bluuebunny/crossref_metadata_2025 huggingface dataset:
Nestboxes augment seabird breeding performance in a high‐density colony: Insight from 15 years of monitoring data
Authors: Burke Brian , O'Connell Darren P. , Kinchin‐Smith David , Sealy Síofra , Newton Stephen F.
Published: August 2022

The provision of artificial nest structures is used in the conservation of a broad range of bird groups including raptors, owls, ducks, passerines and seabirds, with varying degrees of success.

Artificial nestboxes have been provided to increase the density and breeding success of Roseate Tern pairs at colonies in north‐west Europe and the eastern seaboard of the USA and Canada, but their effect on breeding productivity has never been comprehensively quantified.

Using 15 years of monitoring data, based on daily nest monitoring visits, we carried out a comparative analysis of the breeding performance of Roseate Tern pairs utilizing artificial nestboxes with those in open nests, on Rockabill Island (Ireland), to evaluate the effectiveness of nestbox installation as a conservation measure.

Nestboxes were used ahead of open sites early in the season, likely by the experienced breeding pairs. Hatching success and fledging success were higher for pairs in nestboxes compared with those in open nest sites. Earlier clutches were more successful than later ones, independent of the effects of nest site type.

The results of this study show definitively that Roseate Terns nesting in nestboxes perform better than those using open nest sites at their largest European colony and that nestboxes are chosen ahead of other sites, likely by the experienced breeding pairs. We recommend the continued and expanded use of nestboxes to help maximize the densities and breeding performance of the Roseate Tern.
Applying a CT texture analysis model trained with deep‐learning reconstruction images to iterative reconstruction images in pulmonary nodule diagnosis
Authors: Wang Qingle , Xu Shijie , Zhang Guozhi , Zhang Xingwei , Gu Junying , Yang Shuyi , Zeng Mengsu , Zhang Zhiyong
Published: August 2022

Objective

To investigate the feasibility and accuracy of applying a computed tomography (CT) texture analysis model trained with deep‐learning reconstruction images to iterative reconstruction images for classifying pulmonary nodules.

Materials and methods

CT images of 102 patients, with a total of 118 pulmonary nodules (52 benign, 66 malignant) were retrospectively reconstructed with a deep‐learning reconstruction (artificial intelligence iterative reconstruction [AIIR]) and a hybrid iterative reconstruction (HIR) technique. The AIIR data were divided into a training (n = 96) and a validation set (n = 22), and the HIR data were set as the test set (n = 118). Extracted texture features were compared using the Mann‐Whitney U test and t‐test. The diagnostic performance of the classification model was analyzed with the receiver operating characteristic curve (ROC), the area under ROC (AUC), sensitivity, specificity, and accuracy.

Results

Among the obtained 68 texture features, 51 (75.0%) were not influenced by the change of reconstruction algorithm (p > 0.05). Forty‐four features were significantly different between benign and malignant nodules (p < 0.05) for the AIIR dataset, which were selected to build the classification model. The accuracy and AUC of the classification model were 92.3% and 0.91 (95% confidence interval [CI], 0.74−0.90) with the validation set, which were 80.0% and 0.80 (95% CI, 0.68−0.86) with the test set.

Conclusion

With the CT texture analysis model trained with deep‐learning reconstruction (AIIR) images showing favorable diagnostic accuracy in discriminating benign and malignant pulmonary nodules, it also has certain applicability to the iterative reconstruction (HIR) images.
Fuzzy analytic hierarchy process‐based risk priority number for risk assessments of commissioning process of a ring gantry LINAC
Authors: Chang Jina , Jang Siyoung , Lalonde Ron , Huq Saiful M.
Published: August 2022

Purpose

We propose a fuzzy analytic hierarchy process (AHP)‐based risk priority number (RPN) method in failure modes and effects analysis (FMEA) to overcome the shortcomings of traditional RPN‐based FMEA. Our research group has previously published the FMEA to mitigate the failure modes (FMs) for the commissioning process of a ring gantry LINAC. However, inter‐relationships among FMs were observed in high ranked FMs due to a heavy reliance on imaging system.

Methods

Fuzzy AHP was applied to determine relative weights of risk impacts based on inter‐relationships among FMs. Since the time sequence dependency is a major factor for risk factors, a hierarchical structure of AHP was used to reflect the directional impacts such as causal influence and feedback loop. Two fuzzy weighted RPNs, called (RPNW and FRPNW, were calculated depending on the input values of severity (S), occurrence (O), and probability of not being detected (D) from the evaluators. The RPNW used numerical values, whereas the fuzzy values were used for FRPNW. Both RPNs were calculated by multiplying the weighted O, S, and D using the fuzzy AHP method.

Results

The differences between the two fuzzy RPN rankings are due to inherent fuzzy uncertainty and deviations in O, S, and D values submitted by the evaluators. Considering all results of traditional and fuzzy‐based FMEA, the two most highly ranked FMs were identified: errors in determining the non‐isocentric SSD and SSD from MV images because of the unique features of the ring gantry LINAC.

Conclusion

This study has demonstrated the feasibility of the use of a fuzzy AHP‐based RPN to perform comprehensive analysis and prioritization of FMs. The risk analysis using fuzzy AHP can be improved and/or refined based on the department's specific workflow and clinical preferences taking various priority weighting approaches into account.
Tunable PEG Hydrogels for Discerning Differential Tumor Cell Response to Biomechanical Cues
Authors: Katz Rachel R. , West Jennifer L.
Published: August 2022

Increased extracellular matrix (ECM) density in the tumor microenvironment has been shown to influence aspects of tumor progression such as proliferation and invasion. Increased matrix density means cells experience not only increased mechanical properties, but also a higher density of bioactive sites. Traditional in vitro ECM models like Matrigel and collagen do not allow these properties to be investigated independently. In this work, a poly(ethylene glycol)‐based scaffold is used which modifies with integrin‐binding sites for cell attachment and matrix metalloproteinase 2 and 9 sensitive sites for enzyme‐mediated degradation. The polymer backbone density and binding site concentration are independently tuned and the effect each of these properties and their interaction have on the proliferation, invasion, and focal complex formation of two different tumor cell lines is evaluated. It is seen that the cell line of epithelial origin (Hs 578T, triple negative breast cancer) proliferates more, invades less, and forms more mature focal complexes in response to an increase in matrix adhesion sites. Conversely, the cell line of mesenchymal origin (HT1080, fibrosarcoma) proliferates more in 2D culture but less in 3D culture, invades less, and forms more mature focal complexes in response to an increase in matrix stiffness.
In Vivo Cellular Magnetic Imaging: Labeled versus Unlabeled Cells
Authors: Bulte Jeff W. M. , Wang Chao , Shakeri‐Zadeh Ali
Published: August 2022

Superparamagnetic iron oxide (SPIO)‐labeling of cells has been applied for magnetic resonance imaging (MRI) cell tracking for over 30 years, having resulted in a dozen or so clinical trials. SPIO nanoparticles are biodegradable and can be broken down into elemental iron, and hence the tolerance of cells to magnetic labeling has been overall high. Over the years, however, single reports have accumulated demonstrating that the proliferation, migration, adhesion, and differentiation of magnetically labeled cells may differ from unlabeled cells, with inhibition of chondrocytic differentiation of labeled human mesenchymal stem cells (hMSCs) as a notable example. This historical perspective provides an overview of some of the drawbacks that can be encountered with magnetic labeling. Now that magnetic particle imaging (MPI) cell tracking is emerging as a new in vivo cellular imaging modality, there has been a renaissance in the formulation of SPIO nanoparticles this time optimized for MPI. Lessons learned from the occasional past pitfalls encountered with SPIO‐labeling of cells for MRI may expedite the possible future clinical translation of (combined) MRI/MPI cell tracking.
Shining a Light on Cancer—Photonics in Microfluidic Tumor Modeling and Biosensing
Authors: Guimarães Carlos F. , Cruz‐Moreira Daniela , Caballero David , Pirraco Rogério P. , Gasperini Luca , Kundu Subhas C. , Reis Rui L.
Published: August 2022

Microfluidic platforms represent a powerful approach to miniaturizing important characteristics of cancers, improving in vitro testing by increasing physiological relevance. Different tools can manipulate cells and materials at the microscale, but few offer the efficiency and versatility of light and optical technologies. Moreover, light‐driven technologies englobe a broad toolbox for quantifying critical biological phenomena. Herein, the role of photonics in microfluidic 3D cancer modeling and biosensing from three major perspectives is reviewed. First, optical‐driven technologies are looked upon, as these allow biomaterials and living cells to be manipulated with microsized precision and present opportunities to advance 3D microfluidic models by engineering cancer microenvironments' hallmarks, such as their architecture, cellular complexity, and vascularization. Second, the growing field of optofluidics is discussed, exploring how optical tools can directly interface microfluidic chips, enabling the extraction of relevant biological data, from single fluorescent signals to the complete 3D imaging of diseased cells within microchannels. Third, advances in optical cancer biosensing are reviewed, focusing on how light–matter interactions can detect biomarkers, rare circulating tumor cells, and cell‐derived structures such as exosomes. Photonic technologies' current challenges and caveats in microfluidic 3D cancer models are overviewed, outlining future research avenues that may catapult the field.
In Situ Silver‐Based Electrochemical Oncolytic Bioreactor
Authors: Huang Yong , Zhong Liping , Li Xiaotong , Wu Pan , He Jian , Tang Chao , Tang Zhiping , Su Jing , Feng Zhenbo , Wang Bing , Ma Yun , Peng Hongmei , Bai Zhihao , Zhong Yi , Liang Ying , Lu Wenxi , Luo Ruiyu , Li Jinghua , Li Haiping , Deng Zhiming , Lan Xianli , Liu Ziqun , Zhang Kun , Zhao Yongxiang
Published: August 2022

In this study, it is shown for the first time that a reduced graphene oxide (rGO) carrier has a 20‐fold higher catalysis rate than graphene oxide in Ag+ reduction. Based on this, a tumor microenvironment‐enabled in situ silver‐based electrochemical oncolytic bioreactor (SEOB) which switched Ag+ prodrugs into in situ therapeutic silver nanoparticles with and above 95% transition rate is constructed to inhibit the growths of various tumors. In this SEOB‐enabled intratumoral nanosynthetic medicine, intratumoral H2O2 and rGO act as the reductant and the catalyst, respectively. Chelation of aptamers to the SEOB‐unlocked prodrugs increases the production of silver nanoparticles in tumor cells, especially in the presence of Vitamin C, which is broken down in tumor cells to supply massive amounts of H2O2. Consequently, apoptosis and pyroptosis are induced to cooperatively contribute to the considerably‐elevated anti‐tumor effects on subcutaneous HepG2 and A549 tumors and orthotopic implanted HepG2 tumors in livers of nude mice. The specific aptamer targeting and intratumoral silver nanoparticle production guarantee excellent biosafety since it fails to elicit tissue damages in monkeys, which greatly increases the clinical translation potential of the SEOB system.
Controllable Access to Furans and Dihydrofurans through Cyclization/Coupling of Internal Acetylenic β‐Ketoesters with Aryl Bromides
Authors: Bisek Bartosz , Chaładaj Wojciech
Published: August 2022

Pd‐catalyzed tandem cyclization/coupling of internal β‐propargylic‐β‐ketoesters with (hetero)aryl bromides is described. Two protocols are established which selectively lead to 2‐benzylidene‐dihydrofurans, when isomerization is inhibited under mild conditions (temp. ≤40 °C and weak base – K2CO3), or to 2‐benzyl‐furans when base‐induced aromatization is enabled. A catalytic cycle involving oxidative addition, substitution of bromide with alkyne, rate limiting anti‐selective 5‐exo‐dig oxocyclization followed by fast deprotonation of the oxonium intermediate, and reductive elimination is proposed based on detailed experimental and theoretical studies.

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Synthesis of Diarylaminoacridinium Photocatalysts by Halogen‐Metal Exchange Combined with Directed ortho Metalations
Authors: Jakobi Markus , Zilate Bouthayna , Sparr Christof
Published: August 2022

Photostability is an essential design aspect for the overall performance of photocatalysts, particularly as groups introduced to adjust redox properties often constitute sites of potential reactivity. Herein, we describe a modular and flexible synthetic approach to incorporate diarylamino moieties with increased photostability that allow to efficiently tune the redox behavior of a new generation of organic acridinium photocatalysts. A series of cross‐coupling reactions gave access to precursors for halogen metal exchange reactions combined with directed ortho‐metalations to provide reagents that allow the formation of acridinium salts with adjustable redox properties and enhanced photostability in good yields.

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Heterogeneous Reinforcements to Mitigate Li Penetration through Solid Electrolytes in All‐Solid‐State Batteries
Authors: Yuan Chunhao , Sheldon Brian W. , Xu Jun
Published: August 2022

Dendrite growth is one of the leading factors that cause cycling deterioration for all‐solid‐state batteries (ASSBs). However, using a single dominant material to form the solid electrolyte has encountered several setbacks due to the intrinsically competing factors in mechanics and electrochemistry. Inspired by the “brick‐and‐mortar” structure, a strategy of embedding heterogeneous blocks (HBs) within the solid electrolyte (SE) is proposed to mitigate and suppress dendrite growth‐induced internal short circuits (ISCs). A phase‐field‐based multiphysics model is established to describe the dendrite growth behavior. Results reveal that the characteristic length ratio e between the HBs and SE is the governing factor that dominates the dendrite growth path. The results show that a single long HB and multiple HBs in medium length with specific layouts can suppress and divert dendrite growth and avoid ISCs completely. For short HB cases, HBs can delay the ISC to a certain extent. The results imply that adding an appropriately designed heterogeneous layer into the SE will effectively block dendrites, and also define desired mechanical property domains. This work provides a multiphysics mechanistic understanding of the dendrite growth and SE cracking and opens new perspectives for the material selection and structural design of SEs for long lifecycle ASSBs.
Survey‐rated personality traits and experimentally measured coping style and stress reactivity, in wild baboons
Authors: Pritchard Alexander J. , Palombit Ryne A.
Published: August 2022

The coping style and stress reactivity framework for individual differences in the stress response has been of increasing utility within primatological research. Such differences are often quantified using an experimental approach, but many primatological studies have historically been reliant on a personality‐like framework. The personality‐like research is derived from human personality literature using survey ratings, while approaches focused on coping styles are often used to interpret differences in small rodents and birds. Experimental approaches benefit from a constrained situation that facilitates control, but sacrifice utility via the generalizability afforded via ratings. Resolving how these two theoretical and methodological approaches intersect is paramount to establishing a biological synthesis between two robust fields of research on individual differences. We applied these frameworks to adult wild olive baboons (Papio anubis) at a field site in Laikipia, Kenya. We quantified coping style and stress reactivity using individually targeted field experiments. We quantified personality trait differences using observer ratings of the monkeys. We isolated three personality trait factors: Neuroticism, Assertiveness, and Friendliness. Personality trait differences showed little association with coping style, but Neuroticism was predicted by stress reactivity.
Missing data in bioarchaeology I: A review of the literature
Authors: Wissler Amanda , Blevins Kelly E. , Buikstra Jane E.
Published: August 2022

Objectives

Missing data are a frequent and unavoidable challenge in bioarchaeological research, yet researchers seldom make explicit statements about the bias and inferential limitations that missing data introduce into their studies. There are no guidelines for best practices for the treatment or reporting of missing data. As an initial step in taking stock and exploring approaches to missing data in bioarchaeology, this study reviews bioarchaeological publications to identify methods currently in use for addressing this significant problem.

Materials and Methods

Over 950 bioarchaeology articles (2011–2020) from four major anthropology journals were surveyed, searching for the terms “missing,” “absent,” “unobserv,” “replace,” and “imputat.” The 267 articles so identified were categorized into one of nine bioarchaeological subtopics and scored according to a set of six broad approaches for handling missing data.

Results

Results indicate that bioarchaeologists handle missing data in a variety of ways. Methods such as antimere substitution, listwise deletion and pairwise deletion are widely used. Subject subtopics favor different techniques for handling missing values. Bioarchaeological articles categorized as archaeology, pathology, and trauma used basic missing data approaches, while those such as biodistance and morphology more often employed advanced statistics. Despite the ubiquity of missing data, considerations of how they introduce bias were uncommon and standards for reporting were inconsistent.

Conclusions

These findings highlight areas in which bioarchaeologists can improve techniques for handling and reporting missing data. Greater attention to these shortcomings will increase the statistical rigor of the field.
Isothermal Rolling Circle Amplification and Lanthanide‐Based FRET for Femtomolar Quantification of MicroRNA
Authors: Dekaliuk Mariia , Busson Pierre , Hildebrandt Niko
Published: August 2022

Invited for this month′s cover are the collaborating groups of Prof. Niko Hildebrandt at Université de Rouen Normandie, France, and Dr. Pierre Busson at Gustave Roussy, France. The cover picture shows a Rolling Circle Amplification (RCA) product formed from a single microRNA and its detection via lanthanide (Tb and Eu) based multicolor FRET. More information can be found in the Research Article by N. Hildebrandt and co‐workers.
Trace determination of Cu(II) in milk samples after preconcentration on Fe3O4@graphene oxide composite based imprinted polymer
Authors: Islam Aminul , Javed Hina
Published: August 2022

A new tailor‐fitted graphene oxide‐vinyl pyridine ion‐imprinted polymer (mGOVP/IIP), was synthesized using ethylene glycol dimethacrylate as a cross‐linking agent and 2,2′‐azo‐bis‐isobutyronitrile as an initiator to develop dispersive magnetic‐solid‐phase extraction method for the preconcentration of Cu(II) prior to the determination by flame atomic absorption spectrometry. The material was characterized and optimized for various parameters by batch mode, which includes the effect of initial concentration, contact time, temperature, and eluents. Herein, IIP demonstrated a high sorption capacity (63.54 mg g−1) at pH 5.6, with fast kinetics (15 min). The heterogeneity and chemisorption, mechanistic interpretation was explained by the Freundlich isotherm, pseudo‐second‐order kinetic model, respectively. Moreover, the higher selectivity coefficients for Cu(II) in the binary mixturess of concomitant ions signified preferential affinity over similar structural analogues. Additionally, it can be regenerated up to 7 runs and effectively eluted by 1 M HNO3. This developed method exhibited higher accuracy, precision (relative standard deviation <5%), and preconcentration factor (60). The IIP also described potential applications for Cu(II) determination in milk and its by‐products. Overall, the material exhibits ease of access and removal of template ion from the binding sites, cost‐effectiveness, fast mass transfer, promoted competitiveness, reproducibility, reliability, and good regeneration efficiency.
Optimizing cure temperature of polyimide flyer for exploding foil initiator applications
Authors: Sun Laixi , Zhan Zhiqiang , Wu Zhiqing , Zou Ruijiao , Zhu Ye , Yi Tao , Luo Jiangshan , Niu Gao , Lei Fan , Wang Jin , Yang Bo , Fu Qiubo
Published: August 2022

Polyimide (PI) is an ideal flyer material commonly used for exploding foil initiator (EFI) systems. The material properties of PI influence the flight ability of the flyer. Curing temperature during the preparation process of PI is one of the key factors influencing the material properties. In this study, we investigated the effect of the PI film curing temperature on the material properties and the flight ability by characterizing IR transmittance, XPS, and nano‐hardness. The results show that the flight ability of the flyer is highly dependent on the curing temperature. Curing at 250°C is beneficial for the flyer to have an optimal flight velocity, which was attributed to the good chemical and mechanical behavior of the material. Increase in curing temperature would weaken the material properties to some extent. High‐temperature cure (e.g., 400°C), would break the molecular chain and carbonize the material, causing significant drop in flight velocity of the flyer. The study is expected to contribute to the development of high‐performance flyer for EFI applications.
Why does currency denomination in external liabilities of small island developing states matter? Evidence from Fiji
Authors: Jain Devendra Kumar , Singh Rup , Kumar Henali , Kumar Nikeel , Patel Arvind
Published: August 2022

The valuation effects on international investment position induced by the exchange rate volatility are not uniform or easily manageable in small and vulnerable economies when compared with larger developing or developed countries. To investigate the underlying dynamics, we developed a foreign currency exposure index over the period 2006–2019. The positive reading of the index suggests that though Fiji has a high net negative international investment position (90% of its GDP), it does not pose any serious risk. To ascertain determinants of Fijiʼs exposure index, we applied fully modified ordinary least square and autoregressive distributed lag bounds test. We have compared both estimates for consistency. Our findings suggest that the underlying determinants of Fijiʼs currency exposure are foreign debt, trade openness and exchange rate. This article bridges the gap in the literature on currency exposure risks in small island developing states and is the first study of its kind for the Pacific region.
Protocol to control the invasive alga Avrainvillea lacerata in a shallow Hawaiian reef flat
Authors: Van De Verg Scott E. , Smith Celia M.
Published: August 2022

Premise

A novel control technique was developed to mitigate an invasive siphonous green alga, Avrainvillea lacerata (Dichotomosiphonaceae), within a shallow degraded reef flat in Oʻahu, Hawaiʻi.

Methods and Results

Replicated treatments of 3% and 10% hydrogen peroxide (H2O2) were administered into individual basal attachments of the bed‐forming invasive seaweed on the Paikō reef, Oʻahu. Relative electron transport rate maxima (rETRm) were measured using a Walz Diving Pulse Amplitude Modulated Fluorometer in two replicate 100‐m2 plots in 2020. Over the period of this short‐term study, rETRm decreased following injections of either concentration of H2O2 in contrast with negative and positive controls.

Conclusions

Compared with existing techniques that have used oxidizing agents in the marine environment in localized areas, the protocol described here has the potential to successfully decrease macroalgal carbon gain, potentially leading to loss of biomass at larger scales.
Recent advances in the development of celecoxib analogs as anticancer agents: A review
Authors: Abdelhaleem Eman F. , Kassab Asmaa E. , El‐Nassan Hala B. , Khalil Omneya M.
Published: August 2022

Celecoxib is a nonsteroidal anti‐inflammatory drug (NSAID) designed to be a selective cyclooxygenase‐2 (COX‐2) inhibitor. It was approved by the U.S. Food and Drug Administration for the treatment of inflammatory diseases such as osteoarthritis and rheumatoid arthritis. Additionally, celecoxib demonstrated potent antitumor and chemopreventive effects in vitro, in vivo, and in patients. The mechanism of celecoxib's chemopreventive effect is still not fully identified, but it is assumed to be multifactorial. Celecoxib's anticancer activity has been described both as independent of and dependent on its COX‐2 inhibitory activity. The current review summarizes the recent advances published between 2000 and 2022 on the structure‐based optimization of celecoxib to develop compounds with promising anticancer activity. The structure–activity relationships of celecoxib analogs are discussed, which may be beneficial in the design and development of novel analogs as potent antiproliferative agents in the future.
Sustainable approaches towards green synthesis of TiO2 nanomaterials and their applications in photocatalysis‐mediated sensing to monitor environmental pollution
Authors: Singh Tripti , Sharma Shalini , Singh Rajeev , Pal Dan Bahadur , Ahmad Irfan , Alam Mohammad Mahtab , Singh Nand Lal , Srivastava Manish , Srivastava Neha
Published: August 2022

Nanomaterials are gaining enormous interests due to their novel applications that have been explored nearly in every field of our contemporary society. In this scenario, preparations of nanomaterials following green routes have attracted widespread attention in terms of sustainable, reliable, and environmentally friendly practices to produce diverse nanostructures. In this review, we summarize the fundamental processes and mechanisms of green synthesis approaches of TiO2 nanoparticles (NPs). We explore the role of plants and microbes as natural bioresources to prepare TiO2 NPs. Particularly, focus has been made to explore the potential of TiO2‐based nanomaterials to design a variety of sensing platforms by exploiting the photocatalysis efficiency under the influence of a light source. These types of sensing are of massive importance for monitoring environmental pollution and therefore for inventing advanced strategies to remediate hazardous pollutants and offer a clean environment.
A validated liquid chromatography–tandem mass spectrometry method for the determination of l‐hyoscyamine in human plasma: Application in a clinical study
Authors: Duan Yunhai , Zuo Zhenglong , Chen Yinchun , Song Qingqing , Yu Mingming , Yang Yong
Published: August 2022

Atropine is a racemic mixture of d‐ and l‐hyoscyamine, but only l‐hyoscyamine is the effective ingredient. In this study, a new, sensitive, stable, and selective LC/MS assay was developed for the determination of l‐hyoscyamine and applied to a clinical study. The parent–product (m/z) transition pair of l‐hyoscyamine was 290.1 → 124.1. Chromatographic separations were performed using a chiral MZ column (250 mm × 4.6 mm, 5.0 μm) by a stepwise gradient elution mode with n‐hexane, isopropanol, and diethylamine as mobile phases. l‐Hyoscyamine in human plasma was extracted by liquid–liquid extraction. This assay displayed a good linearity over a concentration range of 20.0–400 pg/mL for l‐hyoscyamine. The accuracy of the validation assay for l‐hyoscyamine ranged from −2.7% to 4.5%, and the precision was within 6.3% coefficient of variation. l‐Hyoscyamine in human plasma remained stable at different storage conditions. The method has been successfully applied to plasma samples obtained from a safety study in humans.
Predictive biomarkers of survival in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab treatment
Authors: Chon Young Eun , Cheon Jaekyung , Kim Hyeyeong , Kang Beodeul , Ha Yeonjung , Kim Do young , Hwang Seong Gyu , Chon Hong Jae , Kim Beom Kyung
Published: August 2022

Background

Since atezolizumab plus bevacizumab (ATE+BEV) regimen for patients with unresectable hepatocellular carcinoma (HCC) was released quite recently, real‐world data are lacking. We evaluated efficacy, safety, and predictive biomarkers for survival in patients receiving ATE+BEV.

Methods

Between 2020 and 2021, HCC patients receiving ATE+BEV at academic teaching hospitals were recruited. Treatment response was assessed using the Response Evaluation Criteria in Solid Tumors (version 1.1.).

Results

Among 121 patients enrolled, the median age was 63 years, with male predominance (82.6%). Complete response, partial response, stable disease, and progressive disease were identified in 2.5%, 26.4%, 54.5%, and 16.6%, respectively. Patients with alpha‐fetoprotein and des‐gamma‐carboxy prothrombin (DCP) response, defined as ≥30% and ≥50% decreases, respectively, at the first response evaluation relative to baseline, and those with neutrophil‐to‐lymphocyte ratio (NLR) <2.5, had significantly higher objective response rates (42.6% vs. 21.5%, 50.0% vs. 26.2%, and 39.0% vs. 19.4%, respectively; all p < 0.05). During follow‐up, the median overall survival (OS) was not reached, and the median progression‐free survival (PFS) was 5.7 months. Multivariable analyses showed that macrovascular invasion (adjusted hazard ratio [aHR] 2.541; p = 0.017), DCP ≥186 mAU/ml (aHR 5.102; p < 0.001), NLR ≥2.5 (aHR 3.584; p = 0.001), and an NLR decrease ≥10% at the first response (aHR 0.305; p = 0.002) were independent predictors of OS, and DCP ≥186 mAU (aHR 2.311; p = 0.002) and NLR ≥2.5 (aHR 1.938; p = 0.012) were independent predictors of PFS. Grade ≥3 treatment‐related adverse events (AEs) occurred in 33 (27.3%) patients.

Conclusion

ATE+BEV showed favorable efficacy and safety. Baseline high DCP and NLR may be useful prognostic predictors for OS and PFS.
Using a social robot for children with autism: A therapist‐robot interactive model
Authors: Lin Jiayu , Li Jiefeng , She Yingying , Lin Lin , Wu Hang , Zhang E. , Lei Jiayi , Huang Wei , Li Jufeng
Published: August 2022

Social robots have great potential for the therapy of children with autism spectrum disorder, but the practical use of them is challenging. In this article, we presented a social robot YANG, which can interact with children with autism in their daily training. We propose a therapist‐robot interactive (TRI) model, which integrates with the practice of discrete trial training (DTT), a basic method utilized in autism training. To evaluate the TRI model, we implemented the model in YANG and conducted a single‐subject experiment in a rehabilitation training center. Data were collected on three children (ages 3–4) and their three therapists as they interacted with YANG in training sessions. Results showed that the children's learning ability significantly improved. YANG formed natural and friendly relationships with the children and delivered substantial support to therapists. Our research brings insight into using social robots for children with autism.
Synthesis and Molecular Docking of New Bis‐Thiazolidinone‐Based Chalcone Analogs as Effective Inhibitors of Acetylcholinesterase and Butyrylcholinesterase
Authors: Hussain Rafaqat , Rahim Fazal , Rehman Wajid , Taha Muhammad , Khan Shoaib , Zaman Khalid , Adnan Ali Shah Syed , Wadood Abdul , Imran Syahrul , Abdellatif Magda H.
Published: August 2022

This work reports the convenient strategy for the synthesis of bis‐thiazolidinone based chalcone analogs (1–20) from readily available thiosemicarbazide hydrochloride, ammonium thiocyanate and benzaldehyde. All the newly afforded bis‐thiazolidinone based chalcone analogs (1–20) were screened in vitro for their acetylcholinesterase and butyrylcholinesterase inhibition profile. It was noteworthy, that all the synthetic analogs (except analogs 10, 12 and 14, which are found to be inactive) showed moderate to good inhibitory potentials on screening against acetylcholinesterase having range of inhibitory with IC50 values from 0.070±0.050 to 7.60±0.10 μM, and similarly for butyrylcholinesterase with range IC50 values from 0.10±0.050 μM to 10.70±0.20 μM, respectively as compared to standard Donepezil inhibitor (IC50=2.16±0.12 μM), (IC50=4.5±0.11 μM).Among the series, the analogs with hydroxy group showed superior inhibitory potentials against acetylcholinesterase and butyrylcholinesterase enzymes. Therefore, analog 20 (IC50=0.070±0.050 μM), (IC50=0.10±0.050 μM) bearing trihydroxy substitutions on ortho‐, meta‐ and para‐position of both rings A and B was found to be the most active inhibitor of acetylcholinesterase and butyrylcholinesterase enzymes among the current synthesized series (1–23). Analog 19 (IC50=0.15±0.050 μM), (IC50=0.20±0.050 μM) bearing dihydroxy substitutions on ortho‐ and meta‐position of both ring A and ring B was identified as the second most potent inhibitor against both these enzymes. Interestingly, the compound (16) (IC50=1.50±0.10 μM against AChE) has a better selectivity index (2.60) than standard Donepezil drug (2.083) for AChE over BuChE. The different types of spectroscopic techniques such as HR‐EI‐MS, 1H‐ and 13C‐ NMR were used to confirm the structure of all the newly synthetics analogs. To find structure‐activity relationship, molecular docking studies were carried out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data.
Supramolecular Host‐Guest Interaction‐Driven Electrochemical Recognition for Pyrophosphate and Alkaline Phosphatase Analysis
Authors: Qin Lingxia , Ren Xinxin , Hu Kaiyue , Wu Di , Guo Zhiyong , Wang Sui , Jiang Linwen , Hu Yufang
Published: August 2022

We report an electrochemical biosensor based on the supramolecular host‐guest recognition between cucurbit[7]uril (CB[7]) and L‐phenylalanine‐Cu(II) complex for pyrophosphate (PPi) and alkaline phosphatase (ALP) analysis. First, L‐Phe‐Cu(II) complex is simply synthesized by the complexation of Cu(II) (metal node) with L‐Phe (bioorganic ligand), which can be immobilized onto CB[7] modified electrode via host‐guest interaction of CB[7] and L‐Phe. In this process, the signal of the complex‐triggered electro‐catalytic reduction of H2O2 can be captured. Next, due to the strong chelation between PPi and Cu(II), a biosensing system of the model “PPi and Cu(II) premixing, then adding L‐Phe” was designed and the platform was applied to PPi analysis by hampering the formation of L‐Phe‐Cu(II) complex. Along with ALP introduction, PPi can be hydrolyzed to orthophosphate (Pi), where abundant Cu(II) ions are released to form L‐Phe‐Cu(II) complex, which gives rise to the catalytic reaction of complex to H2O2 reduction. The quantitative analysis of H2O2, PPi and ALP activity was achieved successfully and the detection of limits are 0.067 μM, 0.42 μM and 0.09 mU/mL (S/N=3), respectively. With its high sensitivity and selectivity, cost‐effectiveness, and simplicity, our analytical system has great potential to for use in diagnosis and treatment of ALP‐related diseases.
Extracellular vesicles from bone marrow mesenchymal stromal cells of severe aplastic anemia patients attenuate hematopoietic functions of CD34+ hematopoietic stem and progenitor cells
Authors: Srivastava Jyotika , Katiyar Shobhita , Chaturvedi Chandra P. , Nityanand Soniya
Published: August 2022

Mesenchymal stromal cells (MSC) regulate hematopoiesis in the bone marrow (BM) niche and extracellular vesicles (EVs) released by BM‐MSC are important mediators of the cross‐talk between BM‐MSC and hematopoietic stem and progenitor cells (HSPC). We have previously demonstrated that BM‐MSC of severe aplastic anemia (SAA) patients have an altered expression of hematopoiesis regulatory molecules. In the present study, we observed that CD34+ HSPC when cocultured with BM‐MSC EVs from aplastic anemia patients exhibited a significant reduction in colony‐forming units (p = .001), cell proliferation (p = .002), and increased apoptosis (p > .001) when compared to coculture with BM‐MSC EVs from controls. Collectively, our results highlight that EVs derived from the BM‐MSC of SAA patients impair the hematopoiesis supporting function of HSPC.
P53 in endothelial function and unfolded protein response regulation
Authors: Kubra Khadeja‐Tul , Barabutis Nektarios
Published: August 2022

Vascular barrier dysfunction due to endothelial hyperpermeability has been associated with the pathophysiology of sepsis and severe lung injury, which may inflict acute respiratory distress syndrome (ARDS). Our group is focused on the mechanisms operating towards the regulation of endothelial permeability, to contribute in the development of efficient and targeted countermeasures against ARDS. Unfortunately, the number of ARDS‐related deaths in the intensive care units has dramatically increased during the COVID‐19 era. The findings described herein inform the corresponding scientific and medical community on the relation of P53 and stress responses in barrier function.
Ligand Assisted CO2 Activation and Catalytic Valorization by an NHI‐Stabilized Stannylene
Authors: Sarkar Debotra , Groll Lisa , Munz Dominik , Hanusch Franziska , Inoue Shigeyoshi
Published: August 2022

The aryl(imino)stannylene MesTer[N(IDipp)]Sn could be obtained by treating NHILi (NHI=N(IDipp), IDipp=C[N‐(2,6‐iPr2C6H3)CH]2) with MesTerSnCl (MesTer=2,6‐Mes2C6H3) and offers a unique reactivity pattern compared to conventional single site tetrylene catalyzed CO2 reduction reactions. The Sn(II) center, stabilized by the NHI ligand enabled the sequestration and valorization of CO2 to C1 feedstock stoichiometrically, as well as catalytically, utilizing HBpin (pin=pinacolato) as reductant. The experimental comparison with aryl(amido)stannylene MesTer(NPh2)Sn and aryl(phosphinidene)stannylene MesTer[P(IDipp)]Sn, as well as computational analysis, rationalize the electronic features and key role of the NHI ligand in the CO2 reduction process. In case of the phosphorus congener, Sn−P bonding with pronounced double‐bond character is obtained, which prevents swift dissociation, thus preventing CO2 uptake. Instead, hard/soft mismatch between tin and the NHI induces zwitterionic and single‐bond character, switching on the intermediate dissociation of Sn(II)/NHI, followed by a tin hydride mediated reduction step, and thus allows for efficient catalysis under mild conditions.
Using Macrocyclic G‐Quadruplex Ligands to Decipher the Interactions Between Small Molecules and G‐Quadruplex DNA
Authors: Andréasson Måns , Bhuma Naresh , Pemberton Nils , Chorell Erik
Published: August 2022

This study aims to deepen the knowledge of the current state of rational G4‐ligand design through the design and synthesis of a novel set of compounds based on indoles, quinolines, and benzofurans and their comparisons with well‐known G4‐ligands. This resulted in novel synthetic methods and G4‐ligands that bind and stabilize G4 DNA with high selectivity. Furthermore, the study corroborates previous studies on the design of G4‐ligands and adds deeper explanations to why a) macrocycles offer advantages in terms of G4‐binding and ‐selectivity, b) molecular pre‐organization is of key importance in the development of strong novel binders, c) an electron‐deficient aromatic core is essential to engage in strong arene‐arene interactions with the G4‐surface, and d) aliphatic amines can strengthen interactions indirectly through changing the arene electrostatic nature of the compound. Finally, fundamental physicochemical properties of selected G4‐binders are evaluated, underscoring the complexity of aligning the properties required for efficient G4 binding and stabilization with feasible pharmacokinetic properties.
Advance and Designing Strategies in Polymeric Antifungal Agents Inspired by Membrane‐Active Peptides
Authors: Jiang Weinan , Wu Yueming , Zhou Min , Song Gonghua , Liu Runhui
Published: August 2022

The high‐mortality invasive fungal infections seriously threaten the lives of immunocompromised people. Host defense peptides and cell‐penetrating peptides are representative membrane‐active peptides with different functions. Among them, host defense peptides mimicking is a valid strategy in the design of synthetic antifungal agents. Despite the brilliance in the field of intracellular delivery, the potential of cell‐penetrating peptides and their mimics for designing antifungal agents has been overlooked. In this concept article, we describe the structural design of synthetic antifungal polymers as mimics of host defense peptides, and highlight the effectiveness and potential of cell‐penetrating peptide‐inspired strategy in designing potent and selective antifungal polymeric agents. In addition, an outlook for further expanding the design horizons of antifungal polymers is also presented.
Copper‐Zinc Oxide Catalysts for Aldehyde Hydrogenation by Direct Reductive Activation of Precursors
Authors: Hiller Max , Köhler Klaus
Published: August 2022

Bulk copper‐zinc oxide hydrogenation catalysts are generally prepared by calcination of co‐precipitated precursors followed by reduction. This study reports the direct reduction in hydrogen of co‐precipitated oxy/hydroxy‐carbonate precursors omitting calcination. Dried and incompletely calcined precursors are compared with calcined catalysts. The reduction reactions in hydrogen were monitored in situ by XRD and TGA‐MS. Direct activation of precursors led to higher copper dispersions and increased catalytic activity in the hydrogenation of butyraldehyde to butanol as test reaction.
Optimization of green extraction of high‐value components from Eugenia uniflora leaves: Thermal stability and in‐vitro biological activity
Authors: Farias Fabiane O. , Marques Caroline , Fragoso Jaqueline N. H. , Toci Aline Theodoro , Mafra Marcos R. , Igarashi‐Mafra Luciana
Published: August 2022

Deep eutectic solvents (DES) were evaluated as a sustainable route to obtain bioactive compounds from Eugenia uniflora L. leaves (EUL). Completely randomized experimental designs determined the process conditions. The DES composed of cholinium chloride as hydrogen bond acceptor (HBA) and lactic acid, glycerol, or 1,2‐propanediol as hydrogen bond donor (HBD) showed the best extraction capacity. The better conditions were 150 min, 65°C, and a solid:liquid ratio of 1:30. The major constituents of the extracts, quantified by high‐performance liquid chromatography (HPLC), were naringin and caffeic acid. Moreover, the DES promoted a preservative effect on the EUL extracts against thermal treatments. All extracts exhibited high antioxidant and antiglycation activities and iron‐chelating potential. Moreover, when lactic acid was the HBD, the extracts showed considerable antibacterial activity. Therefore, it was effectively proposed as an effective and green route to obtain extracts with potential applications in the food, cosmetic, and pharmaceutical industries.
Not quite “mast”ered: Patients and providers report limitations in the management of systemic mastocytosis
Authors: Curtis Casey , Vaughn Jennifer E.
Published: August 2022

In this issue, Mesa et al. present the results of two independent surveys: the TouchStone SM Survey, which reports patient experiences with systemic mastocytosis (SM), and the TouchStone Healthcare Provider Survey, which reports perceptions of health care providers who care for patients with SM. Both patients and providers report significant symptom burden experienced by patients with SM, and discrepancies between provider perceptions and the existing literature warrant further investigation.
Adherence to the American Cancer Society Guidelines on nutrition and physical activity for cancer prevention and obesity‐related cancer risk and mortality in Black and Latina Women's Health Initiative participants
Authors: Pichardo Margaret S. , Esserman Denise , Ferrucci Leah M. , Molina Yamile , Chlebowski Rowan T. , Pan Kathy , Garcia David O. , Lane Dorothy S. , Shadyab Aladdin H. , Lopez‐Pentecost Melissa , Luo Juhua , Kato Ikuko , Springfield Sparkle , Rosal Milagros C. , Bea Jennifer W. , Cespedes Feliciano Elizabeth M. , Qi Lihong , Nassir Rami , Snetselaar Linda , Manson JoAnn , Bird Chloe , Irwin Melinda L.
Published: August 2022

Background

Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity‐related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI).

Methods

Semi‐Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking.

Results

Over a median of 11.1, 12.5, and 3.7 years of follow‐up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all‐cause deaths (Black/Latina women: 1576/394), and 341 ORC‐related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause‐specific hazard ratio [CSHR]highvs.low: 0.72; 95% CI, 0.55–0.94) and Latina (CSHRhighvs.low: 0.58, 95% CI, 0.36–0.93) women; but not conditional all‐cause mortality (Black hazard ratio [HR]highvs.low: 0.86; 95% CI, 0.53–1.39; Latina HRhighvs.low: 0.81; 95% CI, 0.32–2.06). Higher adherence was associated with lower incidence of less common ORC (Ptrend = .025), but conditional mortality events were limited. Adherence and ORC‐specific deaths were not associated and there was no evidence of effect modification.

Conclusions

Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC‐related mortality.

Lay summary

Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color.

Adherence to the guidelines and risk of developing one of 13 obesity‐related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity‐related cancer.

These findings support public health interventions to reduce growing racial/ethnic disparities in obesity‐related cancers.