bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Effect of Macroeconomic Activities on the Adjusted Net National Income in Promoting Sustainable Economic Development in Iraq
Authors: Rasheed Mustafa Kamil , Muneer Amer Sami , Zahra Sohaila Abdul
Published: November 2022

Economic activities are the basis that stimulates the productive sectors and strengthens the interdependence between them and then supports the gross domestic product. All economic policies seek to stimulate macroeconomic changes towards national income, which in turn stimulates its components towards supporting the gross domestic product. After taking the environmental dimension, the national income was adjusted to include the environmental impact on the population. The sample included taking the added value of the economic sectors (agriculture, industry, and services) and the environmentally adjusted national income for the period (2004-2018) has been converted into quarterly data to support the standard model used, which is the (ARDL) model in Iraq. The hypothesis of the research is that the impact of the activities of the economic sectors is significant on the adjusted national income of the oil countries in general, Iraq in particular, for the damages resulting from the process of extracting crude oil. The problem of the research is that Iraq needs to take into account the environmental dimension to maintain the populations standard of life, in connection with their daily production activity, which in turn is linked to sustainable development that supports the green environment. The importance of the research the follow-up to the environmental impacts in todays world in light of the high indicators of environmental pollution is one of the most important components and indicators of economic studies, so the economic activities must interact with each other to support the environmentally adjusted national income. The research concluded that the macroeconomic sectors exert a clear and good influence on the adjusted national income, so the research recommended that the decision maker pay attention to these economic sectors to increase the amount of the adjusted national income, which would support sustainable economic development plans in the long term and protect the Iraqi environment from pollution.
Slowly Progressive Cerebellar Ataxia in a 55-Year-Old Female Patient
Authors: Tuesta Bernaola Mellany , Ganguly Jacky , Jog Mandar
Published: November 2022

A 55-year-old female patient with a history of hypercholesterolemia and anxiety presented for imbalance, fear of falling, and progressive disability. Examination revealed gaze-evoked horizontal nystagmus, ataxic dysarthria, sensory neuronopathy, and cerebellar atrophy. What is your diagnosis?
High-risk Therapeutic Devices Approved by the US Food and Drug Administration for Use in Children and Adolescents From 2016 to 2021
Authors: Pathak Kavya , Narang Claire , Hwang Thomas J. , Espinoza Juan C. , Bourgeois Florence T.
Published: November 2022

This cohort study examines the characteristics of high-risk therapeutic devices approved by the US Food and Drug Administration for use in children and adolescents between 2016 and 2021.
Identification of novel meQTLs strongly associated with rheumatoid arthritis by large‐scale epigenome‐wide analysis
Authors: Tang Guoping , Sun Chen , Lv Hongchao , Zhang Mingming , Jiang Yongshuai , Xu Jing
Published: November 2022

Rheumatoid arthritis (RA) is highly heritable, and previous studies have suggested that genetic variation may affect susceptibility to RA by altering epigenetic modifications (e.g. DNA methylation). Here we examined how genetic variation influences DNA methylation (DNAm) in RA by integrating individual genetic variation and DNAm data. Epigenome‐wide meQTL (methylation quantitative trait loci) analysis was performed on 354 RA patients and 335 controls, scanning 30,101,744 relationships between 62 SNPs and 485,512 DNA methylation sites. Two regulatory relationship pairs (FDR < 0.05) showed very strong associations with RA risk. One was rs10796216‐cg00475509, and the DNAm decreased by 0.0168 per addition of allele rs10796216‐A. The other was rs6546473‐cg13358873, for which a 0.0365 reduction of DNAm at cg13358873 was observed for each addition of allele rs6546473‐A, and lower DNAm was found to be significantly associated with RA risk (P = 2.0407e‐28). Moreover, both pairs of meQTL showed a strong regulatory relationship only in RA samples, so they can be subsequently considered as risk markers for RA. In conclusion, our integrated analysis of genetic and epigenetic variation suggests that genetic variation may affect the risk of RA by regulating DNA methylation levels. Alterations of DNAm at cg00475509 and cg13358873 loci conferred by rs10796216‐A and rs6546473‐A allele may suggest a potential risk for RA. Our results deepen our understanding of the genetic and epigenetic mechanisms of RA and provide novel associations that can be further investigated in future studies.
Mimicking tracing actions enhances young children's mathematical learning
Authors: Smyrnis Eleni , Ginns Paul , Bobis Janette
Published: November 2022

Learning mathematical concepts and procedures typically requires extended cognitive effort, presenting a challenge for many children. People can make tracing actions with the index finger, as well as mimic another's movements, with little or no conscious effort. From the perspective of cognitive load theory, such biologically primary actions may facilitate learning biologically secondary concepts and skills requiring extensive cognitive effort, such as mathematics. The present study investigated effects on learning processes and outcomes of students mimicking a teacher's tracing actions from the perspective of an evolutionarily informed cognitive load theory. One hundred and thirteen Grade Two children learned about number lines, either observing a teacher tracing out elements of worked examples with her index finger, or mimicking the teacher's tracing actions with their own index finger. In accord with hypotheses, results indicated enhanced performance due to mimicking on cognitive load, motivation, and post‐test performance. Directions for future research are discussed.
Controllable Modulation of Efficient Phosphorescence Through Dynamic Metal‐Ligand Coordination for Reversible Anti‐Counterfeiting Printing of Thermal Development
Authors: Dai Wenbo , Li Gengchen , Zhang Yongfeng , Ren Yue , Lei Yunxiang , Shi Jianbing , Tong Bin , Cai Zhengxu , Dong Yuping
Published: November 2022

Dynamically tunable room‐temperature phosphorescence (RTP) organic materials have attracted considerable attention in recent years due to their great potential over a wide variety of advanced applications. However, the precise regulation of the intersystem crossing (ISC) process for efficient RTP materials with dynamically modulated properties in a rigid environment is challenging. Herein, an effective strategy for RTP material preparation with controllably regulated properties is developed via the construction of dynamic metal‐ligand coordination in a host‐guest doped system. The coordination interaction promotes ISC and phosphorescence emission of the guest, thus allowing the modulation of the photophysical properties of doped materials by changing the doping ratio and Zn2+ counterions. By taking advantage of the reversible metal‐ligand coordination interaction, the coordination‐activated, and dissociation‐deactivated RTP is dynamically manipulated. With the unique Zn2+‐responsible RTP enhancement materials, the anti‐counterfeiting applications of thermal development, and color inversion have been constructed for inkjet printing of high‐resolution patterns with high reversibility for many write/erase cycles. The results show that dynamic metal‐ligand coordination strategy is a promising approach for achieving efficient RTP materials with controllably modulated properties.
Self‐Assembled Integrative Nutrient Carrier Platform Containing Green Tea Catechin for Short Bowel Syndrome Treatment
Authors: Zhou Zhengming , Li Ke , Shi Lei , Wang Yunfeng , He Yunxiang , Hu Wen , Guo Junling
Published: November 2022

Extensive resection of the small intestine leads to the development of short bowel syndrome (SBS), which reduces the effective absorptive surface area of the intestine and predisposes patients to emaciation, malnutrition, and other severe symptoms. Herein, green tea catechin (−)‐epigallocatechin gallate (EGCG) and ferrous ions (Fe2+) are utilized to construct a nutrient carrier platform that self‐assembles with nutrients to form phenolic‐based nutrient complexes (PNCs). PNCs effectively prolong the residence and absorption time of nutrients in the intestine. Further this platform is applied to integrate full nutrient formula, an enteral nutrition (EN) preparation containing a range of full nutrient components. In an SBS rat model, the prepared phenolic‐based integrative nutrient complexes (PINCs) enhance nutritional status, improve anemia and immune function, as well as facilitate the growth of remaining intestinal villi and crypts, and maintain the integrity of the intestinal barrier. In addition, PINCs enable the modulation of gut microbial dysbiosis, enrich the abundance of beneficial bacteria, and have no toxic effects after the long‐term ingestion. These results provide a proof of principle for the use of polyphenol‐based nanocomplexes as EN preparation, offering a feasible strategy for both nutritional support and therapeutic perspectives for SBS treatment.
Janus Microdroplets with Tunable Self‐Recoverable and Switchable Reflective Structural Colors
Authors: Liu Mingzhu , Fu Jiemin , Yang Shengsong , Wang Yuchen , Jin Lishuai , Nah So Hee , Gao Yuchong , Ning Yifan , Murray Christopher B. , Yang Shu
Published: November 2022

Microdroplets made from chiral liquid crystals (CLCs) can display reflective structural colors. However, the small area of reflection and their isotropic shape limit their performance. Here, Janus microdroplets are synthesized through phase separation between CLCs and silicone oil. The as‐synthesized Janus microdroplets show primary structural colors with ≈14 times larger area compared to their spherical counterparts at a specific orientation; the orientation and thus the colored/transparent states can be switched by applying a magnetic field. The color of the Janus microdroplets can be tuned ranging from red to violet by varying the concentration of the chiral dopant in the CLC phase. Due to the density difference between the two phases, the Janus microdroplets prefer to orientate the silicone oil side up vertically, enabling the self‐recoverable structural color after distortion. The Janus microdroplets can be dispersed in aqueous media to track the configuration and speed of magnetic objects. They can also be patterned as multiplexed labels for data encryption. The magnetic field‐responsive Janus CLC microdroplets presented here offer new insights to generate and switch reflective colors with high color saturation. It also paves the way for broader applications of CLCs, including anti‐counterfeiting, data encryption, display, and untethered speed sensors.
Efficient Combination of Surface Texturing and Functional Coating for Very Low Secondary Electron Yield Surfaces and Rough Nonevaporable Getter Films
Authors: Himmerlich Marcel , Zanin Danilo A. , Taborelli Mauro , Granadeiro Costa Angelo Rafael , Costa Pinto Pedro , Lain Amador Lucia , Vollenberg Wilhelmus , Baris Adrienn , Garcia‐Tabares Valdivieso Elisa , Perez Fontenla Ana Teresa , Wackerow Stefan , Abdolvand Amin
Published: November 2022

The formation of a fissured copper surface by picosecond pulsed laser irradiation is combined with functional coatings consisting of Ti and amorphous carbon layers or a Ti–Zr–V compound film to fabricate surfaces with the maximum of the secondary electron yield being as low as 0.4. By structural and spectroscopic analysis of the formed surfaces it is demonstrated that both coatings enclose the nanostructures generated by redeposition of metal structures from the laser‐induced plasma plume, keeping the initial topography intact. This allows an efficient elimination of secondary electron emission by combining the benefits from structural surface modification and adaption of electronic surface properties to efficiently dissipate the energy of impinging electrons. Thermal activation tests of the Ti–Zr–V nonevaporable getter films revealed that for films on nanostructured substrates, which have a much higher effective surface, a slight diminution of surface activation occurs at 160 and 200 °C, while this effect is completely compensated when heating up to 250 °C indicating promising pumping capabilities. Both examples highlight the benefits from combining 3D substrate patterning with classical 2D deposition technologies.
Exosomes Derived from miR‐195‐5p Transfected Bone Marrow Mesenchymal Stem Cells Alleviate Pelvic Floor Dysfunction in Rats
Authors: Chen Ying , Wan Sheng , Zhou Chenchen , Gu Shengyi , Zhou Tianfan , Yao Liping , Pei Jindan , Hua Xiaolin
Published: November 2022

Bone marrow‐derived mesenchymal stem cells (BMSCs) can alleviate pelvic floor dysfunction (PFD) in rats. Whether exosomes derived from miR‐195‐5p transfected BMSCs can alleviate PFD is investigated. The rat vaginal distention model is constructed to mimic PFD. miR‐195‐5p is transfected into BMSCs, and exosomes derived from miR‐195‐5p transfected BMSCs are injected into PFD rats via caudal veins. Luciferase reporter assay is performed to confirm the direct interaction between SMAD7 3′‐UTR and miR‐195‐5p mimics. Void volume, bladder void pressure, leak point pressure, and peak bladder pressure are used to evaluate urodynamic function. It is found that miR‐195‐5p directly targets Smad7 and regulates the relative Smad7 expression in rat BMSCs. Exosomes derived from miR‐195‐5p transfected BMSCs can improve urodynamic function than exosomes derived from BMSCs. On the other hand, exosomes derived from miR‐195‐5p transfected BMSCs inhibit the expressions of Smad7 but promote the expressions of elastin in PFD rats with diminished expression of MMP2 and MMP9. This study demonstrates that exosomes derived from miR‐195‐5p genetically engineered BMSCs can target the Tgf‐β/Smad7 pathway to repair connective tissues and restore damaged urodynamic function in PFD rats.
Examining the influence of group diversity on the functioning of community‐based participatory research partnerships: A mixed methods study
Authors: Chandanabhumma P. Paul , Fàbregues Sergi , Oetzel John , Duran Bonnie , Ford Chandra
Published: November 2022

Public health has endorsed the use of community‐based participatory research (CBPR) to address health inequities involving diverse and marginalized communities. However, few studies have examined how group diversity among members of CBPR partnerships influenced how well the partnerships achieve their goals of addressing health inequities through equitable collaboration. We conducted secondary, convergent, mixed methods analysis to (1) evaluate the association between group diversity and participatory decision‐making within CBPR partnerships, and (2) identify the perceived characteristics, benefits, and challenges of group diversity within CBPR partnerships. Using data from a cross‐site study of federally funded CBPR partnerships, we analyzed and integrated data from surveys of 163 partnerships (n = 448 partners) and seven in‐depth case study interviews (n = 55 partners). Quantitatively, none of the measured characteristics of group diversity was associated with participatory decision‐making within the partnerships. Qualitatively, we found that partnerships mainly benefited from membership differences in functional characteristics (e.g., skillset) but faced challenges from membership differences in sociocultural characteristics (e.g., gender and race). The integrated findings suggest the need to further understand how emergent group characteristics and how practices that engage in group diversity contribute to collective functioning of the partnerships. Attention to this area can help promote health equity achievements of CBPR partnerships.
Water‐soluble Self‐assembled {Pd84}Ac Polyoxopalladate Nano‐wheel as a Supramolecular Host
Authors: Sinclair Zoë L. , Bell Nicola L. , Bame Jessica R. , Long De‐Liang , Cronin Leroy
Published: November 2022

Polyoxopalladates (POPs) are a class of self‐assembling palladium‐oxide clusters that span a variety of sizes, shapes and compositions. The largest of this family, {Pd84}Ac, is constructed from 14 building units of {Pd6} and lined on the inner and outer torus by 28 acetate ligands. Due to its high water solubility, large hydrophobic cavity and distinct 1H NMR fingerprint {Pd84}Ac is an ideal molecule for exploring supramolecular behaviour with small organic molecules in aqueous media. Molecular visualisation studies highlighted potential binding sites between {Pd84}Ac and these species. Nuclear Magnetic Resonance (NMR) techniques, including 1H NMR, 1H Diffusion Ordered Spectroscopy (DOSY) and Nuclear Overhauser Spectroscopy (NOESY), were employed to study the supramolecular chemistry of this system. Here, we provide conclusive evidence that {Pd84}Ac forms a 1 : 7 host‐guest complex with benzyl viologen (BV2+) in aqueous solution.
Kombination von Deep Eutectic Solvents mit TEMPO‐basierten Polymerelektroden: Einfluss des Molaren Verhältnisses auf das Elektrodenverhalten**
Authors: Uhl Matthias , Geng Tanja , Schuster Philipp A. , Schick Benjamin W. , Kruck Matthias , Fuoss Alexander , Kuehne Alexander J. C. , Jacob Timo
Published: November 2022

Vollorganische Batterien auf Grundlage redoxaktiver Polymere versprechen eine Alternative zu Lithium‐Ionen‐Batterien für die nachhaltige Energiespeicherung zu werden. Polymere tragen bisher als Elektroden oder als feste Elektrolyte zum Ziel einer rein organischen Zelle bei. Hier ersetzen wir den Elektrolyten durch ein Deep Eutectic Solvent (DES), das aus Natriumbis(trifluormethansulfonyl)imid (NaTFSI) und N‐Methylacetamid (NMA) besteht, und verwenden Poly(2,2,6,6‐tetramethylpiperidin‐1‐yl‐oxylmethacrylat) (PTMA) als Kathode. Von der erfolgreichen Kombination eines DES mit einer Polymerelektrode wird hier zum ersten Mal berichtet. Die elektrochemische Stabilität von PTMA‐Elektroden im DES ist beim eutektischen Stoffmengenverhältnis von 1 : 6 mit herkömmlichen Batterieelektrolyten vergleichbar. Viskosere Elektrolyte mit höherer Salzkonzentration können das Zykeln bei hohen Raten behindern. Eine niedrigere Salzkonzentration führt zu sinkenden Kapazitäten und schnellerer Zersetzung. Die eutektische Mischung von 1 : 6 ist am besten geeignet, um hohe Stabilität und moderate Viskosität zu vereinen.
Antiaromatic Sapphyrin Isomer: Transformation into Contracted Porphyrinoids with Variable Aromaticity
Authors: Li Qizhao , Ishida Masatoshi , Wang Yunyun , Li Chengjie , Baryshnikov Glib , Zhu Bin , Sha Feng , Wu Xinyan , Ågren Hans , Furuta Hiroyuki , Xie Yongshu
Published: November 2022

Sapphyrin is a pentapyrrolic expanded porphyrin with a 22π aromatic character. Herein, we report the synthesis of a 20π antiaromatic sapphyrin isomer 1 by oxidative cyclization of a pentapyrrane precursor P5 with a terminal β‐linked pyrrole. The resulting isomer 1, containing a mis‐linked bipyrrole unit in the skeleton, exhibits a reactivity for further oxidation due to the distinct antiaromatic electronic structure, affording a fused macrocycle 2, possessing a spiro‐carbon‐containing [5.6.5.6]‐tetracyclic structure. Subsequent treatment with an acid afforded a weakly aromatic pyrrolone‐appended N‐confused corrole 3, and thermal fusion gave a [5.6.5.7]‐tetracyclic‐ring‐embedded 14π aromatic triphyrin(2.1.1) analog 4. The cyclization at the mis‐linked pyrrole moiety of P5 played a crucial role in synthesizing the antiaromatic porphyrinoid susceptible to facile transformation to novel porphyrinoids with variable aromaticity.
Rhodium‐Catalyzed Anti‐Markovnikov Transfer Hydroiodination of Terminal Alkynes**
Authors: Boehm Philip , Kehl Niklas , Morandi Bill
Published: November 2022

A rhodium‐catalyzed anti‐Markovnikov hydroiodination of aromatic and aliphatic terminal alkynes is reported. Depending on the choice of ligand and substrate, either (E)‐ or (Z)‐configured alkenyl iodides are obtained in high to exclusive isomeric purity. The reaction exhibits a broad substrate scope and high functional group tolerance, employing easily accessible or commercially available aliphatic iodides as HI surrogates through a shuttle process. The synthesized vinyl iodides were applied in several C−C and C−heteroatom bond‐forming reactions with full retention of the stereoselectivity. The developed method could be used to significantly shorten the total synthesis of a marine cis‐fatty acid. Additionally, initial deuterium‐labeling experiments and stoichiometric reactions shed some light on the potential reaction mechanism.
CO2 Induces Symmetry Breaking in Layered Dipeptide Crystals
Authors: Li Xianbao , Li Qi , Wu Aoli , Li Junbai
Published: November 2022

Control of symmetry breaking of materials provides large opportunities to regulate their properties and functions. Herein, we report breaking the symmetry of layered dipeptide crystals by utilizing CO2 to induce the adjacent monomolecular layers to stack from the opposite to the same direction. The role of CO2 is to cover the interlayer interaction sites and force the dipeptides to adsorb at asymmetric positions. Further, the dipeptide crystals exhibit far superior piezoelectricity after symmetry breaking and the piezoelectric voltage generated from the dipeptide‐based generators becomes more than 500 % higher than before. This work reveals a potential route to engineer structures and properties of layered materials and provides a deep insight into the control of non‐covalent interactions.
In Vivo Biocatalytic Cascades Featuring an Artificial‐Enzyme‐Catalysed New‐to‐Nature Reaction**
Authors: Ofori Atta Linda , Zhou Zhi , Roelfes Gerard
Published: November 2022

Artificial enzymes utilizing the genetically encoded non‐proteinogenic amino acid p‐aminophenylalanine (pAF) as a catalytic residue are able to react with carbonyl compounds through an iminium ion mechanism to promote reactions that have no equivalent in nature. Herein, we report an in vivo biocatalytic cascade that is augmented with such an artificial enzyme‐catalysed new‐to‐nature reaction. The artificial enzyme in this study is a pAF‐containing evolved variant of the lactococcal multidrug‐resistance regulator, designated LmrR_V15pAF_RMH, which efficiently converts benzaldehyde derivatives produced in vivo into the corresponding hydrazone products inside E. coli cells. These in vivo biocatalytic cascades comprising an artificial‐enzyme‐catalysed reaction are an important step towards achieving a hybrid metabolism.
Analysis of periodic magnetohydrodynamics effects on triple diffusive nonlinear mixed convective flow of Eyring–Powell nanoliquid
Authors: Patil Prabhugouda Mallangouda , Kulkarni Madhavarao
Published: November 2022

The article spotlights aspects of the triply diffusive mixed convective flow of Eyring–Powell nanoliquid over a vertical plate. A periodic magnetic field with nonlinear convection is exhibited. The governing partial differential equations (PDEs) with boundary restrictions are the case paradigm transformed into a non‐dimensional system by feasible non‐similar transformations. The quasilinearization technique combined with an implicit finite difference scheme is used for numerical simulation, resulting in a block‐tridiagonal matrix form. Furthermore, a system of algebraic linear equations has been solved through Varga's algorithm. The numerical outcomes are correlated with various physical parameters graphically. The variations in the nonlinear mixed convection parameter and Powell–Eyring liquid parameter raise the skin friction coefficient more than a Newtonian fluid. In a periodic magnetic field, the fluid temperature rises and drops in the corresponding energy transfer rate. Also, wavy variations have been observed because of oscillatory magnetic fields. The current study can find its potential applications in medical, engineering and industrial developments, including polymer sheet manufacture, medicine cover coating, fibre production, crystal growth, heat exchangers and metal extrusion.
Modeling the evolution of graphene agglomeration and the electrical and mechanical properties of graphene/polypropylene nanocomposites
Authors: Du Han , Zhang Juanjuan , Fang Chao , Weng George J.
Published: November 2022

Graphene agglomeration tends to develop with the increase of graphene loading. In this article, we present a unified model that first considers the evolution of graphene agglomeration and then incorporates it into the calculation of electrical and mechanical properties of agglomerated graphene/polymer nanocomposites. In the evolution of graphene agglomerates, a modified nanoparticle distance in terms of yield strength is introduced, while in the calculation of composite properties, a two‐scale framework that consists of the graphene‐rich agglomerates and the remainder as the graphene‐poor region is constructed. In electrical conduction, electron tunneling is modeled through Simmons formula and its difference with the widely used Cauchy function is compared. We highlight that both Simmons and Cauchy functions could well describe the interfacial tunneling activity, but the former is physics‐based while the latter is statistics‐based. In the calculation of nonlinear elastoplastic response, a field‐fluctuation method is adopted. We also demonstrated how the presented model gives rise to experimentally consistent electrical and mechanical properties of graphene/polypropylene nanocomposites, and how filler agglomeration hinders the performance of the materials.
Highly selective adsorption of Pt(IV) from spent catalyst by polyethyleneimine functionalized polyethylene/polypropylene non‐woven fabric
Authors: Feng Xinxin , He Yulong , Xing Zhe , Zhang Mingxing , Li Rong , Wu Guozhong
Published: November 2022

Aiming at efficient recovery of platinum (Pt) from aqueous solution, the aminated polyethylene/polypropylene non‐woven fabric (PE/PP NWF) was synthesized via radiation grafting of glycidyl methacrylate (GMA), followed by ring‐opening reaction with polyethyleneimine (PEI). The effects of different parameters, including pH, sorption time, initial Pt(IV) concentration, competing ions and adsorbent dosage on the Pt(IV) adsorption performance were investigated by batch adsorption tests. A high Pt(IV) adsorption capacity of 485.0 mg g−1 (initial concentration: 263.5 mg L−1) was achieved, and the adsorption kinetics and isotherm conformed to the pseudo‐second‐order model and the Langmuir isotherm model, respectively. Moreover, the PEI functionalized PE/PP NWF exhibited excellent adsorption performance over the wide pH range (1–6), and also good selectivity for Pt(IV) over multiple coexisting metal cations (Ni, Cu, Co, Pb, Mg, and Zn). The recovery ratio of Pt from spent proton exchange membrane fuel cell (PEMFC) catalysts reached 89.7% after three cycles of regeneration.
Discovery of novel pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives as cyclooxygenase inhibitors (COX‐1 and COX‐2) using molecular modeling simulation
Authors: Ayman Radwa , Radwan A. M. , Elmetwally Amira M. , Ammar Yousry A. , Ragab Ahmed
Published: November 2022

Searching for effective and selective anti‐inflammatory agents, our study involved designing and synthesizing new pyrazole and pyrazolo[1,5‐a]pyrimidine derivatives 4–11. The structures of the synthesized derivatives were confirmed using different spectroscopic techniques. Virtual screening was achieved for the newly designed derivatives using in silico docking simulation inside the active sites of four proteins classified as two cyclooxygenases (COX)‐1 (PDB: 3KK6 and 4OIZ) and two COX‐2 (PBD: 1CX2 and 3LN1). Among them, six derivatives 4c, 5b, 6a, 7a, 7b, and 10b displayed the highest binding energy. These derivatives were evaluated for their in vitro COX‐1 and COX‐2 inhibitory activities and their selectivity indexes were calculated. Additionally, these derivatives displayed IC50 values ranging between 4.909 ± 0.25 and 57.53 ± 2.91 µM, and 3.289 ± 0.14 and 124 ± 5.32 µM, against COX‐1 and COX‐2, respectively. Furthermore, the tested derivatives were found to have selective inhibitory activity on the COX‐2 enzyme. Surprisingly, the two pyrazole derivatives 4c and 5b were found to be the most active, with IC50 values of 9.835 ± 0.50 and 4.909 ± 0.25 µM and 4.597 ± 0.20 and 3.289 ±  0.14 µM compared with meloxicam (1.879 ± 0.1 and 5.409 ±  0.23 µM) and celecoxib (5.439 ± 0.28 and 2.164 ± 0.09 µM) against COX‐1/‐2, respectively. Besides, two pyrazole derivatives, 4c and 5b, displayed a COX‐1/COX‐2 SI of 2.14 and 1.49. Computational techniques such as molecular docking, density function theory (DFT) calculation, and chemical absorption, distribution, metabolism, excretion, and toxicity evaluation were applied to explain the molecules’ binding mode, chemical nature, drug likeness, and toxicity prediction.
Measurement invariance of the Autism Impact Measure (AIM) across sex in children with autism spectrum disorder
Authors: Zhong Nicole H. , Grimm Ryan P. , Kanne Stephen M. , Mazurek Micah O.
Published: November 2022

Measurement invariance, or the degree to which an instrument measures constructs consistently across subgroups, is critical for appropriate interpretations of measures. Given sex differences in the phenotypic and clinical presentation of autism spectrum disorder (ASD), it is particularly important to examine measurement invariance in autism instruments to ensure that ASD measures are not biased toward the more common male ASD phenotype. This study represents an important preliminary investigation evaluating the measurement equivalence of the Autism Impact Measure (AIM) across children and adolescents with ASD. The results indicated that the AIM demonstrated measurement invariance at the configural, metric, and scalar levels across sex in all five domains, including Repetitive Behavior, Communication, Atypical Behavior, Social Reciprocity, and Peer Interaction. These results suggest that ASD core symptoms assessed by the AIM were similar among male and female groups. In addition, the latent means for all five factors were not statistically significantly different across sex groups, revealing no systematic differences on any of the AIM subscales for males and females. Overall, this study showed that the AIM detects core ASD symptoms across all five areas equivalently in males and females and is not biased toward males with ASD.
Embryo‐fetal developmental toxicity and toxicokinetics of loxoprofen tromethamine intravenously administered to pregnant rats
Authors: Yue Peng , Zhao Xinxin , Lu Fan , Gao Qingfa , Qiao Hongqun , Liu Jing
Published: November 2022

Background

Loxoprofen tromethamine is a novel structural compound related to loxoprofen. It has been used for the treatment of pain and inflammation. However, the embryo‐fetal developmental toxicity (EFDT) of loxoprofen tromethamine has not been evaluated in detail in vivo. This study investigated the EFDT and toxicokinetics of loxoprofen tromethamine in rats.

Methods

The aim of this study was to investigate the potential reproductive toxicity on embryo‐fetal development of loxoprofen tromethamine (0, 1, 3, and 10 mg/kg/day) and sodium cyclophosphamide (CP) (2.8 mg/kg/day) administered by intravenous injection to pregnant rats during gestation days (GDs) 6–15. Pregnant rats were euthanized on GD20. The numbers of live/dead fetuses, resorptions, implantations, and corpora lutea, gravid uterus mass, placenta mass, fetal gender ratios, body weight, and skeletal development were evaluated. In a concomitant toxicokinetic (TK) study (10 pregnant rats per group), plasma TK parameters and the tissue distribution of loxoprofen tromethamine were tested.

Results

On GD20, rats were anesthetized and dissected by caesarean section. The appearance, internal organs, gravid uterus weight, embryo implantation number, and implantation loss rate in maternal rats of each group did not reveal any lesions. In fetuses, there were no significant differences in the fetus weight, embryo resorption number, stillbirth number, or fetal visceral examination in all test groups compared to the negative control group. However, in the high‐dose group, the fetuses showed significant differences in the anomalies of the bones compared to the negative control group. The TK study showed that in the dose range of 1–10 mg/kg, the Cmax and AUC(0–t) of loxoprofen tromethamine in animals after the first administration increased proportionally to the dose, showing linear kinetic characteristics; after the last administration, the Cmax and AUC(0–t) increased disproportionately to the dose, showing nonlinear kinetic characteristics. The results of tissue distribution show that loxoprofen tromethamine was mainly distributed in the placenta and lung after the intravenous administration to pregnant rats; the content in the liver was lower and increased sharply in the heart with increasing doses; the content in all tissues was lower than that in the plasma. Loxoprofen tromethamine in fetal tissues and organs was mainly distributed in fetal lungs, liver and heart, and the lowest content was in amniotic fluid.

Conclusions

In conclusion, the no‐observed‐adverse‐effect level (NOAEL) and lowest‐observed‐adverse‐effect level (LOAEL) of loxoprofen tromethamine were considered to be 1 and 10 mg/kg/day, respectively.
Proteomic profiling of intestinal epithelial‐like cell‐derived exosomes regulated by epigallocatechin gallate
Authors: Yano Satoshi , Suzuki Katsuhiko , Hara Taichi
Published: November 2022

Exosomes are extracellular vesicles primarily responsible for intercellular communication, and they contain nucleic acids and proteins. Exosome secretion has been observed in the intestines, suggesting their physiological effects on the receptor cells of target tissues. It is possible that intestinal epithelial cells recognize food components as ligands, resulting in exosome secretion. However, research on intestine‐derived exosomes regulated by food ingredients is limited. In this study, Caco‐2 cells were utilized as an intestinal epithelial model for proteomic profiling. NanoLC‐MS/MS analysis revealed the alteration of exosome properties by epigallocatechin gallate (EGCG) in differentiated Caco‐2 cells. This natural polyphenol reduced both the number and size of secreted exosomes and altered the expression of exosomal proteins. The enriched proteins in exosomes were involved in immune response and cell proliferation. In contrast, those in the EGCG‐treated group had distinctive functions in the maintenance of skin homeostasis. We also found variable expression of galectin‐3‐binding protein and fibronectin as molecular signatures in exosomes derived from EGCG‐treated cells. These results could help elucidate the expression and mechanism of exosomal proteins related to food components.
Face painting as an anatomical learning tool based on individual ultrasonographic examination
Authors: Hu Hyewon , Piao Jiong‐Zhen , Lee Ji‐Hyun , Bae Hyungkyu , Choi You‐Jin , Hong Sung Ok , Gil Young‐Chun , Hu Kyung‐Seok , Kim Hee‐Jin
Published: November 2022

Considering the shift to online education during the COVID‐19 pandemic, new and easily accessible educational videos and content on clinical anatomy are necessary. This study utilized numerous references and data on the anatomy of Asian facial muscles and blood vessels to accurately depict human anatomy through face painting. It aimed to provide clinicians accurate educational video content on anatomy to help prevent possible complications during noninvasive facial and surgical procedures. A 26‐year‐old Korean‐Chinese male volunteer was used as a face painting model. The location of the blood vessels of the face was confirmed through ultrasonography images using a real‐time two‐dimensional B‐mode. The model's face was painted by an artist majoring in anatomy. To reveal most anatomical structures on both sides of the face, the left side showed the structures observed when the skin and superficial fat layer are removed, and the right side revealed the deeper layer structures that can be seen when some muscles are cut. Fifteen superficial and deep muscles important in esthetic procedures were meticulously painted on the face. The face painting took a total of 6 h, and the video was edited to 5 min. This study merged the advantages of 2D and 3D by painting directly on the skin surface of a living model. Thus, it can provide more dynamic surface anatomy data. These contents inform clinicians about 3D anatomic location, which can help avoid complications when performing clinical procedures on the face.
The rational application of liquid biopsy based on next‐generation sequencing in advanced non‐small cell lung cancer
Authors: Zhao Chenglong , Li Jianghua , Zhang Yongchang , Han Rui , Wang Yubo , Li Li , Zhang Yimin , Zhu Mengxiao , Zheng Jie , Du Haiwei , Hu Chen , Zhou Chengzhi , Yang Nong , Cai Shangli , He Yong
Published: November 2022

Background

Plasma and tissue biopsy have both used for targeting actionable driver gene mutations in lung cancer, whose concordance is imperfect. A reliable method to predict the concordance is urgently needed to ease clinical application.

Methods

A total of 1012 plasma samples, including 519 with paired‐tissue biopsy samples, derived from lung adenocarcinoma patients were retrospectively enrolled. We assessed the associations of several clinicopathological characteristics and serum tumor markers with the concordance between plasma and tissue biopsies.

Results

When carcinoembryonic antigen (CEA) levels were higher than thresholds of 15.01 ng/ml and 51.15 ng/ml, the positive predictive value of concordance reached 90% and 95%, respectively. When CEA levels were lower than thresholds of 5.19 ng/ml and 3.26 ng/mL, the negative predictive value of concordance reached 45% and 50%. The performance of CYFRA21‐1 in predicting concordance was similar but inferior to CEA (AUC: 0.727 vs. 0.741, p = 0.633). The performance of CEA combined with CYFRA21‐1 in predicting the concordance was similar to that of the combination of independent factors derived from the LASSO regression model (AUC: 0.796 vs. 0.818, p = 0.067). CEA (r = 0.47, p < 0.01) and CYFRA21‐1 levels (r = 0.45, p < 0.05) were significantly correlated with the maximum variant allele frequency, respectively.

Conclusions

CEA combined with CYFRA21‐1 could effectively predict the concordance between plasma and tissue biopsies, which could be used for evaluating the priority of plasma and tissue biopsies for gene testing to timely guide clinical applications in advanced lung adenocarcinoma patients.
Perioperative treatment and biomarker analysis of LP002, an anti‐PD‐L1 antibody, plus chemotherapy in resectable gastric and gastroesophageal junction cancer
Authors: Tang Jia‐lin , Zhang Bo , Xu Jian‐ping , Qi Ling , Xin Dao , Wang Lin , Wang Bing‐zhi , Tian Yan‐tao , Li Yong , Huang Jing
Published: November 2022

Background

The addition of immune checkpoint inhibitors to perioperative chemotherapy in operable gastric or gastroesophageal junction (GEJ) cancer has become one of the research hotspots, while reliable biomarkers for efficacy are lacking. We conducted a phase 1 trial to assess the safety and efficacy of LP002, an anti‐PD‐L1 antibody, plus chemotherapy as perioperative treatment in patients with gastric or GEJ cancer.

Methods

We enrolled patients with resectable and PD‐L1 positive gastric or GEJ cancers. Eligible patients received three preoperative and six postoperative cycles of intravenous LP002 with cisplatin and 5‐fluorouracil, repeated every 2 weeks. The primary endpoint was safety. Secondary endpoints included rate of margin‐free (R0) resection and pathological complete response (pCR). We also characterized changes in the tumor immune microenvironment using multiplex immunofluorescence (MIF) staining and next‐generation sequencing (NGS) with pre‐ and post‐treatment tumor samples.

Results

Thirty patients were enrolled, of whom 28 had GEJ cancer. With a median follow‐up of 7.9 months, all patients completed preoperative treatment, and 27 patients underwent surgery. Twenty‐four patients underwent R0 resection. Six patients (20.0%) had Mandard tumor regression grade (TRG) 1–3, including one achieving pCR. Twenty‐seven patients had treatment‐related adverse events (TRAEs), while grade 3–4 TRAEs were observed in 11 patients. No treatment‐related deaths occurred. MIF staining revealed that TRG 1–3 group was associated with a higher density of PD‐L1+/CD68+ cells in the pre‐treatment tumor parenchyma than TRG 4–5 group (p = 0.048). NGS studies with paired pre‐ and post‐treatment tumor samples revealed the disappearance of pre‐existing mutations, the emergence of new mutations, and variations in the abundance of mutations after preoperative LP002 and chemotherapy. Meanwhile, tumor mutational burden decreased in patients with TRG 1–3 (p = 0.0313).

Conclusions

LP002 plus cisplatin and 5‐fluorouracil are safe in patients with gastric or GEJ cancer, and patient selection via appropriate biomarkers is needed in the future.
Development and validation of novel risk prediction models of breast cancer based on stanniocalcin‐1 level
Authors: Huang Sheng , Chen Yuyuan , Wu Jiong , Chi Yayun
Published: November 2022

Purpose

The function of stanniocalcin‐1 (STC‐1) in the oncogenesis and progression of tumors has been extensively studied. The purpose of this study was to investigate the relationship between secreted STC‐1 and prognosis in patients with breast cancer (BC) and to determine whether STC‐1 could be a key prognostic factor in BC.

Methods

The STC‐1 level was measured by ELISA and clinical data from 1210 female patients with BC were used to develop and validate nomograms. We then verified the models through the plotting of ROC curves and calibration curves, calculating the C‐index, and performing decision curve analyses (DCA).

Results

The level of STC‐1 in the peripheral plasma was significantly correlated with the T stage, N stage, clinical stage, grade, hormone receptors, HER‐2 status, and tumor subtype. Cox regression analyses revealed that estrogen receptor(ER) status, N stage, and STC‐1 level were risk factors for overall survival (OS), whereas T stage, N stage, and STC‐1 level were independent prognostic factors for distant disease‐free survival (DDFS) and disease‐free survival (DFS). Both the ROC curve and the C‐index confirmed the high resolution of these models, while the DCA identified the feasibility of their practical application. In addition, the calibration curves indicated good consistency between the predicted and actual survival rates.

Conclusion

Nomograms were created based on STC‐1 levels for 3‐, 5‐, and 7‐year OS, DDFS, and DFS of patients with BC respectively. As a key prognostic factor for BC, peripheral blood STC‐1 level can be used clinically as a liquid biopsy indicator.
Cutaneous and rheumatological manifestations of reactive arthritis: A case report
Authors: Slouma Maroua , Ben Dhia Siwar , Dhahri Rim , Litaiem Noureddine , Metoui Leila , Gharsallah Imen , Louzir Bassem
Published: November 2022

Reactive arthritis is a rare form of spondyloarthropathies occurring after genital or enteric infection. It is most often self‐limited but can progress to chronic spondylarthritis. We report the case of a 30‐year‐old man who presented with acute arthritis occurring 2 months after an episode of urethral discharge. Physical examination revealed polyarthritis, dactylitis, sacroiliac joint involvement, and plantar papulosquamous plaques. The human leukocyte antigen B27 was positive. Detection of Chlamydia trachomatis and Gonococcus in the first catch urine specimen was negative. Hepatitis B and C, Chlamydia trachomatis, human immunodeficiency virus, and syphilis serologic test results were negative. Pelvic magnetic resonance imaging revealed left sacroiliitis. The patient was treated with antibiotics, diclofenac, and sulfasalazine. After 6 months of follow‐up, a significant clinical improvement was obtained without remission, suggesting an evolution to chronic spondylarthritis. Diagnosis of Reactive arthritis is difficult since microbiologic examinations are commonly negative. This disease should be considered in patients with rheumatologic manifestations occurring after a urogenital or enteric infection, mainly when associated with skin manifestations and human leukocyte antigen B27.
Right lower quadrant abdominal mass: A case report
Authors: Chalise Anup , Kathayat Lok Bahadur , Poudel Prabhat , Rajbhandari Ashish Prasad , Koirala Rabin
Published: November 2022

Right lower quadrant mass in the abdomen has many causes, but gastric perforation is rare. We discuss a 65‐year‐old lady who presented with a history of pain in her abdomen followed by swelling in her right lower abdomen. During the evaluation, a diagnosis of gastric perforation was made.
A hyperechoic mass in femoral vein
Authors: Kaku Naoko , Sugiyama Hiroki , Nakamura Kazufumi , Furutani Tomoki , Hongo Takashi , Ito Hiroshi
Published: November 2022

Here, we present a case of fat embolism syndrome (FES) in which ultrasound sonography and computed tomography successfully visualized fat embolus in the femoral vein. A multimodality approach was particularly useful for early and specific diagnosis.
Primary cutaneous B‐Cell lymphoblastic lymphoma presenting with solitary scalp mass in a female child: A case report and review of the literature
Authors: Montazer Fatemeh , Motlagh Alireza Sanei , Dastgir Ramtin
Published: November 2022

Lymphoblastic lymphoma is a group of non‐Hodgkin lymphomas that account for approximately 2% of all lymphomas. This is a report of a case of a young girl presenting with a solitary scalp mass which was resected. Histopathological examination of the mass along with bone marrow analysis revealed primary cutaneous B‐cell lymphoblastic lymphoma. A nine‐year‐old girl presenting with an asymptomatic erythematous, non‐tender scalp mass present for 12 months was admitted. Skull and brain were intact and devoid of any pathological findings on computed tomography imaging. Systemic examination also showed no evidence of mass lesion in other parts of the body. The lesion was resected and referred for pathological analysis. Microscopic study revealed heavy diffuse dermal and subcutaneous infiltration of monomorphous medium‐sized mononuclear cells, with fine chromatin, scant cytoplasm, and variable nucleoli along with intact epidermis and presence of grenz zone. Tumor cells dissect through the collagen fibers. Extensive mitotic figures and focal infiltration of the skin adnexa are seen. IHC study revealed that TdT, CD79a, CD99, CD45, CD20, and Ki67 markers were positive. According to these findings, a definitive diagnosis of primary cutaneous lymphoblastic lymphoma of B cell type was concluded. The 1‐year follow up after necessary treatment revealed normal findings without traces of recurrence. Lymphoblastic lymphomas (LBL) are a neoplasm of immature B cells belonging to the B‐(B‐LBL) or T‐cell lineage (T‐LBL) that accounts for approximately 2% of all lymphomas. Lymphoblastic lymphoma (LBL) is similar to acute lymphoblastic leukemia (ALL) and the differentiation between these neoplasms is based upon proportion of involvement of lymphoblasts in bone marrow. It has a higher male to female predominance, higher incidence in older children and younger adults, and a relatively higher frequency of CNS and gonadal involvement. The differential diagnosis is based on immunohistochemistry study of B‐cell linage tumor markers. Cutaneous involvement is present in about one third of patients with B‐LBL but rarely in patients with ALL.
Combined type of nodular and diffuse forms of pigmented villonodular synovitis in a single knee joint of a child
Authors: Kim Dong Hwan , Noh Jung Ho
Published: November 2022

There are two types of pigmented villonodular synovitis (PVNS), nodular and diffuse. Two types generally do not coexist, and only one type usually occurs. This report presents a rare case of 12‐year‐old boy with combined type of PVNS in the knee joint who was treated arthroscopically.