bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR007: Genomic characterization of endometrial cancer patient-derived xenografts reveals intratumor heterogeneity
Authors: Kondrashova Olga , Bonazzi Vanessa F. , Smith Deborah , Nones Katia , Sengal Asmerom , Ju Robert , Packer Leisl M. , Koufariotis Lambros T , Kazakoff Stephen H. , Davidson Aimee L. , Ramarao-Milne Priya , Lakis Vanessa , Newell Felicity , Rogers Rebecca , Davies Claire , Chetty Naven , Perrin Lewis , Pearson John , Patch Ann-Marie , Garrett Andrea , Waddell Nicola , Pollock Pamela , Nicklin James 
Published: February 2021

Abstract
Endometrial cancer is a major gynaecological cancer with a high incidence resulting in over 500 Australian women dying every year. Good pre-clinical models are urgently needed to study the biology of this disease, and to develop and test novel treatment strategies. Most current pre-clinical research is conducted in cell lines that often do not resemble the disease on the molecular level and do not recapitulate tumour heterogeneity, which results in untranslatable research findings. Patient-derived xenograft (PDX) models overcome the issues of representing tumour molecular landscape and heterogeneity, making them a translatable pre-clinical cancer model. Here, we generated and genomically characterised 11 PDX models by performing whole genome or whole exome sequencing of primary patient tumours and matched PDX samples. We performed a detailed genomic characterisation of these models to determine their suitability as pre-clinical models, study tumour heterogeneity and identify biomarkers of response and resistance. PDX models were successfully generated from all four molecular subtypes of EC and uterine carcinosarcomas, and they recapitulated morphology and the molecular landscape of primary tumors without major genomic drift. We also observed a wide range of inter-tumor and intra-tumor heterogeneity, well captured by different PDX lineages, which could lead to different treatment responses. An in vivo response to talazoparib was detected in two p53mut models consistent with stable disease, however both lacked the HR deficiency genomic signature. EC PDX models represent the four molecular subtypes of disease and can capture intra-tumoral heterogeneity of the original primary tumor. PDXs of the p53mut molecular subtype showed sensitivity to PARPi, however, deeper and more durable responses will likely require combination of PARPi with other agents.
Citation Format: Olga Kondrashova, Vanessa F. Bonazzi, Deborah Smith, Katia Nones, Asmerom Sengal, Robert Ju, Leisl M. Packer, Lambros T Koufariotis, Stephen H. Kazakoff, Aimee L. Davidson, Priya Ramarao-Milne, Vanessa Lakis, Felicity Newell, Rebecca Rogers, Claire Davies, Naven Chetty, Lewis Perrin, John Pearson, Ann-Marie Patch, Andrea Garrett, Nicola Waddell, Pamela Pollock, James Nicklin. Genomic characterization of endometrial cancer patient-derived xenografts reveals intratumor heterogeneity [abstract]. In: Proceedings of the AACR Virtual Special Conference: Endometrial Cancer: New Biology Driving Research and Treatment; 2020 Nov 9-10. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(3_Suppl):Abstract nr PR007.
Impact of New Grading System and New Hemodynamic Classification on Long-Term Outcome in Patients With Severe Tricuspid Regurgitation
Authors: Omori Taku , Uno Goki , Shimada Shunsuke , Rader Florian , Siegel Robert J. , Shiota Takahiro 
Published: February 2021

Background:
A new grading of tricuspid regurgitation (TR) beyond severe has been proposed. However, few studies assessing the validity of such a new grading scheme of TR have been conducted. Therefore, we evaluated associations of TR grades beyond severe with patient outcome and hemodynamics.

Methods:
We retrospectively studied patients who underwent 2-dimensional echocardiography and were diagnosed with severe TR between January 2014 and December 2015. According to the vena contracta width of TR (VC), the patients were classified into 2 groups: VC under 14 mm (VC<14 mm) and VC 14 mm or greater (VC≥14 mm). Hemodynamic parameters were estimated by echocardiography and were obtained by right heart catheterization. Cardiovascular events were defined as cardiovascular death or admission for heart failure.

Results:

A total of 679 patients (mean 72±17 years, 56% women) were included. During follow-up (median, 158 days; range, 29–891), 210 patients experienced cardiovascular events. By multivariate analysis, VC≥14 mm and left ventricular ejection fraction were independent predictors of cardiovascular events (hazard ratio, 1.57 [1.06–2.33]; hazard ratio, 0.99 [0.98–0.99], respectively). Patients with VC≥14 mm had significantly lower cardiac index (median, 1.8 versus 2.1 L/min per m
2
,
P
=0.001) and a higher prevalence of right atrial pressure 15 mm Hg (74% versus 60%,
P
<0.001) on echocardiography. Also, right heart catheterization confirmed higher right atrial pressure in patients with VC≥14 mm than those with VC<14 mm (16±8 versus 12±6 mm Hg,
P
=0.004). The new subset classification developed by cardiac index and right atrial pressure both on echocardiography predicted cardiovascular events (Log-rank
P
<0.001).

Conclusions:
The relationship of VC≥14 mm to adverse outcome and poor hemodynamics showed the clinical relevance and need of a new grading system beyond severe. The new hemodynamic subset classification provides additional prognostic value for cardiovascular events in patients with severe TR.
Impact of Statins on Hematoma, Edema, Seizures, Vascular Events, and Functional Recovery After Intracerebral Hemorrhage
Authors: Sprügel Maximilian I. , Kuramatsu Joji B. , Volbers Bastian , Saam Justina I. , Sembill Jochen A. , Gerner Stefan T. , Balk Stefanie , Hamer Hajo M. , Lücking Hannes , Hölter Philip , Nolte Christian H. , Scheitz Jan F. , Rocco Andrea , Endres Matthias , Huttner Hagen B. 
Published: February 2021

Background and Purpose:
The impact of statins on hematoma characteristics, perihemorrhagic edema (PHE), cardiovascular events, seizures, and functional recovery in patients with intracerebral hemorrhage (ICH) is insufficiently studied.

Methods:

Patients with ICH of the prospective UKER-ICH (Universitätsklinikum Erlangen Cohort of Patients With Spontaneous Intracerebral Hemorrhage) study (URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03183167) were analyzed by multivariable regression modeling and propensity score matching, and PHE volumes were volumetrically assessed. Outcomes comprised hematoma characteristics, the impact of continuation, discontinuation, and initiation of statins on peak PHE extent, and the influence of statin treatment on the occurrence of seizures, cardiovascular adverse events, and functional recovery after ICH.

Results:

A total of 1275 patients with ICH with information on statin treatment were analyzed. Statin treatment on hospital admission (21.7%) was associated with higher rates of lobar versus nonlobar ICH (odds ratio, 1.57 [1.03–2.40];
P
=0.038). Initiation of statins after ICH was associated with increased peak PHE (β=0.12, SE=0.06,
P
=0.008), whereas continuation versus discontinuation of prior statin treatment was not significantly associated with edema formation (
P
>0.10). There were no significant differences in the incidence of remote symptomatic seizures according to statin exposure during follow-up (statins: 11.5% versus no statins: 7.8%, subdistribution hazard ratio: 1.15 [0.80–1.66];
P
=0.512). Patients on statins revealed less cardiovascular adverse events and more frequently functional recovery after 12 months (functional recovery: 57.7% versus 45.0%, odds ratio 1.67 [1.09–2.56];
P
=0.019).

Conclusions:
Among statin users, lobar ICH occurs more frequently as compared with nonstatin users. While continuation of prior statin treatment appears to be safe regarding PHE formation, the initiation of statins during the first days after ICH may increase PHE extent. However, statins should be initiated thereafter (eg, at hospital discharge) to prevent cardiovascular events and potentially improve functional recovery.
Association of Plasma Neurofilament Light With Small Vessel Disease Burden in Nondemented Elderly
Authors: Qu Yi , Tan Chen-Chen , Shen Xue-Ning , Li Hong-Qi , Cui Mei , Tan Lan , Dong Qiang , Yu Jin-Tai ,   on behalf of the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2021

Background and Purpose:
Neurofilament light chain (NfL) is a promising predictive biomarker of active axonal injury and neuronal degeneration diseases. We aimed to evaluate if an increase in plasma NfL levels could play a monitoring role in the progression of cerebral small vessel disease (CSVD) among the nondemented elders, which are highly prevalent in elderly individuals and associated with an increased risk of stroke and dementia.

Methods:
The study included 496 nondemented participants from the Alzheimer disease neuroimaging initiative database. All participants underwent plasma NfL measurements and 3.0-Tesla magnetic resonance imaging of the brain; 387 (78.0%) underwent longitudinal measurements. The number of cerebral microbleeds, lacunar infarcts, and volumetric white matter hyperintensities, as well as Fazekas scores, were measured. Cross-sectional and longitudinal associations between CSVD burden and NfL levels were evaluated using multivariable-adjusted models.

Results:
Plasma NfL was higher in the moderate-severe CSVD burden group (45.2±16.0 pg/mL) than in the nonburden group (34.3±15.1 pg/mL; odds ratio [OR]=1.71 [95% CI, 1.24–2.35]) at baseline. NfL was positively associated with the presence of cerebral microbleeds (OR=1.29 [95% CI, 1.01–1.64]), lacunar infarcts (OR=1.43 [95% CI, 1.06–1.93]), and moderate-severe white matter hyperintensities (OR=1.67 [95% CI, 1.24–2.25]). Longitudinally, a higher change rate of NfL could predict more progression of CSVD burden (OR=1.38 [95% CI, 1.08–1.76]), white matter hyperintensities (OR=1.41 [95% CI, 1.10–1.79]), and lacunar infarcts (OR=1.99 [95% CI, 1.42–2.77]).

Conclusions:
Plasma NfL level is a valuable noninvasive biomarker that supplements magnetic resonance imaging scans and possibly reflects the severity of CSVD burden. Furthermore, high plasma NfL levels tend to represent an increased CSVD risk, and dynamic increases in NfL levels might predict a greater progression of CSVD.
Populism, Constitutional Counter-Narratives and Comparative Law
Authors: Martinico Giuseppe 
Published: February 2021

Abstract
This article tries to explore the relationship between constitutionalism and populism in conceptual terms. This piece is divided into two parts. In the first part it will be argued that the relationship between populism and constitutionalism should not be seen in terms of mutual exclusion and perfect opposition. In the second part I shall look at comparative law in order to explore its incredible anti-populist potential. More in general, as I shall try to explain, the very idea of populist constitutionalism is not consistent with the legacy of post-wwii constitutionalism.
Local Atmospheric Response to the Kuroshio Large Meander Path in Summer and Its Remote Influence on the Climate of Japan
Authors: Sugimoto Shusaku , Qiu Bo , Schneider Niklas 
Published: February 2021

AbstractThe Kanto district in Japan, including Tokyo, has 40 million inhabitants and its summer climate is characterized by high temperature and humidity. The Kuroshio that flows off the southern coast of the Kanto district has taken a large meander (LM) path since the summer of 2017 for the first time since the 2004–05 event. Recently developed satellite observations detected marked coastal warming off the Kanto–Tokai district during the LM path period. By conducting regional atmospheric model experiments, it is found that summertime coastal warming increases water vapor in the low-level atmosphere through enhanced evaporation from the ocean and influences near-surface winds via the vertical mixing effect over the warming area. These two changes induce an increase in water vapor in Kanto district, leading to an increase in downward longwave radiation at the surface and then surface warming through a local greenhouse effect. As a result, summer in Kanto district becomes increasingly hot and humid in LM years, with double the number of discomfort days compared with non-LM years. Our simulations and supplementary observational studies reveal the significant impacts of the LM-induced coastal warming on the summertime climate in Japan, which can exceed previously identified atmospheric teleconnections and climate patterns. Our results could improve weather and seasonal climate forecasts in this region.
Diversity of the Madden–Julian Oscillation: Initiation Region Modulated by the Interaction between the Intraseasonal and Interannual Variabilities
Authors: Takasuka Daisuke , Satoh Masaki 
Published: February 2021

AbstractAs one of the aspects of the diversity of the Madden–Julian oscillation (MJO), the modulation of initiation regions of the boreal-winter MJO is studied in terms of the relationship between intraseasonal and interannual variabilities. MJOs are categorized as those initiating in the Indian Ocean (IO), Maritime Continent (MC), and western Pacific (WP), referred to herein as IO-MJOs, MC-MJOs, and WP-MJOs, respectively. The composite analyses for each MJO category using observational data reveal that the diversity of MJO initiation regions directly results from the modulation of areas where horizontal advective premoistening efficiently occurs via intraseasonal/synoptic-scale winds. This is supported by the difference in the zonal location of equatorial intraseasonal circulations established before MJO initiation, which is related to a spatial change in background convection and associated Walker circulations forced by interannual sea surface temperature (SST) variability. Compared to IO-MJOs (favored in the climatological background on average), MC-MJOs tend to be realized under the eastern-Pacific El Niño–like condition, as a result of eastward-shifted intraseasonal convection and circulation patterns induced by background suppressed convection in the eastern MC. WP-MJOs are frequently initiated under the central-Pacific El Niño–like and positive IO dipole–like conditions, in which the WP is selectively moistened with the aid of background enhanced (suppressed) convection over the WP (the southeastern IO and the central-to-eastern Pacific). This major tendency derived from sample-limited observations is verified by a set of 15-yr numerical experiments with a global nonhydrostatic MJO-permitting model under a perpetual boreal-winter condition where observation-based SSTs are prescribed.
2019 Atlantic Hurricane Forecasts from the Global-Nested Hurricane Analysis and Forecast System: Composite Statistics and Key Events
Authors: Hazelton Andrew , Zhang Zhan , Liu Bin , Dong Jili , Alaka Ghassan , Wang Weiguo , Marchok Tim , Mehra Avichal , Gopalakrishnan Sundararaman , Zhang Xuejin , Bender Morris , Tallapragada Vijay , Marks Frank 
Published: February 2021

AbstractNOAA’s Hurricane Analysis and Forecast System (HAFS) is an evolving FV3-based hurricane modeling system that is expected to replace the operational hurricane models at the National Weather Service. Supported by the Hurricane Forecast Improvement Program (HFIP), global-nested and regional versions of HAFS were run in real time in 2019 to create the first baseline for the HAFS advancement. In this study, forecasts from the global-nested configuration of HAFS (HAFS-globalnest) are evaluated and compared with other operational and experimental models. The forecasts by HAFS-globalnest covered the period from July through October during the 2019 hurricane season. Tropical cyclone (TC) track, intensity, and structure forecast verifications are examined. HAFS-globalnest showed track skill superior to several operational hurricane models and comparable intensity and structure skill, although the skill in predicting rapid intensification was slightly inferior to the operational model skill. HAFS-globalnest correctly predicted that Hurricane Dorian would slow and turn north in the Bahamas and also correctly predicted structural features in other TCs such as a sting jet in Hurricane Humberto during extratropical transition. Humberto was also a case where HAFS-globalnest had better track forecasts than a regional version of HAFS (HAFS-SAR) due to a better representation of the large-scale flow. These examples and others are examined through comparisons with airborne tail Doppler radar from the NOAA WP-3D to provide a more detailed evaluation of TC structure prediction. The results from this real-time experiment motivate several future model improvements, and highlight the promise of HAFS-globalnest for improved TC prediction.
The Effect of Anticoagulation and Antiplatelet Use in Trauma Patients on Mortality and Length of Stay
Authors: Narula Nisha , Tsikis Savas , Jinadasa Sayuri P. , Parsons Charles S. , Cook Charles H. , Butt Bonnie , Odom Stephen R. 
Published: February 2021

Background Though many trauma patients are on anticoagulation or antiplatelet therapy (AAT), there are few generalizable data on the risks for these patients. The purpose of this study was to analyze the impact of anticoagulation (AC) and antiplatelet (AP) therapy on mortality and length of stay (LOS) in general trauma patients. Methods A retrospective review was performed of patients in the institutional trauma registry during 2019 to determine AAT use on admission and discharge. Outcomes were compared using standard statistics. Results Of 2261 patients who met the inclusion criteria, 2 were excluded due to an incomplete medication reconciliation, resulting in 2259 patients. Patients on AAT had a higher mortality (4.5% vs 2.1%). On multivariable analysis, preadmission AC (odds ratio OR, 3.325, P = .001), age (OR 1.040, P < .001), and injury severity score ((ISS) 1.094, P < .001) were associated with mortality. Anticoagulation use was also associated with longer LOS on multivariable analysis (OR: 1.626, P = .005). Antiplatelet use was not associated with higher mortality or longer LOS. More patients on AAT were unable to be discharged home. However, patients on AAT did not have a greater blood transfusion requirement or need more hemorrhage control procedures. Lastly, 23.7% of patients on preadmission AAT were not discharged on any AAT. Discussion These data demonstrate that patients on AC, but not AP, have greater mortality and longer hospital LOS. This may provide guidance for those being newly started on AAT. Further work to determine which patients benefit most from restarting AAT would lead to improvement in the care of trauma patients.
Can the Expiratory Disproportion Index Distinguish PVFMD from Subglottic Stenosis in Obese Patients?
Authors: Calamari Kevin , Politano Stephen , Matrka Laura 
Published: February 2021

Objectives: Expiratory disproportion index (EDI) is the ratio of forced expiratory volume in 1 second (FEV1) divided by peak expiratory flow rate (PEFR) multiplied by 100. Prominent EDI (>50) values can differentiate subglottic stenosis (SGS) from paradoxical vocal fold movement disorder (PVFMD), but this has not been verified when considering body habitus. We hypothesize that the predictive value of elevated EDI in differentiating SGS from PVFMD will be lower in obese patients than non-obese patients. Methods: Patients ≥ 18 years old with recorded PFT values, BMI, and airway imaging were reviewed retrospectively from 01/2011 to 10/2018. EDI was recorded for 4 cohorts: non-obese/SGS, non-obese/ PVFMD, obese/SGS, and obese/ PVFMD, to determine the mean EDI and the sensitivity/specificity of an elevated EDI. Results: Mean EDI values were 69.32 and 48.38 in the non-obese SGS and PVFMD groups, respectively ( P < .01). They were 58.89 and 47.67 in the obese SGS and PVFMD groups, respectively ( P < .05). At a threshold of >50, EDI had a sensitivity of 90.0% and specificity of 51.6% in differentiating between SGS and PVFMD cases in non-obese patients and 51.6% and 63.6% in obese patients. Conclusion: Prior literature has established that EDI can distinguish SGS from PVFMD in the general population. Our results show that the mean EDI values were significantly different in both cohorts, but an elevated EDI was not as sensitive at identifying SGS cases in obese patients. This suggests that the EDI should be used with caution in obese patients and should not be relied upon to rule out SGS. Level of Evidence: 3
Physical activity levels during physical education in Spanish children
Authors: Huertas-Delgado Francisco Javier , Segura-Jiménez Víctor , Ávila-García Manuel , Cardon Greet , Tercedor Pablo 
Published: February 2021

Introduction: Physical education (PE) can contribute to total daily physical activity (PA) among children. In consequence, the Spanish Ministry of Education, Culture and Sport has developed 16 teaching units focused on increasing PA levels during PE lessons, called Unidades Didácticas Activas (UDA; Active Teaching Units). Objectives: The goal of this study was to compare whether children participating in UDA lessons spent more time in moderate-to-vigorous physical activity (MVPA) than children participating in traditional lessons. Design: Quasi-experimental design. Methods: A total of 355 children (8–9 years old, 53.9% boys) from 7 schools in Granada participated in the study. Students were divided into two groups: a traditional PE group ( n = 204) and a UDA group ( n = 151). Time spent in MVPA was assessed using tri-axial accelerometers. Results: Time spent in MVPA was higher in the group engaged in the UDA lessons compared to the group that received traditional lessons (13.6 vs 15.2 minutes, p = .021, Standard Error = 0.27). The percentage of children who met international MVPA recommendations was similar for both groups (UDAs: 12.7% and traditional: 13.2%, p = .504). Conclusions: UDA lessons and their methodology favoured greater participation in MVPA compared to a traditional PE approach. It will be important to change PE methodology (including duration, frequency and focus) to achieve MVPA goals.
Public governance tensions: a managerial artefacts-based view
Authors: Bennani Khouloud Senda , Hassine Anissa Ben , Mazouz Bachir 
Published: February 2021

The aim of this article is to categorise the factors of tension in public organisational settings. The context of the administrative reforms undertaken in Tunisia has been chosen as an empirical illustration of the public governance tensions associated with managerial artefacts. The study focuses on three types of factors. An analysis of these factors confirms the theories on the appropriation of management tools and helps raise the existing level of knowledge in relation to the processes to mitigate public governance tensions within public organisations. Points for practitioners Today, the modernisation of public governance goes hand in hand with the introduction of new public management tools in administrative settings. On a practical level, the appropriation of these tools generates a tense relationship between political decision-makers and public managers. Often perceived from the perspective of paradoxical demands and antagonistic relationships that disrupt the daily life of state organisations, public governance tensions can be managed as long as they are identified and categorised in the light of the factors of tension associated with the reforms undertaken.