bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Heisenberg–Euler Lagrangian to the discovery of Chromomagnetic Gluon Condensation
Authors: Savvidy George 
Published: February 2020

AbstractI reexamine the phenomena of the chromomagnetic gluon condensation in Yang–Mills theory. The extension of the Heisenberg–Euler Lagrangian to the Yang–Mills theory allows to calculate the effective action, the energy-momentum tensor and demonstrate that the energy density curve crosses the zero energy level of the perturbative vacuum state at nonzero angle and continuously enters to the negative energy density region. At the crossing point and further down the effective coupling constant is small and demonstrate that the true vacuum state of the Yang–Mills theory is below the perturbative vacuum state and is described by the nonzero chromomagnetic gluon condensate. The renormalisation group analyses allows to express the energy momentum tensor, its trace and the vacuum magnetic permeabilities in QED and QCD in terms of effective coupling constant and Callan–Symanzik beta function. In the vacuum the energy-momentum tensor is proportional to the space-time metric, and it induces a negative contribution to the effective cosmological constant.
Karmarkar scalar condition
Authors: Ospino J. , Núñez L. A. 
Published: February 2020

AbstractIn this work we present the Karmarkar condition in terms of the structure scalars obtained from the orthogonal decomposition of the Riemann tensor. This new expression becomes an algebraic relation among the physical variables, and not a differential equation between the metric coefficients. By using the Karmarkar scalar condition we implement a method to obtain all possible embedding class I static spherical solutions, provided the energy density profile is given. We also analyse the dynamic adiabatic case and show the incompatibility of the Karmarkar condition with several commonly assumed simplifications to the study of gravitational collapse. Finally, we consider the dissipative dynamic Karmarkar collapse and find a new solution family.
Shared hyperplanes and normal families of holomorphic curves
Authors: Liu Xiaojun , Pang Xuecheng 
Published: February 2020

In this paper, we continue to discuss the normality of holomorphic curves concerning hyperplanes shared by their derived curves and remove the restriction of the first coefficients of hyperplanes in the case [Formula: see text] and get the following result: Let [Formula: see text] be a family of holomorphic maps of a domain [Formula: see text] to [Formula: see text]. Let [Formula: see text] and [Formula: see text] be hyperplanes in [Formula: see text] located in general position, where [Formula: see text], [Formula: see text]. Assume the following conditions hold for every [Formula: see text]: (i) [Formula: see text] if and only if [Formula: see text], [Formula: see text]. (ii) If [Formula: see text], then [Formula: see text], where [Formula: see text] is a constant. Then [Formula: see text] is normal on [Formula: see text].
Angiotensin-(1–7) reduces doxorubicin-induced cardiac dysfunction in male and female Sprague-Dawley rats through antioxidant mechanisms
Authors: Rahimi Omeed , Kirby Jay , Varagic Jasmina , Westwood Brian , Tallant E. Ann , Gallagher Patricia E. 
Published: February 2020

Doxorubicin (Dox) is an effective chemotherapeutic for a variety of pediatric malignancies. Unfortunately, Dox administration often results in a cumulative dose-dependent cardiotoxicity that manifests with marked oxidative stress, leading to heart failure. Adjunct therapies are needed to mitigate Dox cardiotoxicity and enhance quality of life in pediatric patients with cancer. Angiotensin-(1–7) [Ang-(1–7)] is an endogenous hormone with cardioprotective properties. This study investigated whether adjunct Ang-(1–7) attenuates cardiotoxicity resulting from exposure to Dox in male and female juvenile rats. Dox significantly reduced body mass, and the addition of Ang-(1–7) had no effect. However, adjunct Ang-(1–7) prevented Dox-mediated diastolic dysfunction, including markers of decreased passive filling as measured by reduced early diastole mitral valve flow velocity peak ( E) ( P < 0.05) and early diastole mitral valve annulus peak velocity ( e′; P < 0.001) and increased E/e′ ( P < 0.001), an echocardiographic measure of diastolic dysfunction. Since Dox treatment increases reactive oxygen species (ROS), the effect of Ang-(1–7) on oxidative by-products and enzymes that generate or reduce ROS was investigated. In hearts of male and female juvenile rats, Dox increased NADPH oxidase 4 ( P < 0.05), a major cardiovascular NADPH oxidase isozyme that generates ROS, as well as 4-hydroxynonenal ( P < 0.001) and malondialdehyde ( P < 0.001), markers of lipid peroxidation; Ang-(1–7) prevented these effects of Dox. Cotreatment with Dox and Ang-(1–7) increased the antioxidant enzymes SOD1 (male: P < 0.05; female: P < 0.01) and catalase ( P < 0.05), which likely contributed to reduced ROS. These results demonstrate that Ang-(1–7) prevents diastolic dysfunction in association with a reduction in ROS, suggesting that the heptapeptide hormone may serve as an effective adjuvant to improve Dox-induced cardiotoxicity. NEW & NOTEWORTHY Ang-(1–7) is a clinically safe peptide hormone with cardioprotective and antineoplastic properties that could be used as an adjuvant therapy to improve cancer treatment and mitigate the long-term cardiotoxicity associated with doxorubicin in pediatric patients with cancer.
iNOS Regulates the Therapeutic Response of Pancreatic Cancer Cells to Radiotherapy
Authors: Pereira Patricia M.R. , Edwards Kimberly J. , Mandleywala Komal , Carter Lukas M. , Escorcia Freddy E. , Campesato Luis Felipe , Cornejo Mike , Abma Lolkje , Mohsen Abu-Akeel , Iacobuzio-Donahue Christine A. , Merghoub Taha , Lewis Jason S. 
Published: February 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is highly resistant to radiotherapy, chemotherapy, or a combination of these modalities, and surgery remains the only curative intervention for localized disease. Although cancer-associated fibroblasts (CAF) are abundant in PDAC tumors, the effects of radiotherapy on CAFs and the response of PDAC cells to radiotherapy are unknown. Using patient samples and orthotopic PDAC biological models, we showed that radiotherapy increased inducible nitric oxide synthase (iNOS) in the tumor tissues. Mechanistic in vitro studies showed that, although undetectable in radiotherapy-activated tumor cells, iNOS expression and nitric oxide (NO) secretion were significantly increased in CAFs secretome following radiotherapy. Culture of PDAC cells with conditioned media from radiotherapy-activated CAFs increased iNOS/NO signaling in tumor cells through NF-κB, which, in turn, elevated the release of inflammatory cytokines by the tumor cells. Increased NO after radiotherapy in PDAC contributed to an acidic microenvironment that was detectable using the radiolabeled pH (low) insertion peptide (pHLIP). In murine orthotopic PDAC models, pancreatic tumor growth was delayed when iNOS inhibition was combined with radiotherapy. These data show the important role that iNOS/NO signaling plays in the effectiveness of radiotherapy to treat PDAC tumors.Significance:A radiolabeled pH-targeted peptide can be used as a PET imaging tool to assess therapy response within PDAC and blocking iNOS/NO signaling may improve radiotherapy outcomes.
Efficacy, Safety, and Biomarkers of Toripalimab in Patients with Recurrent or Metastatic Neuroendocrine Neoplasms: A Multiple-Center Phase Ib Trial
Authors: Lu Ming , Zhang Panpan , Zhang Yanqiao , Li Zhongwu , Gong Jifang , Li Jie , Li Jian , Li Yan , Zhang Xiaotian , Lu Zhihao , Wang Xicheng , Zhou Jun , Peng Zhi , Wang Weifeng , Feng Hui , Wu Hai , Yao Sheng , Shen Lin 
Published: February 2020

Abstract

Purpose:
Patients with recurrent or metastatic neuroendocrine neoplasms (NEN) had a poor prognosis and few treatment options. Toripalimab, a humanized IgG4 antibody specific for human PD-1 receptor, was first approved to treat second-line metastatic melanoma in China in 2018.

Patients and Methods:
The multiple-center phase Ib trial enrolled patients with NENs (Ki-67 ≥ 10%) after failure of first-line therapy received 3 mg/kg toripalimab once every two weeks. The primary objective was objective response rate (ORR) and safety. PD-L1 expression and whole-exome sequencing were performed on tumor biopsies. Secondary objectives included duration of response (DOR), disease control rate (DCR), and progression-free survival and overall survival.

Results:
Of 40 patients included from April 2017 to December 2018, 8 partial responses and 6 stable diseases were observed, for a 20% ORR and a 35% DCR. The median DOR was 15.2 months. Patients with PD-L1 expression (≥10%) or high tumor mutational burden (TMB) had better ORR than PD-L1 &lt;10% (50.0% vs. 10.7%, P = 0.019) and TMB-low patients (75.0% vs. 16.1%, P = 0.03). Three of 8 (37.5%) responders harbored ARID1A mutations, whereas only 1 of 27 nonresponders had mutations (P = 0.03). Of note, 1 exceptional responder with TMB-L, microsatellite stable (MSS), and PD-L1–negative had multiple genomic arrangements with high prediction score for neoantigens.

Conclusions:
Toripalimab had antitumor activity and safety in treating recurrent or metastatic NENs. Patients with positive PD-L1 expression, TMB-H (top 10%), and/or microsatellite instable (MSI-H) might preferentially benefit from the treatment. The genomic mutation of ARID1A and high genomic rearrangements might be correlated with clinical benefit.
Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs
Authors: Dobson Stephanie M. , García-Prat Laura , Vanner Robert J. , Wintersinger Jeffrey , Waanders Esmé , Gu Zhaohui , McLeod Jessica , Gan Olga I. , Grandal Ildiko , Payne-Turner Debbie , Edmonson Michael N. , Ma Xiaotu , Fan Yiping , Voisin Veronique , Chan-Seng-Yue Michelle , Xie Stephanie Z. , Hosseini Mohsen , Abelson Sagi , Gupta Pankaj , Rusch Michael , Shao Ying , Olsen Scott R. , Neale Geoffrey , Chan Steven M. , Bader Gary , Easton John , Guidos Cynthia J. , Danska Jayne S. , Zhang Jinghui , Minden Mark D. , Morris Quaid , Mullighan Charles G. , Dick John E. 
Published: February 2020

Abstract

Disease recurrence causes significant mortality in B-progenitor acute lymphoblastic leukemia (B-ALL). Genomic analysis of matched diagnosis and relapse samples shows relapse often arising from minor diagnosis subclones. However, why therapy eradicates some subclones while others survive and progress to relapse remains obscure. Elucidation of mechanisms underlying these differing fates requires functional analysis of isolated subclones. Here, large-scale limiting dilution xenografting of diagnosis and relapse samples, combined with targeted sequencing, identified and isolated minor diagnosis subclones that initiate an evolutionary trajectory toward relapse [termed diagnosis Relapse Initiating clones (dRI)]. Compared with other diagnosis subclones, dRIs were drug-tolerant with distinct engraftment and metabolic properties. Transcriptionally, dRIs displayed enrichment for chromatin remodeling, mitochondrial metabolism, proteostasis programs, and an increase in stemness pathways. The isolation and characterization of dRI subclones reveals new avenues for eradicating dRI cells by targeting their distinct metabolic and transcriptional pathways before further evolution renders them fully therapy-resistant.

Significance:
Isolation and characterization of subclones from diagnosis samples of patients with B-ALL who relapsed showed that relapse-fated subclones had increased drug tolerance and distinct metabolic and survival transcriptional programs compared with other diagnosis subclones. This study provides strategies to identify and target clinically relevant subclones before further evolution toward relapse.
See related video: https://vimeo.com/442838617
See related article by E. Waanders et al .
New Nutraceutical Combination Reduces Blood Pressure and Improves Exercise Capacity in Hypertensive Patients Via a Nitric Oxide–Dependent Mechanism
Authors: Carrizzo Albino , Moltedo Ornella , Damato Antonio , Martinello Katiuscia , Di Pietro Paola , Oliveti Marco , Acernese Fausto , Giugliano Giuseppe , Izzo Raffaele , Sommella Eduardo , Migliarino Serena , Piazza Ornella , Izzo Carmine , Virtuoso Nicola , Strianese Andrea , Trimarco Valentina , Campiglia Pietro , Fucile Sergio , Puca Annibale , Trimarco Bruno , Vecchione Carmine 
Published: February 2020

Background

High blood pressure (
BP
) has long been recognized as a major health threat and, particularly, a major risk factor for stroke, cardiovascular disease, and end‐organ damage. However, the identification of a novel, alternative, integrative approach for the control of
BP
and cardiovascular protection is still needed.

Methods and Results

Sixty‐nine uncontrolled hypertension patients, aged 40 to 68 years, on antihypertensive medication were enrolled in 2 double‐blind studies. Forty‐five were randomized to placebo or a new nutraceutical combination named AkP05, and
BP
, endothelial function, and circulating nitric oxide were assessed before and at the end of 4 weeks of treatment. Twenty‐four patients were randomized to diuretic or AkP05 for 4 weeks and underwent a cardiopulmonary exercise test to evaluate the effects of AkP05 on functional capacity of the cardiovascular, pulmonary, and muscular systems. Vascular and molecular studies were undertaken on mice to characterize the action of the single compounds contained in the AkP05 nutraceutical combination. AkP05 supplementation reduced
BP
, improved endothelial function, and increased nitric oxide release; cardiopulmonary exercise test revealed that AkP05 increased maximum O
2
uptake, stress tolerance, and maximal power output. In mice, AkP05 reduced
BP
and improved endothelial function, evoking increased nitric oxide release through the
PKC
α/Akt/endothelial nitric oxide synthase pathway and reducing reactive oxygen species production via
NADPH
‐oxidase inhibition. These effects were mediated by synergism of the single compounds of AkP05.

Conclusions

This is the first study reporting positive effects of a nutraceutical combination on the vasculature and exercise tolerance in treated hypertensive patients. Our findings suggest that AkP05 may be used as an adjunct for the improvement of cardiovascular protection and to better control
BP
in uncontrolled hypertension.
A Qumran Cave 4 Fragment with Psalm 41:10–11 (4Q98h = 4QPsy)
Authors: Tigchelaar Eibert 
Published: February 2020

Abstract
PAM 43.680 frag. 46 provides the first textual evidence of a manuscript with Psalm 41 among the Qumran scrolls and offers an additional example of stichometrically arranged psalms with one-colon lines.
Rapid Warming in Summer Wet Bulb Globe Temperature in China with Human-Induced Climate Change
Authors: Li Chao , Sun Ying , Zwiers Francis , Wang Dongqian , Zhang Xuebin , Chen Gang , Wu Hui 
Published: February 2020

AbstractOn the basis of a newly developed observational dataset and a suite of climate model simulations, we evaluate changes in summer mean wet bulb globe temperature (WBGT) in China from 1961 through 2080. We show that summer mean WBGT has increased almost everywhere across China since 1961 as a result of human-induced climate change. Consequently, hot summers as measured by summer mean WBGT are becoming more frequent and more conducive to heat stress. Hot summers like the hottest on record during 1961–2015 in western or eastern China are now expected occur once every 3–4 years. These hot WBGT summers have become more than 140 times as likely in eastern China in the present decade (2010s) as in the 1961–90 baseline period and more than 1000 times as likely in western China. The substantially larger influence in western China is associated with its stronger warming signal, which is likely due to the high Bowen ratio of sensible to latent heat fluxes of dry soils and increases in absorbed solar radiation from the decline in mountain snow cover extent. Observation-constrained projections of future summer mean WBGT under the RCP8.5 emissions scenario indicate that, by the 2040s, almost every summer in China will be at least as hot as the hottest summer in the historical record, and by the 2060s it will be common (on average, every other year) for summers to be as much as 3.0°C hotter than the historical record, pointing to potentially large increases in the likelihood of human heat stress and to a massive adaption challenge.
Factors influencing outcomes of rheolytic thrombectomy on thrombosed dialysis access grafts: Door to angiographic bed time and what else?
Authors: Ierardi Anna Maria , Carnevale Aldo , Coppola Andrea , Renzulli Matteo , Crippa Matteo , Fumarola Enrico Maria , Golfieri Rita , Giganti Melchiore , Carrafiello Gianpaolo 
Published: February 2020

Background: The aim of this study was to investigate the effect of the time interval from clinical presentation of arteriovenous graft thrombosis and the thrombectomy procedure by the AngioJet system in terms of technical and clinical success and to identify factors influencing success. Methods: A total of 60 consecutive patients (35 men and 25 women; mean age = 52 ± 7.89 years) who had undergone percutaneous thrombectomy by the AngioJet device from 2016 to 2019 were retrospectively enrolled. Demographics and fistula data, previous treatments, time from clinical onset of thrombosis to intervention, procedural details and complications were recorded. Technical and clinical success and primary and secondary patency rates were calculated. One-way analysis of variance was performed to test any correlation between patient-related and fistula/procedure-related variables and technical/clinical success. Odds ratio and relative risk were also calculated when necessary. Results: Technical success and clinical success were 95% and 91.7%, respectively. Post-interventional primary and secondary patency rates at 1 year were 72.5% and 84.3%, respectively. Complication rate was 6.7%. One-way analysis of variance showed that clinical success was higher in patients with no previous treatment (p = 0.015). Furthermore, clinical success was significantly associated with door to angiographic bed time (p = 0.002): p-value for the 24-h and the 72-h cut-off was 0.012 and 0.006, respectively. Conclusion: Percutaneous rheolytic thrombectomy is safe and effective for thrombosed arteriovenous grafts, with acceptable primary and secondary patency rates. Higher clinical success was found in patients never treated before and when the procedure was carried out within 24 h from the clinical onset of thrombosis.
High level of fetal-globin reactivation by designed transcriptional activator-like effector
Authors: Zhan Jun , Irudayam Maria Johnson , Nakamura Yukio , Kurita Ryo , Nienhuis Arthur W. 
Published: February 2020

Abstract
The fetal-to-adult hemoglobin switch has been a focus of a long-standing effort to potentially treat sickle cell disease and β thalassemia by induction of fetal hemoglobin. In a continuation of this effort, we designed specific transcriptional activator-like effectors (TALEs) to target both the Gγ and Aγ-globin promoters. We fused the TALEs to a LIM domain binding protein (Ldb1) dimerization domain, followed by a T2A green fluorescent protein (GFP) cassette, which were assembled into a lentiviral vector. To prevent deletions caused by the repeats of TALEs during the lentivirus packing process, we changed the TALE encoding DNA by codon optimization. Intriguingly, 5 of 14 TALEs showed forced reactivation of fetal-globin expression in human umbilical cord blood-derived erythroid progenitor (HUDEP-2) cells, with a significant increase in the γ-globin mRNA level by more than 70-fold. We also observed a more than 50% reduction of β-globin mRNA. High-performance liquid chromatography analysis revealed more than 30% fetal globin in TALE-induced cells compared with the control of 2%. Among several promoters studied, the β-globin gene promoter with the locus control region (LCR) enhancer showed the highest TALE expression during CD34 erythroid differentiation. At day 19 of differentiation, 2 TALEs increased fetal-globin expression more than 40-fold in the mRNA level and up to 70% of the total globin protein. These TALEs have potential for clinical translation.
Correction to: Proteomic analysis of degradation ubiquitin signaling by ubiquitin occupancy changes responding to 26S proteasome inhibition
Authors: Hristova Ventzislava , Sun Shisheng , Zhang Hui , Chan Daniel W. 
Published: February 2020

In the original publication of the article, Figure 2d was published incorrectly. The corrected Fig. 2 was given in this Correction article [1]. The original article has been corrected.
NucBreak: location of structural errors in a genome assembly by using paired-end Illumina reads
Authors: Khelik Ksenia , Sandve Geir Kjetil , Nederbragt Alexander Johan , Rognes Torbjørn 
Published: February 2020

Abstract
Background
Advances in whole genome sequencing strategies have provided the opportunity for genomic and comparative genomic analysis of a vast variety of organisms. The analysis results are highly dependent on the quality of the genome assemblies used. Assessment of the assembly accuracy may significantly increase the reliability of the analysis results and is therefore of great importance.

Results
Here, we present a new tool called NucBreak aimed at localizing structural errors in assemblies, including insertions, deletions, duplications, inversions, and different inter- and intra-chromosomal rearrangements. The approach taken by existing alternative tools is based on analysing reads that do not map properly to the assembly, for instance discordantly mapped reads, soft-clipped reads and singletons. NucBreak uses an entirely different and unique method to localise the errors. It is based on analysing the alignments of reads that are properly mapped to an assembly and exploit information about the alternative read alignments. It does not annotate detected errors. We have compared NucBreak with other existing assembly accuracy assessment tools, namely Pilon, REAPR, and FRCbam as well as with several structural variant detection tools, including BreakDancer, Lumpy, and Wham, by using both simulated and real datasets.

Conclusions
The benchmarking results have shown that NucBreak in general predicts assembly errors of different types and sizes with relatively high sensitivity and with lower false discovery rate than the other tools. Such a balance between sensitivity and false discovery rate makes NucBreak a good alternative to the existing assembly accuracy assessment tools and SV detection tools. NucBreak is freely available at https://github.com/uio-bmi/NucBreak under the MPL license.