bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppressed physical aging in PMMA‐titanium oxide nanocomposites by controlling alignment of nanoparticles
Authors: Huo Miao , Ma Mingchao , Teng Yinuo , Xiao Yuhan , Guo Yunlong
Published: May 2023

This study investigates the physical aging process of PMMA‐TiO2 nanocomposites with different particle alignments. By using an external electric field to control the alignment of TiO2 particles, a uniform distribution of TiO2 particles in PMMA is transformed into a micrometer‐level pillar structure. The physical aging process is measured using differential scanning calorimetry, and the particle alignment is confirmed by microscopy. Comparison of the aging behavior of different samples shows that the addition of randomly distributed TiO2 nanoparticles accelerates the aging rate of the material. However, when the nanoparticles are realigned into a pillar structure, the aging rate significantly decreases. Moreover, in our experimental time scale, a dual‐relaxation mechanism of aging is observed in the PMMA/TiO2 nanocomposites. This work highlights the importance of particle alignment and structure on the aging behavior of polymer nanocomposites, which could have implications for designing materials with improved stability in applications that require slow aging.
Disturbance‐observer‐based adaptive finite‐time dynamic surface control for PMSM with time‐varying asymmetric output constraint
Authors: Li Menghan , Zhang Junxing , Li Shaobo , Wu Fengbin , Zhang Tao , Zhou Peng
Published: May 2023

This article presents a disturbance‐observer‐based adaptive finite‐time dynamic surface control scheme, capable of guaranteeing transient behavior for the PMSM with arbitrary asymmetric time‐varying output constraint and unmatched external disturbance. The major challenge of this paper is devising efficient strategies to tackle the nonsymmetric output restraints with arbitrary characteristics and unmatched external perturbation for the system under the finite‐time backstepping framework. Given this, a nonlinear transformation function is adopted to coordinate from the output‐constrained dynamic model to an uncontained one, and a finite‐time disturbance observer is introduced to evaluate the unmatched external perturbation. Then, a dynamic surface control approach having adaptive properties for PMSM is conceived by combing a neural network to evaluate the nonlinear functions and a first‐order filter to handle the “explosion of complexity.” Additionally, it is proved that the signals in the closed‐loop system can narrow down to a bounded region and the tracking error can merge in a limited time to tiny vicinity of zero by employing a fast finite‐time stability principle. Eventually, simulation cases and contrast results reveal the tracking performance and immunity to the disturbance of the devised controller.
Model‐free predictive control for a class of asymmetric nonlinear systems
Authors: Su Baili , Tian Ye , Wang Yunshuo
Published: May 2023

A model‐free predictive control (MFPC) method is proposed for a kind of discrete nonlinear asymmetric systems (NASs) whose models are undefined. According to the dynamic characteristics of the asymmetric system, the compact format dynamic linearization (CFDL) technology and the improved projection algorithm are adopted to set up models for the controlled NAS. Then, based on the estimation models, the explicit analytical solution of the controller is obtained by solving the quadratic function of finite‐time domain rolling optimization. Finally, a switching law is designed to make the system switch reasonably between the positive and negative models, thus ensuring the stability of the whole system. The effectiveness of the proposed method is testified by a simulation example.
A truncated scale factor to realize cosmological bounce under the purview of modified gravity
Authors: Chokyi Khandro K. , Chattopadhyay Surajit
Published: May 2023

The present paper reports a study on bounce realization with a truncated scale factor and the holographic fluid taken in the form of holographic Ricci Dark Energy, which is a particular case of holographic Nojiri–Odintsov model (Nojiri & Odintsov, 2006, Gen. Relativ. Gravit., 38(8), 1285). We have investigated the realization of bounce due to the application of a holographic fluid in the early scenario of the universe. We started with a de‐Sitter scale factor in our study and derived two modified forms using Taylor's series expansion. After studying the behavior of the resulting Hubble parameter, we identified as the suitable form of the scale factor to realize the bounce. It satisfied the conditions , , and before, at, and after the turn‐around point. We have also observed that the resulting equation of state (EoS) parameter violates the null energy condition required by the bounce realization. We have studied the bounce scenario in a modified gravity framework and derived the slow roll parameters. We have studied the behavior of the potential along with the slow‐roll parameters in this bouncing scenario.
Traumatic brain injury alters the relationship between brain structure and episodic memory
Authors: Taing Abbie S. , Mundy Matthew E. , Ponsford Jennie L. , Spitz Gershon
Published: May 2023

Background

Focal and diffuse pathology resulting from traumatic brain injury (TBI) often disrupts brain circuitry that is critical for episodic memory, including medial temporal lobe and prefrontal regions. Prior studies have focused on unitary accounts of temporal lobe function, associating verbally learned material and brain morphology. Medial temporal lobe structures, however, are domain‐sensitive, preferentially supporting different visual stimuli. There has been little consideration of whether TBI preferentially disrupts the type of visually learned material and its association with cortical morphology following injury. Here, we investigated whether (1) episodic memory deficits differ according to the stimulus type, and (2) the pattern in memory performance can be linked to changes in cortical thickness.

Methods

Forty‐three individuals with moderate‐severe TBI and 38 demographically similar healthy controls completed a recognition task in which memory was assessed for three categories of stimuli: faces, scenes, and animals. The association between episodic memory accuracy on this task and cortical thickness was subsequently examined within and between groups.

Results

Our behavioral results support the notion of category‐specific impairments: the TBI group had significantly impaired accuracy for memory for faces and scenes, but not animals. Moreover, the association between cortical thickness and behavioral performance was only significant for faces between groups.

Conclusion

Taken together, these behavioral and structural findings provide support for an emergent memory account, and highlight that cortical thickness differentially affects episodic memory for specific categories of stimuli.
Follow‐up on the U.S. Central Intelligence Agency's (CIA) remote viewing experiments☆
Authors: Escolà‐Gascón Álex , Houran James , Dagnall Neil , Drinkwater Kenneth , Denovan Andrew
Published: May 2023

Objectives

Since 1972, the U.S. Central Intelligence Agency (CIA) commissioned several research programs on remote viewing (RV) that were progressively declassified from 1995 to 2003. The main objectives of this research were to statistically replicate the original findings and address the question: What are the underlying cognitive mechanisms involved in RV? The research focused on emotional intelligence (EI) theory and intuitive information processing as possible hypothetical mechanisms.

Methods

We used a quasi‐experimental design with new statistical control techniques based on structural equation modeling, analysis of invariance, and forced‐choice experiments to accurately objectify results. We measured emotional intelligence with the Mayer—Salovey–Caruso Emotional Intelligence Test. A total of 347 participants who were nonbelievers in psychic experiences completed an RV experiment using targets based on location coordinates. A total of 287 participants reported beliefs in psychic experiences and completed another RV experiment using targets based on images of places. Moreover, we divided the total sample into further subsamples for the purpose of replicating the findings and also used different thresholds on standard deviations to test for variation in effect sizes. The hit rates on the psi‐RV task were contrasted with the estimated chance.

Results

The results of our first group analysis were nonsignificant, but the analysis applied to the second group produced significant RV‐related effects corresponding to the positive influence of EI (i.e., hits in the RV experiments were 19.5% predicted from EI) with small to moderate effect sizes (between 0. 457 and 0.853).

Conclusions

These findings have profound implications for a new hypothesis of anomalous cognitions relative to RV protocols. Emotions perceived during RV sessions may play an important role in the production of anomalous cognitions. We propose the Production‐Identification‐Comprehension (PIC) emotional model as a function of behavior that could enhance VR test success.
‘Big brothers and sisters have my back’: Benefits and risks of befriending older peers as a strategy to deal with school bullying
Authors: Zhu Yan
Published: May 2023

Befriending ‘brothers’ and ‘sisters’ from older year groups was a strategy used by children to gain protection against being bullied by same‐age peers at school, especially in contexts, such as Chinese rural boarding schools, where children spend a long time with peers under limited adult supervision. However, it is alarming that such close connections with older children, in some cases, could give children a feeling of having power over their same‐age peers, leading them to engage in bullying. In addition, since the roles as the provider and receiver of protection could cause an unbalanced power between the older ones and younger ones, younger children might have to experience a ‘dark’ side of such cross‐age peer relationships, such as exploitation, in some cases. Such experiences could be further strengthened by the Chinese values of ‘giving’ and ‘gaining’ in relationships. Therefore, based on an ethnographic study in a rural primary boarding school in China, this article argues that befriending older peers could contribute to increasing the safety of children at school. However, it is also necessary to be aware of potential risks associated with such peer relationships, because of the unbalanced power relation amongst children caused by age.
Helping in times of crisis: Examining the social identity and wellbeing impacts of volunteering duringCOVID‐19
Authors: Gray Debra , Randell Jordan , Manning Rachel , Cleveland Michelle
Published: May 2023

COVID‐19 produced the largest mass mobilisation of collective helping in a generation. Currently, the impact of this voluntary activity is not well understood, particularly for specific groups of volunteers (e.g., new vs. existing) and for different amounts of voluntary activity. Drawing on social psychological work on collective helping, and work from the Social Identity Approach to Health, we seek to address this gap through an analysis of survey data from 1,001 adults living in the south of England (333 men; 646 women; age range = 16–85) during the first UK lockdown. Measures included time spent volunteering pre‐/post‐COVID, community identification, subjective wellbeing, and volunteering intentions. Those who volunteered during COVID‐19 reported higher levels of community identification than those who did not. However, subjective wellbeing benefits were only found for those volunteers who maintained the same level of volunteering (in terms of time) pre‐and post‐COVID lockdown. New volunteers showed significantly lower levels of wellbeing when they were undertaking 5 or more hours of volunteering a week. Our findings provide unique insight into the variable relationship with wellbeing for different groups of volunteers, as well as how the experiences and functioning of ‘crisis’ volunteering are different from volunteering during ‘normal’ times.
Insights into CD154‐mediated pathways in ocular hypertensive glaucoma: The role of Müller cells and P2X7 in retinal neuroprotection and therapeutic potential
Authors: Hu Huiling , Liu Xinhua , Nie Danyao , Fang Min , Zhang Jing , Zhang Guoming
Published: May 2023

An elevation of pathologic intraocular pressure (IOP) is the greatest risk factor for glaucoma. CD154 has been reported to bind to CD40 expressed by orbital fibroblasts and be involved in immune and inflammatory responses. However, the function and mechanism of CD154 in ocular hypertensive glaucoma (OHG) are not fully understood. We isolated and characterized Müller cells and subsequently examined the effect of CD154 on ATP release from those cells. After being cocultured with CD154‐pretreated Müller cells, retinal ganglion cells (RGCs) were treated with P2X7 siRNAs or a P2X7 inhibitor. Furthermore, mouse models of glaucoma (GC) were injected with P2X7 shRNA. p21, p53, and P2X7 expression were examined, and cellular senescence and apoptosis were detected by β‐Gal and TUNEL staining, retinal pathology was examined by H&E staining, and CD154 and β‐Gal expression were detected by ELISA. CD154 induced ATP release from Müller cells and accelerated the senescence and apoptosis of RGCs that had been cocultured with Müller cells. We also found that treatment with P2X7 could attenuate the senescence and apoptosis of RGCs mediated by Müller cells pretreated with CD154. In vivo studies in GC model mice verified that P2X7 silencing attenuated pathological damage and prevented the senescence and apoptosis of retinal tissue. The study demonstrates how CD154 accelerates the aging and apoptosis of RGCs by co‐cultivating Müller cells pretreated with CD154 in OHG. The research implies that CD154 has the potential to become a new therapeutic target for ocular hypertension glaucoma, providing a new research direction for its treatment.
The trap of genetic tag: The importance of pathogenicity prediction tools in the correct interpretation of variants of uncertain significance in the era of high‐throughput genome sequencing
Authors: Pellegrino Francesco
Published: May 2023

Although recent advancements in DNA sequencing technologies and their widely used, the interpretation of variants of uncertain significance from these large datasets is not clear‐cut. Here, we present the case of a family referred to our metabolic disease department, in which three males' individuals were affected by a suspected a genetic inherited disease, resulting from next‐generation sequencing results. A correct assessment of the clinical significance of the genetic variant found in our cases, with a review of the literature, the evaluation of population database and the use of computational predictive program changed the initial suspect. Despite NGS technologies have increased diagnostic sensitivity, most of these variants remains of uncertain clinical significance. An efficient systematic approach is fundamental to determine the pathogenicity of a variant, avoiding incorrect interpretation in a clinical setting.
Successful complex percutaneous intervention in patient with Fontan circulation and severe heart failure: A case report
Authors: Wittczak Andrzej , Dryżek Paweł , Maciejewski Marek , Kula‐Mazurek Anna , Moszura Tomasz , Bikiewicz Agata , Bielecka‐Dabrowa Agata
Published: May 2023

We report the case of a successful complex percutaneous intervention in a patient with Fontan circulation and severe heart failure. The patient presented with cyanosis; Fontan conduit stenosis was detected, and the fenestration was patent. The complex interventional procedure allowed for a long‐term stabilization of the patient's condition.
Development of Bifunctional, Raman Active Diyne‐Girder Stapled α‐Helical Peptides**
Authors: Morgan Danielle C. , McDougall Laura , Knuhtsen Astrid , Jamieson Andrew G.
Published: May 2023

Stapled peptides are a unique class of cyclic α‐helical peptides that are conformationally constrained via their amino acid side‐chains. They have been transformative to the field of chemical biology and peptide drug discovery through addressing many of the physicochemical limitations of linear peptides. However, there are several issues with current chemical strategies to produce stapled peptides. For example, two distinct unnatural amino acids are required to synthesize i, i+7 alkene stapled peptides, leading to high production costs. Furthermore, low purified yields are obtained due to cis/trans isomers produced during ring‐closing metathesis macrocyclisation. Here we report the development of a new i, i+7 diyne‐girder stapling strategy that addresses these issues. The asymmetric synthesis of nine unnatural Fmoc‐protected alkyne‐amino acids facilitated a systematic study to determine the optimal (S,S)‐stereochemistry and 14‐carbon diyne‐girder bridge length. Diyne‐girder stapled T‐STAR peptide 29 was demonstrated to have excellent helicity, cell permeability and stability to protease degradation. Finally, we demonstrate that the diyne‐girder constraint is a Raman chromophore with potential use in Raman cell microscopy. Development of this highly effective, bifunctional diyne‐girder stapling strategy leads us to believe that it can be used to produce other stapled peptide probes and therapeutics.
Deep learning‐based hybrid reconstruction algorithm for fibre instance segmentation from 3D x‐ray tomographic images
Authors: Fang Mengqi , Sibellas Aurélien , Drummond James , Cao Yankai , Phillion Andre , Martinez Mark , Pediredla Vijay Kumar , Gopaluni Bhushan
Published: May 2023

3D x‐ray tomography is a powerful scanning technique used for generating images of complex fibre structures. A novel machine‐learning algorithm to identify and separate individual fibres using 3D images is proposed in this article. The developed four‐step hybrid 3D fibre segmentation algorithm involves deep‐learning aided semantic segmentation that slices 3D images to create 2D images for fibre extraction, elliptical contour estimation combined with the marker‐controlled watershed algorithm for separating fibres from the background area, identifying individual fibres through 3D reconstruction, and, lastly, the 3D object refining approach based on outlier object detection and replacement. The proposed methodology is implemented on a real‐time sample of nylon fibre bundle under compression and its 3D x‐ray image volume to validate the performance. The results show its superior performance compared to off‐the‐shelf image processing algorithms in terms of precision, that is, with a validation accuracy greater than 90%, and efficiency, that is, preventing the need for a huge data set and reducing the complexity.
Modelling and parameter estimation of trans‐β‐farnesene coordination polymerization
Authors: de Sá Marília Caroline C. , Córdova Teresa , Melo Príamo A. , de León Ramón Díaz , Pinto José Carlos
Published: May 2023

trans‐β‐Farnesene is a bio‐derived terpene monomer that can polymerize, generating polymers with properties that can be similar to the properties of conventional petroleum‐derived polymers. For this reason, in the present study, several coordination polymerizations of trans‐β‐farnesene are carried out using the Ziegler–Natta catalyst system composed by neodymium versatate (), diisobutylaluminum hidride (DIBAH), and dimethyldichlorosilane (DMDCS) in order to evaluate the influence of key operation variables on the control of average molar masses and monomer conversion. A phenomenological model is proposed to describe the coordination polymerization of trans‐β‐farnesene, and the kinetic parameters required to simulate the reactions are estimated. The initial concentration of DIBAH used as a chain transfer agent (CTA) is calculated by a data reconciliation procedure since this very active compound can participate in undesired side reactions. It is shown that the initial monomer, DIBAH, and concentrations exert strong influences on the monomer conversion and average molar masses of (poly)farnese while the temperature effect is not so pronounced. The proposed kinetic mechanism was able to predict well the experimental data collected during the reactions, with the successful reconciliation of CTA concentrations and estimation of model parameters.
Study on the adsorption–desorption behaviours of La3+, Sm3+, and Y3+ by HEHEHP extraction resin in chloride medium
Authors: Guo Haoran , Yang Youming , Niu Fei , Zhang Qian , Lan Qiaofa , Liu Donghui , Zhang Xiaolin
Published: May 2023

The adsorption–desorption behaviours of La3+, Sm3+, and Y3+ on 2‐ethylhexylphosphonic acid mono‐2‐ethyl hexyl ester (HEHEHP) extraction resin were investigated in a chloride medium. The effects of reaction time, pH, hydrochloric acid concentration, flow rate, and adsorption mechanism were studied in detail using static and dynamic experimental methods. The results show that La3+ is the first to reach adsorption equilibrium, followed by Sm3+ and Y3+; the highest adsorption capacities of La3+, Sm3+, and Y3+ are obtained at solution pH of 4 and in the order of Y3+ > Sm3+ > La3+. La3+, Sm3+, and Y3+ can be eluted by 0.3, 0.5, and 3 mol/L hydrochloric acid, respectively, indicating that La3+ elutes most easily, and Y3+ is difficult. Moreover, the flow rate has little effect on the peak of rare earth desorption. The adsorption process is chemisorption; the slope method indicates that for each mol Sm3+ or Y3+ ion adsorbed, 3 mol H+ ions are simultaneously released, but two for La3+ under the given pH conditions. It is expected to provide theoretical and technical support for preparation of ultra‐high purity rare earth by HEHEHP extraction resin.
Complexity‐to‐Diversity and Pseudo‐Natural Product Strategies as Powerful Platforms for Deciphering Next‐Generation Therapeutics
Authors: Alkubaisi Bilal O. , Shahin Afnan I. , Zenati Ruba A. , Ravi Anil , Alchami Riema , Alkalla Mohammad , Khaled Rawan , El‐Gamal Mohammed I. , Al‐Tel Taleb H.
Published: May 2023

Stereochemical and skeletal complexity are particularly important vis‐à‐vis the cross‐talks between a small molecule and a complementary active site of a biological target. This intricate harmony is known to increase selectivity, reduce toxicity, and increase the success rate in clinical trials. Therefore, the development of novel strategies for establishing underrepresented chemical space that is rich in stereochemical and skeletal diversity is an important milestone in a drug discovery campaign. In this review, we discuss the evolution of interdisciplinary synthetic methodologies utilized in chemical biology and drug discovery that has revolutionized the discovery of first‐in‐class molecules over the last decade with an emphasis on complexity‐to‐diversity and pseudo‐natural product strategies as a remarkable toolbox for deciphering next‐generation therapeutics. We also report how these approaches dramatically revolutionized the discovery of novel chemical probes that target underrepresented biological space. We also highlight selected applications and discuss key opportunities offered by these tools and important synthetic strategies used for the construction of chemical spaces that are rich in skeletal and stereochemical diversity. We also provide insight on how the integration of these protocols has the promise of changing the drug discovery landscape.
Synthesis of Thieno[3,2‐d]pyrimidine Derivatives through Sequential SNAr and Suzuki Reactions as Selective h‐NTPDase Inhibitors
Authors: Zaman Gohar , Ullah Saif , Uzair Muhammad , Batool Sania , Ahmad Haseen , Ullah Farman , Pelletier Julia , Sévigny Jean , Iqbal Jamshed , Hassan Abbas
Published: May 2023

In this study various of thieno[3,2‐d]pyrimidine derivatives have been synthesized by treating different secondary amines through aromatic nucleophilic substitution reaction (SNAr) followed by Suzuki reaction with aryl and heteroaryl boronic acids. A bis‐Suzuki coupling was also performed to generate bis‐aryl thienopyrimidine derivatives. The synthesized compounds were screened for the hydrolytic activity of h‐NTPdase1, h‐NTPdase2, h‐NTPdase3, and h‐NTPdase8. The compound N‐benzyl‐N‐methyl‐7‐phenylthieno[3,2‐d]pyrimidin‐4‐amine 3 j selectively inhibits the activity of h‐NTPdase1 with IC50 value of 0.62±0.02 μM whereas, the compound 4 d was the most potent inhibitor of h‐NTPdase2 with sub‐micromolar IC50 value of 0.33±0.09 μM. Similarly, compounds 4 c and 3 b were found to be selective inhibitors for isozymes h‐NTPdase3 (IC50=0.13±0.06 μM) and h‐NTPdase8 (IC50=0.32±0.10 μM), respectively. The molecular docking study of the compounds with the highest potency and selectivity revealed the interactions with the important amino acid residues.
Evaluation of the Cytochrome P450 3A and P‐glycoprotein Drug‐Drug Interaction Potential of Futibatinib
Authors: Yamamiya Ikuo , Hunt Allen , Takenaka Toru , Sonnichsen Daryl , Mina Mark , He Yaohua , Benhadji Karim A. , Gao Ling
Published: May 2023

Futibatinib, a selective, irreversible fibroblast growth factor receptor 1–4 inhibitor, is being investigated for tumors harboring FGFR aberrations and was recently approved for the treatment of FGFR2 fusion/rearrangement‐positive intrahepatic cholangiocarcinoma. In vitro studies identified cytochrome P450 (CYP) 3A as the major CYP isoform in futibatinib metabolism and indicated that futibatinib is likely a P‐glycoprotein (P‐gp) substrate and inhibitor. Futibatinib also showed time‐dependent inhibition of CYP3A in vitro. Phase I studies investigated the drug‐drug interactions of futibatinib with itraconazole (a dual P‐gp and strong CYP3A inhibitor), rifampin (a dual P‐gp and strong CYP3A inducer), or midazolam (a sensitive CYP3A substrate) in healthy adult participants. Compared with futibatinib alone, coadministration of futibatinib with itraconazole increased futibatinib mean peak plasma concentration and area under the plasma concentration–time curve by 51% and 41%, respectively, and coadministration of futibatinib with rifampin lowered futibatinib mean peak plasma concentration and area under the plasma concentration–time curve by 53% and 64%, respectively. Coadministration of midazolam with futibatinib had no effect on midazolam pharmacokinetics compared with midazolam administered alone. These findings suggest that concomitant use of dual P‐gp and strong CYP3A inhibitors/inducers with futibatinib should be avoided, but futibatinib can be concomitantly administered with other drugs metabolized by CYP3A. Drug‐drug interaction studies with P‐gp–specific substrates and inhibitors are planned.
Prediction of Nucleophilicity and Electrophilicity Based on a Machine‐Learning Approach
Authors: Liu Yidi , Yang Qi , Cheng Junjie , Zhang Long , Luo Sanzhong , Cheng Jin‐Pei
Published: May 2023

Nucleophilicity and electrophilicity dictate the reactivity of polar organic reactions. In the past decades, Mayr et al. established a quantitative scale for nucleophilicity (N) and electrophilicity (E), which proved to be a useful tool for the rationalization of chemical reactivity. In this study, a holistic prediction model was developed through a machine‐learning approach. rSPOC, an ensemble molecular representation with structural, physicochemical and solvent features, was developed for this purpose. With 1115 nucleophiles, 285 electrophiles, and 22 solvents, the dataset is currently the largest one for reactivity prediction. The rSPOC model trained with the Extra Trees algorithm showed high accuracy in predicting Mayr's N and E parameters with R2 of 0.92 and 0.93, MAE of 1.45 and 1.45, respectively. Furthermore, the practical applications of the model, for instance, nucleophilicity prediction of NADH, NADPH and a series of enamines showed potential in predicting molecules with unknown reactivity within seconds. An online prediction platform (http://isyn.luoszgroup.com/) was constructed based on the current model, which is available free to the scientific community.
The clinical potential of optogenetic interrogation of pathogenesis
Authors: Gao Tianyu Terry , Oh Teak‐Jung , Mehta Kritika , Huang Yu‐En Andrew , Camp Tyler , Fan Huaxun , Han Jeong Won , Barnes Collin Michael , Zhang Kai
Published: May 2023

Background

Opsin‐based optogenetics has emerged as a powerful biomedical tool using light to control protein conformation. Such capacity has been initially demonstrated to control ion flow across the cell membrane, enabling precise control of action potential in excitable cells such as neurons or muscle cells. Further advancement in optogenetics incorporates a greater variety of photoactivatable proteins and results in flexible control of biological processes, such as gene expression and signal transduction, with commonly employed light sources such as LEDs or lasers in optical microscopy. Blessed by the precise genetic targeting specificity and superior spatiotemporal resolution, optogenetics offers new biological insights into physiological and pathological mechanisms underlying health and diseases. Recently, its clinical potential has started to be capitalized, particularly for blindness treatment, due to the convenient light delivery into the eye.

Aims and methods

This work summarizes the progress of current clinical trials and provides a brief overview of basic structures and photophysics of commonly used photoactivable proteins. We highlight recent achievements such as optogenetic control of the chimeric antigen receptor, CRISPR‐Cas system, gene expression, and organelle dynamics. We discuss conceptual innovation and technical challenges faced by current optogenetic research.

Conclusion

In doing so, we provide a framework that showcases ever‐growing applications of optogenetics in biomedical research and may inform novel precise medicine strategies based on this enabling technology.
Dihydroartemisinin inhibited stem cell‐like properties and enhanced oxaliplatin sensitivity of colorectal cancer via AKT/mTOR signaling
Authors: Wang Yujun , Yang Zhirong , Zhu Wanglong , Chen Yuzhuo , He Xingqiang , Li Jiaofeng , Han Zhengyu , Yang Yuhan , Liu Wei , Zhang Kun
Published: May 2023

Colorectal cancer (CRC) is a common tumor with high morbidity and mortality. The use of oxaliplatin (L‐OHP) as a first‐line treatment for CRC is limited due to chemoresistance. Growing evidence have revealed that the existence of cancer stem‐like cells (CSLCs) is one of the important reasons for drug resistance and recurrence of cancers. Dihydroartemisinin (DHA), a derivative of artemisinin, has showed anticancer effects on a variety of malignancies, in addition to its antimalarial effects. However, the effect and mechanism of DHA on CSLCs and chemosensitivity in CRC cells remains unclear. In this study, we found that DHA inhibited cell viability in HCT116 and SW620 cells. Moreover, DHA decreased cell clonogenicity, and improved L‐OHP sensitivity. Furthermore, DHA treatment attenuated tumor sphere formation, and the expressions of stem cell surface marker (CD133 and CD44) and stemness‐associated transcription factor (Nanog, c‐Myc, and OCT4). Mechanistically, the present findings showed that DHA inhibited of AKT/mTOR signaling pathway. The activation of AKT/mTOR signaling reversed DHA‐decreased cell viability, clonogenicity, L‐OHP resistance, tumor sphere, and expressions of stemness‐associated protein in CRC. The inhibitory effect of DHA on tumorigenicity of CRC cells has also been demonstrated in BALB/c nude mice. In conclusion, this study revealed that DHA inhibited CSLCs properties in CRC via AKT/mTOR signaling, suggesting that DHA may be used as a potential therapeutic agent for CRC.
The increase in medical admissions with anorexia nervosa during the COVID‐19 pandemic in Western Australia
Authors: Wong Jessica W. S. , Skeldon Sarah , Gill Emma , Taylor Ellen , Billingham Wesley , Stevenson Paul Geoffrey , Shipton Nicolene , Ferguson Grant , Collins Rachel , Newton Rachel , Newell Amanda , Martin Andrew C.
Published: May 2023

Objective

A comparative study to describe the increase in medical admissions of children and adolescents with anorexia nervosa (AN) in Western Australia in 2019 (pre‐pandemic) and 2020 (peri‐pandemic).

Method

Patient demographics, physiological parameters, length of stay, time to assessment by the Eating Disorder Service (EDS), and commencement of specialist eating disorder (ED) outpatient treatment was collected for adolescents admitted with AN between 1st January 2019 and 31st December 2020.

Results

The number of admissions doubled from 126 in 2019 to 268 in 2020. The number of children admitted increased by 52%. The median length of hospital stay was shorter in 2020 (12 vs. 17 days; p < .001), but the 28‐day readmission rate was greater (39.9% vs. 22.2%; p < .001). At the time of hospital discharge in 2020, only 60% of patients were able to step‐down into specialist ED outpatient treatment, compared to 93% in 2019. The mean number of admissions per child before completing EDS assessment increased significantly in 2020 (2.75 vs. 0, p < .001).

Discussion

Shorter inpatient stays and delays in the commencement of specialist ED outpatient treatment may have contributed to the increased readmission rate seen in 2020.

Public significance

This research is important as it explores the reasons for increased medical presentations and admissions of youth with AN during the COVID‐19 pandemic in Western Australia. We hope that our lessons learned may be helpful to others trying to balance similar clinical workloads.
Microplastic burden in invasive signal crayfish (Pacifastacus leniusculus) increases along a stream urbanization gradient
Authors: Dent Abigail R. , Chadwick Daniel D. A. , Eagle Lawrence J. B. , Gould Alex N. , Harwood Matthew , Sayer Carl D. , Rose Neil L.
Published: May 2023

Microplastics are a globally pervasive pollutant with the potential to directly impact species and accumulate in ecosystems. However, there remains a relative paucity of research addressing their accumulation in freshwater ecosystems and a near absence of work in crayfish, despite their high ecological and economic importance. This study investigated the presence of microplastics in the invasive signal crayfish Pacifastacus leniusculus along a stream urbanization gradient. The results demonstrate a ubiquitous presence of microplastics in crayfish digestive tracts at all sites and provide the first evidence of microplastic accumulation in tail tissue. Evidence of a positive linear trend was demonstrated between microplastic concentration in crayfish and upstream urban area size in generalized linear models. Evidence for a positive effect of the upstream urban area and a negative effect of crayfish length on microplastic concentrations in crayfish was demonstrated in multiple generalized linear regression models. Our results extend the current understanding of microplastics presence in freshwater ecosystems and demonstrate their presence in crayfish in the wild for the first time.
Species asynchrony stabilizes productivity over 20 years in Northeast China
Authors: Jia Bo , He Jingyuan , Wang Xinjie
Published: May 2023

The stability of forest productivity can reflect the functioning of forest ecosystems. It is a crucial topic to understand the relationship between biodiversity and ecosystem functions in ecology. Although previous studies have made great progress in understanding the effects of diversity, species asynchrony, and other factors on community biomass and productivity, few studies have explored how these factors affect the temporal stability of productivity. In this study, we hypothesized that diversity, species asynchrony, and topography would directly or indirectly impact the temporal stability of productivity. To test this hypothesis, we used a multiple regression model and a piecewise structural equation model based on the inventory data over 20 years (5‐year intervals) from 1992 to 2012 at Jingouling Forest Farm in Northeast China. Our results showed that species asynchrony was the main driving factor affecting the temporal stability of productivity. Structural diversity significantly decreased community stability, while species diversity had a nonsignificant effect on it. We found the combination of a multiple regression model and a piecewise structural equation model is an effective method for evaluating the factors that influence community stability. The effect of species asynchrony is crucial for understanding the ecological mechanisms underlying the diversity–stability relationship in mixed forests.
Barriers and enablers of environmental policy coherence: A systematic review
Authors: Fopa Tchinda Alain , Talbot David
Published: May 2023

The literature on policy coherence (PC) examines contradictions and synergies between policies. This systematic review explores factors that facilitate or disrupt PC in the environmental field. Based on 70 empirical studies, this research describes the evolution of the PC literature, identifying eight critical PC factors. Furthermore, this study identifies six avenues for future research on PC, such as methodological innovations and including stakeholders in the policy development process. In addition to drawing on contradictions and synergies for PC analysis, this study suggests an integrative framework of barriers and enablers. These findings have implications for policymakers and program managers in the environmental field.
Basicity‐Controlled [3+2] Cyclization of 3‐Hydroxyquinolin‐ones and β‐Chlorinated Nitrostyrenes
Authors: Wu Jiamin , Hu Fei , Bai Guishun , Yang Yang , Bonne Damien , Rodriguez Jean , Yue Congyong , Wang Hong , Bao Xiaoze
Published: May 2023

The construction of novel skeletons through the recombination of natural products ring systems is attractive. Herein, a basicity‐controlled synthesis of (dihydro)furo[2,3‐c]quinolin‐4(5H)‐one derivatives through (3+2) cyclization between 3‐hydroxyquinolin‐2‐ones and β‐chlorinated nitrostyrenes was developed. In addition, preliminary study gave the chiral dihydrofuro[2,3‐c]quinolin‐4(5H)‐one derivatives with up to 83 % ee.
Pushing too far? Negotiations of non‐compliance and resistance to the COVID‐19 cabin ban in Norway
Authors: Moss Sigrun Marie , Sandbakken Ella Marie
Published: May 2023

Many societies experienced pushback against governmental COVID‐19 measures. When the Norwegian government made it a punishable offence to spend the night at privately owned cabins in the first phase of the pandemic, this resulted in discussions and pushback. Basing our research on in‐depth interviews at three different time points during the pandemic, we ask how Norwegian participants discursively explain why the cabin ban was the first measure that evoked pushback in Norway. We conducted a Foucauldian discourse analysis (FDA), exploring three overarching explanations provided by the interview participants. In the first explanation, the pushback was presented as a result of the cultural importance of the cabin. Here, participants partly legitimised the pushback when constructing it as a predictable reaction in this cultural context. In the second explanation, participants constructed the pushback as an expression of ‘cabin people’ in particular and Norwegians in general being ‘too privileged’ to acknowledge the measure's necessity. Here, the pushback was constructed as an illegitimate reaction. In the third explanation, participants explained the pushback as a result of people seeing the measure as meaningless. This interpretation constructs pushback as a legitimate response to an illogical measure. These different constructions illustrate the complexity of compliance with COVID measures, where people negotiated individual freedom against solidarity, and compliance against critical thinking. The article contributes to the understanding of people's negotiations of resistance and pushback against restrictive measures. We argue that social psychological theory and research need to acknowledge the temporal, contextual and ideological specificities in understanding compliance and non‐compliance.
Household socioeconomic status relates to specific hippocampal subfield volumes across development
Authors: Canada Kelsey L. , Homayouni Roya , Yu Qijing , Foster Da' Jonae , Ramesh Sruthi , Raz Sarah , Daugherty Ana M. , Ofen Noa
Published: May 2023

The hippocampus is composed of cytoarchitecturally distinct subfields that support specific memory functions. Variations in total hippocampal volume across development have been linked to socioeconomic status (SES), a proxy for access to material resources, medical care, and quality education. High childhood household SES is associated with greater cognitive abilities in adulthood. Currently, it is not known whether household SES differentially impacts specific hippocampal subfield volumes. We assessed susceptibility of subfields to variations in household SES across development in a sample of 167 typically developing 5‐ to 25‐year‐old. Bilateral cornu ammonis (CA) 1–2, combined CA3‐dentate gyrus (DG), and subiculum (Sub) volumes were measured by highly reliable manual segmentation of high‐resolution T2‐weighted images and adjusted for intracranial volume. A summary component score of SES measures (paternal education, maternal education, and income‐to‐needs ratio) was used to examine variability in volumes across ages. We did not identify age‐related differences in any of the regional volumes, nor did age modify SES‐related effects. Controlling for age, larger volumes of CA3‐DG and CA1‐2 were associated with lower SES, while Sub volume was not. Overall, these findings support the specific impact of SES on CA3‐DG and CA1‐2 and highlight the importance of considering environmental influences on hippocampal subfield development.
Report of PRPF19 as a novel partner of RARG and the recurrence of interposition‐type fusion in variant acute promyelocytic leukemia
Authors: Wu Huanling , Li Hongjun , Zhou Xiaosu , Zhao Zongchen , Cao Panxiang , Li Li , Ma Xiaoli , Yuan Lili , Wang Fang , Zhang Yang , Chen Jiaqi , Fang Jiancheng , Liu Ming , Liu Mingyue , Chen Xue , Liu Hongxing
Published: May 2023

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML) which is characterized by specific clinical and biological features. Typical APL cases are caused by PML::RARA fusion gene and are exquisitely sensitive to all‐trans retinoic acid (ATRA) and arsenic trioxide (ATO). Rarely, APLs are caused by atypical fusions involving RARA or, in fewer cases still, fusions involving other members of the retinoic acid receptors (RARB or RARG). To date, seven partner genes of RARG have been reported in a total of 18 cases of variant APL. Patients with RARG fusions showed distinct clinical resistance to ATRA and had poor outcomes. Here, we report PRPF19 gene as a novel partner of RARG and identify a rare interposition‐type gene fusion in a variant APL patient with a rapidly fatal clinical course. The incomplete ligand‐binding domain of RARG in the fusion protein may account for the clinical ATRA resistance in this patient. These results broaden the spectrum of variant APL associated molecular aberrations. Accurately and timely identification of these rare gene fusions in variant APL is essential to guide therapeutic decisions.
Asthma control and care among six public health clinic attenders in Malaysia: A cross‐sectional study
Authors: Hussein Norita , Liew Su May , Hanafi Nik Sherina , Lee Ping Yein , Cheong Ai Theng , Ghazali Sazlina Shariff , Chinna Karuthan , Pang Yong Kek , Kassim Asiah , Parker Richard A. , Schwarze Jürgen , Sheikh Aziz , Pinnock Hilary , Khoo Ee Ming ,   the RESPIRE Collaborators
Published: May 2023

Background and Aims

Asthma is common in Malaysia but neglected. Achieving optimal asthma control and care is a challenge in the primary care setting. In this study, we aimed to identify the risk factors for poor asthma control and pattern of care among adults and children (5–17 years old) with asthma attending six public health clinics in Klang District, Malaysia.

Methods

We conducted a cross‐sectional study collecting patients’ sociodemographic characteristics, asthma control, trigger factors, healthcare use, asthma treatment, and monitoring and use of asthma action plan. Descriptive statistics and stepwise logistic regression were used in data analysis.

Results

A total of 1280 patients were recruited; 85.3% adults and 14.7% children aged 5–17 years old. Only 34.1% of adults had well‐controlled asthma, 36.5% had partly controlled asthma, and 29.4% had uncontrolled asthma. In children, 54.3% had well‐controlled asthma, 31.9% had partly controlled, and 13.8% had uncontrolled asthma. More than half had experienced one or more exacerbations in the last 1 year, with a mean of six exacerbations in adults and three in children. Main triggers for poor control in adults were haze (odds ratio [OR] 1.51; 95% confidence interval [CI] 1.13–2.01); cold food (OR 1.54; 95% CI 1.15–2.07), extreme emotion (OR 1.90; 95% CI 1.26–2.89); air‐conditioning (OR 1.63; 95% CI 1.20–2.22); and physical activity (OR 2.85; 95% CI 2.13–3.82). In children, hot weather (OR 3.14; 95% CI 1.22–8.11), and allergic rhinitis (OR 2.57; 95% CI 1.13–5.82) contributed to poor control. The majority (81.7% of adults and 64.4% of children) were prescribed controller medications, but only 42.4% and 29.8% of the respective groups were compliant with the treatment. The importance of an asthma action plan was reported less emphasized in asthma education.

Conclusion

Asthma control remains suboptimal. Several triggers, compliance to controller medications, and asthma action plan use require attention during asthma reviews for better asthma outcomes.
Preisolation measures and clinical features for pediatric patients with suspicious COVID‐19
Authors: Li Xiaoyu , Jiang Fengqiong , Qiu Yun , Yu Jing , Zhu Yan , Tang Xiaoli , Chen Hongyan , Hu Tingting , Zhao Yinghan
Published: May 2023

Background

In December 2019, many cases of COVID‐19 were reported in Wuhan City, Hubei Province, China. In the following 3 months, the disease out broke in China. Preisolation measures was used to screen out COVID‐19 patients in the pediatric respiratory ward of our hospital.

Aims

To investigate the new measures for screening COVID‐19 patients and to analyze the clinical features of children with suspicious COVID‐19.

Methods

A total of 50 preisolated children with suspicious COVID‐19 who were admitted to our hospital in Mianyang, China, between January 28 and March 5, 2020, were included. Patients presented with fever and cough or fever accompanied by vomiting and diarrhea. A detailed epidemiological history screening was performed. A real‐time reverse‐transcriptase–polymerase‐chain‐reaction (RT‐PCR) was used to detect SARS‐COV‐2 nucleic acid. Low‐dose chest computed tomography (CT) was applied when pneumonia was suspicious. Routine blood tests were performed to rule out COVID‐19. Patients' data were collected, and the basic clinical features, epidemiological history, clinical manifestations, auxiliary examination results, and outcomes were analyzed and summarized.

Results

No definite cases were detected, while two patients were suspected of having COVID‐19. The pathogenic results of the 50 patients mainly included Mycoplasma pneumoniae, followed by Epstein–Barr virus, and rotavirus. Thirty‐five patients suffered from bronchopneumonia. The preisolated patients had similar clinical and epidemiological characteristics as patients with fever, cough, vomiting, and diarrhea.

Conclusions

Preisolation measures combined with pathogen screening can minimize the risk of hospital‐acquired infections by preventing patients with suspicious COVID‐19 from contacting other patients before they are explicitly excluded. Clinical analysis of the patients was helpful for clinical nursing management.