bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stochastic Inversion of Gaussian Random Media Using Transverse Coherence Functions for Reflected Waves: Theory and Method
Authors: Hu Hao , Zheng Yingcai 
Published: November 2020

AbstractThe transverse coherence functions (TCFs) of phase and amplitude fluctuations of a seismic wave are powerful to estimate the spatial distribution, length scales, and strength of random heterogeneities. However, TCFs have been formulated for transmitted waves only, not for reflected waves. In this paper, we derive reflection TCFs for Gaussian random media using the mirror reflection principle. Furthermore, we propose to invert for Gaussian random media using the reflection TCFs based on a grid search. We validate the new reflection TCF formulas using 2‐D elastic finite‐difference numerically modeled seismic data. We also show the feasibility and efficiency of the inverse problem. The stochastic inversion using reflected waves can be used in both exploration and global seismology.
Functional screening identifies aryl hydrocarbon receptor as suppressor of lung cancer metastasis
Authors: Nothdurft Silke , Thumser-Henner Clotilde , Breitenbücher Frank , Okimoto Ross A. , Dorsch Madeleine , Opitz Christiane A. , Sadik Ahmed , Esser Charlotte , Hölzel Michael , Asthana Saurabh , Forster Jan , Beisser Daniela , Kalmbach Sophie , Grüner Barbara M. , Bivona Trever G. , Schramm Alexander , Schuler Martin 
Published: November 2020

AbstractLung cancer mortality largely results from metastasis. Despite curative surgery many patients with early-stage non-small cell lung cancer ultimately succumb to metastatic relapse. Current risk reduction strategies based on cytotoxic chemotherapy and radiation have only modest activity. Against this background, we functionally screened for novel metastasis modulators using a barcoded shRNA library and an orthotopic lung cancer model. We identified aryl hydrocarbon receptor (AHR), a sensor of xenobiotic chemicals and transcription factor, as suppressor of lung cancer metastasis. Knockdown of endogenous AHR induces epithelial–mesenchymal transition signatures, increases invasiveness of lung cancer cells in vitro and metastasis formation in vivo. Low intratumoral AHR expression associates with inferior outcome of patients with resected lung adenocarcinomas. Mechanistically, AHR triggers ATF4 signaling and represses matrix metalloproteinase activity, both counteracting metastatic programs. These findings link the xenobiotic defense system with control of lung cancer progression. AHR-regulated pathways are promising targets for innovative anti-metastatic strategies.
Tumor necrosis factor α inhibition overcomes immunosuppressive M2b macrophage-induced bevacizumab resistance in triple-negative breast cancer
Authors: Liu Yu , Ji Xuemei , Kang Nannan , Zhou Junfei , Liang Xue , Li Jiaxin , Han Tianzhen , Zhao Chen , Yang Tianwu 
Published: November 2020

AbstractBevacizumab in neoadjuvant therapy provides a new hope of improved survival for patients with triple-negative breast cancer (TNBC) by targeting vascular endothelial growth factor in combination with chemotherapy, but curative effect is limited by bevacizumab’s continuous use while mechanisms remain incompletely understood. More and more researches reported that tumor-associated macrophages mediate resistance to chemotherapy and radiotherapy in various tumors. Here we developed a TNBC model resistant to bevacizumab under bevacizumab continuous administration. It was found that proportion of a specific subset of tumor-associated macrophages characterized as M2b (CD11b+ CD86high IL10high) increased and responsible for acquired resistance to bevacizumab. Then, we showed that RAW264.7 macrophages could be polarized to M2b subtype on simultaneous exposure to bevacizumab and TLR4 ligands as occurs in the context of continuous bevacizumab treatment. Concordantly, in TLR4-deleted C57BL/10ScNJNju (TLR4lps–del) mut/mut mice with bevacizumab treatment model, it was verified that the M2b macrophage could be induced by Fc gamma receptor-TLR4 cross-talk. In MDA-MB-231-resistant tumor-bearing mice, the content of TNFα in serum kept going up consistent with CCL1, a chemokine of M2b macrophage. In vitro neutralizing tumor necrosis factor α (TNFα) could inhibit the tumor progression caused by M2b culture medium and tumor IDO1 expression. Therefore, we thought that TNFα is a key tumor-promoting effector molecule secreted by M2b macrophage. Accordingly, the curative effect of bevacizumab was proved to be significantly improved by neutralizing TNFα with anti-TNFα nanobody. This study is expected to provide theoretical and clinical evidence elucidating the drug resistance in patients receiving bevacizumab.
NQO1 protects obese mice through improvements in glucose and lipid metabolism
Authors: Di Francesco Andrea , Choi Youngshim , Bernier Michel , Zhang Yingchun , Diaz-Ruiz Alberto , Aon Miguel A. , Kalafut Krystle , Ehrlich Margaux R. , Murt Kelsey , Ali Ahmed , Pearson Kevin J. , Levan Sophie , Preston Joshua D. , Martin-Montalvo Alejandro , Martindale Jennifer L. , Abdelmohsen Kotb , Michel Cole R. , Willmes Diana M. , Henke Christine , Navas Placido , Villalba Jose Manuel , Siegel David , Gorospe Myriam , Fritz Kristofer , Biswal Shyam , Ross David , de Cabo Rafael 
Published: November 2020

AbstractChronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes to energy metabolism regulation. Here, inducible activation of Nrf2 in mice and transgenesis of the Nrf2 target, NQO1, conferred protection from diet-induced metabolic defects through preservation of glucose homeostasis, insulin sensitivity, and lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated the association with and inhibition of the translational machinery in skeletal muscle of NQO1 transgenic mice. NQO1-Tg mice on high-fat diet had lower adipose tissue macrophages and enhanced expression of lipogenic enzymes coincident with reduction in circulating and hepatic lipids. Metabolomics data revealed a systemic metabolic signature of improved glucose handling, cellular redox, and NAD+ metabolism while label-free quantitative mass spectrometry in skeletal muscle uncovered a distinct diet- and genotype-dependent acetylation pattern of SIRT3 targets across the core of intermediary metabolism. Thus, under nutritional excess, NQO1 transgenesis preserves healthful benefits.
Effectiveness of antipsychotic drugs in schizophrenia: a 10-year retrospective study in a Korean tertiary hospital
Authors: Oh Sanghoon , Lee Tae Young , Kim Minah , Kim Se Hyun , Lee Suehyun , Cho Sunwoo , Kim Ju Han , Kwon Jun Soo 
Published: November 2020

AbstractExtensive research has been carried out on the comparative effectiveness of antipsychotic medications. Most studies, however, have been performed in Western countries. The purpose of this study was to compare the effectiveness, indicated by time to any-cause discontinuation, of antipsychotic drugs in a large number of patients with schizophrenia in South Korea. We identified 1458 patients with schizophrenia or schizophreniform disorder who were treated with antipsychotic medications using a clinical data warehouse at the Seoul National University Hospital between March 2005 and February 2014. Kaplan–Meier survival analyses were used to estimate the time to discontinuation of antipsychotic drugs. We compared the survival curves of different antipsychotics using log-rank tests. Overall, the median time to discontinuation for any cause was 133 days (95% CI, 126–147). The longest time to discontinuation was observed for clozapine, followed by aripiprazole, paliperidone, olanzapine, amisulpride, risperidone, quetiapine, ziprasidone, and haloperidol. Specifically, clozapine was significantly different from all other antipsychotic drugs (allp < 0.001). Aripiprazole also had a significantly longer time to discontinuation than amisulpride (p = 0.001), risperidone (p < 0.001), quetiapine (p < 0.001), ziprasidone (p < 0.001), and haloperidol (p < 0.001). In Asian patients with schizophrenia, clozapine was the most effective antipsychotic in terms of time to discontinuation, followed by aripiprazole. This study extends the findings of previous effectiveness studies from Western populations and suggests the need to develop guidelines for the pharmacotherapy of schizophrenia tailored to Asian individuals.
Episiotomy practices in France: epidemiology and risk factors in non-operative vaginal deliveries
Authors: Clesse Christophe , Cottenet Jonathan , Lighezzolo-Alnot Joelle , Goueslard Karine , Scheffler Michele , Sagot Paul , Quantin Catherine 
Published: November 2020

AbstractEpisiotomy use has decreased due to the lack of evidence on its protective effects from maternal obstetric anal sphincter injuries. Indications for episiotomy vary considerably and there are a great variety of factors associated with its use. The aim of this article is to describe the episiotomy rate in France between 2013 and 2017 and the factors associated with its use in non-operative vaginal deliveries. In this retrospective population-based cohort study, we included vaginal deliveries performed in French hospitals (N = 584) and for which parity was coded. The variable of interest was the rate of episiotomy, particularly for non-operative vaginal deliveries. Trends in the episiotomy rates were studied using the Cochran-Armitage test. Hierarchical logistic regression was used to identify variables associated with episiotomy according to maternal age and parity. Between 2013 and 2017, French episiotomy rates fell from 21.6 to 14.3% for all vaginal deliveries (p < 0.01), and from 15.5 to 9.3% (p < 0.01) for all non-operative vaginal deliveries. Among non-operative vaginal deliveries, epidural analgesia, non-reassuring fetal heart rate, meconium in the amniotic fluid, shoulder dystocia, and newborn weight (≥ 4,000 g) were risk factors for episiotomy, both for nulliparous and multiparous women. On the contrary, prematurity reduced the risk of its use. For nulliparous women, breech presentation was also a risk factor for episiotomy, and for multiparous women, scarred uterus and multiple pregnancies were risk factors. In France, despite a reduction in episiotomy use over the last few years, the factors associated with episiotomy have not changed and are similar to the literature. This suggests that the decrease in episiotomies in France is an overall tendency which is probably related to improved care strategies that have been relayed by hospital teams and perinatal networks.
Evaluation of right ventricular performance and impact of continuous positive airway pressure therapy in patients with obstructive sleep apnea living at high altitude
Authors: Chu Ai-Ai , Yu Hong-Mei , Yang Hui , Tian Li-Min , Hu Zhong-Yuan , Jiang Na , Xie Wan-Xia , Huang Yan 
Published: November 2020

AbstractObstructive sleep apnea syndrome (OSAS) can lead to alterations in right ventricular (RV) performance and pulmonary vascular haemodynamics. Additionally, altitude-related hypoxia is associated with pulmonary vasoconstriction, and the effect of high-altitude on the pulmonary circulation in OSAS patients can be further altered. We sought to assess alterations in RV morphology and function in OSAS patients living at high altitude by way of 2-dimensional speckle tracking echocardiography (2D-STE), real-time 3- dimensional echocardiography (RT-3DE) and cardiac biomarkers. We also evaluate the impact of continuous positive airway pressure (CPAP) treatment on RV performance. Seventy-one patients with newly diagnosed OSAS and thirty-one controls were included in this study. All individuals were assessed for cardiac biomarkers as well as underwent 2D-STE and RT-3DE. Forty-five OSAS patients underwent CPAP therapy for at least 24 weeks and were studied before and after CPAP treatment. RT-3DE was used to measure RV volume, and calculate RV 3D ejection fraction (3D RVEF). Peak systolic strain was determined. Cardiac biomarkers, including C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide, and cardiac troponin T were also measured. Right atrium volume index, RV volume, RV volume index, systolic pulmonary artery pressure (sPAP), pulmonary vascular resistance (PVR) and level of serum CRP were significantly higher in OSAS group, while OSAS patients showed lower 3D RVEF and RV longitudinal strains. Compared to the patients with sPAP < 40 mmHg, RV longitudinal strains in patients with sPAP ≥ 40 mmHg were lower. Both RV global longitudinal strain and sPAP were associated with apnea–hypopnea index. Patients treated with 6 months of CPAP therapy had significant improvement in RV geometry and performance. RV structural abnormalities and RV function impairments were observed in OSAS patients living at moderate high altitude compared to control highlanders. The reversibility of these changes after application of CPAP were further confirmed.
Full wave 3D inverse scattering transmission ultrasound tomography in the presence of high contrast
Authors: Wiskin James , Malik Bilal , Borup David , Pirshafiey Nasser , Klock John 
Published: November 2020

AbstractWe present here a quantitative ultrasound tomographic method yielding a sub-mm resolution, quantitative 3D representation of tissue characteristics in the presence of high contrast media. This result is a generalization of previous work where high impedance contrast was not present and may provide a clinically and laboratory relevant, relatively inexpensive, high resolution imaging method for imaging in the presence of bone. This allows tumor, muscle, tendon, ligament or cartilage disease monitoring for therapy and general laboratory or clinical settings. The method has proven useful in breast imaging and is generalized here to high-resolution quantitative imaging in the presence of bone. The laboratory data are acquired in ~ 12 min and the reconstruction in ~ 24 min—approximately 200 times faster than previously reported simulations in the literature. Such fast reconstructions with real data require careful calibration, adequate data redundancy from a 2D array of 2048 elements and a paraxial approximation. The imaging results show that tissue surrounding the high impedance region is artifact free and has correct speed of sound at sub-mm resolution.
Investigating the origin and authenticity of Victoria Cross medals using X-ray fluorescence spectrometry
Authors: Marriott Andrew , Prendergast James G. D. 
Published: November 2020

AbstractThe Victoria Cross is the United Kingdom’s premier military award for bravery, presented for gallantry during active operations. Since its inception in 1856 just 1358 have been awarded, and, due to their rarity and historic interest, have become highly prized amongst private and public collections. Unresolved, however, is a debate about the source material of the medals. Some authorities adhere to a traditional belief that all medals have been cast from the bronze of guns captured from the Russians at Sebastopol. Furthermore, controversy is attached to the authenticity of some VCs. In this study we used X-ray fluorescence spectrometry data to compare the metal compositions of 100 Victoria Crosses, covering 7% of those ever issued. Using Gaussian mixture modelling we identify that Victoria Crosses fall into four distinct clusters, confirming that the primary split occurred between medals issued prior to and after 1914. Using these data we investigate the potential of X-ray fluorescence to inform the study of medals whose authenticity have been queried, showing some have unusually similar compositions to other VCs. This paper highlights how X-ray fluorescence data in conjunction with clustering approaches can be used to effectively and non-destructively investigate the authenticity and history of Victoria Crosses.
DNA damage induced by KP372-1 hyperactivates PARP1 and enhances lethality of pancreatic cancer cells with PARP inhibition
Authors: Viera Talysa , Patidar Praveen L. 
Published: November 2020

AbstractThe overall prognosis for pancreatic cancer remains dismal and potent chemotherapeutic agents that selectively target this cancer are critically needed. Elevated expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) is frequent in pancreatic cancer, and it offers promising tumor-selective targeting. Recently, KP372-1 was identified as a novel NQO1 redox cycling agent that induces cytotoxicity in cancer cells by creating redox imbalance; however, the mechanistic basis of KP372-1-induced cytotoxicity remains elusive. Here, we show that KP372-1 sensitizes NQO1-expressing pancreatic cancer cells and spares immortalized normal pancreatic duct cells, hTERT-HPNE. Notably, we found that KP372-1 is ~ 10- to 20-fold more potent than β-lapachone, another NQO1 substrate, against pancreatic cancer cells. Mechanistically, our data strongly suggest that reactive oxygen species produced by NQO1-dependent redox cycling of KP372-1 cause robust DNA damage, including DNA breaks. Furthermore, we found that KP372-1-induced DNA damage hyperactivates the central DNA damage sensor protein poly(ADP-ribose) polymerase 1 (PARP1) and activates caspase-3 to initiate cell death. Our data also show that the combination of KP372-1 with PARP inhibition creates enhanced cytotoxicity in pancreatic cancer cells. Collectively, our study provides mechanistic insights into the cytotoxicity instigated by KP372-1 and lays an essential foundation to establish it as a promising chemotherapeutic agent against cancer.
Neutrophil extracellular traps are induced in a psoriasis model of interleukin-36 receptor antagonist-deficient mice
Authors: Watanabe Soichiro , Iwata Yohei , Fukushima Hidehiko , Saito Kenta , Tanaka Yoshihito , Hasegawa Yurie , Akiyama Masashi , Sugiura Kazumitsu 
Published: November 2020

AbstractLoss-of-function mutations in the interleukin (IL)-36 gene IL36RN are associated with psoriasis. The importance of neutrophil extracellular traps (NETs), web-like structures composed of neutrophil DNA, in the pathogenesis of psoriasis has been unclear. Here, we aimed to clarify the role of NET signaling in the deficiency of IL36 receptor antagonist (DITRA). We evaluated the severity of psoriasis-like lesions induced by imiquimod cream treatment in Il36rn−/− mice. The mRNA levels of psoriasis-related cytokines were measured via real-time reverse transcription polymerase chain reaction, and the effects of Cl-amidine, a peptidyl arginine deiminase 4 (PAD4) inhibitor, on psoriasis-like lesions were evaluated. PAD4 is a histone-modifying enzyme that is involved in NET formation. Psoriasis area and severity index scores, epidermal thickness, and infiltrated neutrophil counts were significantly increased in Il36rn−/− mice; NET formation was confirmed pathologically. Several cytokines and chemokines were upregulated in the skin lesions of Il36rn−/− mice and Cl-amidine treatment improved these psoriasis-like lesions. These results suggest that NET formation plays an important role in the pathology of psoriasis-like lesions in these mice and might represent a promising therapeutic target for DITRA.
Earthquakes and extreme rainfall induce long term permeability enhancement of volcanic island hydrogeological systems
Authors: Vittecoq B. , Fortin J. , Maury J. , Violette S. 
Published: November 2020

AbstractEarthquakes affect near-surface permeability, however temporal permeability evolution quantification is challenging due to the scarcity of observations data. Using thirteen years of groundwater level observations, we highlight clear permeability variations induced by earthquakes in an aquifer and overlaying aquitard. Dynamic stresses, above a threshold value PGV > 0.5 cm s−1, were mostly responsible for these variations. We develop a new model using earth tides responses of water levels between earthquakes. We demonstrate a clear permeability increase of the hydrogeological system, with the permeability of the aquifer increasing 20-fold and that of the aquitard 300-fold over 12 years, induced by fracture creation or fracture unclogging. In addition, we demonstrate unprecedented observations of increase in permeability due to the effect of extreme tropical deluges of rainfall and hurricanes. The water pressure increase induced by the exceptional rainfall events thus act as piston strokes strong enough to unclog congested fractures by colloids, particles or precipitates. Lastly, an analysis of regional permeabilities also highlights a permeability increase over geological timeframes (× 40 per million years), corroborating the trend observed over the last decade. This demonstrates that permeability of aquifers of andesitic volcanic islands, such as the Lesser Antilles, significantly evolve with time due to seismic activity and extreme rainfall.
Characterization of Plasmodium falciparum NEDD8 and identification of cullins as its substrates
Authors: Bhattacharjee Manish , Adhikari Navin , Sudhakar Renu , Rizvi Zeba , Das Divya , Palanimurugan R. , Sijwali Puran Singh 
Published: November 2020

AbstractA variety of post-translational modifications of Plasmodium falciparum proteins, including phosphorylation and ubiquitination, are shown to have key regulatory roles during parasite development. NEDD8 is a ubiquitin-like modifier of cullin-RING E3 ubiquitin ligases, which regulates diverse cellular processes. Although neddylation is conserved in eukaryotes, it is yet to be characterized in Plasmodium and related apicomplexan parasites. We characterized P. falciparum NEDD8 (PfNEDD8) and identified cullins as its physiological substrates. PfNEDD8 is a 76 amino acid residue protein without the C-terminal tail, indicating that it can be readily conjugated. The wild type and mutant (Gly75Ala/Gly76Ala) PfNEDD8 were expressed in P. falciparum. Western blot of wild type PfNEDD8-expressing parasites indicated multiple high molecular weight conjugates, which were absent in the parasites expressing the mutant, indicating conjugation of NEDD8 through Gly76. Immunoprecipitation followed by mass spectrometry of wild type PfNEDD8-expressing parasites identified two putative cullins. Furthermore, we expressed PfNEDD8 in mutant S. cerevisiae strains that lacked endogenous NEDD8 (rub1Δ) or NEDD8 conjugating E2 enzyme (ubc12Δ). The PfNEDD8 immunoprecipitate also contained S. cerevisiae cullin cdc53, further substantiating cullins as physiological substrates of PfNEDD8. Our findings lay ground for investigation of specific roles and drug target potential of neddylation in malaria parasites.
Strategies to produce T-DNA free CRISPRed fruit trees via Agrobacterium tumefaciens stable gene transfer
Authors: Dalla Costa Lorenza , Piazza Stefano , Pompili Valerio , Salvagnin Umberto , Cestaro Alessandro , Moffa Loredana , Vittani Lorenzo , Moser Claudio , Malnoy Mickael 
Published: November 2020

AbstractGenome editing via CRISPR/Cas9 is a powerful technology, which has been widely applied to improve traits in cereals, vegetables and even fruit trees. For the delivery of CRISPR/Cas9 components into dicotyledonous plants, Agrobacterium tumefaciens mediated gene transfer is still the prevalent method, although editing is often accompanied by the integration of the bacterial T-DNA into the host genome. We assessed two approaches in order to achieve T-DNA excision from the plant genome, minimizing the extent of foreign DNA left behind. The first is based on the Flp/FRT system and the second on Cas9 and synthetic cleavage target sites (CTS) close to T-DNA borders, which are recognized by the sgRNA. Several grapevine and apple lines, transformed with a panel of CRISPR/SpCas9 binary vectors, were regenerated and characterized for T-DNA copy number and for the rate of targeted editing. As detected by an optimized NGS-based sequencing method, trimming at T-DNA borders occurred in 100% of the lines, impairing in most cases the excision. Another observation was the leakage activity of Cas9 which produced pierced and therefore non-functional CTS. Deletions of genomic DNA and presence of filler DNA were also noticed at the junctions between T-DNA and genomic DNA. This study proved that many factors must be considered for designing efficient binary vectors capable of minimizing the presence of exogenous DNA in CRISPRed fruit trees.