shows that 125I seed implantation is a safe and effective means of delivering radiotherapy to young children with head and neck RMSs. It may be an option for children with RMSs for whom surgery or external radiotherapy is unsuitable.
Pyrotinib alone or in combination with docetaxel in refractory HER2‐positive gastric cancer: A dose‐escalation phase I study
Authors: Liu Dan , Kou Furong , Gong Jifang , Wang Zhiqiang , Zhang Xiaotian , Li Jian , Li Yan , Li Jie , Zhou Jun , Lu Ming , Wang Xicheng , Lu Zhihao , Cao Yanshuo , Zou Jianjun , Zhu Xiaoyu , Xu Ruihua , Shen Lin
Published: April 2023

Aim

Pyrotinib (an irreversible pan‐ErbB small‐molecular tyrosine kinase inhibitor) was approved in human epidermal growth factor receptor 2 (HER2)‐positive breast cancer and showed great antitumor activity in preclinical studies of gastric cancer (GC). This study was first designed to prospectively assess pyrotinib in pretreated HER2‐positive GC.

Methods

This multicenter, phase I study followed a standard “3 + 3” design and included two parts. In the pyrotinib part, pyrotinib was administered orally, once per day at dose levels of 240, 320, 400, and 480 mg. In the pyrotinib plus docetaxel part, patients received pyrotinib (qd, d1‐21, q3W) combined with docetaxel (60 mg/m2, d1, q3W) at dose levels of 240, 320, and 400 mg. Primary endpoints were to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of pyrotinib as monotherapy or coadministered with docetaxel.

Results

A total of 25 patients were enrolled and received pyrotinib (n = 15) or pyrotinib plus docetaxel (n = 10). One DLT was observed in pyrotinib monotherapy part (Grade 3 uncontrolled diarrhea after supportive care) and pyrotinib plus docetaxel part (Grade 4 neutropenia and leukopenia). In the pyrotinib monotherapy part, MTD was not reached. Diarrhea, anemia, neutropenia, and leukopenia were the most common treatment‐related adverse events (TRAEs). The RP2D for pyrotinib monotherapy was recommended as 400 mg. After combining with docetaxel, the risk of leukopenia and neutropenia was increased. Grade ≥3 TRAEs were reported for four patients in the monotherapy part and for eight patients in the combination part. Mean t1/2 was approximately 20 h. Pyrotinib exposure was dose‐dependent with a nonlinear relationship versus dose. There were five patients who had confirmed partial response (monotherapy: one each at 240, 400, and 480 mg dose cohort; combination therapy: two at 240 mg dose cohort), resulting in an objective response rate of 21% and 20%, respectively.

Conclusions

Pyrotinib alone and combined with docetaxel showed acceptable toxicities in patients with pretreated HER2‐positive GC.

Trial Registration

This study was registered with ClinicalTrials.gov, NCT02378389.
Variations in colorectal cancer pattern of care by age and comorbidity in South Australia
Authors: Gheybi Kazzem , Buckley Elizabeth , Vitry Agnes , Roder David
Published: April 2023

Background

Advanced age is associated with decreased likelihood of colorectal cancer treatment. Here, we investigated the extent to which comorbidities are accountable for this lesser treatment.

Methods

Using population‐based datasets, the pattern of care among CRC cases in South Australia during 2004–2013 was investigated. Models were used to investigate associations of age with each treatment type, and differences in these associations were explored by comorbidity and cancer site.

Results

The presence of comorbidity was associated with a significantly weaker relationship of age with surgery and chemotherapy. The association of age with surgery also varied for colon and rectal primary cancer sites. Individual comorbidity types varied in their associations with each treatment category. For example, dementia was associated with less chemotherapy provision, however, it was not significantly related to the likelihood of surgery.

Conclusion

This study indicates that the association of age with surgical treatment differed significantly by the CRC subsite. Comorbidity moderated the negative association of age with chemotherapy, and less so, with extent of surgery. Results were novel in indicating associations of multiple individual comorbidity types with CRC treatment modalities. The data suggest that different individual comorbidity types may have different effects on treatment and should be studied separately.
Efficacy of post‐first‐line agents for advanced gastrointestinal stromal tumors following imatinib failure: A network meta‐analysis
Authors: Hu Kehan , Zhang Hu , Shu Mingrong , Wang Xingyue
Published: April 2023

Background

Imatinib is the standard first‐line treatment for advanced gastrointestinal stromal tumors (GISTs); however, most patients eventually develop imatinib resistance, leading to considerable clinical challenges. Few direct comparisons have been made between different post‐first‐line therapies on clinical efficacy in advanced GIST following imatinib failure.

Methods

Databases including PubMed, Embase, Scopus, Google Scholars, and Cochrane Library from inception to February 2023 were retrieved for randomized controlled trials evaluating the clinical efficacy of different post‐first‐line agents for advanced GIST following imatinib failure. Network and conventional meta‐analysis were carried out using Stata/MP 16.0.

Results

Ripretinib showed significant improvement in progression‐free survival (PFS) rates from the 2nd to the 12th month compared to placebo, while there was virtually no evidence that the rest active agents had a significant benefit at the 12th month. Masitinib, ripretinib, sunitinib, regorafenib, and pimitespib exhibited significantly longer median PFS than placebo, and pairwise comparisons indicated there were no significant differences among masitinib, ripretinib, and sunitinib. These post‐first‐line agents decreased the risk of disease progression or death by 65% (HR = 0.35, 95% CI: 0.26–0.47) compared to placebo. Ripretinib and sunitinib came into effect earlier and exhibited more consistent overall survival (OS) rate improvements than masitinib and pimitespib, while pairwise comparisons revealed no significant differences in these four active agents concerning the improvement in OS rate. These post‐first‐line agents decreased the risk of death by 39% (HR = 0.61, 95% CI: 0.44–0.83) over placebo for advanced GIST following imatinib failure.

Conclusion

The active agents in our analysis as post‐first‐line therapies are able to provide superior clinical efficacy, with improved PFS rate and OS rate at certain time points, as well as absolute values of PFS and OS for advanced GIST. Ripretinib might be the optimal recommendation as a post‐first‐line treatment for advanced GIST following imatinib failure.
Pre‐treatment comorbidities, C‐reactive protein and eosinophil count, and immune‐related adverse events as predictors of survival with checkpoint inhibition for multiple tumour entities
Authors: Mehra Tarun , Dongre Kanchan , Boesing Maria , Frei Patricia , Suenderhauf Claudia , Zippelius Alfred , Leuppi Joerg D. , Wicki Andreas , Leuppi‐Taegtmeyer Anne B.
Published: April 2023

Background

The development of immune‐related adverse events (irAEs) may be associated with clinical efficacy of checkpoint inhibitors (CPIs) in patients with cancer. We therefore investigated the effect of irAEs and pre‐treatment parameters on outcome in a large, real‐life patient cohort.

Methods

We performed a single‐centre, retrospective, observational study including patients who received CPIs from 2011 to 2018 and followed until 2021. The primary outcome was overall survival, and the secondary outcome was the development of irAEs.

Results

In total, 229 patients with different tumour entities (41% non‐small cell lung cancer [NSCLC], 29% melanoma) received a total of 282 CPI treatment courses (ipilimumab, nivolumab, pembrolizumab or atezolizumab). Thirty‐four percent of patients developed irAEs (of these 17% had CTCAE Grade ≥3). Factors independently associated with mortality were pre‐treatment CRP ≥10 mg/L (hazard ratio [HR] 2.064, p = 0.0003), comorbidity measured by Charlson comorbidity index (HR 1.149, p = 0.014) and irAEs (HR 0.644, p = 0.036) (age‐adjusted, n = 216). Baseline eosinophil count ≤0.2 × 109/L was a further independent predictor of mortality (age‐, CRP‐, CCI‐ and irAE‐adjusted HR = 2.252, p = 0.002, n = 166). Anti‐CTLA‐4 use (p < 0.001), and pre‐treatment CRP <10 mg/L were independently associated with irAE occurrence (p = 0.037).

Conclusions

We found an independent association between irAE occurrence and improved overall survival in a real‐life cohort spanning multiple tumour entities and treatment regimens. Pre‐treatment comorbidities, CRP and eosinophil count represent potential markers for predicting treatment response.