bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes
Authors: Liu Yan , Zhang Ai , Bao Ping-Ping , Lin Li , Wang Yina , Wu Haijian , Shu Xiao-Ou , Liu Aiguo , Cai Qiuyin 
Published: January 2021

Abstract
Emerging evidence indicates that microRNAs (miRNAs) play a critical role in breast cancer development. We recently reported that a higher expression of miR-374b in tumor tissues was associated with a better disease-free survival of triple-negative breast cancer (TNBC). However, the functional significance and molecular mechanisms underlying the role of miR-374b in breast cancer are largely unknown. In this current study, we evaluated the biological functions and potential mechanisms of miR-374b in both TNBC and non-TNBC. We found that miR-374b was significantly downregulated in breast cancer tissues, compared to adjacent tissues. MiR-374b levels were also lower in breast cancer cell lines, as compared to breast epithelial cells. In vitro and in vivo studies demonstrated that miR-374b modulates the malignant behavior of breast cancer cells, such as cell proliferation in 2D and 3D, cell invasion ability, colony-forming ability and tumor growth in mice. By using bioinformatics tools, we predicted that miR-374b plays a role in breast cancer cells through negatively regulating cyclin D1 (CCND1) and transforming growth factor alpha (TGFA). We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.
L-Histidinium Chiral Ionic Liquid Functionalized β-Cyclodextrin as Chiral Selector in Capillary Electrophoresis
Authors: Ma Xiaofei , Li Jingtang , Li Xiaoqi , Feng Zijie , Yang Xuan , Liu Jie , Du Yingxiang 
Published: January 2021

AbstractNowadays, ionic liquids (ILs) functionalized cyclodextrins (CDs) have drawn increasing attention in chiral separation. Herein, a novel β-CD derivative functionalized by L-histidinium IL, mono-6-deoxy-6-L-histidinium-β-cyclodextrin chloride (L-HMCDCl), was synthesized for the first time and utilized for enantioseparation of nefopam and chlorphenamine in capillary electrophoresis. The L-HMCDCl exhibited superior enantioselectivity compared with native β-CD. The effect of some key parameters such as chiral selector concentration, buffer pH and applied voltage on the enantioseparation was investigated in detail. In the interest of the chiral discrimination mechanism and the enhanced enantioselectivity of L-HMCDCl, molecular modeling with AutoDock was employed to study the interaction, which was in good agreement with experimental results.
The Politics of Power Projection: The Pivot to Asia, Its Failure, and the Future of American Primacy
Authors: Harris Peter , Trubowitz Peter 
Published: January 2021

Abstract
Why did the Obama administration's attempted pivot (or “rebalance”) to Asia fail? In this article, we argue that three interrelated domestic factors are to blame: hyper-partisanship in Washington, DC; the lack of a compelling foreign-policy narrative to make the pivot intelligible and attractive to a broad slice of the political class and domestic public; and the related failure to convince enough Americans that the pivot was necessary to boost their economic fortunes. These domestic stumbling blocks made it impossible for the Obama administration to invest US power assets toward a long-term programmatic endeavor in the Asia-Pacific. In making this argument about the domestic foundations of US power-projection, we improve upon existing explanations of the pivot's undoing that focus on international-level obstacles, problems with the pivot's design and implementation, or the unexpected election of Donald Trump as Obama's successor. We conclude by drawing implications for US power projection beyond the pivot and, indeed, beyond East Asia—suggesting that the US political system has become a weak foundation upon which to build any ambitious foreign-policy superstructure.
A multicenter prospective audit to investigate the current management of patients undergoing anti-reflux surgery in the UK: Audit & Review of Anti-Reflux Operations & Workup
Authors:   The ARROW Study Group, Walker Rob , Wiggins Tom , Blencowe Natalie S , Findlay John M , Wilson Michael , Currie Andrew C , Hornby Steve , Markar Sheraz R , Rahman Saqib , Lloyd Megan , Hollyman Marianne , Jaunoo Shameen 
Published: January 2021

Abstract

Background
There are a variety of surgical and endoscopic interventions available to treat gastroesophageal reflux disease. There is, however, no consensus on which approach is best.
The aim of this national audit is to describe the current variation in the UK clinical practice in relation to anti-reflux surgery (ARS) and to report adherence to available clinical guidelines.

Methods
This national audit will be conducted at centers across the UK using the secure online web platform ALEA. The study will comprise two parts: a registration questionnaire and a prospective multicenter audit of ARS. All participating centers will be required to complete the registration questionnaire comprising details regarding pre-, peri-, and post-operative care pathways and whether or not these are standardized within each center. Following this, a 12-month multicenter prospective audit will be undertaken to capture data including patient demographics, predominant symptoms, preoperative investigations, surgery indication, intraoperative details, and postoperative outcomes within the first 90 days.
Local teams will retain access to their own data to facilitate local quality improvement. The full dataset will be reported at national and international scientific congresses and will contribute to peer-reviewed publications and national quality improvement initiatives.

Conclusions
This study will identify and explore variation in the processes and outcomes following ARS within the UK using a collaborative cohort methodology. The results generated by this audit will facilitate local and national quality improvement initiatives and generate new possibilities for future research in anti-reflux interventions.
Camilo Barcia Trelles on Francisco de Vitoria: At the Crossroads of Carl Schmitt’s Grossraum and James Brown Scott’s ‘Modern International Law’
Authors: Beneyto José María 
Published: January 2021

Abstract
Carl Schmitt’s The Nomos of the Earth in the International Law of the Jus Publicum Europaeum (1950) undertook a re-interpretation of the modern origins of the discipline of international law, placing Vitoria at its pivot, as the Spanish international law professor Camilo Barcia Trelles (1888–1977) had done before. Barcia’s work had a strong influence on some of the seminal pieces on international law and geopolitics that Schmitt wrote in the period from 1941 to 1950. This was the case for Schmitt’s historical mythology of the opposition between sea and earth and its juridical consequence, his doctrine of the Grossraum, which had as its basis Barcia’s account of the Monroe Doctrine, and also of Schmitt’s critique of the ‘discrimination of war’ formalized in the Kellogg–Briand Pact. According to Barcia, the exclusion of European powers from the American continent by the United States as a rising hegemon was transformed – thanks to its domination of the sea – into the global reach of a world police power. Barcia did not agree with Brown Scott’s transformation of international law through American liberal internationalism into ‘modern international law’. While Brown Scott and Schmitt were competing for two opposing vernaculars of the discipline in search for a new definition and to shape it, Barcia was instrumental in the opposed efforts of these two apparently very dissimilar representatives of international law by ushering Vitoria into their service.
‘Belly-Worshippers and Greed-Paunches’: Fatness and the Belly in the Lutheran Reformation
Authors: Fletcher Holly 
Published: January 2021

Abstract
Corpulence is an area of body-history which is receiving increased attention in line with current concerns about rising obesity as well as social movements which champion body positivity and fat acceptance. Historians have challenged the traditional narrative that in past societies being ‘fat’ was simply viewed as a positive sign of wealth and prosperity, showing instead that fatness could be criticized as early as the sixteenth century. Yet the complexities and contradictions present in historical understandings of bodyweight and size often remain overlooked. This article explores such nuances in conceptions of fatness and thinness by examining the various ways in which bodyweight and size held meaning in the specific context of the Lutheran Reformation. Through a consideration of the bodily resurrection, apocalyptic belief and the form of heavenly bodies, it demonstrates how discussions of weight and fatness were embedded in fundamental debates about sin and salvation. Within these discussions, the significance of the belly comes to the fore. For Luther in particular, the belly was a source of nuance, enabling understandings of weight to be flexible and presenting the complexity of differentiating between fat and thin bodies, where ‘fat’ could be deployed as a metaphor regardless of actual physicality. Luther’s own large size has been shown to be linked to his theology as well as to his success as a reformer, and this article takes this position further, using the figure of Luther as a lens through which to view the wider significance of bodyweight and size in the Reformation.
Streamlining data-intensive biology with workflow systems
Authors: Reiter Taylor , Brooks† Phillip T , Irber† Luiz , Joslin† Shannon E K , Reid† Charles M , Scott† Camille , Brown C Titus , Pierce-Ward N Tessa 
Published: January 2021

Abstract
As the scale of biological data generation has increased, the bottleneck of research has shifted from data generation to analysis. Researchers commonly need to build computational workflows that include multiple analytic tools and require incremental development as experimental insights demand tool and parameter modifications. These workflows can produce hundreds to thousands of intermediate files and results that must be integrated for biological insight. Data-centric workflow systems that internally manage computational resources, software, and conditional execution of analysis steps are reshaping the landscape of biological data analysis and empowering researchers to conduct reproducible analyses at scale. Adoption of these tools can facilitate and expedite robust data analysis, but knowledge of these techniques is still lacking. Here, we provide a series of strategies for leveraging workflow systems with structured project, data, and resource management to streamline large-scale biological analysis. We present these practices in the context of high-throughput sequencing data analysis, but the principles are broadly applicable to biologists working beyond this field.
Dolutegravir pharmacokinetics during co-administration with either artemether/lumefantrine or artesunate/amodiaquine
Authors: Kawuma Aida N , Walimbwa Stephen I , Pillai Goonaseelan (Colin) , Khoo Saye , Lamorde Mohammed , Wasmann Roeland E , Denti Paolo 
Published: January 2021

Abstract

Background
In sub-Saharan Africa, artemisinin-containing therapies for malaria treatment are regularly co-administered with ART. Currently, dolutegravir-based regimens are recommended as first-line therapy for HIV across most of Africa.

Objectives
To investigate the population pharmacokinetics of dolutegravir during co-administration with artemether/lumefantrine or artesunate/amodiaquine, two commonly used antimalarial therapies.

Methods
We developed a population pharmacokinetic model of dolutegravir with data from 26 healthy volunteers in two Phase 2 studies with a total of 403 dolutegravir plasma concentrations at steady state. Volunteers received 50 mg of dolutegravir once daily alone or in combination with standard treatment doses of artemether/lumefantrine (80/480 mg) or artesunate/amodiaquine (200/540 mg).

Results
A two-compartment model with first-order elimination and transit compartment absorption best described the concentration–time data of dolutegravir. Typical population estimates for clearance, absorption rate constant, central volume, peripheral volume and mean absorption transit time were 0.713 L/h, 1.68 h−1, 13.2 L, 5.73 L and 1.18 h, respectively. Co-administration of artemether/lumefantrine or artesunate/amodiaquine increased dolutegravir clearance by 10.6% (95% CI 4.09%–34.5%) and 26.4% (95% CI 14.3%–51.4%), respectively. Simulations showed that simulated trough concentrations of dolutegravir alone or in combination with artemether/lumefantrine or artesunate/amodiaquine are maintained above the dolutegravir protein-adjusted IC90 of 0.064 mg/L for more than 99% of the individuals.

Conclusions
Dolutegravir dose adjustments are not necessary for patients who are taking standard 3 day treatment doses of artemether/lumefantrine or artesunate/amodiaquine.
High susceptibility to zoliflodacin and conserved target (GyrB) for zoliflodacin among 1209 consecutive clinicalNeisseria gonorrhoeaeisolates from 25 European countries, 2018
Authors: Unemo Magnus , Ahlstrand Josefine , Sánchez-Busó Leonor , Day Michaela , Aanensen David , Golparian Daniel , Jacobsson Susanne , Cole Michelle J ,   the European Collaborative Group, Torreblanca Raquel Abad , Ásmundsdóttir Lena Rós , Balla Eszter , De Baetselier Irith , Bercot Beatrice , Carannante Anna , Caugant Dominique , Borrego Maria José , Buder Susanne , Cassar Robert , Cole Michelle , Dam Alje van , Eder Claudia , Hoffmann Steen , Hunjak Blazenka , Jeverica Samo , Kirjavainen Vesa , Maikanti-Charalambous Panayiota , Miriagou Vivi , Mlynarczyk-Bonikowska Beata , Pakarna Gatis , Patterson Lynsey , Pavlik Peter , Perrin Monique , Shepherd Jill , Stefanelli Paola , Unemo Magnus , Viktorova Jelena , Zákoucká Hana 
Published: January 2021

AbstractObjectivesNovel antimicrobials for treatment of gonorrhoea are imperative. The first-in-class spiropyrimidinetrione zoliflodacin is promising and currently in an international Phase 3 randomized controlled clinical trial (RCT) for treatment of uncomplicated gonorrhoea. We evaluated the in vitro activity of and the genetic conservation of the target (GyrB) and other potential zoliflodacin resistance determinants among 1209 consecutive clinical Neisseria gonorrhoeae isolates obtained from 25 EU/European Economic Area (EEA) countries in 2018 and compared the activity of zoliflodacin with that of therapeutic antimicrobials currently used.MethodsMICs of zoliflodacin, ceftriaxone, cefixime, azithromycin and ciprofloxacin were determined using an agar dilution technique for zoliflodacin or using MIC gradient strip tests or an agar dilution technique for the other antimicrobials. Genome sequences were available for 96.1% of isolates.ResultsZoliflodacin modal MIC, MIC50, MIC90 and MIC range were 0.125, 0.125, 0.125 and ≤0.004–0.5 mg/L, respectively. The resistance was 49.9%, 6.7%, 1.6% and 0.2% to ciprofloxacin, azithromycin, cefixime and ceftriaxone, respectively. Zoliflodacin did not show any cross-resistance to other tested antimicrobials. GyrB was highly conserved and no zoliflodacin gyrB resistance mutations were found. No fluoroquinolone target GyrA or ParC resistance mutations or mutations causing overexpression of the MtrCDE efflux pump substantially affected the MICs of zoliflodacin.ConclusionsThe in vitro susceptibility to zoliflodacin was high and the zoliflodacin target GyrB was conserved among EU/EEA gonococcal isolates in 2018. This study supports further clinical development of zoliflodacin. However, additional zoliflodacin data regarding particularly the treatment of pharyngeal gonorrhoea, pharmacokinetics/pharmacodynamics and resistance selection, including suppression, would be valuable.
Defining Multimorbidity and Its Impact in Older United States Veterans Newly Treated for Multiple Myeloma
Authors: Fillmore Nathanael R , DuMontier Clark , Yildirim Cenk , La Jennifer , Epstein Mara M , Cheng David , Cirstea Diana , Yellapragada Sarvari , Abel Gregory A , Gaziano J Michael , Do Nhan , Brophy Mary , Kim Dae H , Munshi Nikhil C , Driver Jane A 
Published: January 2021

Abstract

Background
Traditional count-based measures of comorbidity are unlikely to capture the complexity of multiple chronic conditions (multimorbidity) in older adults with cancer. We aimed to define patterns of multimorbidity and their impact in older United States veterans with multiple myeloma (MM).

Methods
We measured 66 chronic conditions in 5076 veterans aged 65 years and older newly treated for MM in the national Veterans Affairs health-care system from 2004 to 2017. Latent class analysis was used to identify patterns of multimorbidity among these conditions. These patterns were then assessed for their association with overall survival, our primary outcome. Secondary outcomes included emergency department visits and hospitalizations.

Results
Five patterns of multimorbidity emerged from the latent class analysis, and survival varied across these patterns (log-rank 2-sided P &lt; .001). Older veterans with cardiovascular and metabolic disease (30.9%, hazard ratio [HR] = 1.33, 95% confidence interval [CI] = 1.21 to 1.45), psychiatric and substance use disorders (9.7%, HR = 1.58, 95% CI = 1.39 to 1.79), chronic lung disease (15.9%, HR = 1.69, 95% CI = 1.53 to 1.87), and multisystem impairment (13.8%, HR = 2.25, 95% CI = 2.03 to 2.50) had higher mortality compared with veterans with minimal comorbidity (29.7%, reference). Associations with mortality were maintained after adjustment for sociodemographic variables, measures of disease risk, and the count-based Charlson Comorbidity Index. Multimorbidity patterns were also associated with emergency department visits and hospitalizations.

Conclusions
Our findings demonstrate the need to move beyond count-based measures of comorbidity and consider cancer in the context of multiple chronic conditions.
A new tension in the cosmological model from primordial deuterium?
Authors: Pitrou Cyril , Coc Alain , Uzan Jean-Philippe , Vangioni Elisabeth 
Published: January 2021

ABSTRACT
Recent measurements of the D(p,γ)3He nuclear reaction cross-section and of the neutron lifetime, along with the reevaluation of the cosmological baryon abundance from cosmic microwave background (CMB) analysis, call for an update of abundance predictions for light elements produced during the big-bang nucleosynthesis (BBN). While considered as a pillar of the hot big-bang model in its early days, BBN constraining power mostly rests on deuterium abundance. We point out a new ≃1.8σ tension on the baryonic density, or equivalently on the D/H abundance, between the value inferred on one hand from the analysis of the primordial abundances of light elements and, on the other hand, from the combination of CMB and baryonic oscillation data. This draws the attention on this sector of the theory and gives us the opportunity to reevaluate the status of BBN in the context of precision cosmology. Finally, this paper presents an upgrade of the BBN code primat.
ASKAP observations of multiple rapid scintillators reveal a degrees-long plasma filament
Authors: Wang Yuanming , Tuntsov Artem , Murphy Tara , Lenc Emil , Walker Mark , Bannister Keith , Kaplan David L , Mahony Elizabeth K 
Published: January 2021

ABSTRACT
We present the results from an Australian Square Kilometre Array Pathfinder search for radio variables on timescales of hours. We conducted an untargeted search over a 30 deg2 field, with multiple 10-h observations separated by days to months, at a central frequency of 945 MHz. We discovered six rapid scintillators from 15-min model-subtracted images with sensitivity of $\sim\! 200\, \mu$Jy/beam; two of them are extreme intra-hour variables with modulation indices up to $\sim 40{{\ \rm per\ cent}}$ and timescales as short as tens of minutes. Five of the variables are in a linear arrangement on the sky with angular width ∼1 arcmin and length ∼2 degrees, revealing the existence of a huge plasma filament in front of them. We derived kinematic models of this plasma from the annual modulation of the scintillation rate of our sources, and we estimated its likely physical properties: a distance of ∼4 pc and length of ∼0.1 pc. The characteristics we observe for the scattering screen are incompatible with published suggestions for the origin of intra-hour variability leading us to propose a new picture in which the underlying phenomenon is a cold tidal stream. This is the first time that multiple scintillators have been detected behind the same plasma screen, giving direct insight into the geometry of the scattering medium responsible for enhanced scintillation.
Survey of Gravitationally Lensed Objects in HSC Imaging (SuGOHI) – VII. Discovery and confirmation of three strongly lensed quasars†
Authors: Jaelani Anton T , Rusu Cristian E , Kayo Issha , More Anupreeta , Sonnenfeld Alessandro , Silverman John D , Schramm Malte , Anguita Timo , Inada Naohisa , Kondo Daichi , Schechter Paul L , Lee Khee-Gan , Oguri Masamune , Chan James H H , Wong Kenneth C , Inoue Kaiki T 
Published: January 2021

ABSTRACT
We present spectroscopic confirmation of three new two-image gravitationally lensed quasars, compiled from existing strong lens and X-ray catalogues. Images of HSC J091843.27–022007.5 show a red galaxy with two blue point sources at either side, separated by 2.26 arcsec. This system has a source and a lens redshifts zs = 0.804 and zℓ = 0.459, respectively, as obtained by our follow-up spectroscopic data. CXCO J100201.50+020330.0 shows two point sources separated by 0.85 arcsec on either side of an early-type galaxy. The follow-up spectroscopic data confirm the fainter quasar has the same redshift with the brighter quasar from the Sloan Digital Sky Survey (SDSS) fiber spectrum at zs = 2.016. The deflecting foreground galaxy is a typical early-type galaxy at a redshift of zℓ = 0.439. SDSS J135944.21+012809.8 has two point sources with quasar spectra at the same redshift zs = 1.096, separated by 1.05 arcsec, and fits to the HSC images confirm the presence of a galaxy between these. These discoveries demonstrate the power of the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP)’s deep imaging and wide sky coverage. Combined with existing X-ray source catalogues and follow-up spectroscopy, the HSC-SSP provides us unique opportunities to find multiple-image quasars lensed by a foreground galaxy.