bluuebunny/crossref_metadata_2025_split huggingface dataset:
The spatial phenotype of genotypically distinct meningiomas demonstrate potential implications of the embryology of the meninges
Authors: Fountain Daniel M. , Smith Miriam J. , O’Leary Claire , Pathmanaban Omar N. , Roncaroli Federico , Bobola Nicoletta , King Andrew T. , Evans Dafydd Gareth 
Published: December 2020

AbstractMeningiomas are the most common primary brain tumor and their incidence and prevalence is increasing. This review summarizes current evidence regarding the embryogenesis of the human meninges in the context of meningioma pathogenesis and anatomical distribution. Though not mutually exclusive, chromosomal instability and pathogenic variants affecting the long arm of chromosome 22 (22q) result in meningiomas in neural-crest cell-derived meninges, while variants affecting Hedgehog signaling, PI3K signaling,TRAF7,KLF4, andPOLR2Aresult in meningiomas in the mesodermal-derived meninges of the midline and paramedian anterior, central, and ventral posterior skull base. Current evidence regarding the common pathways for genetic pathogenesis and the anatomical distribution of meningiomas is presented alongside existing understanding of the embryological origins for the meninges prior to proposing next steps for this work.
Autism-associated miR-873 regulates ARID1B, SHANK3 and NRXN2 involved in neurodevelopment
Authors: Lu Jing , Zhu Yan , Williams Sarah , Watts Michelle , Tonta Mary A. , Coleman Harold A. , Parkington Helena C. , Claudianos Charles 
Published: December 2020

AbstractAutism spectrum disorders (ASD) are highly heritable neurodevelopmental disorders with significant genetic heterogeneity. Noncoding microRNAs (miRNAs) are recognised as playing key roles in development of ASD albeit the function of these regulatory genes remains unclear. We previously conducted whole-exome sequencing of Australian families with ASD and identified four novel single nucleotide variations in mature miRNA sequences. A pull-down transcriptome analysis using transfected SH-SY5Y cells proposed a mechanistic model to examine changes in binding affinity associated with a unique mutation found in the conserved ‘seed’ region of miR-873-5p (rs777143952: T > A). Results suggested several ASD-risk genes were differentially targeted by wild-type and mutant miR-873 variants. In the current study, a dual-luciferase reporter assay confirmed miR-873 variants have a 20-30% inhibition/dysregulation effect on candidate autism risk genesARID1B, SHANK3andNRXN2and also confirmed the affected expression with qPCR. In vitro mouse hippocampal neurons transfected with mutant miR-873 showed less morphological complexity and enhanced sodium currents and excitatory neurotransmission compared to cells transfected with wild-type miR-873. A second in vitro study showed CRISPR/Cas9 miR-873 disrupted SH-SY5Y neuroblastoma cells acquired a neuronal-like morphology and increased expression of ASD important genesARID1B,SHANK3,ADNP2, ANK2andCHD8. These results represent the first functional evidence that miR-873 regulates key neural genes involved in development and cell differentiation.
Squeezing through the microcirculation: survival adaptations of circulating tumour cells to seed metastasis
Authors: Perea Paizal Julia , Au Sam H. , Bakal Chris 
Published: December 2020

AbstractDuring metastasis, tumour cells navigating the vascular circulatory system—circulating tumour cells (CTCs)—encounter capillary beds, where they start the process of extravasation. Biomechanical constriction forces exerted by the microcirculation compromise the survival of tumour cells within capillaries, but a proportion of CTCs manage to successfully extravasate and colonise distant sites. Despite the profound importance of this step in the progression of metastatic cancers, the factors about this deadly minority of cells remain elusive. Growing evidence suggests that mechanical forces exerted by the capillaries might induce adaptive mechanisms in CTCs, enhancing their survival and metastatic potency. Advances in microfluidics have enabled a better understanding of the cell-survival capabilities adopted in capillary-mimicking constrictions. In this review, we will highlight adaptations developed by CTCs to endure mechanical constraints in the microvasculature and outline how these mechanical forces might trigger dynamic changes towards a more invasive phenotype. A better understanding of the dynamic mechanisms adopted by CTCs within the microcirculation that ultimately lead to metastasis could open up novel therapeutic avenues.
Infiltrating T-cell markers in cervical carcinogenesis: a systematic review and meta-analysis
Authors: Litwin Tamara R. , Irvin Sarah R. , Chornock Rebecca L. , Sahasrabuddhe Vikrant V. , Stanley Margaret , Wentzensen Nicolas 
Published: December 2020

Abstract
Background
The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis.

Methods
A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis.

Results
There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels.

Conclusions
Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies.
Ultra-monochromatic far-infrared Cherenkov diffraction radiation in a super-radiant regime
Authors: Karataev P. , Fedorov K. , Naumenko G. , Popov K. , Potylitsyn A. , Vukolov A. 
Published: December 2020

AbstractNowadays, intense electromagnetic (EM) radiation in the far-infrared (FIR) spectral range is an advanced tool for scientific research in biology, chemistry, and material science because many materials leave signatures in the radiation spectrum. Narrow-band spectral lines enable researchers to investigate the matter response in greater detail. The generation of highly monochromatic variable frequency FIR radiation has therefore become a broad area of research. High energy electron beams consisting of a long train of dense bunches of particles provide a super-radiant regime and can generate intense highly monochromatic radiation due to coherent emission in the spectral range from a few GHz to potentially a few THz. We employed novel coherent Cherenkov diffraction radiation (ChDR) as a generation mechanism. This effect occurs when a fast charged particle moves in the vicinity of and parallel to a dielectric interface. Two key features of the ChDR phenomenon are its non-invasive nature and its photon yield being proportional to the length of the radiator. The bunched structure of the very long electron beam produced spectral lines that were observed to have frequencies upto 21 GHz and with a relative bandwidth of 10–4 ~ 10–5. The line bandwidth and intensity are defined by the shape and length of the bunch train. A compact linear accelerator can be utilized to control the resonant wavelength by adjusting the bunch sequence frequency.
Overland and oversea migration of white storks through the water barriers of the straits of Gibraltar
Authors: Blas Julio , Salas Reyes , Flack Andrea , Torres-Medina Fernando , Sergio Fabrizio , Wikelski Martin , Fiedler Wolfgang 
Published: December 2020

AbstractSoaring landbirds typically exploit atmospheric uplift as they fly overland, displaying a highly effective energy-saving locomotion. However, large water bodies lack thermal updrafts, potentially becoming ecological barriers that hamper migration. Here we assessed the effects of a sea surface on the migratory performance of GPS-tagged white storks (Ciconia ciconia) before, during and after they crossed the straits of Gibraltar. Oversea movements involved only flapping and gliding and were faster, traversed in straighter, descending trajectories and resulted in higher movement-related energy expenditure levels than overland, supporting the water barrier hypothesis. Overland movements at both sides of the sea straits resulted in tortuous routes and ascending trajectories with pre-crossing flights showing higher elevations and more tortuous routes than post-crossing, thus supporting the barrier negotiation hypothesis. Individual positions at both ends of the sea narrow were predicted by zonal winds and storks´ location at entry in the European hinterland, and birds did not show compensational movements overland in anticipation to subsequent wind displacements oversea. The length of the water narrow at departure shore, the elevation therein and the winds on route affected major components of sea crossing performance (such as distances and times overwater, minimum elevations, climb angles, speeds and energy expenditure), supporting the departure position and oversea winds hypotheses. In summary, our study provides a prime example at high temporal resolution of how birds adjust their behavior and physiology as they interact with the changing conditions of the travelling medium, reallocating resources and modifying their movement to overcome an ecological barrier.
Silicon twisted cone structure produced by optical vortex pulse with structure evaluation by radiation hydrodynamic simulation
Authors: Nakamura Daisuke , Tasaki Ryohei , Kawamoto Miki , Oshima Hiroki , Higashihata Mitsuhiro , Ikenoue Hiroshi , Wakayama Toshitaka , Sunahara Atsushi , Higashiguchi Takeshi 
Published: December 2020

AbstractWe demonstrate a radiation hydrodynamic simulation of optical vortex pulse-ablated microcone structures on silicon (Si) substrates. Doughnut-shaped craters were formed by single pulse irradiation on the Si substrate, and a twisted cone structure with a height of 3.5 µm was created at the center of the irradiation spot by the circularly polarized optical vortex pulse. A two-dimensional (2-D) radiation hydrodynamic simulation reproduced the cone structure well with a height of 3 µm. The central part of the incident laser power was lowered from the initial profile due to plasma shielding over the laser pulse duration for an inverted double-well laser profile. The acute tip shape of the silicon surface can survive over the laser irradiation period.
The influence of rat strain on the development of neuropathic pain and comorbid anxio-depressive behaviour after nerve injury
Authors: Hestehave Sara , Abelson Klas S. P. , Brønnum Pedersen Tina , Finn David P. , Andersson Daniel R. , Munro Gordon 
Published: December 2020

AbstractBack-translating the clinical manifestations of human disease burden into animal models is increasingly recognized as an important facet of preclinical drug discovery. We hypothesized that inbred rat strains possessing stress hyper-reactive-, depressive- or anxiety-like phenotypes may possess more translational value than common outbred strains for modeling neuropathic pain. Rats (inbred: LEW, WKY, F344/ICO and F344/DU, outbred: Crl:SD) were exposed to Spared Nerve Injury (SNI) and evaluated routinely for 6 months on behaviours related to pain (von Frey stimulation and CatWalk-gait analysis), anxiety (elevated plus maze, EPM) and depression (sucrose preference test, SPT). Markers of stress reactivity together with spinal/brain opioid receptor expression were also measured. All strains variously developed mechanical allodynia after SNI with the exception of stress-hyporesponsive LEW rats, despite all strains displaying similar functional gait-deficits after injury. However, affective changes reflective of anxiety- and depressive-like behaviour were only observed for F344/DU in the EPM, and for Crl:SD in SPT. Although differences in stress reactivity and opioid receptor expression occurred, overall they were relatively unaffected by SNI. Thus, anxio-depressive behaviours did not develop in all strains after nerve injury, and correlated only modestly with degree of pain sensitivity or with genetic predisposition to stress and/or affective disturbances.
Direct observation of morphological transition for an adsorbed single polymer chain
Authors: Oda Yukari , Kawaguchi Daisuke , Morimitsu Yuma , Yamamoto Satoru , Tanaka Keiji 
Published: December 2020

AbstractA better understanding of the structure of polymers at solid interfaces is crucial for designing various polymer nano-composite materials from structural materials to nanomaterials for use in industry. To this end, the first step is to obtain information on how synthetic polymer chains adsorb onto a solid surface. We closely followed the trajectory of a single polymer chain on the surface as a function of temperature using atomic force microscopy. Combining the results with a full-atomistic molecular dynamics simulation revealed that the chain became more rigid on the way to reaching a pseudo-equilibrium state, accompanied by a change in its local conformation from mainly loops to trains. This information will be useful for regulating the physical properties of polymers at the interface.
18F-meta-fluorobenzylguanidine (18F-mFBG) to monitor changes in norepinephrine transporter expression in response to therapeutic intervention in neuroblastoma models
Authors: Turnock Stephen , Turton David R. , Martins Carlos Daniel , Chesler Louis , Wilson Thomas C. , Gouverneur Véronique , Smith Graham , Kramer-Marek Gabriela 
Published: December 2020

AbstractTargeted radiotherapy with 131I-mIBG, a substrate of the human norepinephrine transporter (NET-1), shows promising responses in heavily pre-treated neuroblastoma (NB) patients. Combinatorial approaches that enhance 131I-mIBG tumour uptake are of substantial clinical interest but biomarkers of response are needed. Here, we investigate the potential of 18F-mFBG, a positron emission tomography (PET) analogue of the 123I-mIBG radiotracer, to quantify NET-1 expression levels in mouse models of NB following treatment with AZD2014, a dual mTOR inhibitor. The response to AZD2014 treatment was evaluated in MYCN amplified NB cell lines (Kelly and SK-N-BE(2)C) by Western blot (WB) and immunohistochemistry. PET quantification of 18F-mFBG uptake post-treatment in vivo was performed, and data correlated with NET-1 protein levels measured ex vivo. Following 72 h AZD2014 treatment, in vitro WB analysis indicated decreased mTOR signalling and enhanced NET-1 expression in both cell lines, and 18F-mFBG revealed a concentration-dependent increase in NET-1 function. AZD2014 treatment failed however to inhibit mTOR signalling in vivo and did not significantly modulate intratumoural NET-1 activity. Image analysis of 18F-mFBG PET data showed correlation to tumour NET-1 protein expression, while further studies are needed to elucidate whether NET-1 upregulation induced by blocking mTOR might be a useful adjunct to 131I-mIBG therapy.
Pluripotent epigenetic regulator OBP-801 maintains filtering blebs in glaucoma filtration surgery model
Authors: Yamamoto Yuji , Mukai Atsushi , Ikushima Toru , Urata Yasuo , Kinoshita Shigeru , Hamuro Junji , Ueno Morio , Sotozono Chie 
Published: December 2020

AbstractInhibition of fibrosis is indispensable for maintaining filtering blebs after glaucoma filtration surgery (GFS). The purpose of this study was to investigate the ability of a pluripotent epigenetic regulator OBP-801 (OBP) to ameliorate extracellular matrix formation in a rabbit model of GFS. Rabbits that underwent GFS were treated with OBP. The gene expression profiles and intraocular pressure (IOP) were monitored until 30 postoperative days. The bleb tissues were evaluated for tissue fibrosis at 30 postoperative days. In in vitro models, OBP interfered the functions of diverse genes during the wound-healing process. In in vivo GFS models, the expressions of TGF-β3, MMP-2, TIMP-2 and 3, LOX, COL1A and SERPINH1 were significantly inhibited at 30 postoperative days in the OBP group compared with those in the vehicle control group. OBP treatment involving subconjunctival injection or eye drops showed no adverse effects, and reduced levels of α-SMA and collagen deposition at the surgical wound site. OBP maintained the long-lived bleb without scar formation, and IOP was lower at 30 postoperative days compared with the vehicle control group. These findings suggest that OBP is an effective and useful candidate low-molecular-weight agent for improving wound healing and surgical outcomes in a rabbit model of GFS.
High efficiency dielectric photonic crystal fiber metalens
Authors: Kim Myunghwan , Kim Soeun 
Published: December 2020

AbstractOptical fibers have been utilized in various fields owing to their superior guiding performance. However, the modification of optical properties and light manipulation in fibers are restricted by the limitation of the core and cladding materials. In addition, the spot size of the light is constrained by the diffraction limit. In this study, we propose an all-dielectric metalens patterned on the facet of a photonic crystal fiber. The metasurface, which contains Si pillars, satisfies the required phase diagram for focusing light with high transmission. The proposed metalens has a focal length of 30 µm and achieves an outstanding efficiency of up to 88% at a wavelength of 1.55 µm, which is approximately 5 times higher than that of a metal-based metalens. We believe that this scheme may pave the way for in-fiber metasurface applications.
Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer
Authors: Zhang Zhimin , Lian Xiaojuan , Xie Wei , Quan Jin , Liao Maojun , Wu Yan , Yang Zhen-Zhou , Wang Ge 
Published: December 2020

AbstractResistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has become the main clinical challenge of advanced lung cancer. This research aimed to explore the role of PARP1-mediated autophagy in the progression of TKI therapy. PARP1-mediated autophagy was evaluated in vitro by CCK-8 assay, clonogenic assay, immunofluorescence, and western blot in the HCC-827, H1975, and H1299 cells treated with icotinib (Ico), rapamycin, and AZD2281 (olaparib) alone or in combination. Our results and GEO dataset analysis confirmed that PARP1 is expressed at lower levels in TKI-sensitive cells than in TKI-resistant cells. Low PARP1 expression and high p62 expression were associated with good outcomes among patients with NSCLC after TKI therapy. AZD2281 and a lysosomal inhibitor reversed resistance to Ico by decreasing PARP1 and LC3 in cells, but an mTOR inhibitor did not decrease Ico resistance. The combination of AZD2281 and Ico exerted a markedly enhanced antitumor effect by reducing PARP1 expression and autophagy in vivo. Knockdown of PARP1 expression reversed the resistance to TKI by the mTOR/Akt/autophagy pathway in HCC-827IR, H1975, and H1299 cells. PARP1-mediated autophagy is a key pathway for TKI resistance in NSCLC cells that participates in the resistance to TKIs. Olaparib may serve as a novel method to overcome the resistance to TKIs.
Functionalization of eggshell membranes with CuO–ZnO based p–n junctions for visible light induced antibacterial activity against Escherichia coli
Authors: Preda Nicoleta , Costas Andreea , Beregoi Mihaela , Apostol Nicoleta , Kuncser Andrei , Curutiu Carmen , Iordache Florin , Enculescu Ionut 
Published: December 2020

AbstractBiopolymers provide versatile platforms for designing naturally-derived wound care dressings through eco-friendly pathways. Eggshell membrane (ESM), a widely available, biocompatible biopolymer based structure features a unique 3D porous interwoven fibrous protein network. The ESM was functionalized with inorganic compounds (Ag, ZnO, CuO used either separately or combined) using a straightforward deposition technique namely radio frequency magnetron sputtering. The functionalized ESMs were characterized from morphological, structural, compositional, surface chemistry, optical, cytotoxicity and antibacterial point of view. It was emphasized that functionalization with a combination of metal oxides and exposure to visible light results in a highly efficient antibacterial activity against Escherichia coli when compared to the activity of individual metal oxide components. It is assumed that this is possible due to the fact that an axial p–n junction is created by joining the two metal oxides. This structure separates into components the charge carrier pairs promoted by visible light irradiation that further can influence the generation of reactive oxygen species which ultimately are responsible for the bactericide effect. This study proves that, by employing inexpensive and environmentally friendly materials (ESM and metal oxides) and fabrication techniques (radio frequency magnetron sputtering), affordable antibacterial materials can be developed for potential applications in chronic wound healing device area.
Functional characterization of Caenorhabditis elegans cbs-2 gene during meiosis
Authors: Santonicola Pamela , Germoglio Marcello , d’Abbusco Domenico Scotto , Adamo Adele 
Published: December 2020

AbstractCystathionine β-synthase (CBS) is a eukaryotic enzyme that maintains the cellular homocysteine homeostasis and catalyzes the conversion of homocysteine to L-cystathionine and Hydrogen sulfide, via the trans-sulfuration pathway. In Caenorhabditis elegans, two cbs genes are present: cbs-1 functions similarly as to human CBS, and cbs-2, whose roles are instead unknown. In the present study we performed a phenotypic characterization of the cbs-2 mutant. The null cbs-2 mutant is viable, fertile and shows the wild-type complement of six bivalents in most oocyte nuclei, which is indicative of a correct formation of crossover recombination. In absence of synaptonemal complex formation (syp-2 mutant), loss of cbs-2 leads to chromosome fragmentation, suggesting that cbs-2 is essential during inter-sister repair. Interestingly, although proficient in the activation of the DNA damage checkpoint after exposure to genotoxic stress, the cbs-2 mutant is defective in DNA damage-induced apoptosis in meiotic germ cells. These results suggest possible functions for CBS-2 in meiosis, distinct from a role in the trans-sulfuration pathway. We propose that the C. elegans CBS-2 protein is required for both inter-sister repair and execution of DNA damage-induced apoptosis.