bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultra‐Large Stress and Strain Polymer Nanocomposite Actuators Incorporating a Mutually‐Interpenetrated, Collective‐Deformation Carbon Nanotube Network
Authors: Chen Kun , Li Meng , Yang Zifan , Ye Ziming , Zhang Ding , Zhao Bo , Xia Zhiyuan , Wang Qi , Kong Xiaobing , Shang Yuanyuan , Liu Chenyang , Yu Haifeng , Cao Anyuan
Published: April 2024

Stimulus‐responsive polymer‐based actuators are extensively studied, with the challenging goal of achieving comprehensive performance metrics that include large output stress and strain, fast response, and versatile actuation modes. The design and fabrication of nanocomposites offer a promising route to integrate the advantages of both polymers and nanoscale fillers, thus ensuring superior performance. Here, it is started from a three‐dimensional (3D) porous sponge to fabricate a mutually interpenetrated nanocomposite, in which the embedded carbon nanotube (CNT) network undergoes collective deformation with the shape memory polymer (SMP) matrix during large‐degree stretching and releasing, increases junction density with polymer chains and enhances molecular orientation. These features result in substantial improvement of the overall mechanical properties and during thermally actuated contraction, the bulk SMP/CNT composites exhibit output stresses up to 19.5 ± 0.97 MPa and strains up to 69%, accompanied by a rapid response and high energy density, exceeding the majority of recent reports. Furthermore, electrical actuation is also demonstrated via uniform Joule heating across the self‐percolated CNT network. Applications such as low‐temperature thermal actuated vascular stent and wound dressing are explored. These findings lay out a universal blueprint for developing robust and highly deformable SMP/CNT nanocomposite actuators with broad potential applications.
Charge Protection in Electret Air Filtration Nonwoven Materials
Authors: Lavoie Joseph , Rojas Orlando J. , Khan Saad A. , Shim Eunkyoung
Published: April 2024

Nonwoven media used as electret air filters are often embedded with charges to improve particle capture efficiency. These charged filters are invariably exposed to low surface tension fluids such as oils and alcohols leading to charge loss. In this study, filtration media are endowed with charge protection through increased surface repellency using melt additives that can migrate to the surface during processing. Nonwovens containing fluorochemical melt additives are produced, and examined to determine the relationship between surface chemistry, isopropyl alcohol (IPA) repellency, resultant charge retention, and filtration characteristics. Surface fluorine/carbon (F/C) ratios of ≈0.2 are sufficient to protect filtration performance from vapor discharging methods. Samples with bulk additive loadings of 1.2% or higher are found to achieve the necessary repellency to resist discharging independent of the migration state of the sample, while samples loaded at the 0.6% level required sufficient migration to achieve the requisite F/C ratio of 0.2 in order to be protected. Samples that achieved the necessary surface chemistry to provide significant IPA repellency retained > 80% of electret charge and corresponding filtration performance. These results have special significance in the design of filtration media relevant in global healthcare and other industrial settings.
Laser Parallel Nanofabrication of Dual‐Au‐Nanoholes on Microsphere‐Lens‐Array for Polarization‐Dependent SERS
Authors: Wang Mengyuan , Yan Yinzhou , Zhao Chen , Jiang Yijian
Published: April 2024

High‐efficient fabrication of well‐ordered nanostructures on flexible substrates is a challenge to surface‐enhanced Raman spectroscopy (SERS) for analytical fingerprinting trace‐detection. In this work, a laser parallel nanofabrication method is reported via incident‐angle‐dependent photonic nanojet ablating Au film on the bottom surface of microsphere‐lens‐array (MLA), for combination with formed dual Au‐nanoholes (MLA/2‐AuNHs) as the flexible SERS substrates. The process parameters, i.e., pulsed laser energy, MLA diameter, Au film thickness, and laser incident angle, are optimized for high finish‐quality of dual‐AuNHs with a diameter of ≈875 nm and a tip gap of ≈90 nm. The SERS substrate demonstrates the limit of detection down to 10−11 M for 4‐nitrobenzenethiol molecules by the multiple optical regulations, including self‐aligned focusing to the hotspots and directional antenna, the strongly localized surface plasmon resonances, and optical whispering‐gallery modes for resonance energy transfer. The flexible PDMS film supporting the rigid MLA holds the SERS performance of MLA/2‐AuNHs with high flexibility. Moreover, the MLA/2‐AuNHs SERS substrate exhibits differential responses to orthogonally polarized excitation, by which the background noises can be eliminated to improve the Raman spectrum. The present work opens new opportunities to fabricate dielectric‐metal flexible SERS substrates by laser parallel nanofabrication via MLA for Raman trace detection.
All‐Optical Excitatory and Inhibitory Synapses Based on Reversible Photo‐Induced Phase Transition in Single‐Crystal CsPbBr3 Perovskite
Authors: Cheng Pengpeng , Liu Zehan , Zhou Jian , Kang Ruyan , Wang Xiaoshan , Li Xiaoxuan , Zhao Xian , Zhao Jia , Zuo Zhiyuan
Published: April 2024

The hardware‐level construction of artificial synapses, mimicking the functionality of biological synapses, is widely acknowledged as a pivotal stride in artificial intelligence systems. Particularly, establishing all‐optical artificial synapses for neuromorphic computing, leveraging on‐chip optical interconnects instead of conventional wired connections, has garnered widespread attention. Here, high‐quality CsPbBr3 single crystals are synthesized, and intriguing relaxation processes associated with reversible photo‐induced phase transition (PIPT) are observed, leading to a corresponding change in the birefringence effect. The birefringence change is systematically analyzed by an optical system. The relaxation time of reversible PIPT is similar to the behavior patterns of biological synapses, enabling the device to mimic synaptic features. The device successfully mimics excitatory/inhibitory synaptic behaviors such as EPSP/IPSP, PPF, SDDP, SFDP, and SIDP by using 1310 nm signal. Furthermore, the device continues to exhibit excitatory/inhibitory synaptic functionality when 940 and 1550 nm signals are applied, achieving multi‐wavelength synaptic behaviors. The all‐optical devices have the advantages of low crosstalk, fast signaling, and wide optical bandwidth, which lays the foundation of all‐optical hardware for neuromorphic computing systems.
Rh(II)‐Catalyzed Homocoupling/[4+1] Cycloaddition Cascade of Diazobarbiturates with Diazopyrazolones to Prepare Spirobarbiturates
Authors: Wang Kuo , Zhang Yue , Mi Yu‐Hang , Zhao Hong‐Wu , Song Xiu‐Qing , Li Jin‐Tao , Zhang Fang
Published: April 2024

Under the catalysis of Rh2(OAc)4 (10 mol%) and (±)‐Me‐Pybox (20 mol%) in 1,2‐DCE at 80 °C, the homocoupling/[4+1] cycloaddition cascade of diazobarbiturates with diazopyrazolones proceeded readily and provided spirobarbiturates in 32–88% chemical yields. The chemical structure of the obtained spirobarbiturates was identified by X‐ray diffraction analysis.
Opsonization Inveigles Macrophages Engulfing Carrier‐Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy
Authors: Huang Huirong , Zheng Shimin , Wu Jianing , Liang Xindan , Li Shengjie , Mao Pengfei , He Zhinan , Chen Yahui , Sun Lining , Zhao Xinyu , Cai Aimin , Wang Luhui , Sheng Huixiang , Yao Qing , Chen Ruijie , Zhao Ying‐Zheng , Kou Longfa
Published: April 2024

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease‐modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G‐conjugated bilirubin/JPH203 self‐assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra‐articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa‐B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier‐free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.
Trends in Medicare utilization and reimbursement for hematology/oncology procedures from 2012 to 2023: A geriatric oncology perspective
Authors: Conic J. , Reske T.
Published: April 2024

Objectives

Given the scarcity of data exploring reimbursement trends in the field of hematology/oncology, we sought to characterize these trends for common procedures in this field from 2012 to 2023.

Methods

Using the Centers for Medicare and Medicaid Services' Physician Fee Schedule Look‐Up Tool we collected reimbursement data for 40 hematology/oncology procedure codes from 2012 to 2023. Data was adjusted to 2023 United States (US) dollars using the Consumer Price Index (CPI).

Results

From 2012 to 2023 gross reimbursement for the facility price decreased 4.4% and increased 9.2% for the non‐facility price. When adjusted for inflation, compensation decreased 96.1% and 96.6%, respectively. None of the 40 examined Current Procedural Terminology (CPT) codes increased in net reimbursement over the study period.

Conclusions

Medicare reimbursement for common hematology/oncology procedures decreased from 2012 to 2023. Further research is necessary to explore the implications of these trends on the delivery of patient care.
Palladium‐Catalyzed Carbonylation of Aryl Sulfonium Salts with CO2 as a CO Surrogate
Authors: Guo Yanhui , Wei Li , Jiang Huanfeng , Qi Chaorong
Published: April 2024

Palladium‐catalyzed carbonylation of aryl sulfonium salts with CO2 as a CO surrogate has been successfully developed via a one‐pot two‐step procedure. Thus, by merging thianthrenation and the carbonylation, site‐selective aromatic C−H carbonylation of a plethora of readily available arenes can be realized with CO2, providing access to a variety of structurally diverse and useful benzamides, esters and carboxylic acids. Simple operation, broad substrate scope, good functional group tolerance and mild reaction conditions are the attractive features of the method. Late‐stage functionalization of complex bioactive molecules as well as the precise synthesis of pharmaceuticals 1‐BCP and butoxycaine demonstrated the potential application of the established protocol.
Steering sp‐Carbon Content in Graphdiynes for Enhanced Two‐Electron Oxygen Reduction to Hydrogen Peroxide
Authors: Guo Ying , Zhang Rong , Zhang Shaoce , Hong Hu , Li Pei , Zhao Yuwei , Huang Zhaodong , Zhi Chunyi
Published: April 2024

Compared to sp2‐hybridized graphene, graphdiynes (GDYs) composed of sp and sp2 carbon are highly promising as efficient catalysts for electrocatalytic oxygen reduction into oxygen peroxide because of the high catalytic reactivity of the electron‐rich sp‐carbon atoms. The desired catalytic capacity of GDY, such as catalytic selectivity and efficiency, can theoretically be achieved by strategically steering the sp‐carbon contents or the topological arrangement of the acetylenic linkages and aromatic bonds. Herein, we successfully tuned the electrocatalytic activity of GDYs by regulating the sp‐to‐sp2 carbon ratios with different organic monomer precursors. As the active sp‐carbon atoms possess electron‐sufficient π orbitals, they can donate electrons to the lowest unoccupied molecular orbital (LUMO) orbitals of O2 molecules and initiate subsequent O2 reduction, GDY with the high sp‐carbon content of 50 at % exhibits excellent capability of catalyzing O2 reduction into H2O2. It demonstrates exceptional H2O2 selectivity of over 95.0 % and impressive performance in practical H2O2 production, Faraday efficiency (FE) exceeding 99.0 %, and a yield of 83.3 nmol s−1 cm−2. Our work holds significant importance in effectively steering the inherent properties of GDYs by purposefully adjusting the sp‐to‐sp2 carbon ratio and highlights their immense potential for research and applications in catalysis and other fields.
Photocatalytic degradation of methylene blue by anatase TiO2 coating
Authors: Desch Nikolai , Rheindorf Angela , Fassbender Cornelia , Sloot Marc , Lake Markus
Published: April 2024

Photocatalytic coatings have the potential to contribute to the purification of water via an advanced oxidation process (AOP). A commonly used method for analyzing the mechanism of the photocatalytic performance of a given reactor type is to document the degradation behavior in a solution containing methylene blue. However, since methylene blue is rather unstable, the degradation results should be viewed critically. In this work, the degradation behavior of a test solution with methylene blue on quartz glass surfaces coated with photocatalytic titanium dioxide (TiO2) of the anatase modification was investigated through a variety of different light sources. The coating was deposited by physical vapor deposition (PVD) with the reactive pulsed DC magnetron sputtering ion plating (MSIP) method described in the study by Desch and Lake, while the quartz glasses were coated with a 100 nm thick TiO2 coating on the outside. The same glasses were used for all experiments with TiO2. In the determination of the degradation rate, additional experiments were performed using pure quartz glass without any coating, which made it possible to examine the influence of different light sources on the degradation rate of methylene blue in general. Three different light sources, namely UV‐A, UV‐C, and simple fluorescent lamps were used in this study. The concentration of methylene blue was recorded by photo spectrometer in 10‐min increments throughout the experiment and the experiments were performed for 24 h in all cases. Our data indicates that the methylene blue test is a poor method because the degradation rate is not clearly differentiable due to the low stability of the test substance. Without including reference testing in the absence of a catalyst, data may be subject to misinterpretation.
Identification and expression patterns of somatic piRNAs and PIWI genes in Riptortus pedestris (Hemiptera: Alydidae)
Authors: Ren Yipeng , Dong Wenhao , Bu Wenjun , Xue Huaijun
Published: April 2024

RNA interference (RNAi)‐based gene silencing is a feasible and sustainable technology for the management of hemipteran pests by double‐stranded RNA involvement, including small‐interfering RNA, microRNA, and Piwi‐interacting RNA (piRNA) pathways, that may help to decrease the usage of chemical insecticides. However, only a few data are available on the somatic piRNAs and their biogenesis genes in Riptortus pedestris, which serves as a significant pest of soybean (Glycine max). In this study, two family members of the PIWI gene were identified and characterized in R. pedestris, containing Argonaute3 (RpAgo3) and Aubergine (RpAub) genes with conserved protein domains, and their clusters were validated by phylogenetic analysis. In addition, they were widely expressed in all developmental stages of the whole body of R. pedestris and had lower expression levels in R. pedestris guts under different rearing conditions based on previous transcriptome sequencing. Furthermore, abundant clean reads were filtered to a total number of 45,998 piRNAs with uridine bias at the first nucleotide (nt) position and 26–32 nt in length by mapping onto the reference genome of R. pedestris according to our previous whole‐transcriptome sequencing. Finally, our data revealed that gut bacterial changes were significantly positively or negatively associated with differentially expressed piRNAs among the five comparison groups with Pearson correlation analysis. In conclusion, these findings paved new avenues for the application of RNAi‐based biopesticides for broad‐spectrum hemipteran pest control.
Centromere diversity: How different repeat‐based holocentromeres may have evolved
Authors: Kuo Yi‐Tzu , Schubert Veit , Marques André , Schubert Ingo , Houben Andreas
Published: April 2024

In addition to monocentric eukaryotes, which have a single localized centromere on each chromosome, there are holocentric species, with extended repeat‐based or repeat‐less centromeres distributed over the entire chromosome length. At least two types of repeat‐based holocentromeres exist, one composed of many small repeat‐based centromere units (small unit‐type), and another one characterized by a few large centromere units (large unit‐type). We hypothesize that the transposable element‐mediated dispersal of hundreds of short satellite arrays formed the small centromere unit‐type holocentromere in Rhynchospora pubera. The large centromere unit‐type of the plant Chionographis japonica is likely a product of simultaneous DNA double‐strand breaks (DSBs), which initiated the de novo formation of repeat‐based holocentromeres via insertion of satellite DNA, derived from extra‐chromosomal circular DNAs (eccDNAs). The number of initial DSBs along the chromosomes must be higher than the number of centromere units since only a portion of the breaks will have incorporated eccDNA at an appropriate position to serve as future centromere unit sites. Subsequently, preferential incorporation of the centromeric histone H3 variant at these positions is assumed. The identification of repeat‐based holocentromeres across lineages will unveil the centromere plasticity and elucidate the mechanisms underlying the diverse formation of holocentromeres.
Rational design of structure‐based vaccines targeting misfolded alpha‐synuclein conformers of Parkinson's disease and related disorders
Authors: Flores‐Fernandez Jose Miguel , Pesch Verena , Sriraman Aishwarya , Chimal‐Juarez Enrique , Amidian Sara , Wang Xiongyao , Duckering Caleb , Fang Andrew , Reithofer Sara , Ma Liang , Cortez Leonardo M. , Sim Valerie L. , Tamgüney Gültekin , Wille Holger
Published: April 2024

Synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), are neurodegenerative disorders caused by the accumulation of misfolded alpha‐synuclein protein. Developing effective vaccines against synucleinopathies is challenging due to the difficulty of stimulating an immune‐specific response against alpha‐synuclein without causing harmful autoimmune reactions, selectively targeting only pathological forms of alpha‐synuclein. Previous attempts using linear peptides and epitopes without control of the antigen structure failed in clinical trials. The immune system was unable to distinguish between native alpha‐synuclein and its amyloid form. The prion domain of the fungal HET‐s protein was selected as a scaffold to introduce select epitopes from the surface of alpha‐synuclein fibrils. Four vaccine candidates were generated by introducing specific amino acid substitutions onto the surface of the scaffold protein. The approach successfully mimicked the stacking of the parallel in‐register beta‐sheet structure seen in alpha‐synuclein fibrils. All vaccine candidates induced substantial levels of IgG antibodies that recognized pathological alpha‐synuclein fibrils derived from a synucleinopathy mouse model. Furthermore, the antisera recognized pathological alpha‐synuclein aggregates in brain lysates from patients who died from DLB, MSA, or PD, but did not recognize linear alpha‐synuclein peptides. Our approach, based on the rational design of vaccines using the structure of alpha‐synuclein amyloid fibrils and strict control over the exposed antigen structure used for immunization, as well as the ability to mimic aggregated alpha‐synuclein, provides a promising avenue toward developing effective vaccines against alpha‐synuclein fibrils.
‘We're still here’: Misrecognition and the quest for dual identification of Roma people
Authors: Kende Anna , Sam Nariman Hadi , Ayanian Arin H. , Halabi Slieman , Ivan Claudiu , Karić Tijana , Mihić Vladimir , Nyúl Boglárka , Pántya József , da Silva Caroline , Hopkins Nick
Published: April 2024

Misrecognition describes everyday practices that deny the autonomy of minority members to define who they are and instead impose identities that may diverge from their own sense of self. Being misrecognized is particularly relevant for the historically marginalized Roma people, whose national belonging is repeatedly questioned despite centuries of co‐existence and citizenship. Our aim was to understand whether the experience of misrecognition, along with discrimination, would predict identification patterns that represent an obstacle to dual identification among Roma people in three East‐Central European countries: Hungary, Romania and Serbia. We collected data among Roma participants online and face‐to‐face with convenience sampling (N = 1,325). Latent class analysis revealed three similar classes based on national and ethnic identification scores in all subsamples: (1) disidentification, (2) Roma identification and (3) dual identification. Logistic regression analysis showed that misrecognition and discrimination predicted stronger Roma identity than dual identification in Hungary and Serbia. However, misrecognition predicted stronger dual identification in Romania, possibly as a reaffirmation strategy in response to misrecognition. Our results show that misrecognition can add to our understanding of minority group members' identification with the superordinate category of the nation as well as subgroup ethnic minority identity, and this connection could be key for advancing Roma inclusion.
Cell viability and cytotoxicity assays: Biochemical elements and cellular compartments
Authors: Khalef Lefsih , Lydia Radja , Filicia Khettar , Moussa Berkoud
Published: April 2024

Cell viability and cytotoxicity assays play a crucial role in drug screening and evaluating the cytotoxic effects of various chemicals. The quantification of cell viability and proliferation serves as the cornerstone for numerous in vitro assays that assess cellular responses to external factors. In the last decade, several studies have developed guidelines for defining and interpreting cell viability and cytotoxicity based on morphological, biochemical, and functional perspectives. As this domain continues to experience ongoing growth, revealing new mechanisms orchestrating diverse cell cytotoxicity pathways, we suggest a revised classification for multiple assays employed in evaluating cell viability and cell death. This classification is rooted in the cellular compartment and/or biochemical element involved, with a specific focus on mechanistic and essential aspects of the process. The assays are founded on diverse cell functions, encompassing metabolic activity, enzyme activity, cell membrane permeability and integrity, adenosine 5′‐triphosphate content, cell adherence, reduction equivalents, dye inclusion or exclusion, constitutive protease activity, colony formation, DNA fragmentation and nuclear splitting. These assays present straightforward, reliable, sensitive, reproducible, cost‐effective, and high‐throughput approaches for appraising the effects of newly formulated chemotherapeutic biomolecules on the cell survival during the drug development process.
A Quantitative Method to Distinguish Cytosolic from Endosome‐Trapped Cell‐Penetrating Peptides
Authors: Illien Françoise , Bánóczi Zoltán , Sagan Sandrine
Published: April 2024

Cell‐penetrating peptides are known to penetrate cells through endocytosis and translocation. The two pathways are hardly distinguished in current cell assays. We developed a reliable, simple and robust method to distinguish and quantify independently the two routes. The assay requires (DABCYL) 4‐(dimethylaminoazo)benzene‐4‐carboxylic acid‐ and (CF) carboxyfluorescein‐labeled peptides. When the labeled peptide is intact, the fluorescence signal is weak thanks to the dark quenching property of DABCYL. A 10‐fold higher fluorescence signal is measured when the labeled peptide is degraded. By referring to a standard fluorescent curve according to the concentration of the hydrolyzed peptide, we have access to the internalized peptide quantity. Therefore, cell lysis after internalization permits to determine the total quantity of intracellular peptide. The molecular state of the internalized peptide (intact or degraded), depends on its location in cells (cytosol vs endo‐lysosomes), and can be blocked by boiling cells. This boiling step results indeed in denaturation and inhibition of the cellular enzymes. The advantage of this method is the possibility to quantify translocation at 37 °C and to compare it to the 4 °C condition, where all endocytosis processes are inhibited. We found that ranking of the translocation efficacy is DABCYL‐R6‐(ϵCF)K≫DABCYL‐R4‐(ϵCF)K≥CF‐R9.
Acquired methemoglobinemia due to nitrobenzene poisoning: An unusual acquaintance
Authors: Bhatta Sunil , Awasthi Pusp Raj
Published: April 2024

Key Clinical Message

Nitrobenzene poisoning is a rare yet life‐threatening contention. The ensuing acute methemoglobinemia has a high fatality rate, hence early prompt intervention is required. Methylene blue (intravenous or oral) and ascorbic acid are the cornerstones of management. They must be administered to suspected patients without tardiness.

An aromatic organic chemical used in paints and the printing industry is nitrobenzene. Its poisoning causes potentially fatal methemoglobinemia. One aspect of its management involves reducing the iron moiety from its ferric to ferrous form by administering intravenous methylene blue. A 23‐year‐old man who had deliberately consumed nitrobenzene presented to us with a history of headache and vomiting. He was diagnosed to have methemoglobinemia on the basis of clinical grounds and was managed successfully with intravenous methylene blue and vitamin C.
A Population Pharmacokinetic Assessment of the Effect of Food on Selumetinib in Patients with Neurofibromatosis Type 1‐Related Plexiform Neurofibromas and Healthy Volunteers
Authors: Zuo Peiying , Arefayene Million , Pan Wei‐Jian , Freshwater Tomoko , Monteleone Jonathan
Published: April 2024

Selumetinib is clinically used for pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. Until recently, selumetinib had to be taken twice daily, after 2 hours of fasting and followed by 1 hour of fasting, which could be inconvenient. This population analysis evaluated the effect of low‐ and high‐fat meals on the pharmacokinetic (PK) parameters of selumetinib and its active metabolite N‐desmethyl selumetinib. The dataset comprised 511 subjects from 15 clinical trials who received ≥1 dose of selumetinib and provided ≥1 measurable postdose concentration of selumetinib and N‐desmethyl selumetinib. A 2‐compartment model with sequential 0‐ and 1st‐order delayed absorption and 1st‐order elimination adequately described selumetinib PK characteristics. A 1‐compartment model reasonably described N‐desmethyl selumetinib PK characteristics over time simultaneously with selumetinib. Selumetinib geometric mean area under the concentration–time curve ratio (1‐sided 90% confidence interval [CI] lower bound) was 76.9% (73.3%) with a low‐fat meal and 79.3% (76.3%) with a high‐fat meal versus fasting. The lower bound of the 1‐sided 90% CI demonstrated a difference of <30% between fed and fasted states. Considering the flat exposure‐response relationship within the dose range (20‐30 mg/m2), the observed range of exposure, and the variability in the SPRINT trial, this was not considered clinically relevant.
Association of Three Novel Inflammatory Markers: Lymphocyte to HDL‐C Ratio, High‐Sensitivity C‐Reactive Protein to HDL‐C Ratio and High‐Sensitivity C‐Reactive Protein to Lymphocyte Ratio With Metabolic Syndrome
Authors: Kolahi Ahari Rana , Akbari Nazanin , Babaeepoor Negin , Fallahi Zahra , Saffar Soflaei Sara , Ferns Gordon , Ebrahimi Mahmoud , Moohebati Mohsen , Esmaily Habibollah , Ghayour‐Mobarhan Majid
Published: April 2024

Objective

We aimed to compare the association of three novel inflammatory indicators with metabolic syndrome (MetS) among Mashhad stroke and heart atherosclerotic disorder (MASHAD) cohort participants.

Methods

According to the International Diabetes Federation (IDF) criteria, the cohort participants were divided into the MetS(+) and MetS(−) groups. The lymphocyte to high‐density lipoprotein cholesterol (HDL‐C) ratio (LHR), high‐sensitivity C‐reactive protein (hs‐CRP) to HDL‐C ratio (HCHR) and hs‐CRP to lymphocyte ratio (HCLR) were calculated and were compared between the groups. Binary logistic regression (LR) analysis was performed to find the association of the indices with the presence of MetS among men and women. Receiver‐operating characteristic (ROC) curve analysis was used to establish cut‐off values in predicting MetS for men and women. p‐Values <0.05 were considered as statistically significant.

Results

Among a total of 8890 participants (5500 MetS(−) and 3390 MetS(+)), LHR, HCHR and HCLR were significantly higher in the MetS(+) group than in MetS(−) group (p < 0.001). In LR analysis, after adjusting for multiple cofounders, LHR remained an independent factor for the presence of MetS among men (OR: 1.254; 95% CI: 1.202–1.308; p < 0.001) and women (OR: 1.393; 95% CI: 1.340–1.448; p < 0.001). HCHR also remained an independent factor for the presence of MetS only in women (OR: 1.058; 95% CI: 1.043–1.073; p < 0.001). ROC curve analysis showed that LHR had the higher AUC for predicting MetS in both men (AUC: 0.627; 95% CI: 0.611–0.643; p < 0.001) and women (AUC: 0.683; 95% CI: 0.670, 0.696; p < 0.001).

Conclusion

This suggests that among both genders, the LHR as an inexpensive and easy‐to‐access marker has a better diagnostic performance and could be a promising alternative to the traditional expensive inflammatory markers such as hs‐CRP for the evaluation of inflammation in patients with MetS.
Predominance of M2 macrophages in organized thrombi in chronic thromboembolic pulmonary hypertension patients
Authors: Koudstaal Thomas , van den Bosch Thierry , Bergen Ingrid , Lila Karishma , Bresser Paul , Bogaard Harm Jan , Boomars Karin , Hendriks Rudi , von der Thüsen Jan
Published: April 2024

Chronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right‐sided heart failure. Thrombotic lesions in CTEPH contain CD68+ macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro‐inflammatory M1 macrophages and anti‐inflammatory M2 macrophages, which are involved in wound healing and tissue repair. Currently, the phenotype of macrophages and their localization within thrombotic lesions of CTEPH are largely unknown. In our study, we subclassified thrombotic lesions of CTEPH patients into developing fresh thrombi (FT) and organized thrombi (OT), based on the degree of fibrosis and remodeling. We used multiplex immunofluorescence histology to identify immune cell infiltrates in thrombotic lesions of CPTEH patients. Utilizing software‐assisted cell detection and quantification, increased proportions of macrophages were observed in immune cell infiltrates of OT lesions, compared with FT. Strikingly, the proportions with a CD206+INOS− M2 phenotype were significantly higher in OT than in FT, which mainly contained unpolarized macrophages. Taken together, we observed a shift from unpolarized macrophages in FT toward an expanded population of M2 macrophages in OT, indicating a dynamic role of macrophages during CTEPH pathogenesis.
Considering momentum spillover effects via graph neural network in option pricing
Authors: Wang Yao , Zhao Jingmei , Li Qing , Wei Xiangyu
Published: April 2024

Traditional options pricing relies on underlying asset volatility and contract properties. However, asset volatility is affected by the “lead–lag effects,” known as the “momentum spillover effect.” To address this, we propose a proxy measuring correlated options' influence based on maturity date. Findings indicate that 1‐day‐lagged proxy indicators positively impact option returns. Furthermore, to capture the dynamic effects of correlated options, we introduce a deep graph neural network‐based model (GNN‐MS). Empirical results on Shanghai Stock Exchange 50 exchange‐traded fund options reveal GNN‐MS significantly outperforms classics, enhancing root‐mean‐square error by at least 8.81%. This study provides novel insights into option pricing considering momentum spillover effects.
Comparative analysis of glymphatic system alterations in multiple sclerosis and neuromyelitis optica spectrum disorder using MRI indices from diffusion tensor imaging
Authors: Kim Minchul , Hwang Inpyeong , Park Jung Hyun , Chung Jin Wook , Kim Sung Min , Kim Ji‐hoon , Choi Kyu Sung
Published: April 2024

Objective

The glymphatic system is a glial‐based perivascular network that promotes brain metabolic waste clearance. Glymphatic system dysfunction has been observed in both multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), indicating the role of neuroinflammation in the glymphatic system. However, little is known about how the two diseases differently affect the human glymphatic system. The present study aims to evaluate the diffusion MRI‐based measures of the glymphatic system by contrasting MS and NMOSD.

Methods

This prospective study included 63 patients with NMOSD (n = 21) and MS (n = 42) who underwent DTI. The fractional volume of extracellular‐free water (FW) and an index of diffusion tensor imaging (DTI) along the perivascular space (DTI–ALPS) were used as indirect indicators of water diffusivity in the interstitial extracellular and perivenous spaces of white matter, respectively. Age and EDSS scores were adjusted.

Results

Using Bayesian hypothesis testing, we show that the present data substantially favor the null model of no differences between MS and NMOSD for the diffusion MRI‐based measures of the glymphatic system. The inclusion Bayes factor (BF10) of model‐averaged probabilities of the group (MS, NMOSD) was 0.280 for FW and 0.236 for the ALPS index.

Conclusion

Together, these findings suggest that glymphatic alteration associated with MS and NMOSD might be similar and common as an eventual result, albeit the disease etiologies differ.

Practitioner Points

Previous literature indicates important glymphatic system alteration in MS and NMOSD.

We explore the difference between MS and NMOSD using diffusion MRI‐based measures of the glymphatic system.

We show support for the null hypothesis of no difference between MS and NMOSD.

This suggests that glymphatic alteration associated with MS and NMOSD might be similar and common etiology.
A case of testicular tumor and respiratory failure caused by choriocarcinoma syndrome managed through modified chemotherapy and extracorporeal membrane oxygenation
Authors: Shiraiwa Tetsuro , Katayama Hiromichi , Iwasaki Yudai , Kimura Shingo , Satake Yohei , Sato Takuma , Kawasaki Yoshihide , Kawamorita Naoki , Yamashita Shinichi , Ito Akihiro
Published: April 2024

Introduction

Choriocarcinoma syndrome with multiple lung metastases has a poor prognosis and causes respiratory failure due to alveolar hemorrhage. We encountered a case where the introduction of extracorporeal membrane oxygenation effectively sustained oxygenation until chemotherapy took effect on lung metastases of testicular tumors.

Case presentation

A 35‐year‐old man with dyspnea was referred to our hospital. He showed left testicular tumor with multiple lung metastases. Serum human chorionic gonadotropin level was also elevated. Reduced chemotherapy was initiated and extracorporeal membrane oxygenation was administered because of low oxygen levels on the fourth day. Chemotherapy successfully reduced the size of the lung masses, and extracorporeal membrane oxygenation was discontinued. Respiratory status improved substantially, but the patient died of brain metastases 4 months later.

Conclusion

Extracorporeal membrane oxygenation may be a useful option for managing respiratory failure resulting from choriocarcinoma syndrome until the respiratory condition is improved by chemotherapy for testicular tumors.
Preoperative oral treatment with cyclooxygenase‐2 inhibitor for cystitis glandularis
Authors: Yanagi Masato , Motoda Norio , Katsu Akifumi , Kono Hiroyoshi , Kimata Ryoji , Hamasaki Tsutomu , Kondo Yukihiro
Published: April 2024

Introduction

A previous report has shown that cyclooxygenase‐2 inhibitors can prevent the recurrence of cystitis glandularis postoperatively. Herein, we present a case of cystitis glandularis in which the tumor volume was markedly reduced by preoperative oral administration of a cyclooxygenase‐2 inhibitor.

Case presentation

A 45‐year‐old man with voiding difficulty and lower abdominal pain during urination was referred to our hospital. Cystoscopy revealed multiple cystitis glandularis‐like edematous masses on the trigone and the neck of the bladder, completely involving the bilateral ureteral orifices. Cyclooxygenase‐2 inhibitor was orally administered at the patient's request. Six weeks later, the tumor volume was markedly reduced, bilateral ureteral orifices were identified, and the voiding difficulty and pain on urination disappeared. Complete transurethral resection of the residual tumor was performed, and the pathological diagnosis was intestinal‐type cystitis glandularis.

Conclusion

Cyclooxygenase‐2 inhibition can be considered a useful therapeutic strategy for cystitis glandularis.
Osteosarcoma cell death induced by innovative scaffolds doped with chemotherapeutics
Authors: Lanzillotti Carmen , Iaquinta Maria Rosa , De Pace Raffaella , Mosaico Maria , Patergnani Simone , Giorgi Carlotta , Tavoni Marta , Dapporto Massimiliano , Sprio Simone , Tampieri Anna , Montesi Monica , Martini Fernanda , Mazzoni Elisa
Published: April 2024

Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. In the last years, novel treatment approaches have been proposed, which employ a drug‐delivery system to prevent offside effects and improves treatment efficacy. Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour‐killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium‐doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC‐MTX and SrCPC‐DOX, respectively. The drug‐loaded cements were tested in an in vitro model of human OS cell line SAOS‐2, engineered OS cell line (SAOS‐2‐eGFP) and U2‐OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase‐3/7 activities, respectively. To determine if OS cells grown on doped‐scaffolds change their migratory ability and invasiveness, a wound‐healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived‐mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme‐linked immunosorbent assay test, and (iii) the osteogenic process was studied by real‐time polymerase chain reaction array. The delivery system induced cell‐killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug‐loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy.
Effect of coal gasification coarse slag on soil water and nutrition at an arid opencast coal mine site in Northwest China
Authors: Li Xiaonan , Zhang Kai , Bao Kaikai , Zhao Jiangang , Wang Xiaoyuan , Tang Yuwei
Published: April 2024

Though amendment using coal gasification coarse slag (CGCS) has garnered attention, the intrinsic mechanism of how CGCS, a glassy material, works to amend physicochemical properties in the soil is not yet clear. This study aimed to analyze the effects of different CGCS particle sizes on soil water infiltration and nutrient retention, and to identify the relationship between the physicochemical properties of the amended soil and the water nutrient amendment. The continuous infiltration pattern of soil water and plant growth after the amendment was measured using an indoor continuous dynamic soil column simulation experiment and a field pot experiment of CGCS with different particle sizes (0.25, 1, and 2 mm). The CGCS amendment loosened the soil, improved the pore channels, and amended the water infiltration. However, this process was negatively correlated with CGCS particle size. The Kostiakov performed better in simulating soil water infiltration of heterogeneous dump soil. The CGCS amendment had no heavy metal risk and promoted plant growth. Though amendment enhanced nutrients, in terms of soil organic matter (SOM), the presence of C must be verified by a long team of nutrient cycling if it can be transformed into accessible SOM. Therefore, CGCS amended water nutrition by amending the soil's physical structure. Soil pore adsorption improved water nutrient availability and had a positive effect on chemical properties, which promoted crop growth. The amendment effect was greatest at 0.25 mm particle size.
The World's consumption of free web‐based Otolaryngology‐Head and Neck Surgery educational resources: A global assessment of video usage trends
Authors: Lawrence Amelia S. , Fei‐Zhang David J. , Hassett Leslie C. , Carlson Matthew L. , Wiedermann Joshua P.
Published: April 2024

Objectives

Online educational platforms with open access have seen a growing adoption in the field of medical education. However, the extent of their global usage is still unclear. To fill this knowledge gap, our objective is to examine the usage patterns of two renowned open‐access resources in Otolaryngology. This includes identifying the most sought‐after topics and understanding the demographics of their users.

Methods

Retrospective study of web analytics data between 2016 and 2021 extracted from the Headmirror.com and Mayo Clinic Otolaryngology YouTube channel platforms analyzing demographic and education topic trends via descriptive, geospatial, time‐series, t‐tests, and ANOVA analyses.

Results

Viewership spanned 124 countries in 7 different geographic regions, with 72 countries comprising low‐ to middle‐income countries, mostly represented ages of 25–34 years old, came from high‐income countries rather than low‐income (p < .001), and used mobile phones followed by computers for device access. Video‐educational material comprised of subspecialty topics on Rhinology and Sinus Surgery (25%) at the highest end and Facial Trauma (1%) at the lowest. Controlling for the age of the video content, the most‐accessed videos comprised of subspecialty topics on Head and Neck Surgery at the highest end and Laryngology at the lowest with significant differentiation across topics of interest (p < .044).

Conclusions

This assessment of web‐analytics platforms from two widely used otolaryngology free, online‐access materials showed increasing global usage trends with significant differentiating factors along viewership demographics, as well as sought‐after subspecialty topics of interest. In turn, our results not only lay the groundwork for characterizing the global otolaryngology audience but also for future development of targeted educational materials and accessibility initiatives aimed at ameliorating global educational disparities in the field.
Manipulation of Coupled X‐Ray‐Excited Persistent Luminescence and Upconversion in Er3+ Doped Fluoride Nanoparticles for Multifaceted Applications
Authors: Xu Weixin , Zheng Ye , Liu Xiaofeng , Zhou Min , Deng Renren , Yang Yanmin , Qiu Jianrong
Published: April 2024

Lanthanide doped nanoparticles (NPs) exhibit tunable X‐ray‐excited optical luminescence and X‐ray‐excited persistent luminescence (XEPL), holding broad prospects for applications in display/anti‐counterfeiting and X‐ray imaging. The development of effective strategies for multi‐dimensional applications based on lanthanide‐doped fluoride NPs are a constant challenge. Here, core–shell structured fluoride NPs, in which the heavy metal fluoride shell effectively suppresses the non‐radiative relaxation and simultaneously improve the X‐ray absorption of the shell are designed and fabricated. Under X‐ray irradiation, the developed NPs exhibit an increased number of secondary electrons which migrate to Er3+ centers at the interface and greatly improve the XEPL intensity. Additionally, the introduction of Mn2+ further enhances the XEPL intensity and offers an effective route to control the red‐green ratio of the upconversion spectrum. The NPs co‐doped with Mn2+ exhibit a bright green XEPL under X‐ray irradiation and a red emission under 1532 nm laser excitation. It is further validated that these NPs can be utilized for advanced anti‐counterfeiting and high‐resolution delayed imaging based on a film containing NPs as a scintillation screen. These findings suggest a new strategy of designing Er3+ doped NPs for multi‐dimensional applications.
A promising future of metal‐N‐heterocyclic carbene complexes in medicinal chemistry: The emerging bioorganometallic antitumor agents
Authors: Zhao Qian , Han Bo , Peng Cheng , Zhang Nan , Huang Wei , He Gu , Li Jun‐Long
Published: April 2024

Metal complexes based on N‐heterocyclic carbene (NHC) ligands have emerged as promising broad‐spectrum antitumor agents in bioorganometallic medicinal chemistry. In recent decades, studies on cytotoxic metal–NHC complexes have yielded numerous compounds exhibiting superior cytotoxicity compared to cisplatin. Although the molecular mechanisms of these anticancer complexes are not fully understood, some potential targets and modes of action have been identified. However, a comprehensive review of their biological mechanisms is currently absent. In general, apoptosis caused by metal–NHCs is common in tumor cells. They can cause a series of changes after entering cells, such as mitochondrial membrane potential (MMP) variation, reactive oxygen species (ROS) generation, cytochrome c (cyt c) release, endoplasmic reticulum (ER) stress, lysosome damage, and caspase activation, ultimately leading to apoptosis. Therefore, a detailed understanding of the influence of metal–NHCs on cancer cell apoptosis is crucial. In this review, we provide a comprehensive summary of recent advances in metal–NHC complexes that trigger apoptotic cell death via different apoptosis‐related targets or signaling pathways, including B‐cell lymphoma 2 (Bcl‐2 family), p53, cyt c, ER stress, lysosome damage, thioredoxin reductase (TrxR) inhibition, and so forth. We also discuss the challenges, limitations, and future directions of metal–NHC complexes to elucidate their emerging application in medicinal chemistry.