bluuebunny/crossref_metadata_2025 huggingface dataset:
Job satisfaction and organizational commitment among Catholic primary school teachers of Merauke
Authors: Yunarti Berlinda Setyo , Wullur Mozes M. , Werang Basilius Redan
Published: November 2020

A high rate of teacher absenteeism in Merauke regency, Papua Province, Indonesia might be attributed to the low commitment of primary school teachers to educate the young people of Merauke, Indonesia. This study aimed to examine whether a positive and significant correlation exists between the organizational commitment and job satisfaction of the Catholic primary school teachers of Merauke, Indonesia. Applying a survey approach, two quantitative survey forms were distributed to a total of 157 teachers working in the Catholic primary schools of Merauke, Indonesia. A face-toface way of data collection was employed by having a prior consent from all the informants personally. Using Pearson’s correlation analysis as a tool for analyzing the collected data, the study showed a positive and significant correlation among the two surveyed variables as the amount of Pearson’s correlation coefficient (R) is .875 and the probability coefficient (ρ) is .000. The major conclusion of this study is that the job satisfaction and organizational commitment of the Catholic primary school teachers of Merauke, Indonesia, are significantly positively correlated. Practical implication of the finding is that the need for the school principals to promote the organizational commitment of teachers by enhancing their job satisfaction in order that the Catholic primary school students’ right to be well educated would be addressed adequately. Despite the possibility of the similar conclusion of this study with the previous studies conducting in other countries, the finding may support the current knowledge on the topic by giving a valuable information from an empirical context of Merauke, Indonesia.
Associations Between Alcohol Intake and Genetic Predisposition With Atrial Fibrillation Risk in a National Biobank
Authors: Halford Jennifer L. , Weng Lu-Chen , Choi Seung Hoan , Jurgens Sean J. , Morrill Valerie N. , Khurshid Shaan , Trinquart Ludovic , Benjamin Emelia J. , Ellinor Patrick T. , Lubitz Steven A.
Published: November 2020

Background:

Excess alcohol intake and inherited predisposition may increase risk of atrial fibrillation (AF). We assessed the association between alcohol intake, polygenic predisposition to AF, and incident AF in the UK Biobank, a prospective cohort study.

Methods:

In 376 776 UK Biobank participants enrolled between 2006 and 2010, we tested alcohol consumption (stratified by the Centers of Disease Control and Prevention acceptable range of ≤98 g/wk for women or ≤196 g/wk for men; and as a continuous variable) and an AF polygenic risk score for association with incident AF.

Results:

Among participants (47.5% male, mean age 56.9 years), 6293 developed AF during a median of 6.9 years of follow-up. Alcohol consumption was associated with AF (hazard ratio, 1.10 [95% CI, 1.05–1.16] for intake above an acceptable range; hazard ratio, 1.04 per 100 g/wk [95% CI, 1.02–1.06]). An AF polygenic risk score was associated with AF (hazard ratio, 1.38 per SD [95% CI, 1.35–1.41]). In models including both alcohol and the AF polygenic risk score, each remained associated with AF. The 5-year cumulative risk of AF for individuals with alcohol intake above an acceptable range and in the highest decile of polygenic risk was 2.33% (95% CI, 2.07–2.59), compared with 0.69% (95% CI, 0.58–0.80) for those with alcohol intake within an acceptable range and in the lowest decile of polygenic risk.

Conclusions:

Alcohol consumption is associated with increased risk of AF across a range of polygenic predisposition to AF and adds to inherited and clinical predisposition to increase AF susceptibility. Preventive efforts focused on minimizing alcohol intake may be broadly applicable.
Clonal Hematopoiesis–Driver DNMT3A Mutations Alter Immune Cells in Heart Failure
Authors: Abplanalp Wesley Tyler , Cremer Sebastian , John David , Hoffmann Jedrzej , Schuhmacher Bianca , Merten Maximillian , Rieger Michael A. , Vasa-Nicotera Mariuca , Zeiher Andreas M. , Dimmeler Stefanie
Published: November 2020

Rationale:

Clonal hematopoiesis driven by mutations of DNMT3A (DNA methyltransferase 3a) is associated with increased incidence of cardiovascular disease and poor prognosis of patients with chronic heart failure (HF) and aortic stenosis. Although experimental studies suggest that DNMT3A clonal hematopoiesis–driver mutations may enhance inflammation, specific signatures of inflammatory cells in humans are missing.

Objective:

To define subsets of immune cells mediating inflammation in humans using single-cell RNA sequencing.

Methods and Results:

Transcriptomic profiles of peripheral blood mononuclear cells were analyzed in n=6 patients with HF harboring DNMT3A clonal hematopoiesis–driver mutations and n=4 patients with HF and no DNMT3A mutations by single-cell RNA sequencing. Monocytes of patients with HF carrying DNMT3A mutations demonstrated a significantly increased expression of inflammatory genes compared with monocytes derived from patients with HF without DNMT3A mutations. Among the specific upregulated genes were the prototypic inflammatory IL (interleukin)
IL1B (interleukin 1B), IL6, IL8
, the inflammasome
NLRP3
, and the macrophage inflammatory proteins
CCL3
and
CCL4
as well as resistin, which augments monocyte-endothelial adhesion. Silencing of DNMT3A in monocytes induced a paracrine proinflammatory activation and increased adhesion to endothelial cells. Furthermore, the classical monocyte subset of DNMT3A mutation carriers showed increased expression of T-cell stimulating immunoglobulin superfamily members
CD300LB
,
CD83
,
SIGLEC12
, as well as the CD2 ligand and cell adhesion molecule
CD58
, all of which may be involved in monocyte–T-cell interactions. DNMT3A mutation carriers were further characterized by increased expression of the T-cell alpha receptor constant chain and changes in T helper cell 1, T helper cell 2, T helper cell 17, CD8+ effector, CD4+ memory, and regulatory T-cell–specific signatures.

Conclusions:

This study demonstrates that circulating monocytes and T cells of patients with HF harboring clonal hematopoiesis–driver mutations in DNMT3A exhibit a highly inflamed transcriptome, which may contribute to the aggravation of chronic HF.
Eosinophils Protect Mice From Angiotensin-II Perfusion–Induced Abdominal Aortic Aneurysm
Authors: Liu Cong-Lin , Liu Xin , Zhang Yuanyuan , Liu Jing , Yang Chongzhe , Luo Songyuan , Liu Tianxiao , Wang Yunzhe , Lindholt Jes S. , Diederichsen Axel , Rasmussen Lars M. , Dahl Marie , Sukhova Galina K. , Lu Guanyi , Upchurch Gilbert R. , Libby Peter , Guo Junli , Zhang Jinying , Shi Guo-Ping
Published: November 2020

Rationale:

Blood eosinophil count and ECP (eosinophil cationic protein) associate with human cardiovascular diseases. Yet, whether eosinophils play a role in cardiovascular disease remains untested. The current study detected eosinophil accumulation in human and murine abdominal aortic aneurysm (AAA) lesions, suggesting eosinophil participation in this aortic disease.

Objective:

To test whether and how eosinophils affect AAA growth.

Methods and Results:

Population-based randomized clinically controlled screening trials revealed higher blood eosinophil count in 579 male patients with AAA than in 5063 non-AAA control (0.236±0.182 versus 0.211±0.154, 10
9
/L,
P
<0.001). Univariate (odds ratio, 1.381,
P
<0.001) and multivariate (odds ratio, 1.237,
P
=0.031) logistic regression analyses indicated that increased blood eosinophil count in patients with AAA served as an independent risk factor of human AAA. Immunostaining and immunoblot analyses detected eosinophil accumulation and eosinophil cationic protein expression in human and murine AAA lesions. Results showed that eosinophil deficiency exacerbated AAA growth with increased lesion inflammatory cell contents, matrix-degrading protease activity, angiogenesis, cell proliferation and apoptosis, and smooth muscle cell loss using angiotensin-II perfusion–induced AAA in
Apoe
−/−
and eosinophil-deficient
Apoe
−/−
ΔdblGATA mice. Eosinophil deficiency increased lesion chemokine expression, muted lesion expression of IL (interleukin) 4 and eosinophil-associated-ribonuclease-1 (mEar1 [mouse EOS-associated-ribonuclease-1], human ECP homolog), and slanted M1 macrophage polarization. In cultured macrophages and monocytes, eosinophil-derived IL4 and mEar1 polarized M2 macrophages, suppressed CD11b
+
Ly6C
hi
monocytes, and increased CD11b
+
Ly6C
lo
monocytes. mEar1 treatment or adoptive transfer of eosinophil from wild-type and
Il13
−/−
mice, but not eosinophil from
Il4
−/−
mice, blocked AAA growth in
Apoe
−/−
ΔdblGATA mice. Immunofluorescent staining and immunoblot analyses demonstrated a role for eosinophil IL4 and mEar1 in blocking NF-κB (nuclear factor-κB) activation in macrophages, smooth muscle cells, and endothelial cells.

Conclusions:

Eosinophils play a protective role in AAA by releasing IL4 and cationic proteins such as mEar1 to regulate macrophage and monocyte polarization and to block NF-κB activation in aortic inflammatory and vascular cells.
Normal and Abnormal Relationships of Pulmonary Artery to Wedge Pressure During Exercise
Authors: Bentley Robert F. , Barker Madeleine , Esfandiari Sam , Wright Stephen P. , Valle Felipe H. , Granton John T. , Mak Susanna
Published: November 2020

Background

Resting right heart catheterization can assess both left heart filling and pulmonary artery (PA) pressures to identify and classify pulmonary hypertension. Although exercise may further elucidate hemodynamic abnormalities, current pulmonary hypertension classifications do not consider the expected interrelationship between PA and left heart filling pressures. This study explored the utility of this relationship to enhance the classification of exercise hemodynamic phenotypes in pulmonary hypertension.

Methods and Results

Data from 36 healthy individuals (55, 50–60 years, 50% male) and 85 consecutive patients (60, 49–71 years, 48% male) with dyspnea and/or suspected pulmonary hypertension of uncertain etiology were analyzed. Right heart catheterization was performed at rest and during semiupright submaximal cycling. To classify exercise phenotypes in patients, upper 95% CIs were identified from the healthy individuals for the change from rest to exercise in mean PA pressure over cardiac output (ΔmPAP/ΔCO ≤3.2 Wood units [WU]), pulmonary artery wedge pressure over CO (ΔPAWP/ΔCO ≤2 mm Hg/L per minute), and exercise PA pulse pressure over PAWP (PP/PAWP ≤2.5). Among patients with a ΔmPAP/ΔCO ≤3.2 WU, the majority (84%) demonstrated a ΔPAWP/ΔCO ≤2 mm Hg/L per minute, yet 23% demonstrated an exercise PP/PAWP >2.5. Among patients with a ΔmPAP/ΔCO >3.2 WU, 37% had an exercise PP/PAWP >2.5 split between ΔPAWP/ΔCO groups. Patients with normal hemodynamic classification declined from 52% at rest to 36% with exercise.

Conclusions

The addition of PP/PAWP to classify exercise hemodynamics uncovers previously unrecognized abnormal phenotypes within each ΔmPAP/ΔCO group. Our study refines abnormal exercise hemodynamic phenotypes based on an understanding of the interrelationship between PA and left heart filling pressures.
Survival in Children With Congenital Heart Disease: Have We Reached a Peak at 97%?
Authors: Mandalenakis Zacharias , Giang Kok Wai , Eriksson Peter , Liden Hans , Synnergren Mats , Wåhlander Håkan , Fedchenko Maria , Rosengren Annika , Dellborg Mikael
Published: November 2020

Background

Despite advances in pediatric health care over recent decades, it is not clear whether survival in children with congenital heart disease (CHD) is still increasing.

Methods and Results

We identified all patients with CHD using nationwide Swedish health registries for 1980 to 2017. We examined the survival trends in children with CHD; we investigated the mortality risk in patients with CHD compared with matched controls without CHD from the general population using Cox proportional regression models and Kaplan–Meier survival analysis. Among 64 396 patients with CHD and 639 012 matched controls without CHD, 3845 (6.0%) and 2235 (0.3%) died, respectively. The mean study follow‐up (SD) was 11.4 (6.3) years in patients with CHD. The mortality risk was 17.7 (95% CI, 16.8–18.6) times higher in children with CHD compared with controls. The highest mortality risk was found during the first 4 years of life in patients with CHD (hazard ratio [HR], 19.6; 95% CI, 18.5–20.7). When stratified by lesion group, patients with non‐conotruncal defects had the highest risk (HR, 97.2; 95% CI, 80.4–117.4). Survival increased substantially according to birth decades, but with no improvement after the turn of the century where survivorship reached 97% in children with CHD born in 2010 to 2017.

Conclusions

Survival in children with CHD has increased substantially since the 1980s; however, no significant improvement has been observed this century. Currently, >97% of children with CHD can be expected to reach adulthood highlighting the need of life‐time management.
deus inludens … flenti similis (Οv. Met. 3.650-652)
Authors: Paschalis Sergios
Published: November 2020

Ovid’s fascination with Catullus’ Ariadne throughout his career has been the focus of considerable critical discussion and scholars have identified a plethora of Ovidian female figures imitating the speech of the Catullan heroine. This paper examines an overlooked incarnation of Catullus’ Ariadne in the episode of the Tyrrhenian sailors (Met. 3.577-700). Bacchus stages a reenactment of the tale of Theseus and Ariadne in Catullus 64.50-266 by impersonating the deserted princess and casting the Tyrrhenians in the role of the perfidious hero. The study suggests that the Ovidian god constitutes a unique instance of a male character appropriating the voice of Catullus’ female protagonist. Moreover, Bacchus’ epiphany inverts its Neoteric model: the Catullan ecphrastic account of the Dionysiac thiasos is represented as a vivid narrative teeming with motion and sound, while in the Metamorphoses the Bacchic miracles are figuratively depicted as a still and silent scene in an ecphrasis.
Bioethics Research Group and Beyond: Three Decades of Studies in Ethics and Political Philosophy
Authors: Holtug Nils , Lippert-Rasmussen Kasper , Ryberg Jesper , Sandøe Peter
Published: November 2020

The aim of this paper is to present some important contributions to ethics, value theory and political philosophy the former members of the Bioethics Research Group have made. The group was established at the University of Copenhagen in 1992 and was formally dissolved in 1997, but the members continued to work in ethics and political philosophy and set up research groups and centres at four Danish universities. Within four research themes, contributions made over the years are described. Research outputs of the group have, in various ways, served to bring studies of ethics and political philosophy originating in Denmark into the wider international research arena. Members of the group have increasingly included empirical approaches in their research and have thereby participated in the more general “empirical turn” in analytic philosophy. Some members of the group can also be said to have participated in a “pluralist turn”.
Disentangling vines: a study of morphological crypsis and genetic divergence in vine snakes (Squamata: Colubridae: Ahaetulla) with the description of five new species from Peninsular India
Authors: MALLIK ASHOK KUMAR , SRIKANTHAN ACHYUTHAN N. , PAL SAUNAK P. , D’SOUZA PRINCIA MARGARET , SHANKER KARTIK , GANESH SUMAITHANGI RAJAGOPALAN
Published: November 2020

We carried out a taxonomic revision of Ahaetulla species inhabiting Peninsular India, using a multiple criteria approach (including genetics, morphology, and geography). Our work included populations of the A. nasuta complex (widespread across the entire region, including the Western Ghats), the A. pulverulenta complex (in the Western Ghats, within Peninsular India) and the A. dispar complex (endemic to the Southern Western Ghats) which all revealed undocumented cryptic diversity. Here, we describe five new species and effect nomenclatural changes to some recognised taxa. In the A. nasuta complex, we describe four species from several latitudinal blocks of the Western Ghats and make nomenclatural emendations to the plains populations in the Indian peninsula. We effect nomenclatural change in the A. pulverulenta population of the Western Ghats and describe a new species from the A. dispar group. Our study highlights the use of a multi-criteria approach in unraveling cryptic diversity. This study also reveals a striking case of discordance between morphological and genetic divergence, and the way this is reflected in previous taxonomic and nomenclatural treatments of these populations.
9. The Philosopher’s Virtues
Authors: McAleer Sean
Published: November 2020

Chapter Nine, ‘The Philosopher’s Virtues’, continues to explore the distinction between philosophers and non-philosophers, focusing on their different characters. Central to the discussion is the distinction between virtues of character (for example, justice), intellectual virtues (for example, a good memory), and virtues of personal style (for example, grace and elegance), attending to the light this last category sheds on Plato’s moral vision. As a prelude to the key analogies of Book VI, the rest of this chapter is devoted to the interesting analogies Socrates appeals to in addressing features of the Third Wave.
11. The Allegory of the Cave
Authors: McAleer Sean
Published: November 2020

True to its name, Chapter Eleven, ‘Shedding Light on the Allegory of the Cave’, devotes itself to exploring the famous Allegory of the Cave from Book VII of the Republic, carefully considering its various stages and themes before examining the issue posed by the enlightened philosopher’s return to the Cave. As Socrates describes it, the enlightened philosopher descends back into the Cave not because they want to, but because they recognize that justice requires them to do so. This raises an issue for discussion that Socrates does not seem to notice: the enlightened philosopher would be happier if they ignored the demands of justice and remained in the intelligible world of the Forms, which suggests that, contrary to Socrates’ view, the just life is not happier than the unjust life.
14. Are We There Yet?
Authors: McAleer Sean
Published: November 2020

Chapter Fourteen, ‘Are We There Yet? Tying up Loose Ends in Book X’, explores the three topics of the Republic’s final book, Book X. The first is the status of poetry, which Socrates wants to revisit since he now has a psychology (the three-part soul) that he lacked when poetry was first discussed. He concludes, quite reluctantly, that very little poetry will be allowed in the ideal city, mainly because of its power to corrupt us: we give ourselves over to emotion and thus dethrone reason from its rightful place. After exploring his arguments for this view, we turn to his argument for the immortality of the soul, which Socrates offers in the context of showing the external advantages of living a just life (namely, having a reputation for justice), which were set aside to answer Glaucon’s and Adeimantus’ challenge of showing that justice was intrinsically good—that all by itself it made its possessor better off. Lastly, we attend to the Myth of Er, with which the Republic ends. Er’s story is an allegory about the importance of careful choice in living justly and thus happily. It is a fascinating way to end the Republic, in terms of both content and style; we briefly explore what philosophical points Plato might be making by ending a work of philosophy this way.
A Deep Learning Based Level Set Model for Pancreas Segmentation
Authors: Gong Zhaoxuan , Guo Wei , Zhou Wei , Zhao Dazhe , Tan Wenjun , Zhang Guodong
Published: November 2020

A deep learning based active contour framework is proposed for pancreas segmentation. Data extension and fractional differential operation are firstly applied for pre-processing. Second, deep learning method is designed to acquire the initial contour of pancreas. Subsequently, an intensity
constrained term is designed to stop the contours at the edges. The intensity constrained term is integrated into a variational active contour model with three terms. The accurate pancreas segmentation is obtained by the evolution of the active contour model. Our approach reaches high detection
dice similarity coefficient (DSC) of 83% and sensitivity of 85% in a dataset containing 40 abdominal CT scans. Comparisons with other level set models provide evidence that the proposed method offers desirable performances.
Magnetic Resonance Imaging Manifestations of Brain Metastases in Patients with Lung Cancer
Authors: Wang Wei , Zhang Lijie
Published: November 2020

Objective: Using magnetic resonance imaging (MRI), the clinical and imaging characteristics of brain metastases from lung cancer were analyzed to improve the early diagnosis rate. Computed tomography (CT) was used to confirm the existence of lung lesions. Methods: The
clinical and imaging data of 17 lung cancer brain metastases first diagnosed in neurology were retrospectively analyzed. Results: All patients were diagnosed with neurological symptoms. The main complaints were headache (n = 15), dizziness (n = 10), limb weakness or hemiplegia
(n = 7), sensory disorders (n = 5), and mental and emotional disorders (n = 3), Vision loss (n = 1), and epilepsy (n = 1). Brain metastases was imaged using MRI, and primary lung lesions were indicated by chest CT. The primary lesions were confirmed by puncture
biopsy or surgical pathology. 1 case of single metastases was diagnosed by surgery, 2 cases of single metastases, 15 cases of multiple cases, most common under the cortex, and most were accompanied by peritumoral edema, and 3 cases were cystic. In 2 cases with tumor stroke, the enhancement
was most circular. Conclusions: Lung cancer and brain metastases first diagnosed in neurology are mostly neurological symptoms. Pulmonary symptoms and signs are often lacking or mild. It is easy to miss misdiagnosis based on clinical symptoms. Timely craniocerebral and chest imaging
examinations help to accurately diagnose the condition presented in our study.
Segmentation and Measurements of Carotid Intima-Media Thickness in Ultrasound Images Using the Improved Convolutional Neural Network and Support Vector Machine
Authors: Guo Dequan , Zhang Gexiang , Peng Hui , Yuan Jianying , Paul Prithwineel , Fu Kechang , Zhu Ming
Published: November 2020

In recent years, diseases of cardiovascular and cerebrovascular have attracted much attention due to main causes in death in human beings. To reduce mortality, there are lots of efforts which are focused on early diagnosis and prevention. It is an important reference index for cardiovascular
diseases through the endovascular membrane in carotid artery by medical ultrasound images. The paper proposes a method which finds the region of interest (ROI) by convolutional neural network, segments and measures intima-media membrane mainly using support vector machine (SVM). Essentially,
the task of detecting the membrane is one target detection problem. This paper adopts the strategy, named Yon Only Look Once (YOLO), a new detection algorithm, and follows the convolution neural network algorithm based on end-to-end training. Firstly, sufficient samples are extracted according
to certain characteristics in the special region. It can be trained by the SVM classification model. Then the ROI is processed and all the pixels are classified into boundary points and non-boundary points through the classification model. Thirdly, the boundary points are selected to obtain
the accurate boundary and calculate the intima-media thickness (IMT). In experiments, two hundred ultrasound images are tested, and the results verify that our algorithm is consistent with the results by ground truth (GT). The detection speed of the algorithm in this paper is in real time,
and it has high generalization characteristics. The algorithm computes the intima-media thickness in ultrasound images accurately and quickly with 95% consistence to ground truth.
On the Structure of Instantaneous Radiative Forcing Kernels for Greenhouse Gases
Authors: Maycock Amanda C. , Smith Christopher J. , Rap Alexandru , Rutherford Owain
Published: November 2020

The Suite of Community Radiative Transfer Codes Based on Edwards and Slingo (SOCRATES) offline radiative transfer code is used to investigate the magnitude and structure of the instantaneous radiative forcing kernels (IRFKs) for five major greenhouse gases (GHGs; CO2, CH4, N2O, CFC-11, and O3). All gases produce IRFKs that peak in the tropical upper troposphere. In addition to differences in spectroscopic intensities and the position of absorption features relative to the peak of the Planck function for Earth’s temperature, the variation in current background concentration of gases substantially affects the IRFK magnitudes. When the background concentration of CO2 is reduced from parts per million to parts per trillion levels, the peak magnitude of the IRFK increases by a factor of 642. When all gases are set to parts per trillion concentrations in the troposphere, the peak IRFK magnitudes are 1.0, 3.0, 3.1, 58, and 75 W m−2 ppmv−1 (100 hPa)−1 for CH4, CO2, N2O, O3, and CFC-11, respectively. The altitude of the IRFK maximum also differs, with the maximum for CFC-11 and water vapor occurring above 100 hPa whereas the other gases peak near 150–200 hPa. Overlap with water vapor absorption decreases the magnitude of the IRFKs for all of the GHGs, particularly in the lower-to-middle troposphere, but it does not strongly affect the peak IRFK altitude. Cloud radiative effects reduce the magnitude of the IRFK for CO2 by around 10%–20% in the upper troposphere. The use of IRFKs to estimate instantaneous radiative forcing is found to be accurate for small-amplitude perturbations but becomes inaccurate for large-amplitude changes (e.g., a doubling) for gases with a higher atmospheric optical depth.
Exploring Convection-Allowing Model Evaluation Strategies for Severe Local Storms Using the Finite-Volume Cubed-Sphere (FV3) Model Core
Authors: Gallo Burkely T. , Wolff Jamie K. , Clark Adam J. , Jirak Israel , Blank Lindsay R. , Roberts Brett , Wang Yunheng , Zhang Chunxi , Xue Ming , Supinie Tim , Harris Lucas , Zhou Linjiong , Alexander Curtis
Published: November 2020

Verification methods for convection-allowing models (CAMs) should consider the finescale spatial and temporal detail provided by CAMs, and including both neighborhood and object-based methods can account for displaced features that may still provide useful information. This work explores both contingency table–based verification techniques and object-based verification techniques as they relate to forecasts of severe convection. Two key fields in severe weather forecasting are investigated: updraft helicity (UH) and simulated composite reflectivity. UH is used to generate severe weather probabilities called surrogate severe fields, which have two tunable parameters: the UH threshold and the smoothing level. Probabilities computed using the UH threshold and smoothing level that give the best area under the receiver operating curve result in very high probabilities, while optimizing the parameters based on the Brier score reliability component results in much lower probabilities. Subjective ratings from participants in the 2018 NOAA Hazardous Weather Testbed Spring Forecasting Experiment (SFE) provide a complementary evaluation source. This work compares the verification methodologies in the context of three CAMs using the Finite-Volume Cubed-Sphere Dynamical Core (FV3), which will be the foundation of the U.S. Unified Forecast System (UFS). Three agencies ran FV3-based CAMs during the five-week 2018 SFE. These FV3-based CAMs are verified alongside a current operational CAM, the High-Resolution Rapid Refresh version 3 (HRRRv3). The HRRR is planned to eventually use the FV3 dynamical core as part of the UFS; as such evaluations relative to current HRRR configurations are imperative to maintaining high forecast quality and informing future implementation decisions.
ICAR '96 Conference Highlights - Part 2
Authors: Estey Chris , Grandsard Peter
Published: November 2020

The International Conference on Automation, Robotics and Artificial Intelligence Applied to Analytical Chemistry and Laboratory Medicine has become the premier meeting dedicated to expanding the knowledge base in the rapidly evolving field of laboratory automation. This year was the fifth consecutive year for the International Conference, and we experienced impressive growth in registrations and exhibitions. The conference, held at the Sheraton Hotel and Marina in San Diego, California, featured 51 exhibitors, 14 sponsors, 54 oral presentations, 41 posters, and over 600 registrants and exhibitor associates.

In the last issue of LAN, we covered the first day of scientific sessions which focused on artificial intelligence as well as the final session on novel technology. In this second part of a three-part article, we summarize Part 1 of the parallel scientific session of the conference.
Neural Network
Authors: Herold Christopher D. , Fitzgerald Robert L. , Herold David A. , Lu Taiwei
Published: November 2020

A hybrid neural network (HNN) developed by Physical Optics Corporation (Torrance, CA) is helping a team of scientists with the San Diego Veterans Administration Medical Center and University of California, San Diego Pathology Department automate the detection and identification of Tuberculosis and other mycobacterial infections.
FBXO11-mediated proteolysis of BAHD1 relieves PRC2-dependent transcriptional repression in erythropoiesis
Authors: Xu Peng , Scott Daniel C. , Xu Beisi , Yao Yu , Feng Ruopeng , Cheng Li , Mayberry Kalin , Wang Yong-Dong , Bi Wenjian , Palmer Lance E. , King Moeko T. , Wang Hong , Li Yuxin , Fan Yiping , Alpi Arno F. , Li Chunliang , Peng Junmin , Papizan James , Pruett-Miller Shondra M. , Spallek Ria , Bassermann Florian , Cheng Yong , Schulman Brenda A. , Weiss Mitchell J.
Published: November 2020

The histone mark H3K27me3 and its reader/writer polycomb repressive complex 2 (PRC2) mediate widespread transcriptional repression in stem and progenitor cells. Mechanisms that regulate this activity are critical for hematopoietic development but are poorly understood. Here we show that the E3 ubiquitin ligase F-box only protein 11 (FBXO11) relieves PRC2-mediated repression during erythroid maturation by targeting its newly identified substrate bromo adjacent homology domain–containing 1 (BAHD1), an H3K27me3 reader that recruits transcriptional corepressors. Erythroblasts lacking FBXO11 are developmentally delayed, with reduced expression of maturation-associated genes, most of which harbor bivalent histone marks at their promoters. In FBXO11−/− erythroblasts, these gene promoters bind BAHD1 and fail to recruit the erythroid transcription factor GATA1. The BAHD1 complex interacts physically with PRC2, and depletion of either component restores FBXO11-deficient erythroid gene expression. Our studies identify BAHD1 as a novel effector of PRC2-mediated repression and reveal how a single E3 ubiquitin ligase eliminates PRC2 repression at many developmentally poised bivalent genes during erythropoiesis.
Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set
Authors: Chari Ajai , Samur Mehmet Kemal , Martinez-Lopez Joaquin , Cook Gordon , Biran Noa , Yong Kwee , Hungria Vania , Engelhardt Monika , Gay Francesca , García Feria Ana , Oliva Stefania , Oostvogels Rimke , Gozzetti Alessandro , Rosenbaum Cara , Kumar Shaji , Stadtmauer Edward A. , Einsele Hermann , Beksac Meral , Weisel Katja , Anderson Kenneth C. , Mateos María-Victoria , Moreau Philippe , San-Miguel Jesus , Munshi Nikhil C. , Avet-Loiseau Hervé
Published: November 2020

The primary cause of morbidity and mortality in patients with multiple myeloma (MM) is an infection. Therefore, there is great concern about susceptibility to the outcome of COVID-19–infected patients with MM. This retrospective study describes the baseline characteristics and outcome data of COVID-19 infection in 650 patients with plasma cell disorders, collected by the International Myeloma Society to understand the initial challenges faced by myeloma patients during the COVID-19 pandemic. Analyses were performed for hospitalized MM patients. Among hospitalized patients, the median age was 69 years, and nearly all patients (96%) had MM. Approximately 36% were recently diagnosed (2019-2020), and 54% of patients were receiving first-line therapy. Thirty-three percent of patients have died, with significant geographic variability, ranging from 27% to 57% of hospitalized patients. Univariate analysis identified age, International Staging System stage 3 (ISS3), high-risk disease, renal disease, suboptimal myeloma control (active or progressive disease), and 1 or more comorbidities as risk factors for higher rates of death. Neither history of transplant, including within a year of COVID-19 diagnosis, nor other anti-MM treatments were associated with outcomes. Multivariate analysis found that only age, high-risk MM, renal disease, and suboptimal MM control remained independent predictors of adverse outcome with COVID-19 infection. The management of MM in the era of COVID-19 requires careful consideration of patient- and disease-related factors to decrease the risk of acquiring COVID-19 infection, while not compromising disease control through appropriate MM treatment. This study provides initial data to develop recommendations for the management of MM patients with COVID-19 infection.
Feasibility and success rates of response enhancing strategies in a stepwise prevention program for cardiometabolic diseases in primary care
Authors: Badenbroek Ilse F. , Nielen Marcus M. J. , Hollander Monika , Stol Daphne M. , Kraaijenhagen Roderik A. , de Wit Niek J. , Schellevis François G.
Published: November 2020

Background

Prevention programs for cardiometabolic diseases (CMD), including cardiovascular disease, diabetes mellitus and chronic kidney disease are feasible, but evidence for the cost-effectiveness of selective CMD prevention programs is lacking. Response rates have an important role in effectiveness, but methods to increase response rates have received insufficient attention. The aim of the current study is to determine the feasibility and the success rate of a variety of response enhancing strategies to increase the participation in a selective prevention program for CMD.

Methods

The INTEGRATE study is a Dutch randomised controlled trial to assess the effectiveness and cost-effectiveness of a stepwise program for CMD prevention. During the INTEGRATE study we developed ten different response enhancing strategies targeted at different stages of non-response and different patient populations and evaluated these in 29 general practices.

Results

A face-to-face reminder by the GP increased the response significantly. Digital reminders targeted at patients with an increased CMD risk showed a positive trend towards participation. Sending invitations and reminders by e-mail generated similar response rates, but at lower costs and time investment than the standard way of dissemination. Translated materials, information gatherings at the practice, self-management toolkits, reminders by telephone, information letters, local media attention and SMS text reminders did not increase the response to our program.

Conclusions

Inviting or reminding patients by e-mail or during GPs consultation may enhance response rates in a selective prevention program for CMD. Different response-enhancing strategies have different patient target populations and implementation issues, therefore practice characteristics need to be taken into account when implementing such strategies.

Trial registration

Dutch trial Register number NTR4277. Registered 26 November 2013.
Effectiveness of physical exercise for people with chronic diseases: the EFIKRONIK study protocol for a hybrid, clinical and implementation randomized trial
Authors:   on behalf of the EfiKroniK group, Arietaleanizbeaskoa María Soledad , Sancho Aintzane , Olazabal Iñigo , Moreno Concepcion , Gil Erreka , Garcia-Alvarez Arturo , Mendizabal Nere , de la Fuente Ibon , Dominguez Silvia , Pablo Susana , Grandes Gonzalo
Published: November 2020

Background

Chronic illnesses are the leading cause of morbidity and mortality and threaten the sustainability of healthcare systems worldwide. There is limited evidence in terms of the best modality and intensity of physical activity for improving cardiorespiratory capacity and quality of life in patients with chronic conditions. The objective of the EfiKroniK study is to estimate the common effect of innovative, individualized and supervised physical exercise, on cardiorespiratory functional capacity and quality of life across people with different chronic conditions.

Methods/design

This is a multicentre clinical trial with a type I hybrid effectiveness-implementation design, including 370 patients each with one of four different chronic illnesses: solid cancer, blood cancer, chronic obstructive pulmonary disease or schizophrenia. Patients will be randomly divided into two parallel groups, stratified by illness type. Patients in both groups will receive a standard healthy life prescription (PVS, from the Spanish “Prescribe Vida Saludable”) and additionally, the EfiKroniK group will be prescribed a physical exercise programme tailored to each patient in terms of intensity in each session. The primary outcome variables will be cardiorespiratory functional capacity and quality of life. The secondary outcome variables will be signs and symptoms, psychological and social factors and specific laboratory parameters. We will also analyse the dose-response effect of the physical exercise programme. Qualitative variables will describe patients’ perception of the utility and suitability of the EfiKroniK programme, as well as their expectations and satisfaction, identifying barriers to and facilitators of the EfiKroniK implementation process through discussion groups. The study will be carried out on an intention-to-treat basis, comparing changes throughout the 1-year follow-up between groups, adjusting for baseline, by performing mixed-effect analysis of covariance. We will estimate the effect of time on repeated measures in each subject and changes in the EfiKroniK and PVS groups over time.

Discussion

The study will provide the data necessary to allow us to prescribe physical exercise in a similar way to a drug and as a key part of the treatment of chronic illnesses within our healthcare system.

Trial registration

NCT03810755.

Date and version identifier: October 9, 2020. Version2.0.
Correction to: Integrated GP care for patients with persistent physical symptoms: feasibility cluster randomised trial
Authors:   on behalf of the PRINCE Primary trial team, Patel Meenal , James Kirsty , Moss-Morris Rona , Ashworth Mark , Husain Mujtaba , Hotopf Matthew , David Anthony S. , McCrone Paul , Landau Sabine , Chalder Trudie
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Outpatient Management of Oligosymptomatic Patients with respiratory infection in the era of SARS-CoV-2: Experience from rural German general practitioners
Authors: Wernhart Simon , Förster Tim-Henning , Weihe Eberhard
Published: November 2020

Background

Covid-19 is causing a pandemic and forces physicians to restructure their work. We want to share our experience in the outpatient management of potentially-infected patients with special consideration of altered national test strategies during the crisis.

Methods

We analysed patients with respiratory symptoms reporting to our three rural general practitioner (GP) offices in North Rhine-Westphalia, Germany, from 27.01–20.04.2020 (n = 489 from a total of 6090 patients). A history of symptoms was taken at the doorstep following a specific questionnaire. Patients with respiratory symptoms were examined in a separated isolation area, while the others were allowed to enter the office. We applied the first recommended algorithm of the German Robert Koch Institute (RKI) to test suspected patients and compared our results with an adapted, more liberal version of the RKI, which is currently applied in Germany.

Results

Eighty patients (16.36%, mean age: 47.03 years+ − 18.08) were sent to a nasopharyngeal smear. Five patients (6.25%) proved to be positive, four of whom had established risk factors for COVID-19. Overall, the most common symptoms were cough (83.75%), sore throat (71.25%), as well as myalgia and fatigue (66.25%). The most common diagnoses were rhinopharyngitis (37.22%) and acute bronchitis (30.27%). A sore throat was more common in positively-tested patients (80% vs. 12%). Applying the first RKI test strategy yielded 6.25% of positive tests (n = 80), while the more liberal later RKI recommendation would have achieved 1.36% positive tests from 369 patients. No positive test was missed by applying the conservative strategy. None of our employees called in sick during this period, which emphasises the efficacy and safety of our screening methods.

Conclusion

A clinical distinction between ordinary respiratory infections and COVID-19 is not possible in a low-prevalence population. Our model to prevent unprotected physical contact, screen patients in front of the office with protective equipment, and examine respiratory infections in separated areas works in the GP setting without overt health risks for employees. Thus, this approach should be used as a GP standard to uphold patient care without major health risks for the personnel. Large multi-centre studies are necessary to work out the most suitable test strategy.
Professional language use by alumni of the Harvard Medical School Medical Language Program
Authors: Pereira Joseph A. , Hannibal Kari , Stecker Jasmine , Kasper Jennifer , Katz Jeffrey N. , Molina Rose L.
Published: November 2020

Background

Despite the growing number of patients with limited English proficiency in the United States, not all medical schools offer medical language courses to train future physicians in practicing language-concordant care. Little is known about the long-term use of non-English languages among physicians who took language courses in medical school. We conducted a cross-sectional study to characterize the professional language use of Harvard Medical School (HMS) alumni who took a medical language course at HMS and identify opportunities to improve the HMS Medical Language Program.

Methods

Between October and November 2019, we sent an electronic survey to 803 HMS alumni who took a medical language course at HMS between 1991 and 2019 and collected responses. The survey had questions about the language courses and language use in the professional setting. We analyzed the data using descriptive statistics and McNemar’s test for comparing proportions with paired data. The study was determined not to constitute human subjects research.

Results

The response rate was 26% (206/803). More than half of respondents (n = 118, 57%) cited their desire to use the language in their future careers as the motivation for taking the language courses. Twenty-eight (14%) respondents indicated a change from not proficient before taking the course to proficient at the time of survey whereas only one (0.5%) respondent changed from proficient to not proficient (McNemar’s p-value < 0.0001). Respondents (n = 113, 56%) reported that clinical electives abroad influenced their cultural understanding of the local in-country population and their language proficiency. Only 13% (n = 27) of respondents have worked in a setting that required formal assessments of non-English language proficiency.

Conclusions

HMS alumni of the Medical Language Program reported improved language proficiency after the medical language courses’ conclusion, suggesting that the courses may catalyze long-term language learning. We found that a majority of respondents reported that the medical language courses influenced their desire to work with individuals who spoke the language of the courses they took. Medical language courses may equip physicians to practice language-concordant care in their careers.
Neuronal surface P antigen (NSPA) modulates postsynaptic NMDAR stability through ubiquitination of tyrosine phosphatase PTPMEG
Authors: Espinoza Sofía , Arredondo Sebastián B. , Barake Francisca , Carvajal Francisco , Guerrero Fernanda G. , Segovia-Miranda Fabian , Valenzuela David M. , Wyneken Ursula , Rojas-Fernández Alejandro , Cerpa Waldo , Massardo Loreto , Varela-Nallar Lorena , González Alfonso
Published: November 2020

Background

Cognitive dysfunction (CD) is common among patients with the autoimmune disease systemic lupus erythematosus (SLE). Anti-ribosomal P autoantibodies associate with this dysfunction and have neuropathogenic effects that are mediated by cross-reacting with neuronal surface P antigen (NSPA) protein. Elucidating the function of NSPA can then reveal CD pathogenic mechanisms and treatment opportunities. In the brain, NSPA somehow contributes to glutamatergic NMDA receptor (NMDAR) activity in synaptic plasticity and memory. Here we analyze the consequences of NSPA absence in KO mice considering its structural features shared with E3 ubiquitin ligases and the crucial role of ubiquitination in synaptic plasticity.

Results

Electrophysiological studies revealed a decreased long-term potentiation in CA3-CA1 and medial perforant pathway-dentate gyrus (MPP-DG) hippocampal circuits, reflecting glutamatergic synaptic plasticity impairment in NSPA-KO mice. The hippocampal dentate gyrus of these mice showed a lower number of Arc-positive cells indicative of decreased synaptic activity and also showed proliferation defects of neural progenitors underlying less adult neurogenesis. All this translates into poor spatial and recognition memory when NSPA is absent. A cell-based assay demonstrated ubiquitination of NSPA as a property of RBR-type E3 ligases, while biochemical analysis of synaptic regions disclosed the tyrosine phosphatase PTPMEG as a potential substrate. Mice lacking NSPA have increased levels of PTPMEG due to its reduced ubiquitination and proteasomal degradation, which correlated with lower levels of GluN2A and GluN2B NMDAR subunits only at postsynaptic densities (PSDs), indicating selective trafficking of these proteins out of PSDs. As both GluN2A and GluN2B interact with PTPMEG, tyrosine (Tyr) dephosphorylation likely drives their endocytic removal from the PSD. Actually, immunoblot analysis showed reduced phosphorylation of the GluN2B endocytic signal Tyr1472 in NSPA-KO mice.

Conclusions

NSPA contributes to hippocampal plasticity and memory processes ensuring appropriate levels of adult neurogenesis and PSD-located NMDAR. PTPMEG qualifies as NSPA ubiquitination substrate that regulates Tyr phosphorylation-dependent NMDAR stability at PSDs. The NSPA/PTPMEG pathway emerges as a new regulator of glutamatergic transmission and plasticity and may provide mechanistic clues and therapeutic opportunities for anti-P-mediated pathogenicity in SLE, a still unmet need.