bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling liver cancer microenvironment using a novel 3D culture system
Authors: Al Hrout Ala’a , Cervantes-Gracia Karla , Chahwan Richard , Amin Amr 
Published: May 2022

AbstractThe tumor microenvironment and its contribution to tumorigenesis has been a focal highlight in recent years. A two-way communication between the tumor and the surrounding microenvironment sustains and contributes to the growth and metastasis of tumors. Progression and metastasis of hepatocellular carcinoma (HCC) have been reported to be exceedingly influenced by diverse microenvironmental cues. In this study, we present a 3D-culture model of liver cancer to better mimic in vivo tumor settings. By creating novel 3D co-culture model that combines free-floating and scaffold-based 3D-culture techniques of liver cancer cells and fibroblasts, we aimed to establish a simple albeit reproducible ex vivo cancer microenvironment model that captures tumor-stroma interactions. The model presented herein exhibited unique gene expression and protein expression profiles when compared to 2D and 3D mono-cultures of liver cancer cells. Our results showed that in vivo like conditions cannot be mimicked by simply growing cancer cells as spheroids, but by co-culturing them with 3D fibroblast with which they were able to crosstalk. This was evident by the upregulation of several pathways involved in HCC, and the increase in secreted factors by co-cultured cancer cells, many of which are also involved in tumor-stroma interactions. Compared to the conventional 2D culture, the proposed model exhibits an increase in the expression of genes associated with development, progression, and poor prognosis of HCC. Our results correlated with an aggressive outcome that better mirrors in vivo HCC, and therefore, a more reliable platform for molecular understanding of HCC.
Spatial-dependent quantum dot-photon entanglement via tunneling effect
Authors: Delir Ghaleh Joughi Yaser , Sahrai Mostafa 
Published: May 2022

AbstractUtilizing the vortex beams, we investigate the entanglement between the triple-quantum dot molecule and its spontaneous emission field. We present the spatially dependent quantum dot-photon entanglement created by Laguerre-Gaussian (LG) fields. The degree of position-dependent entanglement (DEM) is controlled by the angular momentum of the LG light and the quantum tunneling effect created by the gate voltage. Various spatial-dependent entanglement distribution is reached just by the magnitude and the sign of the orbital angular momentum (OAM) of the optical vortex beam.
Blood pressure and outcome after aneurysmal subarachnoid hemorrhage
Authors: Darkwah Oppong Marvin , Steinwasser Lisa , Rieß Christoph , Wrede Karsten H. , Dinger Thiemo F. , Ahmadipour Yahya , Dammann Philipp , Rauschenbach Laurèl , Gümüs Meltem , Deuschl Cornelius , Sure Ulrich , Jabbarli Ramazan 
Published: May 2022

AbstractBlood pressure management is crucial in the treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). Possible association between the blood pressure increase and the risk of delayed cerebral ischemia (DCI) and different systemic complications after aSAH is still a matter of debate. This study aims to elucidate the influence of blood pressure levels on the outcome of aSAH. All consecutive aSAH patients (n = 690) treated between 01/2003 and 06/2016 were included. The mean value of the mean arterial pressure (MAP) during 14 days after ictus was calculated for each individual. According to the institutional standards of vasospasm management, the mean 14 days MAP ≥ 95 mmHg was referred as increased (IMAP) and the patients with and without vasospasm were analyzed separately. Study endpoints were the occurrence of DCI on computed tomography scans, development of cardiac and nephrological complications, and poor outcome 6 months after aSAH (mRS > 2). Associations were tested in univariable/multivariable binary logistic regression analysis. IMAP was documented in 474 (68.7%) cases and was more common in individuals with poor neurological conditions at admission (p < 0.001), severe amount of intracranial blood (p = 0.001) and premorbid hypertension (p < 0.001). IMAP was independently associated with the occurrence of DCI (p = 0.014; aOR = 2.97; 95% CI 1.25–7.09) and poor functional outcome (p = 0.020; aOR = 3.14; 95% CI 1.20–8.22) in patients with vasospasm, but not in counterparts without vasospasm (p = 0.113/p = 0.086). IMAP had no influence on cardiac or nephrological complications. In aSAH individuals with cerebral vasospasm, sustained increase of blood pressure exceeding the therapeutic targets is strongly associated with the risk of DCI and poor outcome. Therefore, such an intrinsic increase of blood pressure might reflect the autoregulatory mechanisms against the impending cerebral ischemia in patients with cerebral vasospasm.Trial registration number: German clinical trial registry (DRKS, Unique identifier: DRKS00008749, 06/09/2015).
Soil and landscape factors influence geospatial variation in maize grain zinc concentration in Malawi
Authors: Botoman L. , Chagumaira C. , Mossa A. W. , Amede T. , Ander E. L. , Bailey E. H. , Chimungu J. G. , Gameda S. , Gashu D. , Haefele S. M. , Joy E. J. M. , Kumssa D. B. , Ligowe I. S. , McGrath S. P. , Milne A. E. , Munthali M. , Towett E. , Walsh M. G. , Wilson L. , Young S. D. , Broadley M. R. , Lark R. M. , Nalivata P. C. 
Published: May 2022

AbstractDietary zinc (Zn) deficiency is widespread globally, and in particular among people in sub-Saharan Africa (SSA). In Malawi, dietary sources of Zn are dominated by maize and spatially dependent variation in grain Zn concentration, which will affect dietary Zn intake, has been reported at distances of up to ~ 100 km. The aim of this study was to identify potential soil properties and environmental covariates which might explain this longer-range spatial variation in maize grain Zn concentration. Data for maize grain Zn concentrations, soil properties, and environmental covariates were obtained from a spatially representative survey in Malawi (n = 1600 locations). Labile and non-labile soil Zn forms were determined using isotopic dilution methods, alongside conventional agronomic soil analyses. Soil properties and environmental covariates as potential predictors of the concentration of Zn in maize grain were tested using a priori expert rankings and false discovery rate (FDR) controls within the linear mixed model (LMM) framework that informed the original survey design. Mean and median grain Zn concentrations were 21.8 and 21.5 mg kg−1, respectively (standard deviation 4.5; range 10.0–48.1). A LMM for grain Zn concentration was constructed for which the independent variables: soil pH(water), isotopically exchangeable Zn (ZnE), and diethylenetriaminepentaacetic acid (DTPA) extractable Zn (ZnDTPA) had predictive value (p < 0.01 in all cases, with FDR controlled at < 0.05). Downscaled mean annual temperature also explained a proportion of the spatial variation in grain Zn concentration. Evidence for spatially dependent variation in maize grain Zn concentrations in Malawi is robust within the LMM framework used in this study, at distances of up to ~ 100 km. Spatial predictions from this LMM provide a basis for further investigation of variations in the contribution of staple foods to Zn nutrition, and where interventions to increase dietary Zn intake (e.g. biofortification) might be most effective. Other soil and landscape factors influencing spatially dependent variation in maize grain Zn concentration, along with factors operating over shorter distances such as choice of crop variety and agronomic practices, require further exploration beyond the scope of the design of this survey.
Fibrin-coated collagen fleece versus absorbable dural sealant for sellar closure after transsphenoidal pituitary surgery: a comparative study
Authors: Spitaels Julien , Moore Justin , Zaidman Nathalie , Arroteia Isabel Fernandes , Appelboom Geoffrey , Barrit Sami , Carlot Sébastien , De Maertelaer Viviane , Hassid Sergio , De Witte Olivier 
Published: May 2022

AbstractVarious surgical methods to prevent postoperative cerebrospinal fluid (CSF) leaks during transsphenoidal surgery have been reported. However, comparative studies are scarce. We aimed to compare the efficacy of a fibrin-coated collagen fleece (TachoSil) versus a dural sealant (DuraSeal) to prevent postoperative CSF leakage. We perform a retrospective study comparing two methods of sellar closure during endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenoma resection: TachoSil patching versus DuraSeal packing. Data concerning diagnosis, reconstruction technique, and surgical outcomes were analyzed. The primary endpoint was postoperative CSF leak rate. We reviewed 198 consecutive patients who underwent 219 EETS for pituitary adenoma from February 2007 and July 2018. Intraoperative CSF leak occurred in 47 cases (21.5%). A total of 33 postoperative CSF leaks were observed (15.1%). A reduction of postoperative CSF leaks in the TachoSil application group compared to the conventional technique using Duraseal was observed (7.7% and 18.2%, respectively; p = 0.062; Pearson exact test) although non-statistically significant. Two patients required lumbar drainage, and no revision repair was necessary to treat postoperative CSF rhinorrhea in Tachosil group. Fibrin-coated collagen fleece patching may be a valuable method to prevent postoperative cerebrospinal fluid (CSF) leaks during EETS for pituitary adenoma resection.
Evaluation of the α-casein (CSN1S1) locus as a potential target for a site-specific transgene integration
Authors: Smirnov A. V. , Kontsevaya G. V. , Shnaider T. A. , Yunusova A. M. , Feofanova N. A. , Gerlinskaya L. A. , Serova I. A. , Serov O. L. , Battulin N. R. 
Published: May 2022

AbstractTransgenic animals are an important tool in biotechnology, including the production of recombinant proteins in the milk. Traditionally, expression constructs are based on hybrid vectors bearing mammary gland specific regulatory elements from the α-casein (Csn1s1), β-casein (Csn2), whey acidic protein (WAP), or β-lactoglobulin (BLG) genes. Overexpression from the randomly integrated vectors typically provides high levels of expression, but has drawbacks due to unpredictable genome localization. CRISPR-Cas9 targeted transgene integration into the endogenous casein locus could alleviate the need for extensive animal screening to achieve high and reproducible expression levels. We decided to evaluate such a “precise” integration approach, placing the human granulocyte–macrophage colony-stimulating factor (hGMCSF) gene under control of the mouse endogenous alpha-S1-casein (Csn1s1) promoter. We designed two types of transgene integrations: a knock-in in the second exon of the Csn1s1 (INS-GM) and a full-size Csn1s1 replacement with hGMCSF (REP-GM) which was never tested before. The INS-GM approach demonstrated low transgene expression and milk protein levels (0.4% of Csn2 transcripts; 2–11 µg/ml hGMCSF). This was probably caused by the absence of the 3’-polyadenylation signal in the hGMCSF transgene. REP-GM animals displayed high transgene expression, reaching and slightly exceeding the level of the endogenous Csn1s1 (30–40% of Csn2 transcripts), but yielded less hGMCSF protein than expected (0.2–0.5 mg/ml vs 25 mg/ml of Csn1s1), indicating that translation of the protein is not optimal. Homozygous inserts leading to the Csn1s1 knock-out did not have any long standing effects on the animals’ health. Thus, in our experimental design, site-specific transgene integration into the casein locus did not provide any significant advantage over the overexpression approach.
EGFR inhibition reverses resistance to lenvatinib in hepatocellular carcinoma cells
Authors: He Xiaoping , Hikiba Yohko , Suzuki Yoshimasa , Nakamori Yoshinori , Kanemaru Yushi , Sugimori Makoto , Sato Takeshi , Nozaki Akito , Chuma Makoto , Maeda Shin 
Published: May 2022

AbstractHepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Lenvatinib is approved as a first-line treatment for unresectable HCC. The therapeutic duration of lenvatinib is limited by resistance, but the underlying mechanism is unclear. To establish lenvatinib-resistant cells, Hep3B cells were initially treated with 3 µM lenvatinib. The concentration was gradually increased by 1 µM or 0.5 µM per week and it reached to 7.5 µM 2 months after the initial exposure to lenvatinib. The biological characteristics of these cells were analyzed by ERK activation in the MAPK signaling pathway and a human phospho‐receptor tyrosine kinase (RTK) antibody array. Factors possibly related to lenvatinib resistance were analyzed using inhibitors, and cell proliferation was analyzed. We established lenvatinib-resistant HCC cells (LR cells) by long-term exposure to lenvatinib. Lenvatinib reduced ERK activation in the parent cells, but not in the LR cells. RTK array analysis showed that the activities of EGFR and insulin-like growth factor 1 receptor (IGF1R)/insulin receptor (INSR) were significantly increased in LR cells, whereas the activities of other RTKs were unchanged. Erlotinib, a widely used EGFR inhibitor, downregulated ERK activation in LR cells. The proliferation of LR cells will also be affected when lenvatinib is combined with erlotinib to treat LR cells. In contrast, inhibition of IGFR/INSR did not affect ERK activation or cell proliferation. Scavenging of reactive oxygen species (ROS) ameliorated the enhanced EGFR activation in LR cells. Lenvatinib resistance was induced by enhanced EGFR activation, possibly via ROS accumulation, in lenvatinib- resistant cells. These findings may enable the development of lenvatinib combination therapies for HCC.
TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2
Authors: Egawa Naohiro , Izumi Yuishin , Suzuki Hidefumi , Tsuge Itaru , Fujita Koji , Shimano Hitoshi , Izumikawa Keiichi , Takahashi Nobuhiro , Tsukita Kayoko , Enami Takako , Nakamura Masahiro , Watanabe Akira , Naitoh Motoko , Suzuki Shigehiko , Seki Tsuneyoshi , Kobayashi Kazuhiro , Toda Tatsushi , Kaji Ryuji , Takahashi Ryosuke , Inoue Haruhisa 
Published: May 2022

AbstractDyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia.
One-year outcomes of intravitreal brolucizumab injections in patients with polypoidal choroidal vasculopathy
Authors: Ito Arisa , Maruyama-Inoue Maiko , Kitajima Yoko , Ikeda Shoko , Inoue Tatsuya , Kadonosono Kazuaki 
Published: May 2022

AbstractTo evaluate the 1-year visual outcomes and anatomic responses of Japanese patients who received intravitreal brolucizumab (IVBr) injections for polypoidal choroidal vasculopathy (PCV). This was a retrospective study of 17 treatment-naïve eyes with PCV that were treated with IVBr. We evaluated the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT) and number of injections for 1 year. The eradication of polypoidal lesions was also evaluated using by indocyanine green angiography during the 1-year follow-up. Non-infectious intraocular inflammation developed in two (11.8%) eyes; 15 eyes were assessed at the 1-year follow-up examination. The mean BCVA improved significantly from 0.28 at baseline to 0.13 (P < 0.05) at 1 year. The CMT and CCT decreased significantly after 1 year. The mean number of injections was 6.4 ± 0.13. The rate of complete resolution of polypoidal lesions at 1 year was 93.3%. A dry macula was achieved in 13 eyes (86.6%) after the loading phase and in 11 eyes (73.3%) at 1 year. The IVBr injections appeared to be effective for improving both functional and anatomic outcomes in Japanese patients with PCV, with a high regression rate of polypoidal lesions.
A two‐stage method for single image de‐raining based on attention smoothed dilated network
Authors: Du Shuangli , Fan Hengrui , Zhao Minghua , Zong Haomai , Hu Jing , Li Peng 
Published: May 2022

AbstractRain can severely hamper the visibility of scene objects. Although existing deep learning methods have reported promising performance, they often fail to obtain satisfactory results in many practical situations, especially when the input image contains both rain streaks and haze‐like degradation. In this paper, a new two‐stage method based on attention smoothed dilated network (SDN) is proposed. Unlike most fully‐supervised methods, the mixture of rain streaks and haze‐like effects is considered in the model. The proposed method consists of two stages. First, a generative adversarial network guided by the rain‐streak attention map is proposed to remove rain streaks, where a multi‐stage attention module is used to accurately locate rain streaks in the generator. Second, haze‐like effects are further removed through SDN with the same structure as the generator. Extensive experiments on multiple datasets show that the method outperforms the state‐of‐the‐art in both objective evaluation and visual quality.
Interface quasi‐distributed fibre Bragg grating positioning detection of glaze icing load on composite insulators
Authors: Hao Yanpeng , Huang Lei , Wei Jie , Pan Ruijian , Zhang Weixun , Yang Lin 
Published: May 2022

AbstractThe electrical performance of transmission line insulators will decrease dramatically under ice‐covered conditions, and ice flashover may occur under operating voltage. There is no direct and effective monitoring method for ice cover on insulators of transmission lines. In this paper, the interface quasi‐distributed fibre Bragg grating (FBG) is used to study the positioning detection of glaze icing loads on composite insulators, and a mechanical lever model of single glaze icing load on single umbrella detection with three FBGs is established. Based on this model, a multi‐glaze location detection method on multiple umbrella skirts is proposed. Six optical fibres with 13 quasi‐distributed FBGs each are implanted into the interface of a 110 kV composite insulator. The minimum load test of FBG for detecting glaze icing load, the FBG axial/circumferential sensing rule test for the glaze, and the weight simulation test and laboratory icing verification test for multi‐glazes on multi‐umbrellas location detection method are carried out. The results show that the positioning of glaze simulated by weights is accurate, and the positioning of icing in the laboratory is basically correct.
Using a behavior random permutation model to identify displacement grooming in ungulates
Authors: Luo Yunchao , Wang Lin , Yang Le , Li Xiao-Fen , Anselme Patrick , Wang Xinxin , Tian Xingjun , Li Zhongqiu 
Published: May 2022

Abstract
Behavior affects an individual’s life in all aspects, e.g., enhancing fitness, leveraging predation risk, and reducing competition with conspecifics. However, the sequential distribution of behaviors received less attention and is unclear what the function of displacement behavior is. Displacement activities can be found in vertebrate species but there is no formal method to determine whether a behavior is expressed as a displaced or normal activity. Analyzing the sequential distributions of behaviors in a natural setting may allow researchers to identify unexpected distributions as a possible signature of displacement activities. In this study, we used a behavior random permutation model to detect the presence of a displacement activity in the Tibetan antelope Pantholops hodgsonii and the Tibetan gazelle Procapra picticaudata. The results showed that grooming in both ungulates tended to be accompanied with vigilance, and the frequency of grooming after vigilance was significantly higher than before vigilance. A significant positive correlation between the scan rate and grooming rate in the 2 ungulates was obtained. We suggest that grooming could sometimes be expressed as a displacement activity in ungulates. In addition to providing a general method for further research on displacement activities in a variety of animal species, this study sheds light on the importance of a spectral analysis of sequential distribution of animal behaviors. Behavior random permutation models can be used to explore the relevance between any 2 behaviors in a specific sequence, especially to identify a myriad of unexpected behaviors relative to their normal context of occurrence.
Robust, versatile DNA FISH probes for chromosome-specific repeats in Caenorhabditis elegans and Pristionchus pacificus
Authors: Adilardi Renzo S , Dernburg Abby F 
Published: May 2022

Abstract
Repetitive DNA sequences are useful targets for chromosomal fluorescence in situ hybridization. We analyzed recent genome assemblies of Caenorhabditis elegans and Pristionchus pacificus to identify tandem repeats with a unique genomic localization. Based on these findings, we designed and validated sets of oligonucleotide probes for each species targeting at least 1 locus per chromosome. These probes yielded reliable fluorescent signals in different tissues and can easily be combined with the immunolocalization of cellular proteins. Synthesis and labeling of these probes are highly cost-effective and require no hands-on labor. The methods presented here can be easily applied in other model and nonmodel organisms with a sequenced genome.
Alpha-synuclein overexpression induces epigenomic dysregulation of glutamate signaling and locomotor pathways
Authors: Schaffner Samantha L , Wassouf Zinah , Lazaro Diana F , Xylaki Mary , Gladish Nicole , Lin David T S , MacIsaac Julia , Ramadori Katia , Hentrich Thomas , Schulze-Hentrich Julia M , Outeiro Tiago F , Kobor Michael S 
Published: May 2022

Abstract
Parkinson’s disease (PD) is a neurological disorder with complex interindividual etiology that is becoming increasingly prevalent worldwide. Elevated alpha-synuclein levels can increase risk of PD and may influence epigenetic regulation of PD pathways. Here, we report genome-wide DNA methylation and hydroxymethylation alterations associated with overexpression of two PD-linked alpha-synuclein variants (wild-type and A30P) in LUHMES cells differentiated to dopaminergic neurons. Alpha-synuclein altered DNA methylation at thousands of CpGs and DNA hydroxymethylation at hundreds of CpGs in both genotypes, primarily in locomotor behavior and glutamate signaling pathway genes. In some cases, epigenetic changes were associated with transcription. SMITE network analysis incorporating H3K4me1 ChIP-seq to score DNA methylation and hydroxymethylation changes across promoters, enhancers, and gene bodies confirmed epigenetic and transcriptional deregulation of glutamate signaling modules in both genotypes. Our results identify distinct and shared impacts of alpha-synuclein variants on the epigenome, and associate alpha-synuclein with the epigenetic etiology of PD.