bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2-Overexpressing Ductal Carcinoma In Situ Associated with Increased Risk of Ipsilateral Invasive Recurrence, Receptor Discordance with Recurrence
Authors: O'Keefe Thomas J. , Blair Sarah L. , Hosseini Ava , Harismendy Olivier , Wallace Anne M. 
Published: June 2020

Abstract
The impact of HER2 status in ductal carcinoma in situ (DCIS) on the risk of progression to invasive ductal carcinoma (IDC) has been debated. We aim to use a national database to identify patients with known HER2 status to elucidate the effect of HER2 overexpression on ipsilateral IDC (iIDC) development. We performed survival analysis on patient-level data using the U.S. NCI's Surveillance Epidemiology and End Results program. We identified patients diagnosed with DCIS who underwent lumpectomy and had known HER2 status. Competing risks analysis was performed. A total of 1,540 patients had known HER2 status and met inclusion criteria. Median age at diagnosis was 60, median follow-up time was 44.5 months. A total of 417 (27.1%) patients were HER2 positive and 1,035 (67.2%) were HER2 negative. Twenty-two (1.4%) patients developed iIDC and 27 (1.8%) developed ipsilateral in situ or contralateral disease. The estimated cumulative incidence of iIDC at 5 years was 1.9% for all patients, 1.2% for HER2-negative and borderline patients, and 3.9% for HER2-positive patients. On multivariate competing risks regression, two factors were significant for iIDC: radiation (protective) therapy within 24 months (HR, 0.05; P = 0.00006) and HER2 overexpression (increased likelihood; HR, 2.72; P = 0.044). Patients with HER2-positive DCIS were more likely to have recurrences with receptor discordance. HER2 may serve as a prognostic factor for invasive recurrence and was the only lesion-related factor to significantly relate to iIDC development. It may also be associated with receptor discordance of recurrences. Further large studies will be needed to confirm these results.
Loss of Protease-Activated Receptor 4 Prevents Inflammation Resolution and Predisposes the Heart to Cardiac Rupture After Myocardial Infarction
Authors: Kolpakov Mikhail A. , Guo Xinji , Rafiq Khadija , Vlasenko Liudmila , Hooshdaran Bahman , Seqqat Rachid , Wang Tao , Fan Xiaoxuan , Tilley Douglas G. , Kostyak John C. , Kunapuli Satya P. , Houser Steven R. , Sabri Abdelkarim 
Published: June 2020

Background:
Cardiac rupture is a major lethal complication of acute myocardial infarction (MI). Despite significant advances in reperfusion strategies, mortality from cardiac rupture remains high. Studies suggest that cardiac rupture can be accelerated by thrombolytic therapy, but the relevance of this risk factor remains controversial.

Methods:
We analyzed protease-activated receptor 4 (Par4) expression in mouse hearts with MI and investigated the effects of Par4 deletion on cardiac remodeling and function after MI by echocardiography, quantitative immunohistochemistry, and flow cytometry.

Results:

Par4 mRNA and protein levels were increased in mouse hearts after MI and in isolated cardiomyocytes in response to hypertrophic and inflammatory stimuli. Par4-deficient mice showed less myocyte apoptosis, reduced infarct size, and improved functional recovery after acute MI relative to wild-type (WT). Conversely, Par4
−/−
mice showed impaired cardiac function, greater rates of myocardial rupture, and increased mortality after chronic MI relative to WT. Pathological evaluation of hearts from Par4
−/−
mice demonstrated a greater infarct expansion, increased cardiac hemorrhage, and delayed neutrophil accumulation, which resulted in impaired post-MI healing compared with WT. Par4 deficiency also attenuated neutrophil apoptosis in vitro and after MI in vivo and impaired inflammation resolution in infarcted myocardium. Transfer of Par4
−/−
neutrophils, but not of Par4
−/−
platelets, in WT recipient mice delayed inflammation resolution, increased cardiac hemorrhage, and enhanced cardiac dysfunction. In parallel, adoptive transfer of WT neutrophils into Par4
−/−
mice restored inflammation resolution, reduced cardiac rupture incidence, and improved cardiac function after MI.

Conclusions:
These findings reveal essential roles of Par4 in neutrophil apoptosis and inflammation resolution during myocardial healing and point to Par4 inhibition as a potential therapy that should be limited to the acute phases of ischemic insult and avoided for long-term treatment after MI.
Temporal Trends in Prevalence and Prognostic Implications of Comorbidities Among Patients With Acute Decompensated Heart Failure
Authors: Pandey Ambarish , Vaduganathan Muthiah , Arora Sameer , Qamar Arman , Mentz Robert J. , Shah Sanjiv J. , Chang Patricia P. , Russell Stuart D. , Rosamond Wayne D. , Caughey Melissa C. 
Published: June 2020

Background:
Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established.

Methods:
HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files.

Results:

A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94;
P
<0.0001) and men (5.20 versus 4.82;
P
<0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005–2009 to 5.87 in 2010–2013; men: 4.94 in 2005–2009 and 5.45 in 2010–2013) and HFrEF (women: 4.78 in 2005–2009 to 5.14 in 2010–2013; men: 4.62 in 2005–2009 and 5.06 in 2010–2013;
P
-trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14–1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05–1.14];
P
for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well (
P
for interaction with time=0.002 and 0.02, respectively)

Conclusions:
The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF.
Food source determines stable isotope discrimination factors ΔN and ΔC in tadpoles
Authors: Glos Julian , Ruthsatz Katharina , Schröder Dominik , Riemann Jana C. 
Published: June 2020

Abstract
Analyses of stable isotope ratios are widely applied in studies on a large variety of aspects in trophic ecology. Most studies rely on a precise estimation of the relevant discrimination factor Δ (also called the fractionation factor), that reflects the fractionation or differences in isotope ratios of a certain element (mainly nitrogen N and carbon C) between an animal’s diet and its tissue and is used to identify one step in the food web. We experimentally determined ΔN and ΔC of two species of widespread amphibians in Europe, Rana temporaria and Bufo bufo, and tested for the effect of food source (cyanobacteria Spirulina vs. zooplanktonic Daphnia) on Δ and for interspecific differences. Our study shows high variation in Δ in relation to the food source, but low interspecific differences. Tadpoles that were fed with Spirulina did have considerably lower ΔN than tadpoles fed with Daphnia in both species, and lower ΔC only in R. temporaria. The range of Δ obtained here can be a useful baseline for future trophic studies on tadpoles of Rana and Bufo. The strong diet-dependency of Δ, however, argues strongly against the use of a fixed discrimination factor in future isotope studies.
Resolving the energy restriction at high altitude: variation in the digestive system of Phrynocephalus vlangalii
Authors: Zhao Yang yang , Qi Yue , Wang Xiao ning , Zhao Wei 
Published: June 2020

Abstract
Hypothermic and hypoxic environments create strong selective pressure on native species by affecting, among other things, the relationship between energy intake and allocation. In order to detect the adaptation of Phrynocephalus vlangalii to such energy limitation, the morphological structure and argyrophil cells of the digestive tract of 80 individuals from two different altitudes in the Qinghai-Tibet Plateau were compared using overall anatomy as well as paraffin sectioning of specific organs. Compared with the low-altitude population, the high-altitude individuals were found to have a significantly longer stomach and duodenum, longer and wider villus in the small intestine, larger surface area in duodenum and jejunum, and more argyrophilic cells in stomach and duodenum. Our results indicate that the morphological and histological change of the digestive tract may be conductive to the plateau adaptability of P. vlangalii by enhancing the efficiency of digestion and absorption. For a more general conclusion to be drawn, comparison of more populations at both altitudes is required in addition to verifying how phenotypically flexible these traits are.
Variation in reproductive output as a function of maternal age and weather conditions in the cultured Asian yellow pond turtle, Mauremys mutica
Authors: Wang Yakun , Zhao Jian , Liu Xiaoli , Shangguan Qing , Li Wei , Ouyang Shu , Zhu Xinping 
Published: June 2020

Abstract
Biotic factors (e.g., maternal age) and abiotic factors (e.g., weather) play vital roles in reproduction. However, there is little information about the combined effects of maternal age and weather on the reproductive output of cultured Asian yellow pond turtles, Mauremys mutica. To address this issue, we surveyed and compared the reproductive output of 13-year-old and 25-year-old female turtles on non-rainy and rainy days. The results showed that older females produced larger eggs than younger females regardless of the weather conditions. Females laid larger clutch sizes (number of eggs per nest) under non-rainy conditions compared with those under rainy conditions. However, the variation in clutch frequency (number of clutches per day) was independent of maternal age and weather. There was no effect of an interaction between maternal age and weather on egg mass, clutch size or clutch frequency. Our results suggest that maternal age and weather had significant effects on egg mass and clutch size, respectively. These results imply that maternal age, together with weather conditions (mainly conditions of rain), can affect the reproductive output of M. mutica. Our results provide useful information for the artificial breeding and stock management of M. mutica.
The Allegiance of White American Evangelicals to Donald Trump
Authors: Bieber Kenneth , Beyers Jaco 
Published: June 2020

Abstract
This article discusses why American evangelical Christians, particularly white evangelicals, have granted overwhelming support to Donald Trump, first as a presidential candidate in 2016, and then as president since his inauguration in January 2017. The loyalty afforded to him by this voting bloc results in an abandonment of the values and priorities of the greater Christian mission, exchanging faithful discipleship for political expediency. While this demographic of voters does not explicitly renounce the Christian faith or their belief in the authority of Scripture, the concerns exhibited in their fidelity to President Trump as a monarchical figure stand in contrast to both biblically-based evangelicalism and historic American political values.
The Emperor’s New Clothes – What If No Jus Cogens Claim Can Be Justified?
Authors: Linderfalk Ulf 
Published: June 2020

Abstract
This article deals with an important question of legal justification: What reasons serve to justify a claim that a norm has the status of jus cogens. This question can be approached from two fundamentally different perspectives – in this article referred to as legal positivism and legal idealism. As earlier research has demonstrated, legal positivists have great difficulty justifying their jus cogens claims. What this article argues is that legal idealists face a no less difficult task, and that this prompts an entirely new understanding of the jus cogens discourse. If there is no way for a lawyer to justify a jus cogens claim, then neither is there any way for him or her to refute propositions put forth by others. Jus cogens discourse becomes a safe haven for all kinds of arguments, of which, legally speaking, no one can ever be regarded as any more acceptable than any other.
TWAIL: a Paradox within a Paradox
Authors: al Attar Mohsen 
Published: June 2020

Abstract
What insight do critical perspectives bring to international legal theory? In the following article, I answer this question through an examination of Third World Approaches to International Law (TWAIL). Troubled by geopolitical imbalance in the enterprise of international law, a group of critically minded scholars sought to expand the scope of legal scholarship. They would do so by growing a scholarly community sensitive to Third World concerns in their engagement with international law. Movements are known to collapse just as quickly as they sprout and it is testament to TWAIL’s force that, twenty years on, it is still gaining momentum. Self-described as a theory, method, sensibility, movement, and, as per the moniker, approach, TWAIL’s place in legal theory remains ambiguous. Drawing on a range of TWAIL scholars as well as journeymen commentators, I investigate, first, how its scholars represent TWAIL’s theoretical credentials and, second, where its contribution fits in the field.
Climatology of Orographic Precipitation Gradients in the Contiguous Western United States
Authors: Bohne Lucas , Strong Courtenay , Steenburgh W. James 
Published: June 2020

AbstractOrographic precipitation gradients (OPG) relating to the increase or decrease in precipitation amount with elevation are not well studied or analyzed except for case examples. A quality controlled daily OPG dataset for the western United States that is based on a linear regression framework of gauge precipitation observations and elevation for a 39-yr time period was created and analyzed to identify spatial and temporal patterns and variability in OPG and some of the drivers of variability on seasonal, annual, interannual, and climatological time scales. Most locations in the western United States experience positive OPG during most of the year, exhibiting an annual cycle with the highest magnitude of OPG in the winter season and lowest magnitude of OPG in the summer season. Coastal locations tend to have OPG with higher magnitude and larger variability in OPG than do interior locations during cool seasons. Empirical orthogonal function analysis identifies two principal components that account for 33% of the variability in a subset of the OPG dataset, and these modes of variability are related to precipitation amount and atmospheric circulation over the Pacific Ocean. Comparison of daily OPG with similarly calculated 3-day and monthly OPG identifies that OPG magnitudes are sensitive to the choice of length of the precipitation accumulation period.
Generating Probabilistic Next-Day Severe Weather Forecasts from Convection-Allowing Ensembles Using Random Forests
Authors: Loken Eric D. , Clark Adam J. , Karstens Christopher D. 
Published: June 2020

AbstractExtracting explicit severe weather forecast guidance from convection-allowing ensembles (CAEs) is challenging since CAEs cannot directly simulate individual severe weather hazards. Currently, CAE-based severe weather probabilities must be inferred from one or more storm-related variables, which may require extensive calibration and/or contain limited information. Machine learning (ML) offers a way to obtain severe weather forecast probabilities from CAEs by relating CAE forecast variables to observed severe weather reports. This paper develops and verifies a random forest (RF)-based ML method for creating day 1 (1200–1200 UTC) severe weather hazard probabilities and categorical outlooks based on 0000 UTC Storm-Scale Ensemble of Opportunity (SSEO) forecast data and observed Storm Prediction Center (SPC) storm reports. RF forecast probabilities are compared against severe weather forecasts from calibrated SSEO 2–5-km updraft helicity (UH) forecasts and SPC convective outlooks issued at 0600 UTC. Continuous RF probabilities routinely have the highest Brier skill scores (BSSs), regardless of whether the forecasts are evaluated over the full domain or regional/seasonal subsets. Even when RF probabilities are truncated at the probability levels issued by the SPC, the RF forecasts often have BSSs better than or comparable to corresponding UH and SPC forecasts. Relative to the UH and SPC forecasts, the RF approach performs best for severe wind and hail prediction during the spring and summer (i.e., March–August). Overall, it is concluded that the RF method presented here provides skillful, reliable CAE-derived severe weather probabilities that may be useful to severe weather forecasters and decision-makers.
The Changing Paradigm of Head and Neck Paragangliomas: What Every Otolaryngologist Needs to Know
Authors: Cass Nathan D. , Schopper Melissa A. , Lubin Jonathan A. , Fishbein Lauren , Gubbels Samuel P. 
Published: June 2020

Background: Recommendations regarding head and neck paragangliomas (HNPGL) have undergone a fundamental reorientation in the last decade as a result of increased understanding of the genetic and pathophysiologic basis of these disorders. Objective: We aim to provide an overview of HNPGL and recent discoveries regarding their molecular genetics, along with updated recommendations on workup, treatment, and surveillance, and their implications for otolaryngologists treating patients with these disorders. Results: SDHx susceptibility gene mutations, encoding subunits of the enzyme succinate dehydrogenase (SDH), give rise to the Hereditary Pheochromocytoma/Paraganglioma Syndromes. SDHA, SDHB, SDHC, SDHD, and SDHAF2 mutations each result in unique phenotypes with distinct penetrance and risk for variable tumor development as well as metastasis. Genetic and biochemical testing is recommended for every patient with HNPGL. Multifocal disease should be managed in multi-disciplinary fashion. Patients with SDHx mutations require frequent biochemical screening and whole-body imaging, as well as lifelong follow-up with an expert in hereditary pheochromocytoma and paraganglioma syndromes. Conclusion: Otolaryngologists are likely to encounter patients with HNPGL. Keeping abreast of the latest recommendations, especially regarding genetic testing, workup for additional tumors, multi-disciplinary approach to care, and need for lifelong surveillance, will help otolaryngologists appropriately care for these patients.
Differences in pituitary adenylate cyclase-activating peptide and calcitonin gene-related peptide release in the trigeminovascular system
Authors: Edvinsson Jacob Carl Alexander , Grell Anne-Sofie , Warfvinge Karin , Sheykhzade Majid , Edvinsson Lars , Haanes Kristian Agmund 
Published: June 2020

Background Several neurotransmitters are expressed in the neurons of the trigeminal ganglion. One such signalling molecule is the pituitary adenylate cyclase-activating peptide (PACAP). PACAP signalling has been suggested to have a possible role in the pathophysiology of primary headaches. Objective The present study was designed to investigate the relationship between PACAP and calcitonin gene-related peptide, currently the two most relevant migraine peptides. Methods In the current study, we used ELISA to investigate PACAP and calcitonin gene-related peptide release in response to 60 mM K+ or capsaicin using a rat hemi-skull model. We combined this analysis with qPCR and immunohistochemistry to study the expression of PACAP and calcitonin gene-related peptide receptors and ligands. Results Calcitonin gene-related peptide (CGRP) is released from the trigeminal ganglion and dura mater. In contrast, PACAP is only released from the trigeminal ganglion. We observed a weak correlation between the stimulated release of the two neuropeptides. PACAP-38 immunoreactivity was expressed alone and in a subpopulation of neurons in the trigeminal ganglion that also store calcitonin gene-related peptide. The receptor subtype PAC1 was mainly expressed in the satellite glial cells (SGCs), which envelop the neurons in the trigeminal ganglion, in some neuronal processes, inside the Aδ-fibres and in the outermost layer of the myelin sheath that envelopes the Aδ-fibres. Conclusion Unlike CGRP, PACAP is only released within the trigeminal ganglion. This raises the question of whether a migraine therapy aimed at preventing peripheral PACAP signalling would be as successful as the CGRP signalling targeted treatments.
Oxytocin as a regulatory neuropeptide in the trigeminovascular system: Localization, expression and function of oxytocin and oxytocin receptors
Authors: Warfvinge Karin , Krause Diana N , Maddahi Aida , Grell Anne-Sofie , Edvinsson Jacob CA , Haanes Kristian A , Edvinsson Lars 
Published: June 2020

Background Recent clinical findings suggest that oxytocin could be a novel treatment for migraine. However, little is known about the role of this neuropeptide/hormone and its receptor in the trigeminovascular pathway. Here we determine expression, localization, and function of oxytocin and oxytocin receptors in rat trigeminal ganglia and targets of peripheral (dura mater and cranial arteries) and central (trigeminal nucleus caudalis) afferents. Methods The methods include immunohistochemistry, messenger RNA measurements, quantitative PCR, release of calcitonin gene-related peptide and myography of arterial segments. Results Oxytocin receptor mRNA was expressed in rat trigeminal ganglia and the receptor protein was localized in numerous small to medium-sized neurons and thick axons characteristic of A∂ sensory fibers. Double immunohistochemistry revealed only a small number of neurons expressing both oxytocin receptors and calcitonin gene-related peptide. In contrast, double immunostaining showed expression of the calcitonin gene-related peptide receptor component receptor activity-modifying protein 1 and oxytocin receptors in 23% of the small cells and in 47% of the medium-sized cells. Oxytocin immunofluorescence was observed only in trigeminal ganglia satellite glial cells. Oxytocin mRNA was below detection limit in the trigeminal ganglia. The trigeminal nucleus caudalis expressed mRNA for both oxytocin and its receptor. K+-evoked calcitonin gene-related peptide release from either isolated trigeminal ganglia or dura mater and it was not significantly affected by oxytocin (10 µM). Oxytocin directly constricted cranial arteries ex vivo (pEC50 ∼ 7); however, these effects were inhibited by the vasopressin V1A antagonist SR49059. Conclusion Oxytocin receptors are extensively expressed throughout the rat trigeminovascular system and in particular in trigeminal ganglia A∂ neurons and fibers, but no functional oxytocin receptors were demonstrated in the dura and cranial arteries. Thus, circulating oxytocin may act on oxytocin receptors in the trigeminal ganglia to affect nociception transmission. These effects may help explain hormonal influences in migraine and offer a novel way for treatment.