bluuebunny/crossref_metadata_2025 huggingface dataset:
MiR‐195‐5p represses inflammation, apoptosis, oxidative stress, and endoplasmic reticulum stress in sepsis‐induced myocardial injury by targeting activating transcription factor 6
Authors: Xia Hongxia , Zhao Hui , Yang Weize , Luo Xiaomin , Wei Jie , Xia Hao
Published: November 2021

Myocardial injury (MI) is a common complication of sepsis. MicroRNAs (miRNAs) have been suggested as potential biomarkers of MI; however, their mechanisms in sepsis‐induced MI remain unclear. A sepsis rat model was constructed by use of cecal ligation and puncture (CLP). The levels of miR‐195‐5p and activating transcription factor 6 (ATF6) expression were determined by quantitative reverse‐transcription polymerase chain reaction, and cytokine levels were detected by ELISA. The levels of oxidative stress (OS)‐related indicators and endoplasmic reticulum stress (ERS)‐related proteins were examined, and the regulatory effect of miR‐195‐5p on ATF6 was determined by using the luciferase reporter assay. Our results showed that miR‐195‐5p expression was downregulated and ATF6 expression was upregulated in lipopolysaccharide‐induced cardiomyocytes and mice with CLP‐induced sepsis. We also found that miR‐195‐5p could markedly attenuate the inflammation, apoptosis, OS, and ERS associated with sepsis‐induced MI. Additionally, we verified that miR‐195‐5p could relieve sepsis‐induced MI by targeting ATF6. This study identified potential targets for treating MI after sepsis.
An Isolable Gallium‐Substituted Nitrilimine and its Reactivity with B−H, Si−H and B−B Bonds
Authors: Kassymbek Aishabibi , Gusev Dmitry G. , Dmitrienko Anton , Pilkington Melanie , Nikonov Georgii I.
Published: November 2021

Reaction of the Ga(I) compound NacNacGa (9) with the diazo compound N2CHSiMe3 affords the nitrilimine compound NacNacGa(N‐NCSiMe3)(CH2SiMe3) (10). Carrying out this reaction in the presence of pyridine does not lead to C−H activation on the transient alkylidene NacNacGa=CHSiMe3 but generates a metallated diazo species NacNacGa(NHN=CHSiMe3)(CN2SiMe3) (13) that further rearranges into the isonitrile compound NacNacGa(NHN=CHSiMe3)(N(NC)SiMe3) (15). Reactions of 10 with the silane H3SiPh and the borane HBcat furnished products of 1,3 addition to the nitrilimine moiety NacNacGa{N(ERn)NCSiMe3}(CH2SiMe3), whereas reaction with the diborane B2cat2 gave the product of formal nitrene insertion into the B−B bond. DFT calculations suggest that the interaction of 9 with N2CHSiMe3 proceeds through intermediate formation of an alkylidene compound that undergoes CH activation with a second molecule of N2CHSiMe3. Insertion into the B−B bond likely proceeds through an initial 1,3‐addition of the diborane, followed by boryl migration to the former nitrene center.
From β‐Na2B6O10 to Na3AlB8O15 and Na3Al2B7O15: Structural Tuning of Anionic‐Group Architectures by Substitution of [BO4] by [AlO4] Covalent Tetrahedra
Authors: Jiao Jiahao , Jin Wenqi , Zhang Min , Guo Zhiyong , Yang Zhihua , Pan Shilie
Published: November 2021

Two new sodium aluminum borates, Na3AlB8O15 and Na3Al2B7O15, have been successfully synthesized by the high‐temperature solution method. They crystallize in the different space groups, P21/c and P2/c, respectively. The B−O configurations of β‐Na2B6O10, Na3AlB8O15 and Na3Al2B7O15 are compared to feature complicated different dimensional open‐framework structures caused by the substitution of [BO4] by [AlO4] covalent tetrahedra. Moreover, the experimental results indicate that Na3AlB8O15 and Na3Al2B7O15 have short ultraviolet (UV) cutoff edges (<187 nm). The first‐principles calculations show that Na3AlB8O15 and Na3Al2B7O15 have moderate birefringence (0.075 and 0.041@1064 nm, respectively).
Membrane Catalysis: N2O Decomposition over La0.2Sr0.8Ti0.2Fe0.8O3–δ Membrane with Oxygen Permeability
Authors: Liu Mengke , Cao Zhengwen , Liang Wenyuan , Zhang Yan , Jiang Heqing
Published: November 2021

Compared to conventional heterogeneous catalysis, membrane catalysis can facilitate in situ removal of inhibiting species on a catalyst, therefore effectively increases the reaction rate. Herein, kinetically controlled decomposition of N2O was studied employing a La0.2Sr0.8Ti0.2Fe0.8O3–δ (LSTF) perovskite membrane, and the direct catalytic N2O decomposition over membrane surface was compared with membrane catalysis of N2O decomposition involving in situ oxygen removal. In the case of membrane catalysis, oxygen produced from N2O conversion can be in situ removed by using a LSTF oxygen‐permeable membrane, thus increasing the amount of surface active sites for N2O decomposition. By sweeping hydrogen at one side of the membrane to consume the permeated oxygen from the other side N2O conversion was improved.
4‐Dimethylaminopyridine‐Boryl Radical Promoted Monodefluorinative Alkylation of 3,3‐Difluorooxindoles
Authors: Simur Tesfaye Tebeka , Dagnaw Fentahun Wondu , Yu You‐Jie , Zhang Feng‐Lian , Wang Yi‐Feng
Published: November 2021

Comprehensive Summary

A selective monodefluorinative alkylation of 3,3‐difluorooxindoles is achieved. The reaction starts by the attack of a 4‐dimethylaminopyrine‐boryl radical to the carbonyl oxygen atom of 3,3‐difluorooxindoles, followed by a spin‐center shift to generate radical intermediates with the elimination of a fluoride anion. The subsequent radical addition to alkenes affords a range of 3‐alkyl‐fluorooxindoles products. The strategy offers access to C‐3 functionalized oxindoles with wide substrate scope and tolerates a wide range of functional groups.
Complete and durable response of pulmonary large‐cell neuroendocrine carcinoma to pembrolizumab
Authors: Kadota Naoki , Hatakeyama Nobuo , Hino Hiroyuki , Kunishige Michihiro , Kondo Yoshihiro , Okano Yoshio , Machida Hisanori , Naruse Keishi , Shinohara Tsutomu , Sakiyama Shoji , Ogushi Fumitaka , Takeuchi Eiji
Published: November 2021

Background

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established.

Case

A 65‐year‐old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD‐L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3‐positive T cells and CD138‐positive plasma cells. Second‐line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing.

Conclusion

Pembrolizumab may be used as a treatment option for pulmonary LCNEC.
Zoning has little impact on the seasonal diel activity and distribution patterns of wild boar (Sus scrofa) in an UNESCO Biosphere Reserve
Authors: Reinke Henrik , König Hannes J. , Keuling Oliver , Kuemmerle Tobias , Kiffner Christian
Published: November 2021

Understanding the spatio‐temporal distribution of ungulates is important for effective wildlife management, particularly for economically and ecologically important species such as wild boar (Sus scrofa). Wild boars are generally considered to exhibit substantial behavioral flexibility, but it is unclear how their behavior varies across different conservation management regimes and levels of human pressure. To analyze if and how wild boars adjust their space use or their temporal niche, we surveyed wild boars across the core and buffer zones (collectively referred to as the conservation zone) and the transition zone of a biosphere reserve. These zones represent low and high levels of human pressure, respectively. Specifically, we employed a network of 53 camera traps distributed in the Schaalsee UNESCO Biosphere Reserve over a 14‐month period (19,062 trap nights) and estimated circadian activity patterns, diel activity levels, and occupancy of wild boars in both zones. To account for differences in environmental conditions and day length, we estimated these parameters separately for seven 2‐month periods. Our results showed that the wild boars were primarily nocturnal, with diurnal activity occurring dominantly during the summer months. The diel activity patterns in the two zones were very similar overall, although the wild boars were slightly less active in the transition zone than in the conservation zone. Diel activity levels also varied seasonally, ranging from 7.5 to 11.0 h day−1, and scaled positively with the length of the night (R2 = 0.66–0.67). Seasonal occupancy estimates were exceptionally high (point estimates ranged from 0.65 to 0.99) and similar across zones, suggesting that the wild boars used most of the biosphere reserve. Overall, this result suggests that different conservation management regimes (in this case, the zoning of a biosphere reserve) have little impact on wild boar behavior. This finding is relevant for wildlife management in protected areas where possibly high wild boar densities could interfere with conservation goals within these areas and those of agricultural land use in their vicinity.
Forest disturbance and arthropods: small‐scale canopy and understory disturbances alter movement of mobile arthropods
Authors: Perry Kayla I. , Sivakoff Frances S. , Wallin Kimberly F. , Wenzel John W. , Herms Daniel A.
Published: November 2021

Dispersal of ground‐dwelling arthropods is understudied in forest ecosystems, which hinders understanding of effects of disturbances on population dynamics. The objective of the study was to quantify movement of ground‐dwelling arthropods in response to a factorial combination of canopy gap formation via girdling and understory vegetation removal, which was shown in a companion study to alter arthropod abundance and species richness. Arthropod movement was quantified using a self‐mark–capture technique where arthropods were marked as they crossed three concentric bands of different colored fluorescent powders located 3, 8, and 15 m from the center of 30 × 30 m experimental quadrats. The number of colors found on an individual was considered representative of dispersal such that the more colors detected, the more an individual moved. The likelihood that arthropods were marked with fluorescent powder and the number of colors detected differed among taxonomic groups. Most taxa were marked with one color and a high proportion of those individuals were collected adjacent to the band in which they were marked, suggesting limited dispersal. Canopy gaps and understory vegetation removal influenced movement of three taxa of highly mobile arthropods: Parajulidae and Paradoxosomatidae (detritivores), and Opiliones (scavengers). Opiliones were less likely to be marked with fluorescent powder in canopy gaps than under closed canopy in July, but more likely to be marked in August. Paradoxosomatidae were less likely to be marked in canopy gaps than under closed canopy in August, but their movement was unaffected in July. Parajulidae were more likely to be marked with fluorescent powders when understory vegetation was removed in July and August. Limited dispersal of most other ground‐dwelling arthropods suggests that these more sessile taxa may experience decreased survival and reproduction if they are unable to cope with environmental change in response to natural and anthropogenic disturbances. Understanding how disturbances mediate arthropod movement can inform biodiversity conservation strategies and sustainable forest management.
Moment equations for partial filling capillary electrophoresis
Authors: Miyabe Kanji
Published: November 2021

Moment equations were developed for partial filling CE systems, in which solute dissolution phenomena by spherical molecular assemblies or intermolecular interactions take place. Because experimental conditions of partial filling CE are divided into five categories on the basis of the magnitude relationship between the migration velocity of solute molecules and that of molecular assemblies or ligand molecules, the moment equations were systematically developed for each case by using the Einstein equation for diffusion and the random walk model. In order to demonstrate the effectiveness of the moment equations, they were applied to the analysis of partial filling CE behavior, which is correlated with dissolution phenomena of small solute molecules into spherical molecular assemblies as specific examples. Simulation results only in the case that the migration velocity of solute molecules is faster than that of molecular assemblies were represented in this paper. Detailed explanations about the derivation procedure of the moment equations and the simulation results in other cases can be found in the Supporting Information. The moment equations are theoretical bases for applying partial filling CE to the study on solute permeation kinetics at the interface of spherical molecular assemblies and on reaction kinetics of intermolecular interactions.
Three dimensional simulation of short channel effects in junction less FinFETs
Authors: Hosseini Seyed Akram , Eskandarian Abdollah , ghadimi Abbas
Published: November 2021

In this article, n‐channel junction‐less transistors (JLTs) with gate lengths in the range of 20–250 nm, having crystalline‐silicon (c‐Si) and polycrystalline‐silicon (poly‐Si) channels are characterized for the short channel effects (SCEs). The shift of the threshold voltage with the gate length and the drain induced barrier lowering (DIBL) are determined by three dimensional numerical simulations using technology computer aided design (TCAD) software. Conductive channels are considered to be fin like structures surrounded by oxides and gate materials on three sides. The effect of important device parameters are considered. Degradation of SCEs with shortening of the gate length is predicted as expected from two dimensional simulations. In addition, simulations indicate improvements for lower doping. Thinner channels show better DIBL and threshold shift. The fin height dependence is more complicated where undesirable peak in DIBL is observed for mid‐range heights near 200 nm. DIBL sharply drops for lower fin heights but the threshold shift becomes worse. Overall a small gate device of 20 nm with short fins of similar size can be expected to give a threshold shift of less than 30 mV and DIBL about 70 mV/V and, the use of three dimensional dielectric pockets leads to near zero shift of the threshold voltage. The performance of the two material types are comparable.
A geoarchaeological study of the large Early Bronze Age Essentuksky 1 kurgan in Ciscaucasia, Russia
Authors: Khokhlova Olga , Sverchkova Alena , Myakshina Tatyana , Kalmykov Alexey
Published: November 2021

A geoarchaeological study of the large Essentuksky 1 kurgan in the Stavropol region of Russia analyzed the chemical composition and micromorphological features of the kurgan's earthen materials and established their relationships with buried soils in the context of previously conducted paleoclimatic reconstructions. The kurgan was 5.5–6.0 m high and more than 60 m in diameter, and consisted of four earthen and three stone constructions. It was built in the second quarter of the 4th millennium BC (the Early Maykop culture) using a precise plan and utilizing the building skills and technologies available at that time. The earthen constructions consisted of alternating layers of dark‐colored slightly compacted humified and pale‐colored dense carbonate‐rich materials, which, in the moist state, were rammed down by ancient builders. These materials were sourced mainly from local soils and contained admixtures of river silt and, at the final stage of building, dung. The physicochemical properties of the earthen constructions as well as the paleosols buried under them are indicative of a short‐term aridization of the climate within the period of building. A gleyed earth with strong iron staining at the kurgan's base and mortar that held the stone constructions was produced by thoroughly mixing and compacting in a wet state, indicating that they were special construction materials. This kurgan is an example of the ancient earth architecture in the steppe zone of Russia over 5500 years ago.
Role of fractional crystallization and partial melting in the generation of intermediate and acidic magmas of the Andaman Island Ophiolite suite of India
Authors: Saikia Ashima , Akhtar Salim , Negi Priyanka
Published: November 2021

The Mesozoic‐age Andaman Island Ophiolite located in the southeastern fringe of the Indian plate margin is one of the well‐preserved supra‐subduction‐zone oceanic lithospheric slices. It is tectonically associated with the Indonesian arc system and is an extension of the Phanerozoic Indonesian‐Myanmar orogenic belt. Thus, it offers a unique opportunity to study oceanic crust formation and specify magma evolution processes in the Tethyan subduction system. The volcanics of the Andaman Islands ophiolite display a wide compositional variation. Rock types vary from basic (basalts) to intermediate (basaltic‐trachyandesites, basaltic andesites) to acidic differentiates like dacites and rhyolites. This contribution presents the petrochemistry of the intermediate rock types—basaltic‐trachyandesites, trachyandesites and acidic—dacites and rhyodacites of Andaman Island Ophiolite (India). This study examines the role of fractional crystallization and partial melting in the generation of intermediate and acidic magmas of the Andaman Ophiolite suite. Plagioclases and pyroxenes are the major mineral constituents of these rocks on petrographic observation. Plagioclases of the intermediate rocks are of albite composition Ab98‐99. The acidic rocks show compositional variation from albite to oligoclase (Ab83–99). Analysed pyroxenes of intermediate and acidic rocks are augite (Wo46–49En34–41Fs13–17). The studied calc‐alkaline rocks show variable abundance of Large‐Ion Lithophile Elements and display strong positive Pb and negative Ti anomalies. The chondrite‐normalized Rare Earth Elements display an enriched pattern with varying degrees of enrichment. Clinopyroxene thermobarometry reveals that the intermediate magma and acidic magma becomes saturated with clinopyroxene at 1,062–1,133°C and 1,016–1,079°C, respectively, at 2 kbar and H2O = 2 wt%. Petrochemical findings and model calculations using PELE are consistent with a derivation of intermediate rocks from the basaltic melt by fractional crystallization. In contrast, acidic rocks are the product of partial melting of hydrothermally altered oceanic crust. The association of basaltic and intermediate rocks suggests a relatively stable magma chamber to generate differentiated intermediate magmas by fractional crystallization.
Rates of bone reabsorption and union in mandibular reconstruction using the osteocutaneous radial forearm free flap
Authors: Karadaghy Omar A. , Mussatto Caroline C. , Schatz Benjamin A. , Li Jennifer , Norris Taylor W. , Nallani Rohit , Shnayder Lisa , Kakarala Kiran , Tsue Terance T. , Girod Douglas A. , Li Yanming , Koestler Devin C. , Villwock Mark R. , Harn Nick , Bur Andrés M.
Published: November 2021

Background

Historical concerns over bone resorption and malunion of the osteocutaneous radial forearm free flap (OCRFFF) limited its widespread adoption for head and neck reconstruction, despite lack of outcomes data evaluating this notion.

Methods

A retrospective cohort study was performed including patients 18 years or older who underwent reconstruction of the mandible using an OCRFFF. Linear modeling and logistic regression were used to evaluate the change in bone volume and union over time.

Results

One hundred and twenty‐one patients were included in the study. A mixed effects linear model incorporating age, sex, treatment type, and number of bone segments did not demonstrate a significant loss of bone volume over time. A logistic regression model identified lack of adjuvant treatment and time to be significantly associated with complete union.

Conclusion

This study supports that the OCRFFF is a stable form of osseus reconstruction for defects of the head and neck.
The Preparation and Resolution of Novel Axially Chiral Pyrazine‐Containing P,N Ligands for Asymmetric Catalysis and Their Application in Palladium‐Catalysed Allylic Substitution
Authors: Kelly Sarah , Goddard Richard , Guiry Patrick J.
Published: November 2021

The design and synthesis of two novel pyrazine‐containing ligands, 3,6‐diisopropyl‐Pyrazinap and Np−Cy‐Pyrazinap, has been described. Their synthesis was accomplished in six and nine steps, respectively, in which the key steps were the formation of the biaryl linkage through a Suzuki cross‐coupling reaction and the formation of the aryl to phosphorus bond employing nickel catalysis. Both ligands were resolved through the formation of diastereomeric palladacycles and in the case of the isolated diastereomer formed from 3,6‐diisopropyl‐Pyrazinap, an X‐ray crystal structure showed the axial chirality to possess (S)‐configuration. The two enantiopure ligands were applied to the palladium‐catalysed allylic alkylation of 1,3‐diphenylprop‐2‐enyl acetate with dimethyl malonate and afforded conversions of up to 100 % and 99 % with enantioselectivities of up to 92 % ee and 78 % ee, respectively. A series of 1,1,3‐triphenylallyl and 1,3‐diphenylallyl palladium complexes were prepared and their solution structures and dynamic behaviour elucidated by 2D‐COSY and NOESY NMR spectroscopic experiments.
Nasal immune gene expression in response to azelastine and fluticasone propionate combination or monotherapy
Authors: Watts Annabelle M. , West Nicholas P. , Smith Peter K. , Zhang Ping , Cripps Allan W. , Cox Amanda J.
Published: November 2021

Background

The combination of the antihistamine azelastine (AZE) with the corticosteroid fluticasone propionate (FP) in a single spray, has been reported to be significantly more effective at reducing allergic rhinitis (AR) symptoms than treatment with either corticosteroid or antihistamine monotherapy. However, the biological basis for enhanced symptom relief is not known. This study aimed to compare gene expression profiles (760 immune genes, performed with the NanoString nCounter) from peripheral blood and nasal brushing/lavage lysate samples in response to nasal spray treatment.

Methods

Moderate/severe persistent dust mite AR sufferers received either AZE (125 μg/spray) nasal spray (n = 16), FP (50 μg/spray) nasal spray (n = 14) or combination spray AZE/FP (125 μg AZE and 50 μg FP/spray) (n = 14) for 7 days, twice daily. Self‐reported symptom questionnaires were completed daily for the study duration. Gene expression analysis (760 immune genes) was performed with the NanoString nCounter on purified RNA from peripheral blood and nasal brushing/lavage lysate samples.

Results

In nasal samples, 206 genes were significantly differentially expressed following FP treatment; 182 genes downregulated (−2.57 to −0.45 Log2 fold change [FC]), 24 genes upregulated (0.49–1.40 Log2 FC). In response to AZE/FP, only 16 genes were significantly differentially expressed; 10 genes downregulated (−1.53 to −0.58 Log2 FC), six genes upregulated (1.07–1.62 Log2 FC). Following AZE treatment only five genes were significantly differentially expressed; one gene downregulated (−1.68 Log2 FC), four genes upregulated (0.59–1.19 Log2 FC). Immune gene changes in peripheral blood samples following treatment were minimal. AR symptoms improved under all treatments, but improvements were less pronounced following AZE treatment.

Conclusion

AZE/FP, FP, and AZE had diverse effects on immune gene expression profiles in nasal mucosa samples. The moderate number of genes modulated by AZE/FP indicates alternative pathways in reducing AR symptoms whilst avoiding extensive local immune suppression.
Volumetric data analysis enabled spatially resolved optoretinogram to measure the functional signals in the living retina
Authors: Zhang Lijie , Dong Rongyao , Zawadzki Robert J. , Zhang Pengfei
Published: November 2021

Optoretinogram, a technique in which optical coherence tomography (OCT) is used to measure retinal functions in response to a visible light stimulus, can be a potentially useful tool to quantify retinal health alterations. Existing experimental studies on animals have focused on measuring the global retinal response by transversally averaging 3D data across the retina, which minimizes the spatial resolution of the signals, and limits the signal‐to‐noise ratio because only central B‐scans are collected and analyzed. These problems were addressed in this study by collecting volumetric data to probe functional signals and developing an improved 3D registration approach to align such series‐acquired OCT volumes. These data were then divided into small blocks and subject to a spatiotemporal analysis, whose results confirmed the spatial‐dependence of functional signals. By further averaging, the overall measurement accuracies for the position and the scattering signals were estimated to be approximately 30 nm and 1.1 %, respectively. With improved accuracy, this method revealed certain novel functional signals that have not been previously reported. In conclusion, this work provides a powerful tool to monitor retinal local and global functional changes in aging, diseased, or treated rodent eyes.
Macrophage responses to selective laser‐melted Ti‐6Al‐4V scaffolds of different pore geometries and the corresponding osteoimmunomodulatory effects toward osteogenesis
Authors: Wu Yun‐Qi , Liu Zheng , Xu Zhenchao , Zhang Yilu , Ye Hongru , Wang Xiyang
Published: November 2021

Following recent advances in osteoimmunology, there is growing recognition of the vital role of immune cells in the osteogenesis process. The 3D‐printed scaffold, as a substitute for injured and/or diseased bone tissues, has demonstrated satisfactory pro‐osteogenetic performance. However, whether immune cells prompt the above pro‐osteogenetic performance has not been elucidated in detail. In the present study, highly controllable Ti‐6Al‐4V scaffolds with different pore geometries were fabricated using a selective laser‐melting technique, to reveal their osteoimmunological functions with macrophages. The results showed that macrophages displayed characteristics of M2 phenotype in response to scaffolds. As a result, an anti‐inflammatory microenvironment was generated. When the pore geometry was considered, such observations were more apparent with the hexagonal pore scaffold than with the triangular one. In addition, inhibition of the toll‐like receptor signaling pathway in macrophages has been proposed to cause the above phenomenon. Upon applying conditioned media derived from macrophages on pre‐osteoblasts, the hexagonal pore scaffold group was found to significantly enhance osteoblastic differentiation, via macrophage‐to‐implant interactions. However, the effect of triangular pore scaffold was not statistically significant compared to that of hexagonal pore scaffolds or nonporous samples. In an attempt to quantify scaffold pore geometries, it was suggested that pores with higher circularity values tended to induce M2 polarization of macrophages, promote an anti‐inflammatory milieu, and therefore, achieve better osteogenetic performance via immunomodulation.
Fraxetin induces cell death in colon cancer cells via mitochondria dysfunction and enhances therapeutic effects in 5‐fluorouracil resistant cells
Authors: Lee Minkyeong , Yang Changwon , Park Sunwoo , Song Gwonhwa , Lim Whasun
Published: November 2021

Fraxetin is a natural compound extracted from Fraxinus spp. and has various functions such as antibacterial, antioxidant, neuroprotective, and antifibrotic effects. Although studies have reported its anticancer properties in lung and breast cancer, little is known about colon cancer, the most frequent type of cancer. Thus, we used two colon cancer cell lines, HT29 and HCT116 cells, to investigate whether fraxetin could inhibit the capabilities acquired during tumor development. In this study, fraxetin suppressed cell viability and induced apoptotic cell death in HT29 and HCT116 cells. Furthermore, fraxetin regulated the expression of proteins involved in apoptosis in HT29 and HCT116 cells. Additionally, fraxetin induced reactive oxygen species levels and calcium influx with loss of mitochondrial membrane potential (ΔΨm) and endoplasmic reticulum stress. Moreover, fraxetin induced G2/M arrest and modulated the intracellular signaling pathway, including AKT, ERK1/2, JNK, and P38. Nevertheless, we found no cause‐effect correlation between the antiproliferative action of fraxetin and modulation of the phosphorylation state of signaling proteins. Fraxetin‐induced inhibitory effect on colon cancer cell viability was synergistic with 5‐fluorouracil (5‐FU) or irinotecan even in 5‐FU resistant‐HCT116 cells. Collectively, our results suggest that fraxetin can be effectively used as a therapeutic agent for targeting colon cancer, although it is necessary to further elucidate the relationship between the hallmark capabilities that fraxetin inhibits and the intracellular regulatory mechanism.
The influence of age on prostate cancer screening index
Authors: Shan Jiahao , Liu Ziyang , Geng Xinyu , Feng Yuelong , Yang Xiaobo , Xu Haoran , Zhou Xiaojie , Ma Wenzhuo , Zhu Hengyu , Shi Hongbin
Published: November 2021

Purpose

This study aimed to identify parameters with a higher diagnostic value for early screening of prostate cancer (PCa) at different ages.

Materials and Methods

A total of 294 patients were included and divided into two groups according to the age of patients (≤66 and >66 years). Receiver operating characteristic (ROC) curves of total prostate‐specific antigen (TPSA), free PSA (FPSA), (F/T)PSA, PSA density (PSAD), PSA–AV score, the ratio of patients' age to prostate volume (AVR) and (F/T)/PSAD were constructed. The area under the ROC curve (AUC) was calculated, and differences in the AUC values among the above‐mentioned parameters were compared.

Results

There were 121 patients in the ≤66 years age group (benign prostatic hyperplasia BPH, 103 patients; PCa 18 patients) and 173 patients in the >66 years age group (BPH, 100 patients; PCa, 73 patients). In the ≤66 years age group, the AUC value of AVR for PCa diagnosis was the highest; however, there was no statistically significant difference compared with the AUC values of PSAD and (F/T)/PSAD; compared with TPSA, FPSA, (F/T)PSA and PSA‐AV, the differences were statistically significant. In the >66 years age group, the AUC values of PSAD and PSA–AV for PCa diagnosis were higher than those of TPSA, FPSA, (F/T)PSA and (F/T)/PSAD, and the difference was statistically significant; however, the difference was not statistically significant when compared with the AUC value of AVR.

Conclusion

In different age groups, screening indices for PCa diagnosis should be selected according to the age of patients.
On weighted sublinear separators
Authors: Dvořák Zdeněk
Published: November 2021

Consider a graph with an assignment of costs to vertices. Even if and all its subgraphs admit balanced separators of sublinear size, may only admit a balanced separator of sublinear cost after deleting a small set of exceptional vertices. We improve the bound on from to , for any fixed number of iterations of the logarithm.
Seroprevalence and molecular characterization of human respiratory syncytial virus and human adenovirus among children in Ado‐Ekiti, Nigeria
Authors: Idris Olayinka O. , Kolawole Olatunji M.
Published: November 2021

In children, the respiratory syncytial virus and adenovirus majorly cause acute respiratory infections. The study evaluated the seroprevalence and conducted the molecular characterization of human respiratory syncytial virus (HRSV) and human adenovirus (HAdV) among children. Venous blood, nasopharyngeal, and oropharyngeal swabs were collected from children presenting with acute respiratory infections in a tertiary health facility in Ado‐Ekiti, Nigeria. A serological investigation was carried out on the sera samples for the detection of anti‐HRSV immunoglobulin M (IgM), anti‐HRSV IgG, anti‐HAdV IgM, and anti‐HAdV IgG using ELISA (enzyme‐linked immunosorbent assay) kits. The amplification and sequencing of HRSV and HAdV were carried out using specific primer pairs that targeted the glycoprotein (G) gene of HRSV and the hexon gene of HAdV, respectively. The seroprevalence of HRSV IgG and IgM was 73% and 7.5%, respectively, while the seroprevalence of HAdV IgG and IgM was 98.5% and 8.5%, respectively. The age of enrolled children, presence of fever, and cough were associated (p < 0.05) with the infection. HRSV subtype B (HRSV‐B) (13.3%), and species of HAdV (Mastadenovirus B and C) (11.7%) were detected among the studied population. There was no viral coinfection with both HRSV and HAdV. In infancy and early childhood, HRSV‐B, HAdV species B and C are common etiologic agents of respiratory infections as reported in this study. Further studies on molecular characterization of respiratory tract viruses including circulating respiratory syncytial virus and adenovirus are hereby advocated.
Nowhere to grow: Ranking success and turnover composition in elite employers
Authors: Pratt Benjamin R. , Dineen Brian R. , Wu Lusi
Published: November 2021

The rankings literature implicitly assumes that rankings success universally benefits organizations. However, in some instances, this assumption may be unwarranted. In this study, we employ a mixed‐methods approach that moves the literature beyond examining whether employees leave, to examine who leaves elite Best Places to Work (BPTW), defined as organizations which place in the top 10 in BPTW rankings perennially (i.e., year after year). In Study 1, examination of elite BPTW organizations shows that proportions of voluntary turnover comprising high performers increase over associated BPTW ranking cycles. Study 2 commences with 40 semistructured interviews among employees in an elite BPTW organization, from which two relevant and explanatory themes emerge. First, some employees interpret BPTW success as restricting opportunities for advancement within the organization, a phenomenon we term “perceived promotion constraint.” Second, some employees perceive BPTW success as building their own personal resumes. Integrating our findings from Study 1 and the qualitative portion of Study 2 with the career management literature, we propose and deductively test “perceived promotion constraint” and “perceived resume building” as two potential high performer turnover mechanisms, finding that perceived promotion constraint mediates the relationship between performance status and turnover intentions.
Understanding the uncertainty of the long‐term precipitation trend under global warming through the water cycle
Authors: Tu Juqing , Lu Er
Published: November 2021

It is certain that globally the troposphere has warmed since the industrial revolution because of the greenhouse gas emissions. The water vapour content of air increases as the climate warms. However, there is nonsignificant long‐term trend in global‐scale precipitation. This study aims to investigate the sources of the uncertainty of the long‐term precipitation trend under global warming through the water cycle. The data of the historical simulations (1850–2005) from 30 CMIP5 models are used in the estimate. The p‐value is utilized to indicate the significance of the long‐term trend of the water‐vapour‐related variable in the water cycle as well as the air temperature near surface and at the condensation level. For each variable, the p‐value is calculated for each of the grid points. The overall spatial distribution patterns of the p‐values are compared between two variables that linked directly, and a point‐to‐point comparison is also performed to the two fields. Results show that over the globe, the near‐surface specific humidity increases significantly at most of the grid points while the increase of the specific humidity at the condensation level is significant at some, and, however, the long‐term trend of the relative humidity at the condensation level is majorly nonsignificant. This suggests that as assessed from the global grid points, the uncertainty of the long‐term trend of the water‐vapour‐related variable enlarges substantially in the process of condensation, and modestly in the process of the transport of water vapour. Therefore, the uncertainty of the long‐term precipitation trend under global warming is mainly attributed to the condensation and slightly due to the transport of water vapour. The results obtained from the 30 models are consistent with each other, which supports the reliability of the conclusion.
Presence, formation, and elimination of foodborne pathogen persisters
Authors: Xiong Xiaohui , Kong Jiayi , Qi Diya , Xiong Xiong , Liu Yuanjian , Cui Xiaowen
Published: November 2021

Foodborne pathogen persisters are a subgroup of genetic susceptibility and growth arrest. They survive antimicrobial stress by stopping their growth, and can regenerate into normal sensitive bacteria after the stress is removed. Foodborne pathogens can survive by resisting unfavorable factors through the mechanism of persisters and exist for a long time in many food‐related environments. These surviving bacteria are harmful to food safety and human health. There are many ways to remove persisters, but few of them can be used in food. In this review, we aim to provide a clear overview of the importance of research on persisters for the microbiological safety of food and the applications of persisters elimination strategy in food.
Advances in the analytical methods for the determination of fluorinated aromatic carboxylic acids in aqueous matrices: A review
Authors: Kumar Anuj , Sharma Chhaya
Published: November 2021

Fluorobenzoic acids are critically important chemical tracers in hydrothermal, geothermal, leaching, and oilfield applications. Particularly in oilfield applications, these tracers are used to investigate fluid flow paths between injector wells and producer wells, providing valuable information about the enhanced oil recovery process of the oil reservoirs. The detection limit of tracers is a vital subject in field reservoir work because the amount of chemical tracer that must be injected into the injector well is directly related to the amount detected at the producer well after migration and diffusion. The popularity of fluorinated benzoic acids as the tracers is due to their non‐toxicity over radioactive tracers and low detection limit, which is determined using analytical techniques. This review focuses on the improvements/developments in extraction techniques such as solid‐phase extraction and determination techniques such as gas chromatography coupled with mass spectrometry, liquid chromatography with mass spectrometry, isotope dilution gas chromatography‐mass spectrometry, high‐performance liquid chromatography, ion chromatography coupled with electrospray mass spectrometry, and so on for the analysis of fluorinated benzoic acids to achieve the lowest possible limit of concentration.
To protect and support: Why would consumers find foods tastier if these foods help support a desired self‐identity
Authors: Tal Aner , Gvili Yaniv , Amar Moty
Published: November 2021

Identity serves an important role in consumer decisions. Accordingly, understanding when and how products benefit from associations with different identities is crucial for marketers. The present research demonstrates that individuals aiming for a particular identity evaluate food products associated with that identity as tastier. We argue that food tastes better when it fulfills the psychological need of supporting and protecting identity. Across three studies we examined the connections between desire for an identity and consumption experience. In Study 1, participants rated products as tastier the more they desired the associated identities. Study 2 found that the effect of identity desirability on taste experience was moderated by currently held identity. We suggest this occurs because supporting an identity with appropriate consumption is only relevant for those possessing the identity. Finally, Study 3 manipulated the link between products and identity to show a boundary condition for the effect of identity desirability on taste experience. Here, dark chocolate tasted better the more participants wanted to feel sophisticated, but only when the link between dark chocolate and sophistication was made salient. Overall, consumers may find foods tastier if these foods help support a desired identity. More generally, fulfilling psychological needs can improve consumption experience.
Parkinson's Disease Modification Through Abl Kinase Inhibition: An Opportunity
Authors: Werner Milton H. , Olanow C. Warren
Published: November 2021

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system, with an estimated 5 000 000 cases worldwide. Historically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, PD pathology is now known to be widespread and to affect serotonin, cholinergic and norepinephrine neurons as well as nerve cells in the olfactory system, cerebral hemisphere, brain stem, spinal cord, and peripheral autonomic nervous system. PD pathology is characterized by the accumulation of misfolded α‐synuclein, which is thought to play a critical role in the etiopathogenesis of the disease. Animal models of PD suggest that activation of the Abelson tyrosine kinase (c‐Abl) plays an essential role in the initiation and progression of α‐synuclein pathology and neurodegeneration. These studies demonstrate that internalization of misfolded α‐synuclein activates c‐Abl, which phosphorylates α‐synuclein and promotes α‐synuclein pathology within the affected neurons. Additionally, c‐Abl inactivates parkin, disrupting mitochondrial quality control and biogenesis, promoting neurodegeneration. Post‐mortem studies of PD patients demonstrate increased levels of tyrosine phosphorylated α‐synuclein, consistent with the activation of c‐Abl in human disease. Although the c‐Abl inhibitor nilotinib failed to demonstrate clinical benefit in two double‐blind trials, novel c‐Abl inhibitors have been developed that accumulate in the brain and may inhibit c‐Abl at saturating levels. These novel inhibitors have demonstrated benefits in animal models of PD and have now entered clinical development. Here, we review the role of c‐Abl in the neurodegenerative disease process and consider the translational potential of c‐Abl inhibitors from model studies to disease‐modifying therapies for Parkinson's disease. © 2021 Inhibikase Therapeutics, Inc.Movement Disorderspublished by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
Slowing the loss of physical function in amyotrophic lateral sclerosis with edaravone: Post hoc analysis of ALSFRS‐R item scores in pivotal study MCI186‐19
Authors: Brooks Benjamin Rix , Pioro Erik P. , Katz Jonathan , Takahashi Fumihiro , Takei Koji , Zhang Jeffrey , Apple Stephen
Published: November 2021

Introduction

Phase 3 study MCI186‐19 demonstrated less loss of physical function with edaravone versus placebo, as measured by the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS‐R) total score. A 1‐point drop in an individual ALSFRS‐R item may be clinically meaningful. We assessed ALSFRS‐R item score changes to identify clinical features protected by edaravone treatment.

Methods

Time‐to‐event analysis was used to assess the cumulative probabilities of reductions in ALSFRS‐R item scores and Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ‐40) subdomain scores.

Results

Edaravone use was accompanied by: (1) delayed drop of ≥1 point in ALSFRS‐R item score for four items: salivation, walking, climbing stairs, orthopnea (unadjusted), or for two items: walking, climbing stairs (after Bonferroni correction for multiple comparisons); (2) delayed score transition from 4 or 3 at baseline to ≤2 for five items: swallowing, eating motion, walking, climbing stairs, orthopnea (unadjusted), or for one item: climbing stairs (after Bonferroni correction for multiple comparisons); and (3) delayed worsening of ALSAQ‐40 domain scores representing daily living/independence, eating and drinking (unadjusted).

Discussion

These post‐hoc analyses identified the ALSFRS‐R item scores and ALSAQ‐40 domain scores that were associated with preserved gross motor function and health‐related quality of life, respectively, after edaravone treatment. Limitations of post‐hoc analyses should be considered when interpreting these results. We recommend that clinical trials employing the ALSFRS‐R include this type of analysis as a pre‐specified secondary outcome measure.
Dependency of R2 and R2* relaxation on Gd‐DTPA concentration in arterial blood: Influence of hematocrit and magnetic field strength
Authors: van Dorth Daniëlle , Venugopal Krishnapriya , Poot Dirk H. J. , Hirschler Lydiane , de Bresser Jeroen , Smits Marion , Hernandez‐Tamames Juan A. , Debacker Clément S. , van Osch Matthias J. P.
Published: November 2021

Dynamic susceptibility contrast (DSC) MRI is clinically used to measure brain perfusion by monitoring the dynamic passage of a bolus of contrast agent through the brain. For quantitative analysis of the DSC images, the arterial input function is required. It is known that the original assumption of a linear relation between the R2(*) relaxation and the arterial contrast agent concentration is invalid, although the exact relation is as of yet unknown. Studying this relation in vitro is time‐consuming, because of the widespread variations in field strengths, MRI sequences, contrast agents, and physiological conditions. This study aims to simulate the R2(*) versus contrast concentration relation under varying physiological and technical conditions using an adapted version of an open‐source simulation tool. The approach was validated with previously acquired data in human whole blood at 1.5 T by means of a gradient‐echo sequence (proof‐of‐concept). Subsequently, the impact of hematocrit, field strength, and oxygen saturation on this relation was studied for both gradient‐echo and spin‐echo sequences. The results show that for both gradient‐echo and spin‐echo sequences, the relaxivity increases with hematocrit and field strength, while the hematocrit dependency was nonlinear for both types of MRI sequences. By contrast, oxygen saturation has only a minor effect. In conclusion, the simulation setup has proven to be an efficient method to rapidly calibrate and estimate the relation between R2(*) and gadolinium concentration in whole blood. This knowledge will be useful in future clinical work to more accurately retrieve quantitative information on brain perfusion.
A look inside the nonprofit boardroom: Influences on decision comprehensiveness and decision quality
Authors: Tabesh Pooya , Jolly Phillip M.
Published: November 2021

Findings of recent scholarly investigations show that board members of nonprofit organizations (NPOs) have become more directly involved in the process of strategic decision‐making (SDM). Despite these findings, our understanding of decision processes in NPOs is under‐developed and little is known about the factors that impact decision processes and their outcomes in NPOs. In this study, we shed light on the process of SDM within the boardrooms of NPOs by focusing on decision comprehensiveness as an important aspect of the SDM process. Our findings, based on data from a sample of 244 nonprofits, indicate that NPO's mission clarity and decision process fairness within the boardroom increase the comprehensiveness of decision‐making processes and ultimately improve decision quality.