bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interobserver variability in comfort scores for screening colonoscopy
Authors: Naumann David N , Potter-Concannon Sarah , Karandikar Sharad 
Published: March 2019

ObjectiveTo investigate the agreement in comfort scores between patients, endoscopist and specialist screening practitioner (SSP) for colonoscopy, and which factors influence comfort.DesignProspective observational study.SettingSingle-centre UK Bowel Cancer Screening Program colonoscopy service from April 2017 to March 2018.Patients498 patients undergoing bowel cancer screening colonoscopy, with median age of 68 (IQR 64–71). 320 (64.3%) were men.InterventionAll patients underwent screening colonoscopy.Main outcome measureComfort scores on a validated 1 (best) to 5 (worst) ordinal scale were assigned for each colonoscopy by the patient, endoscopist and SSP. Inter-rater agreement of discomfort scores between endoscopist, patient and SSP was investigated using Cohen’s Kappa statistic. Multivariate ordinal logistic regression was used to investigate the effects of patient and colonoscopy factors on comfort scores.ResultsSSPs had superior comfort score agreement with patients (0.638; ‘moderate agreement’) than endoscopists had with the same patients (0.526; ‘weak agreement’). Male patients reported lower scores than female patients (OR 0.483, OR 0.499 [95% CI 0.344 to 0.723]; p<0.001). Endoscopists reported lower scores when there was better bowel prep (OR 0.512 [95% CI 0.279 to 0.938]; p=0.030). Agreement was worse at higher levels of discomfort.ConclusionThere is variability in perceived comfort levels between healthcare providers and patients during screening colonoscopy, which is greater at worse levels of discomfort. Endoscopists who undertake screening colonoscopies may wish to consider both patient and healthcare provider comfort scores in order to improve patient experience while ensuring optimal quality assurance.
Vascular phenotype of amyloid precursor protein-deficient mice
Authors: d’Uscio Livius V. , Katusic Zvonimir S. 
Published: March 2019

The amyloid precursor protein (APP) is expressed in the blood vessel wall, but the physiological function of APP is not completely understood. Previous studies established that APP has amine oxidase activity responsible for degradation of catecholamines. In the present study, we characterized the vascular phenotype of APP-knockout (APP−/−) mice. We demonstrate that circulating levels of catecholamines are significantly increased in male as compared with female APP−/− mice. Studies of vasomotor function in isolated aortas revealed that contractions to the α1-receptor agonist phenylephrine were significantly reduced in male APP−/− mice but not in females. In addition, contractions to G protein activation with sodium fluoride were reduced exclusively in male APP−/− mice aortas. The endothelium-dependent relaxations to acetylcholine were not affected by the loss of APP in mice of both sexes. Further analysis of the mechanisms underlying endothelium-dependent relaxations revealed that inhibition of cyclooxygenase by indomethacin significantly impaired relaxations to acetylcholine exclusively in male APP−/− mice. Furthermore, acetylcholine-induced production of cyclic guanosine monophosphate (cGMP) was significantly reduced in male APP−/− mice aortas while acetylcholine-induced production of cyclic adenosine monophosphate (cAMP) was enhanced. We concluded that altered vascular reactivity to phenylephrine appears to be in part the result of chronic exposure of male APP−/− aorta to high circulating levels of catecholamines. The mechanisms responsible for the impairment of endothelium-dependent cGMP signaling and adaptive enhancement of endothelium-dependent production of cAMP remain to be defined. NEW & NOTEWORTHY Male amyloid precursor protein (APP)-deficient mice have higher circulating levels of catecholamines as compared with female APP-deficient mice. As a consequence, endothelium-dependent and endothelium-independent vasomotor functions of male APP-deficient mice are significantly altered. Under physiological conditions, expression of APP appears to play an important role in vascular function.
Optical Imaging of Glucose Uptake and Mitochondrial Membrane Potential to Characterize Her2 Breast Tumor Metabolic Phenotypes
Authors: Madonna Megan C. , Fox Douglas B. , Crouch Brian T. , Lee Jihong , Zhu Caigang , Martinez Amy F. , Alvarez James V. , Ramanujam Nirmala 
Published: March 2019

AbstractWith the large number of women diagnosed and treated for breast cancer each year, the importance of studying recurrence has become evident due to most deaths from breast cancer resulting from tumor recurrence following therapy. To mitigate this, cellular and molecular pathways used by residual disease prior to recurrence must be studied. An altered metabolism has long been considered a hallmark of cancer, and several recent studies have gone further to report metabolic dysfunction and alterations as key to understanding the underlying behavior of dormant and recurrent cancer cells. Our group has used two probes, 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose (2-NBDG) and tetramethyl rhodamine ethyl ester (TMRE), to image glucose uptake and mitochondrial membrane potential, respectively, to report changes in metabolism between primary tumors, regression, residual disease, and after regrowth in genetically engineered mouse (GEM)-derived mammospheres. Imaging revealed unique metabolic phenotypes across the stages of tumor development. Although primary mammospheres overexpressing Her2 maintained increased glucose uptake (“Warburg effect”), after Her2 downregulation, during regression and residual disease, mammospheres appeared to switch to oxidative phosphorylation. Interestingly, in mammospheres where Her2 overexpression was turned back on to model recurrence, glucose uptake was lowest, indicating a potential change in substrate preference following the reactivation of Her2, reeliciting growth. Our findings highlight the importance of imaging metabolic adaptions to gain insight into the fundamental behaviors of residual and recurrent disease.Implications:This study demonstrates these functional fluorescent probes' ability to report metabolic adaptations during primary tumor growth, regression, residual disease, and regrowth in Her2 breast tumors.
Multiple Immune-Suppressive Mechanisms in Fibrolamellar Carcinoma
Authors: Kim Amy K. , Gani Faiz , Layman Andrew J. , Besharati Sepideh , Zhu Qingfeng , Succaria Farah , Engle Elizabeth L. , Bhaijee Feriyl , Goggins Maria B. , Llosa Nicolas J. , Pawlik Timothy M. , Yarchoan Mark , Jaffee Elizabeth M. , Simons Howard C. , Taube Janis M. , Anders Robert A. 
Published: March 2019

Abstract
Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that affects adolescents and young adults. The most effective treatment for FLC is surgical resection, but no standardized systemic therapy exists for patients with recurrent or unresectable FLC. As a first step to understand the immune microenvironment of FLC, we investigated targetable immune-checkpoint pathways, PD-1, PD-L1, B7-H3, IDO-1, and LAG3, in relation to CD8+ cytotoxic T-lymphocyte density. Thirty-two FLC tumor specimens were analyzed using IHC staining for PD-L1, CD8, PD-1, IDO, LAG3, and B7-H3. Sixty-three percent of FLC cases demonstrated membranous PD-L1 expression on tumor cells, and almost 70% of cases demonstrated PD-L1+ tumor-infiltrating lymphocytes and tumor-associated macrophages (TIL/TAM). Myeloid-derived cells appeared to be a major component of PD-L1+ tumor-infiltrating immune cells. Forty percent of the cases showed B7-H3 expression in the tumor zone, with 91% cases showing B7-H3 expression in TILs and TAMs. IDO and PD-1 expression was highest in the tumor interface zone. B7-H3 or IDO expression on tumor cells significantly correlated with higher CD8+ T-cell density. In conclusion, a high proportion of FLC cases showed robust expression of PD-1, PD-L1, B7-H3, and IDO in an adaptive immune-resistance pattern. Our findings provide further basis for targeting these different immune-checkpoint axes in FLC.
Cardiovascular and Lifestyle Risk Factors and Cognitive Function in Patients With Stable Coronary Heart Disease
Authors: Stewart Ralph A. H. , Held Claes , Krug‐Gourley Sue , Waterworth Dawn , Stebbins Amanda , Chiswell Karen , Hagstrom Emil , Armstrong Paul W. , Wallentin Lars , White Harvey 
Published: March 2019

Background
Vascular risk factors have been associated with differences in cognitive performance in epidemiological studies, but evidence in patients with coronary heart disease is more limited.

Methods and Results

The Montreal Cognitive Assessment score obtained 3.2±0.37 years after randomization to darapladib, a reversible inhibitor of lipoprotein phospholipase A
2
or placebo was evaluated for 10 634 patients with coronary heart disease from 38 countries in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. The Montreal Cognitive Assessment scores for darapladib and placebo groups were similar (mean±
SD
, 25.3±3.84 versus 25.4±3.73, respectively;
P
=0.27) and the adjusted odds ratio (
OR
) for mild cognitive impairment (Montreal Cognitive Assessment score <26) was 1.00 (95%
CI
, 0.93–1.09). Mild cognitive impairment was more likely with increasing age (
OR
, 1.33 [1.27–1.41], +5 years after 65). For other baseline clinical characteristics, the strongest independent predictors of cognitive impairment were education (≤8 years versus college/university,
OR
, 2.95 [2.60–3.35]; >8 years/trade school versus college/university,
OR
, 1.38 [1.25–1.52] and geographic grouping). Cardiovascular risk factors independently associated with cognitive impairment were history of stroke (
OR
, 1.43 [1.20–1.71]); <2.5 hours of moderate or vigorous intensity exercise/week (
OR
, 1.19 [1.04–1.37]); high‐density lipoprotein cholesterol <1.16 mmol/L (
OR
, 1.19 [1.04–1.37]); diabetes mellitus requiring treatment (
OR
, yes versus no: 1.15 [1.05–1.26]); and history of hypertension (
OR
, 1.12 [1.02–1.23]).

Conclusions
In patients with stable coronary heart disease, cognitive performance was associated with modifiable cardiovascular risk factors, educational level, and global region, but was not influenced by darapladib.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00799903.
Lipoprotein(a) Particle Production as a Determinant of Plasma Lipoprotein(a) Concentration Across Varying Apolipoprotein(a) Isoform Sizes and Background Cholesterol‐Lowering Therapy
Authors: Chan Dick C. , Watts Gerald F. , Coll Blai , Wasserman Scott M. , Marcovina Santica M. , Barrett P. Hugh R. 
Published: March 2019

Background
Elevated lipoprotein(a) (Lp(a)), a low‐density lipoprotein‐like particle bound to the polymorphic apolipoprotein(a) (apo(a)), may be causal for cardiovascular disease. However, the metabolism of Lp(a) in humans is poorly understood.

Methods and Results

We investigated the kinetics of Lp(a)‐apo(a) and low‐density lipoprotein‐apoB‐100 in 63 normolipidemic men. The fractional catabolic rate (
FCR
) and production rate
PR
) were studied. Plasma apo(a) concentration was significantly and inversely associated with apo(a) isoform size (
r
=−0.536,
P
<0.001) and apo(a)
FCR
(
r
=−0.363,
P
<0.01), and positively with apo(a)
PR
(
r
=0.877,
P
<0.001). There were no significant associations between the
FCR
s of apo(a) and low‐density lipoprotein‐apoB‐100. Subjects with smaller apo(a) isoform sizes (≤22 kringle
IV
repeats) had significantly higher apo(a)
PR
(
P
<0.05) and lower apo(a)
FCR
(
P
<0.01) than those with larger sizes. Plasma apo(a) concentration was significantly associated with apo(a)
PR
(
r
=0.930,
P
<0.001), but not with
FCR
(
r
=−0.012,
P
>0.05) in subjects with smaller apo(a) isoform size. In contrast, both apo(a)
PR
and
FCR
were significantly associated with plasma apo(a) concentrations (
r
=0.744 and −0.389, respectively,
P
<0.05) in subjects with larger isoforms. In multiple regression analysis, apo(a)
PR
and apo(a) isoform size were significant predictors of plasma apo(a) concentration independent of low‐density lipoprotein‐apoB‐100
FCR
and background therapy with atorvastatin and evolocumab.

Conclusions
In normolipidemic men, the plasma Lp(a) concentration is predominantly determined by the rate of production of Lp(a) particles, irrespective of apo(a) isoform size and background therapy with a statin and a proprotein convertase subtilisin‐kexin type 9 inhibitor. Our findings underscore the importance of therapeutic targeting of the hepatic synthesis and secretion of Lp(a) particles. Lp(a) particle catabolism may only play a modest role in determining Lp(a) concentration in subjects with larger apo(a) isoform size.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02189837.
Central Hemodynamics in Relation to Circulating Desphospho‐Uncarboxylated Matrix Gla Protein: A Population Study
Authors: Wei Fang‐Fei , Thijs Lutgarde , Cauwenberghs Nicholas , Yang Wen‐Yi , Zhang Zhen‐Yu , Yu Cai‐Guo , Kuznetsova Tatiana , Nawrot Tim S. , Struijker‐Boudier Harry A. J. , Verhamme Peter , Vermeer Cees , Staessen Jan A. 
Published: March 2019

Background

Stiffening and calcification of the large arteries are forerunners of cardiovascular complications. MGP (Matrix Gla protein), which requires vitamin K–dependent activation, is a potent locally acting inhibitor of arterial calcification. We hypothesized that the central hemodynamic properties might be associated with inactive desphospho‐uncarboxylated
MGP
(dp‐uc
MGP
).

Methods and Results

In 835 randomly recruited Flemish individuals (mean age, 49.7 years; 45.6% women), we measured plasma dp‐uc
MGP
, using an
ELISA
‐based assay. We derived central pulse pressure and carotid‐femoral pulse wave velocity (PWV) from applanation tonometry and calculated forward and backward pulse waves using an automated, pressure‐based wave separation analysis algorithm. Aortic
PWV
(n=657), central pulse pressure, forward pulse wave, and backward pulse wave mean±
SD
values were 7.34±1.64 m/s, 45.2±15.3 mm Hg, 33.2±10.2 mm Hg, and 21.8±8.6 mm Hg, respectively. The geometric mean plasma concentration of dp‐uc
MGP
was 4.09 μg/L. All hemodynamic indexes increased across tertiles of dp‐uc
MGP
distribution. In multivariable‐adjusted analyses, a doubling of dp‐uc
MGP
was associated with higher
PWV
(0.15 m/s; 95% CI, 0.01–0.28 m/s), central pulse pressure (1.70 mm Hg; 95% CI, 0.49–2.91 mm Hg), forward pulse wave (0.93 mm Hg; 95% CI, 0.01–1.84 mm Hg), and backward pulse wave (0.71 mm Hg; 95% CI, 0.11–1.30 mm Hg). Categorization of aortic
PWV
by tertiles of its distribution highlighted a decreasing trend of
PWV
at low dp‐uc
MGP
(<3.35 μg/L) and an increasing trend at high dp‐uc
MGP
(≥5.31 μg/L).

Conclusions

In people representative for the general population, higher inactive dp‐uc
MGP
was associated with greater
PWV
, central pulse pressure, forward pulse wave, and backward pulse wave. These observations highlight new avenues for preserving vascular integrity and preventing cardiovascular complications (eg, by improving a person's vitamin K status).
Aphelenchoides medicagus n. sp. (Tylenchina: Aphelenchoididae) found in Medicago sativa imported into China from the USA
Authors: Wang Zhen , Bert Wim , Gu Jianfeng , Couvreur Marjolein , Li Hongmei 
Published: March 2019

Summary
Aphelenchoides medicagus n. sp. isolated in Ningbo Port, P.R. China, from dried leaves and shoots of Medicago sativa imported from the USA, is described. It is characterised by a lateral field with four lines (three bands), stylet 9.0-12.0 μm long, excretory pore situated at same level as, or slightly posterior, to the nerve ring, vagina sclerotised, female vulval flap absent, post-uterine sac short, spicules 9.2-14.2 μm long (median curved line), rosethorn-shaped, apex and rostrum rounded, poorly developed, female and male tail conical with terminus bearing star-like processes. The new species belongs to the Group 3 category of Aphelenchoides species sensu Shahina. Phylogenetic analyses based on 18S, ITS and 28S D2-D3 of rDNA and mtCOI sequences confirmed its status as a new species and closely related to A. besseyi and A. fujianensis.
On the Transmission of Indian Medical Texts to the Arabs in the Early Middle Ages
Authors: Kahl Oliver 
Published: March 2019

Abstract
The transmission of Indian scientific and, notably, medical texts to the Arabs during the heyday of the Abbasid caliphate in Baghdad (ca 158/775-205/820) is still largely shrouded in myth; its investigation continues to be hampered not only by serious methodological problems but also by a lack of philological groundwork and a shortage of trained researchers. This article, which in essence is meant to serve as a rough guide into one prospective field of “Indo-Arabic” studies, focuses on a badly neglected though highly promising cluster of texts, namely those that relate to the translation and adaptation of certain Ayurvedic key works from Sanskrit into Arabic. A general assessment of the current state of research, of the factors that condition our knowledge and of the obstacles and limitations posed by the very nature of the subject, is followed by a bio-bibliographical survey of Ayurvedic texts which were subject to transmission; the article is rounded off by six Sanskrit-into-Arabic text samples, with English translations for both.
The International Legal Framework for Post-Brexit EEZ Fisheries Access between the United Kingdom and the European Union
Authors: Schatz Valentin J. 
Published: March 2019

Abstract
On 29 March 2019, the United Kingdom (UK) will leave the European Union (EU). Consequently, the EU’s Common Fisheries Policy (CFP), including the rules on fisheries access, will cease to apply to the UK. The article analyses the legal regime for post-Brexit exclusive economic zone (EEZ) fisheries access between the UK and the EU against the background of the current legal status quo under the CFP. The article then proceeds to an analysis of potential lex ferenda. In this respect, it first discusses the EEZ fisheries access arrangements for the Brexit transition period contained in the prospective withdrawal agreement of 2018. In a second step, the article undertakes to identify key issues faced by the UK and the EU in negotiating a future framework regulating their fisheries access relationship.
Non-state Diplomacy Challenges to Authoritarian States: The Open Russia Movement
Authors: Popkova Anna 
Published: March 2019

Summary
While some scholars assert that non-state actors (NSAs) can be considered as public diplomacy agents in their own right, others argue that NSAs’ work only supplements a state’s public diplomacy efforts. Both groups of scholars, however, focus on collaboration between states and NSAs. This article draws attention to the situations in which transnational NSAs challenge their respective states. Using the transnational movement Open Russia as a case study and drawing on Robert Kelley’s conceptualization of the diplomatic capabilities of NSAs as manifesting themselves in such actions as disruption, agenda-setting, mobilizing and gatekeeping, this article explores the power interplay between Open Russia and its domestic and foreign constituencies. By analysing the potential and the limits of Open Russia’s diplomatic capabilities, the article expands the discussion about NSAs’ role in public diplomacy.
The Corpus of Hebrew and Jewish Autos Sacramentales: Self-deception and Conversion
Authors: Davidi Einat 
Published: March 2019

Abstract
This article identifies a set of plays written in the seventeenth and eighteenth centuries by ‘new Jews’ in the Western Sephardi Diaspora, as autos sacramentales. It discusses essential characteristics of this genre, such as the dual—theomachic and psychomachic—level, the triangle constellation of allegorical characters with human nature in its center and the representatives of good and evil on both sides, and the parallelism created in the play between the cosmic story, the story of humanity, and the story of the individual human soul. It is argued that these characteristics are to be found in plays written by Jews in the Early Modern Era. The article maintains that the appearance of this corpus of plays in the history of Jewish writing indicates that an underlying structure of the psychic and historical consciousness of Western culture had not skipped the Jewish cultural world.
The Dialogical Dimension in the Diary of Chaim Kaplan: 1935–1942
Authors: Ben-Amos Batsheva 
Published: March 2019

Abstract
Chaim Kaplan (1880–1942), principal and owner of a private elementary Hebrew school in Warsaw, wrote a personal diary from 1933 to 1942. So far, only the WWII years have drawn scholarly attention. However, the interpretation of the diary also requires reading his available unpublished entries. An internal dialogical structure dominates his diary where he engages “the other” that interacts with his own inner voice. His pre-war identity is constructed of different and contradicting facets of Zionist ideology, traditional Jewish value system and way of life, and Polish citizenship. When the war broke out, the diary’s range of voices decreased with Kaplan’s position. His rhetoric displays a clear split between “we” and “them” following the ‘dichotomy’ of congregation and segregation. He expresses a greater empathy toward the Jewish “other” as a fellow sufferer, yet his concern with representing truth remains. To maintain this duality, Kaplan developed a literary ‘alter ego.’
[RETRACTED] Evolutionary, Dynamic or Contemporary Interpretation in WTO System?
Authors: Liakopoulos Dimitris 
Published: March 2019

Abstract
The evolutionary interpretation of a norm presents a similar nature—even if obviously not identical—to the modification of the law, which is a process that follows an interpretative method that must be particularly careful not to be in contrast with the intention of the states concerned by the rule. Interpretation in practice, in speciem in the World Trade Organization becomes prescriptive to descriptive, since our aim will be to see the theme of evolutionary interpretation through the jurisprudence of the Organization.
A Human Rights Focus to Upgrade China’s International Lending
Authors: Bohoslavsky Juan Pablo 
Published: March 2019

Abstract
This article offers, using a human rights approach, an in-depth analysis of the functioning of the China’s regulatory framework applicable to external lending through national and international financial institutions as well as concrete proposals to enhance that framework. The article describes and critically assesses the institutional and legal framework of the Chinese international lending and outbound investment, it studies the main trends in the Chinese lending to developing countries in the context of the Chinese “Going Global” strategy, and it presents the human rights impact of external lending and outbound investments in terms of both their positive effects and good practices as well as challenges and concerns. A particular attention is paid to the case of the new pertinent multilateral development banks: New Development Bank and Asian Infrastructure Investment Bank. After presenting the conclusions the article ends proposing for discussion recommendations addressing a wide range of stakeholders.