bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

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

AbstractUnderstanding 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

AbstractDispersal 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

AbstractMoment 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

AbstractIn 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

AbstractA 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

AbstractBackgroundHistorical 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.MethodsA 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.ResultsOne 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.ConclusionThis 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

AbstractThe 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

AbstractBackgroundThe 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.MethodsModerate/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.ResultsIn 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.ConclusionAZE/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

AbstractOptoretinogram, 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

AbstractFollowing 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

AbstractFraxetin 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.