bluuebunny/crossref_metadata_2025 huggingface dataset:
PathWalks: identifying pathway communities using a disease-related map of integrated information
Authors: Karatzas Evangelos , Zachariou Margarita , Bourdakou Marilena M , Minadakis George , Oulas Anastasis , Kolios George , Delis Alex , Spyrou George M
Published: April 2020

Motivation

Understanding the underlying biological mechanisms and respective interactions of a disease remains an elusive, time consuming and costly task. Computational methodologies that propose pathway/mechanism communities and reveal respective relationships can be of great value as they can help expedite the process of identifying how perturbations in a single pathway can affect other pathways.

Results

We present a random-walks-based methodology called PathWalks, where a walker crosses a pathway-to-pathway network under the guidance of a disease-related map. The latter is a gene network that we construct by integrating multi-source information regarding a specific disease. The most frequent trajectories highlight communities of pathways that are expected to be strongly related to the disease under study.

We apply the PathWalks methodology on Alzheimer's disease and idiopathic pulmonary fibrosis and establish that it can highlight pathways that are also identified by other pathway analysis tools as well as are backed through bibliographic references. More importantly, PathWalks produces additional new pathways that are functionally connected with those already established, giving insight for further experimentation.

Availability and implementation

https://github.com/vagkaratzas/PathWalks.

Supplementary information

Supplementary data are available at Bioinformatics online.
Bipartite Functional Fractionation within the Default Network Supports Disparate Forms of Internally Oriented Cognition
Authors: Chiou Rocco , Humphreys Gina F , Lambon Ralph Matthew A
Published: April 2020

Our understanding about the functionality of the brain’s default network (DN) has significantly evolved over the past decade. Whereas traditional views define this network based on its suspension/disengagement during task-oriented behavior, contemporary accounts have characterized various situations wherein the DN actively contributes to task performance. However, it is unclear how different task-contexts drive componential regions of the DN to coalesce into a unitary network and fractionate into different subnetworks. Here we report a compendium of evidence that provides answers to these questions. Across multiple analyses, we found a striking dyadic structure within the DN in terms of the profiles of task-triggered fMRI response and effective connectivity, significantly extending beyond previous inferences based on meta-analysis and resting-state activities. In this dichotomy, one subset of DN regions prefers mental activities “interfacing with” perceptible events, while the other subset prefers activities “detached from” perceptible events. While both show a common “aversion” to sensory-motoric activities, their differential preferences manifest a subdivision that sheds light upon the taxonomy of the brain’s memory systems. This dichotomy is consistent with proposals of a macroscale gradational structure spanning across the cerebrum. This gradient increases its representational complexity, from primitive sensory-motoric processing, through lexical-semantic representations, to elaborated self-generated thoughts.
Severe pulmonary regurgitation mimicking constrictive pericarditis: a case report—the sac or the content? That is the question
Authors: Suto Makiko , Matsumoto Kensuke , Tanaka Hidekazu , Hirata Ken-Ichi
Published: April 2020

Background

Constrictive pericarditis (CP) is a pathological condition of the pericardium, resulting from fibrosis, scarring, and calcification of the pericardium. Other conditions have been reported to mimic ‘constrictive physiology’ despite the presence of an intact pericardium. However, there has been no report of pulmonary regurgitation (PR) mimicking the haemodynamic characteristics of CP.

Case summary

A 51-year-old woman was admitted to our institute because of severe right-sided heart failure. Transthoracic echocardiography revealed severe PR concomitant with significant dilatation of the right-sided heart. Septal bounce and the respiratory reciprocation of the transmitral and transtricuspid inflow velocities were also observed, indicating exacerbated ventricular interdependence. Cardiac catheter examination demonstrated elevated right atrial pressure with a prominent y descent, dip, and plateau waveform in the right ventricular pressure, and equalization of the diastolic pressure of all cardiac chambers, which are quite consistent with CP. On surgical inspection, however, there was no pericardial thickening or adhesion, indicating no obvious signs of CP.

Discussion

Pericardial constriction results from the relative relationship between intrapericardial volume and pericardial reserve. When the intrapericardial volume exceeds the physiological limit, the cardiac chambers compete with each other in a fixed pericardial space. In this case, prominent dilation of the right-sided chambers caused by severe PR resulted in overstretching of the pericardium above the pericardial reserve, which led to a characteristic haemodynamic picture that resembled CP. Thus, it is important to recognize the diagnostic pitfall in the preoperative evaluation of a ‘CP mimic physiology’.
Workers’ resilience in occupied France: workers in Le Havre, 1941–1942
Authors: Shtasel Rebecca
Published: April 2020

Workers in Le Havre developed resilience through trade union activism, political commitment and community engagement in the pre-war period. This resilience allowed them to display their anger at new hardships that appeared at the start of the German occupation. In particular, workers rioted at a major building site and demanded and achieved wage rises; and, as the RAF bombed their town day and night, they continuously made demands for danger money. Indeed, they did not change their behaviour because the circumstances in which they now lived had changed; they continued to use the skills they had learnt during pre-war industrial battles to make demands that would improve the material situation of themselves and their fellow trade unionists. This analysis differs from most of the major historiography on workers during the Occupation which claims workers during the first two years of the Occupation were broadly passive and cite the miners’ strike in the Nord and Pas-de-Calais as the exception which proves the rule.
PAX7 target gene repression associates with FSHD progression and pathology over 1 year
Authors: Banerji Christopher R S
Published: April 2020

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, inherited skeletal myopathy linked to hypomethylation of the D4Z4 macrosatellite at chromosome 4q35. This epigenetic de-repression permits expression of the transcription factor DUX4, which may drive pathology by direct activation of target genes or through inhibition of the homologous transcription factor PAX7. We demonstrated that PAX7 target gene repression is a superior biomarker of FSHD status compared with DUX4 target gene expression. However, despite importance for clinical trials, there remains no transcriptomic biomarker for FSHD progression. A recent study by Wong et al. [Longitudinal measures of RNA expression and disease activity in FSHD muscle biopsies. Hum. Mol. Genet., 29, 1030–1043] performed MRI, muscle biopsy transcriptomics and histopathology on a cohort of FSHD patients with 1-year follow-up. No significant changes in any biomarkers were reported over this time period. However, the authors did not consider PAX7 target gene repression as a marker of FSHD progression. Here we demonstrate that PAX7 target gene repression increases in these paired FSHD samples from year 1 to year 2 and is thus a marker of FSHD progression over 1 year. Moreover, we show that three validated DUX4 target gene expression biomarkers are not associated with FSHD progression over 1 year. We further confirm that PAX7 target gene repression associates with clinical correlates of FSHD disease activity, measured by MRI and histopathology. Thus, PAX7 target gene repression is a uniquely sensitive biomarker of FSHD progression and pathology, valid over a 1 year time frame, implicating its use in clinical trials.
Synj1 haploinsufficiency causes dopamine neuron vulnerability and alpha-synuclein accumulation in mice
Authors: Pan Ping-Yue , Sheehan Patricia , Wang Qian , Zhu Xinyu , Zhang Yuanxi , Choi Insup , Li Xianting , Saenz Jacqueline , Zhu Justin , Wang Jing , El Gaamouch Farida , Zhu Li , Cai Dongming , Yue Zhenyu
Published: April 2020

Synaptojanin1 (synj1) is a phosphoinositide phosphatase with dual SAC1 and 5′-phosphatase enzymatic activities in regulating phospholipid signaling. The brain-enriched isoform has been shown to participate in synaptic vesicle (SV) recycling. More recently, recessive human mutations were identified in the two phosphatase domains of SYNJ1, including R258Q, R459P and R839C, which are linked to rare forms of early-onset Parkinsonism. We now demonstrate that Synj1 heterozygous deletion (Synj1+/−), which is associated with an impaired 5′-phosphatase activity, also leads to Parkinson’s disease (PD)-like pathologies in mice. We report that male Synj1+/− mice display age-dependent motor function abnormalities as well as alpha-synuclein accumulation, impaired autophagy and dopaminergic terminal degeneration. Synj1+/− mice contain elevated 5′-phosphatase substrate, PI(4,5)P2, particularly in the midbrain neurons. Moreover, pharmacological elevation of membrane PI(4,5)P2 in cultured neurons impairs SV endocytosis, specifically in midbrain neurons, and further exacerbates SV trafficking defects in Synj1+/− midbrain neurons. We demonstrate down-regulation of SYNJ1 transcript in a subset of sporadic PD brains, implicating a potential role of Synj1 deficiency in the decline of dopaminergic function during aging.
The Gut Microbial Profile of Preclinical Crohn’s Disease Is Similar to That of Healthy Controls
Authors: Kuballa Anna , Geraci Marco , Johnston Meredith , Sorrentino Dario
Published: April 2020

Background and Aims

It is unclear whether microbial dysbiosis plays an etiologic role in Crohn’s disease (CD) or is the result of protracted inflammation. Here, we test the hypothesis that dysbiosis predates clinical CD in asymptomatic first-degree relatives (FDRs) of CD patients: normal (FDR1), with borderline inflammation (FDR2), and with frank, very early inflammation (FDR3).

Methods

The gut microbial diversity was tested in ileocecal biopsies through next generation sequencing of the 16S rRNA gene in 10 healthy controls (HCs), 22 patients with active, untreated CD, and 25 FDRs (9 FDR1; 12 FDR2; 4 FDR3). The metagenomic functions of 41 microbiome-related processes were inferred by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis.

Results

Compared with HCs, alpha diversity in CD patients was decreased, with an observed decrease in Faecalibacterium prausnitzii and increase in Bacteroides fragilis. In FDRs, microbial diversity was unchanged compared with HCs. In Operational Taxonomic Units and PICRUSt Principal coordinates and component analyses, the ellipse centroid of FDRs was diagonally opposed to that of CD patients, but close to the HC centroid. In both analyses, statistically significant differences in terms of beta diversity were found between CD and HC but not between FDR and HC.

Conclusions

In FDRs (including FDR3—who bear preclinical/biologic onset disease), we found that the microbial profile is remarkably similar to HC. If confirmed in larger studies, this finding suggests that clinical CD-associated dysbiosis could result from the changed microenvironment due to disease evolution over time.
Recognizing, reporting and reducing the data curation debt of cohort studies
Authors: Butters Oliver W , Wilson Rebecca C , Burton Paul R
Published: April 2020

Good data curation is integral to cohort studies, but it is not always done to a level necessary to ensure the longevity of the data a study holds. In this opinion paper, we introduce the concept of data curation debt—the data curation equivalent to the software engineering principle of technical debt. Using the context of UK cohort studies, we define data curation debt—describing examples and their potential impact. We highlight that accruing this debt can make it more difficult to use the data in the future. Additionally, the long-running nature of cohort studies means that interest is accrued on this debt and compounded over time—increasing the impact a debt could have on a study and its stakeholders. Primary causes of data curation debt are discussed across three categories: longevity of hardware, software and data formats; funding; and skills shortages. Based on cross-domain best practice, strategies to reduce the debt and preventive measures are proposed—with importance given to the recognition and transparent reporting of data curation debt. Describing the debt in this way, we encapsulate a multi-faceted issue in simple terms understandable by all cohort study stakeholders. Data curation debt is not only confined to the UK, but is an issue the international community must be aware of and address. This paper aims to stimulate a discussion between cohort studies and their stakeholders on how to address the issue of data curation debt. If data curation debt is left unchecked it could become impossible to use highly valued cohort study data, and ultimately represents an existential risk to studies themselves.
Biomarkers for Disease Severity in Children Infected With Respiratory Syncytial Virus: A Systematic Literature Review
Authors: Öner Deniz , Drysdale Simon B , McPherson Calum , Lin Gu-Lung , Janet Sophie , Broad Jonathan , Pollard Andrew J , Aerssens Jeroen ,   RESCEU Investigators, Nair Harish , Campbell Harry , Openshaw Peter , Beutels Philippe , Bont Louis , Pollard Andrew , Molero Eva , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Fischer Thea Kølsen , van den Berge Maarten , Giaquinto Carlo , Demont Clarisse , Gallichan Scott , Dormitzer Philip , Leach Amanda , Dillon Laura , Aerssens Jeroen , Rosen Brian , Nair Harish , Campbell Harry , Openshaw Peter , Beutels Philippe , Bont Louis , Pollard Andrew , Molero Eva , Martinon-Torres Federico , Heikkinen Terho , Meijer Adam , Fischer Thea Kølsen , van den Berge Maarten , Giaquinto Carlo , Demont Clarisse , Gallichan Scott , Dormitzer Philip , Leach Amanda , Dillon Laura , Aerssens Jeroen , Rosen Brian
Published: April 2020

Background

Clinical manifestations of respiratory syncytial virus (RSV) infection vary widely from mild, self-limiting illness to severe life-threatening disease. There are gaps in knowledge of biomarkers to objectively define severe disease and predict clinical outcomes.

Methods

A systematic search was performed, 1945–March 2019 in databases Ovid Medline, Embase, Global health, Scopus, and Web of Science. Risk of bias was assessed using the Cochrane tool.

Results

A total of 25 132 abstracts were screened and studies were assessed for quality, risk of bias, and extracted data; 111 studies met the inclusion criteria. RSV severity was correlated with antibody titers, reduced T and B cells, dysregulated innate immunity, neutrophil mobilization to the lungs and blood, decreased Th1 response, and Th2 weighted shift. Microbial exposures in respiratory tract may contribute to neutrophil mobilization to the lungs of the infants with severe RSV compared with mild RSV disease.

Conclusions

Although a wide range of biomarkers have been associated with RSV disease severity, robust validated biomarkers are lacking. This review illustrates the broad heterogeneity of study designs and high variability in the definition of severe RSV disease. Prospective studies are required to validate biomarkers. Additional research investigating epigenetics, metabolomics, and microbiome holds promise for novel biomarkers.
Anti-HBV activity of the HBV capsid assembly modulator JNJ-56136379 across full-length genotype A–H clinical isolates and core site-directed mutants in vitro
Authors: Verbinnen Thierry , Tan Ying , Wang Gengyan , Dehertogh Pascale , Vergauwen Karen , Neefs Jean-Marc , Jacoby Edgar , Lenz Oliver , Berke Jan Martin
Published: April 2020

Objectives

To characterize antiviral activity of the capsid assembly modulator (CAM-N) JNJ-56136379 against HBV genotypes and variants carrying amino acid substitutions in the core protein.

Methods

Anti-HBV activity of JNJ-56136379 was investigated against a diverse panel of 53 HBV clinical isolates (genotypes A–H). The impact of core amino acid substitutions using site-directed mutants (SDMs) was assessed in a transient replication assay.

Results

JNJ-56136379 median 50% effective concentration (EC50) values across all genotypes were 10–33 nM versus 17 nM (genotype D reference). JNJ-56136379 remained active against isolates carrying nucleos(t)ide analogue resistance mutations (median EC50 2–25 nM) or basal core promoter (BCP) ± precore (PC) mutations (median EC50 13–20 nM) or PC mutations (median EC50 11 nM), representing activity against isolates from HBeAg-positive and -negative hepatitis B patients. Core amino acid substitutions in the CAM-binding pocket, when tested as SDMs at positions 23, 25, 30, 33, 37, 106, 110, 118, 124, 127 and 128, reduced JNJ-56136379 anti-HBV activity; EC50 fold increases ranged from 3.0 (S106T) to 85 (T33N). All substitutions were rare in a public database of >7600 HBV core sequences (frequencies 0.01%–0.3%). Nucleos(t)ide analogues retained full activity against these core SDMs.

Conclusions

JNJ-56136379, a potent HBV CAM-N, currently in Phase 2 clinical development, was generally fully active against an extensive panel of genotype A–H clinical isolates, regardless of the presence of nucleos(t)ide analogue resistance or BCP/PC mutations. JNJ-56136379 activity was reduced by some core amino acid substitutions in the CAM-binding pocket.
D-Dimer and Fibrin Degradation Products Impair Platelet Signaling: Plasma D-Dimer Is a Predictor and Mediator of Platelet Dysfunction During Trauma
Authors: Verni Christopher C , Davila Antonio , Sims Carrie A , Diamond Scott L
Published: April 2020

Background

Platelet dysfunction often accompanies trauma-induced coagulopathy. Because soluble fibrin impairs platelet glycoprotein VI (GPVI) signaling and platelets of trauma patients can display impaired calcium mobilization, we explored the role of fibrinolysis on platelet dysfunction during trauma.

Methods

Convulxin-induced GPVI calcium mobilization was investigated in healthy platelet-rich plasma (PRP) pretreated with thrombin and tissue plasminogen activator (tPA). Blood samples from healthy participants (n = 7) and trauma patients (n = 22) were tested for platelet calcium mobilization, plasma D-dimer, platelet D-dimer binding (via flow cytometry), and platelet lumi-aggregometry.

Results

For healthy platelets, maximal platelet dysfunction was observed when cross-linked soluble fibrin (no tPA) or cross-linked fibrin degradation products (FDPs) were generated in suspension before convulxin stimulation. Lack of fibrin polymerization (inhibited by Gly-Pro-Arg-Pro [GPRP]) or lack of factor XIIIa cross-linking (T101-inhibited) restored GPVI signaling, whereas non–cross-linked FDPs only partially blocked signaling induced by convulxin. In addition, D-dimer added to healthy PRP impaired platelet aggregation and dense granule release induced by various agonists. Plasma D-dimer level was strongly correlated (R = 0.8236) with platelet dysfunction as measured by platelet calcium mobilization induced with various agonists. By 48 to 120 h after trauma, plasma D-dimer levels declined, and platelet function increased significantly but not to healthy levels. Trauma platelets displayed elevated D-dimer binding that was only partially reduced by αIIbβ3-inhibitor GR144053. After 60-minute incubation, washed healthy platelets resuspended in plasma from trauma patients captured approximately 10 000 D-dimer equivalents per platelet.

Conclusions

During trauma, D-dimer and FDPs inhibit platelets, potentially via GPVI and integrin αIIbβ3 engagement, contributing to a fibrinolysis-dependent platelet loss-of-function phenotype.
Seeing Red: Blood Sample Hemolysis Is Associated with Prolonged Emergency Department Throughput
Authors: Phelan Michael P , Hustey Fredric M , Good Daniel M , Reineks Edmunds Z
Published: April 2020

Introduction

Hemolyzed emergency department (ED) blood specimens impose substantial burdens on various aspects of delivering care. The ED has the highest incidence of hemolysis among hospital departments. This study assessed the association and potential impact of hemolyzed blood samples on patient throughput time using ED length of stay (LOS) as the primary outcome measure.

Methods

This study was a secondary analysis of data collected during a performance improvement project aimed at reducing the incidence of hemolysis in ED blood specimens. The electronic medical record was queried for potassium orders and results and for key patient throughput time points. Throughput times were stratified according to hemolysis, ED disposition (admitted vs discharged), and Emergency Services Index (ESI) triage categorization. Two-tailed t tests were used to compare throughput times for patients with and without hemolysis.

Results

Potassium values were reported for 11 228 patient visits. The mean ED LOS was 287 minutes for patients with nonhemolyzed samples and 349 minutes for patients who had hemolyzed samples, a mean delay of 62 minutes. The mean throughput time for discharged patients was 92 minutes shorter in the group without hemolysis (337 vs 429 minutes). The mean throughput time for admitted patients was 28 minutes shorter in the group without hemolysis (264 vs 292 minutes). The increased LOS for patients with a hemolyzed blood sample was independent of the most commonly encountered ESI levels.

Conclusion

Hemolysis of blood samples obtained in the ED is associated with prolonged patient throughput via delays in patient disposition, independent of various markers of acuity, such as the patients’ ultimate disposition or triage categorization.
Enabling health information exchange at a US Poison Control Center
Authors: Cummins Mollie R , Del Fiol Guilherme , Crouch Barbara I , Ranade-Kharkar Pallavi , Khalifa Aly , Iskander Andrew , Mann Darren , Hoffman Matt , Thornton Sid , Allen Todd L , Bennett Heather
Published: April 2020

Objective

The objective of this project was to enable poison control center (PCC) participation in standards-based health information exchange (HIE). Previously, PCC participation was not possible due to software noncompliance with HIE standards, lack of informatics infrastructure, and the need to integrate HIE processes into workflow.

Materials and Methods

We adapted the Health Level Seven Consolidated Clinical Document Architecture (C-CDA) consultation note for the PCC use case. We used rapid prototyping to determine requirements for an HIE dashboard for use by PCCs and developed software called SNOWHITE that enables poison center HIE in tandem with a poisoning information system.

Results

We successfully implemented the process and software at the PCC and began sending outbound C-CDAs from the Utah PCC on February 15, 2017; we began receiving inbound C-CDAs on October 30, 2018.

Discussion

With the creation of SNOWHITE and initiation of an HIE process for sending outgoing C-CDA consultation notes from the Utah Poison Control Center, we accomplished the first participation of PCCs in standards-based HIE in the US. We faced several challenges that are also likely to be present at PCCs in other states, including the lack of a robust set of patient identifiers to support automated patient identity matching, challenges in emergency department computerized workflow integration, and the need to build HIE software for PCCs.

Conclusion

As a multi-disciplinary, multi-organizational team, we successfully developed both a process and the informatics tools necessary to enable PCC participation in standards-based HIE and implemented the process at the Utah PCC.
Regulation and Practice of Forest-Management Fires on Private Lands in the Southeast United States: Legal Open Burns versus Certified Prescribed Burns
Authors: Han Xue , Frey Gregory E , Sun Changyou
Published: April 2020

Abstract

Forest-management burns have been widely acknowledged as a useful land-management tool in the United States. Nevertheless, fire is inherently risky and may lead to severe damages or create smoke that affects public health. Past research has not explored the difference in policy and practice between open burns, which meet minimum legal criteria, and certified prescribed burns, which follow a higher standard of care. This study seeks to understand the distinction between legal open burns and certified prescribed burns, and, furthermore, to identify trends by type of burn in the Southeast United States. To that end, we compared statutes, regulations, incentives, and notifications of fire as a forest-management tool among nine states in the US Southeast. We found no steady time trends in number or area of burns among the states for the past decade. A nontrivial proportion of legal open burns, which tend to be smaller burns, are noncertified burns, meaning they meet minimum legal requirements, but not the higher standard required for certified prescribed burns.
A Novel X-Linked Inhibitor of Apoptosis Deficient Variant Showing Attenuated Epstein-Barr Virus Response
Authors: Zhong Youjia , Huang Chiung-Hui , Soe Win Mar , Chan Koon Wing , Isa Mas Suhaila , Soh Jianyi , Yap Mark , MacAry Paul Anthony , Lau Yu-Lung , Chai Louis Yi Ann , Shek Lynette Pei-Chi , Lee Bee Wah
Published: April 2020

We report on 2 Asian siblings with X-linked inhibitor of apoptosis deficiency that arose from a novel deletion that presented with Epstein-Barr virus disease and hemophagocytic lymphohistiocytosis. This disease is ascribed to dysfunction in the nucleotide binding and oligomerization domain receptor pathway, tested using a modified muramyl dipeptide–mediated assay.
Splenic abscess after arterial embolization: a rare cause of acute abdomen
Authors: Moyon C Miguel A , Molina Gabriel A , Valencia S Alexandra , Basantes Veronica M , Mecias R Alejandro , Parra Ruben , Yunga Diego R
Published: April 2020

Splenic abscess is a rare disease and a diagnostic challenge for the medical team. Attributable to its high mortality, prompt diagnosis and treatment are essential. A high degree of clinical awareness is required in conjunction with aggressive treatment, as misleading symptoms may delay treatment and worsen the patient’s prognosis. The management of splenic abscess is based on medical therapy, antibiotics and splenectomy or percutaneous drainage. We present the case of a 58-year-old patient presented with a splenic abscess after arterial embolization. He underwent surgery and completely recovered.
Meningioma infiltrating into porous polymethylmethacrylate cranioplasty—report of a unique case
Authors: Schebesch Karl-Michael , Proescholdt Martin , Schmidt Nils Ole , Höhne Julius
Published: April 2020

Implantation of a cranioplasty after osteoclastic craniotomy or craniectomy is one of the most common neurosurgical procedures, and polymethylmethacrylate (PMMA) is one of the most frequently applied materials for cranioplasty. This report describes the unique case of a patient with recurrent transitional meningioma WHO I that infiltrated the PMMA cranioplasty 7 years after primary surgery. We propose to restrict the use of porous PMMA as cranioplasty after the removal of convexity meningioma.
Thoracoabdominal resection of giant malignant esophageal solitary fibrous tumor
Authors: Jacob Samuel , Carroll Nels Davis , El-Sayed Ahmed Magdy M , Attia Steven , “Jim” Zhai Qihui , Bower Steven P , Makey Ian A
Published: April 2020

Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm. It usually originates from the parietal pleura. SFT originating from the esophagus is exceedingly rare and even more so as a malignancy. We report a 57-year-old patient with a malignant 18 cm SFT of the esophagus that was treated with esophagectomy through a left thoracoabdominal incision. We discuss his surgical and oncologic management.
Homeobox transcription factor OsZHD2 promotes root meristem activity in rice by inducing ethylene biosynthesis
Authors: Yoon Jinmi , Cho Lae-Hyeon , Yang Wenzhu , Pasriga Richa , Wu Yunfei , Hong Woo-Jong , Bureau Charlotte , Wi Soo Jin , Zhang Tao , Wang Rongchen , Zhang Dabing , Jung Ki-Hong , Park Ky Young , Périn Christophe , Zhao Yunde , An Gynheung
Published: April 2020

Root meristem activity is the most critical process influencing root development. Although several factors that regulate meristem activity have been identified in rice, studies on the enhancement of meristem activity in roots are limited. We identified a T-DNA activation tagging line of a zinc-finger homeobox gene, OsZHD2, which has longer seminal and lateral roots due to increased meristem activity. The phenotypes were confirmed in transgenic plants overexpressing OsZHD2. In addition, the overexpressing plants showed enhanced grain yield under low nutrient and paddy field conditions. OsZHD2 was preferentially expressed in the shoot apical meristem and root tips. Transcriptome analyses and quantitative real-time PCR experiments on roots from the activation tagging line and the wild type showed that genes for ethylene biosynthesis were up-regulated in the activation line. Ethylene levels were higher in the activation lines compared with the wild type. ChIP assay results suggested that OsZHD2 induces ethylene biosynthesis by controlling ACS5 directly. Treatment with ACC (1-aminocyclopropane-1-carboxylic acid), an ethylene precursor, induced the expression of the DR5 reporter at the root tip and stele, whereas treatment with an ethylene biosynthesis inhibitor, AVG (aminoethoxyvinylglycine), decreased that expression in both the wild type and the OsZHD2 overexpression line. These observations suggest that OsZHD2 enhances root meristem activity by influencing ethylene biosynthesis and, in turn, auxin.
The efficiency of dust trapping in ringed protoplanetary discs
Authors: Rosotti Giovanni P , Teague Richard , Dullemond Cornelis , Booth Richard A , Clarke Cathie J
Published: April 2020

When imaged at high resolution, many protoplanetary discs show gaps and rings in their dust sub-mm continuum emission profile. These structures are widely considered to originate from local maxima in the gas pressure profile. The properties of the underlying gas structures are however unknown. In this paper, we present a method to measure the dust–gas coupling α/St and the width of the gas pressure bumps affecting the dust distribution, applying high-precision techniques to extract the gas rotation curve from emission line data cubes. As a proof of concept, we then apply the method to two discs with prominent substructure, HD 163296 and AS 209. We find that in all cases the gas structures are larger than in the dust, confirming that the rings are pressure traps. Although the grains are sufficiently decoupled from the gas to be radially concentrated, we find that the degree of coupling of the dust is relatively good (α/St ∼ 0.1). We can therefore reject scenarios in which the disc turbulence is very low and the dust has grown significantly. If we further assume that the dust grain sizes are set by turbulent fragmentation, we find high values of the α turbulent parameter (α ∼ 10−2). Alternatively, solutions with smaller turbulence are still compatible with our analysis if another process is limiting grain growth. For HD 163296, recent measurements of the disc mass suggest that this is the case if the grain size is 1 mm. Future constraints on the dust spectral indices will help to discriminate between the two alternatives.
Galactic population of black holes in detached binaries with low-mass stripped helium stars: the case of LB-1 (LS V+22 25)
Authors: Yungelson L R , Kuranov A G , Postnov K A , Kolesnikov D A
Published: April 2020

We model the Galactic population of detached binaries that harbour black holes with 0.5–1.7 M⊙ companions – remnants of case B mass exchange that rapidly cross Hertzsprung gap after the termination of the Roche lobe overflow or as He-shell burning stars. Several such binaries can be currently present in the Galaxy. The range of MBH in them is about 4–10 M⊙, and the orbital periods are tens to hundreds of days. The unique black hole binary LB-1 fits well into this extremely rare class of double stars.
BIOMEX: an interactive workflow for (single cell) omics data interpretation and visualization
Authors: Taverna Federico , Goveia Jermaine , Karakach Tobias K , Khan Shawez , Rohlenova Katerina , Treps Lucas , Subramanian Abhishek , Schoonjans Luc , Dewerchin Mieke , Eelen Guy , Carmeliet Peter
Published: April 2020

The amount of biological data, generated with (single cell) omics technologies, is rapidly increasing, thereby exacerbating bottlenecks in the data analysis and interpretation of omics experiments. Data mining platforms that facilitate non-bioinformatician experimental scientists to analyze a wide range of experimental designs and data types can alleviate such bottlenecks, aiding in the exploration of (newly generated or publicly available) omics datasets. Here, we present BIOMEX, a browser-based software, designed to facilitate the Biological Interpretation Of Multi-omics EXperiments by bench scientists. BIOMEX integrates state-of-the-art statistical tools and field-tested algorithms into a flexible but well-defined workflow that accommodates metabolomics, transcriptomics, proteomics, mass cytometry and single cell data from different platforms and organisms. The BIOMEX workflow is accompanied by a manual and video tutorials that provide the necessary background to navigate the interface and get acquainted with the employed methods. BIOMEX guides the user through omics-tailored analyses, such as data pretreatment and normalization, dimensionality reduction, differential and enrichment analysis, pathway mapping, clustering, marker analysis, trajectory inference, meta-analysis and others. BIOMEX is fully interactive, allowing users to easily change parameters and generate customized plots exportable as high-quality publication-ready figures. BIOMEX is open source and freely available at https://www.vibcancer.be/software-tools/biomex.
Dengue virus targets RBM10 deregulating host cell splicing and innate immune response
Authors: Pozzi Berta , Bragado Laureano , Mammi Pablo , Torti María Florencia , Gaioli Nicolás , Gebhard Leopoldo G , García Solá Martín E , Vaz-Drago Rita , Iglesias Néstor G , García Cybele C , Gamarnik Andrea V , Srebrow Anabella
Published: April 2020

RNA-seq experiments previously performed by our laboratories showed enrichment in intronic sequences and alterations in alternative splicing in dengue-infected human cells. The transcript of the SAT1 gene, of well-known antiviral action, displayed higher inclusion of exon 4 in infected cells, leading to an mRNA isoform that is degraded by non-sense mediated decay. SAT1 is a spermidine/spermine acetyl-transferase enzyme that decreases the reservoir of cellular polyamines, limiting viral replication. Delving into the molecular mechanism underlying SAT1 pre-mRNA splicing changes upon viral infection, we observed lower protein levels of RBM10, a splicing factor responsible for SAT1 exon 4 skipping. We found that the dengue polymerase NS5 interacts with RBM10 and its sole expression triggers RBM10 proteasome-mediated degradation. RBM10 over-expression in infected cells prevents SAT1 splicing changes and limits viral replication, while its knock-down enhances the splicing switch and also benefits viral replication, revealing an anti-viral role for RBM10. Consistently, RBM10 depletion attenuates expression of interferon and pro-inflammatory cytokines. In particular, we found that RBM10 interacts with viral RNA and RIG-I, and even promotes the ubiquitination of the latter, a crucial step for its activation. We propose RBM10 fulfills diverse pro-inflammatory, anti-viral tasks, besides its well-documented role in splicing regulation of apoptotic genes.
Characterization of long G4-rich enhancer-associated genomic regions engaging in a novel loop:loop ‘G4 Kissing’ interaction
Authors: Williams Jonathan D , Houserova Dominika , Johnson Bradley R , Dyniewski Brad , Berroyer Alexandra , French Hannah , Barchie Addison A , Bilbrey Dakota D , Demeis Jeffrey D , Ghee Kanesha R , Hughes Alexandra G , Kreitz Naden W , McInnis Cameron H , Pudner Susanna C , Reeves Monica N , Stahly Ashlyn N , Turcu Ana , Watters Brianna C , Daly Grant T , Langley Raymond J , Gillespie Mark N , Prakash Aishwarya , Larson Erik D , Kasukurthi Mohan V , Huang Jingshan , Jinks-Robertson Sue , Borchert Glen M
Published: April 2020

Mammalian antibody switch regions (∼1500 bp) are composed of a series of closely neighboring G4-capable sequences. Whereas numerous structural and genome-wide analyses of roles for minimal G4s in transcriptional regulation have been reported, Long G4-capable regions (LG4s)—like those at antibody switch regions—remain virtually unexplored. Using a novel computational approach we have identified 301 LG4s in the human genome and find LG4s prone to mutation and significantly associated with chromosomal rearrangements in malignancy. Strikingly, 217 LG4s overlap annotated enhancers, and we find the promoters regulated by these enhancers markedly enriched in G4-capable sequences suggesting G4s facilitate promoter-enhancer interactions. Finally, and much to our surprise, we also find single-stranded loops of minimal G4s within individual LG4 loci are frequently highly complementary to one another with 178 LG4 loci averaging >35 internal loop:loop complements of >8 bp. As such, we hypothesized (then experimentally confirmed) that G4 loops within individual LG4 loci directly basepair with one another (similar to characterized stem–loop kissing interactions) forming a hitherto undescribed, higher-order, G4-based secondary structure we term a ‘G4 Kiss or G4K’. In conclusion, LG4s adopt novel, higher-order, composite G4 structures directly contributing to the inherent instability, regulatory capacity, and maintenance of these conspicuous genomic regions.
Comaneci-Assisted Coiling as a Treatment Option for Acutely Ruptured Wide Neck Cerebral Aneurysm: Case Series of 118 Patients
Authors: Sirakov Alexander , Minkin Krasimir , Penkov Marin , Ninov Kristian , Karakostov Vasil , Sirakov Stanimir
Published: April 2020

Background

Wide-necked cerebral aneurysms in the setting of acute subarachnoid hemorrhage (SAH) remain difficult to treat with endovascular methods despite recent progress in the neuroendovascular field.

Objective

To evaluate the effectiveness and safety of the Comaneci device (Rapid Medical, Israel) in endovascular coil embolization of acutely ruptured, wide-necked sidewall, or bifurcation cerebral aneurysms.

Methods

We retrospectively reviewed 45 anterior communicating artery, 24 internal carotid artery, 21 middle cerebral artery bifurcation, 15 anterior cerebral artery, and 13 posterior circulation aneurysms, which were treated using Comaneci-assisted coil embolization from August 2017 to January 2019. We evaluated procedural complications, clinical outcomes, and mid-term angiographic follow-up. Immediate and 90 d-clinical outcome and radiological follow-up were obtained in all patients.

Results

Comaneci-assisted coil embolization was performed in 118 acutely ruptured aneurysms. The technique was carried out successfully in all cases. Simultaneous application of 2 separated Comaneci devices was performed in 8/118 cases (6.77%). Periprocedural thromboembolic complications related to the device were seen in 7/118 cases (5.93%) and severe vasospasm of the parent artery after manipulation of the Comaneci device occurred in 5/118 cases (4.2%). The procedural-related morbidity rate was 2.54%, and there was no procedural related mortality. Among the available survivors, angiographic follow-ups were obtained at 3 and 6 mo, and complete aneurysmal obliteration was confirmed in 81/112 (72.3%) and 75/112 (66.9%) cases, respectively. Mid-term follow-up reviewed total recanalization rate of 14.28%.

Conclusion

Comaneci-assisted embolization of wide-necked intracranial aneurysms in patients presenting with acute SAH is associated with high procedural safety and adequate occlusion rates. Furthermore, dual antiplatelet therapy can be safely avoided in this patient group.
Correlating the electronic structures of metallic/semiconducting MoTe2 interface to its atomic structures
Authors: Han Bo , Yang Chen , Xu Xiaolong , Li Yuehui , Shi Ruochen , Liu Kaihui , Wang Haicheng , Ye Yu , Lu Jing , Yu Dapeng , Gao Peng
Published: April 2020

Contact interface properties are important in determining the performances of devices that are based on atomically thin two-dimensional (2D) materials, especially for those with short channels. Understanding the contact interface is therefore important to design better devices. Herein, we use scanning transmission electron microscopy, electron energy loss spectroscopy, and first-principles calculations to reveal the electronic structures within the metallic (1T′)-semiconducting (2H) MoTe2 coplanar phase boundary across a wide spectral range and correlate its properties to atomic structures. We find that the 2H-MoTe2 excitonic peaks cross the phase boundary into the 1T′ phase within a range of approximately 150 nm. The 1T′-MoTe2 crystal field can penetrate the boundary and extend into the 2H phase by approximately two unit-cells. The plasmonic oscillations exhibit strong angle dependence, that is a red-shift of π+σ (approximately 0.3–1.2 eV) occurs within 4 nm at 1T′/2H-MoTe2 boundaries with large tilt angles, but there is no shift at zero-tilted boundaries. These atomic-scale measurements reveal the structure–property relationships of the 1T′/2H-MoTe2 boundary, providing useful information for phase boundary engineering and device development based on 2D materials.
The Gay Cake Case: What the Supreme Court Did, and Didn’t, Decide in Ashers
Authors: McCrudden Christopher
Published: April 2020

The Supreme Court got it right in the Ashers (‘Gay cake’) case. It decided correctly the important legal issues central to the case: the scope of indissociability; the scope of ‘associative’ discrimination in sexual orientation goods and services discrimination claims; whose characteristics are relevant for determining whether an action amounts to unlawful discrimination; and the extent of the protection which freedom of expression accords individual service providers and companies from ‘forced’ or ‘compelled’ political and religious expression. Much of the critical commentary that followed the case is overblown. In some respects, the case is somewhat less legally significant, and less legally controversial, than the commentary would suggest. Underlying some of the resistance to the decision is a sense that the Court should have manipulated the legal test of unlawful discrimination to reach a morally satisfying result. This is not how the Court should decide such cases, leading as it does to a severe rupture with the idea of legality and the Rule of Law. In any event, the three (moral) arguments that are drawn on—dignity, equality, and conscience-scepticism—are less helpful that might appear in addressing Ashers-type cases, and do not undermine the normative foundations of the Supreme Court's decision.
ALMA CO observations of a giant molecular cloud in M 33: Evidence for high-mass star formation triggered by cloud–cloud collisions
Authors: Sano Hidetoshi , Tsuge Kisetsu , Tokuda Kazuki , Muraoka Kazuyuki , Tachihara Kengo , Yamane Yumiko , Kohno Mikito , Fujita Shinji , Enokiya Rei , Rowell Gavin , Maxted Nigel , Filipović Miroslav D , Knies Jonathan , Sasaki Manami , Onishi Toshikazu , Plucinsky Paul P , Fukui Yasuo
Published: April 2020

We report the first evidence for high-mass star formation triggered by collisions of molecular clouds in M 33. Using the Atacama Large Millimeter/submillimeter Array, we spatially resolved filamentary structures of giant molecular cloud 37 in M 33 using 12CO(J = 2–1), 13CO(J = 2–1), and C18O(J = 2–1) line emission at a spatial resolution of ∼2 pc. There are two individual molecular clouds with a systematic velocity difference of ∼6 km s−1. Three continuum sources representing up to ∼10 high-mass stars with spectral types of B0V–O7.5V are embedded within the densest parts of molecular clouds bright in the C18O(J = 2–1) line emission. The two molecular clouds show a complementary spatial distribution with a spatial displacement of ∼6.2 pc, and show a V-shaped structure in the position–velocity diagram. These observational features traced by CO and its isotopes are consistent with those in high-mass star-forming regions created by cloud–cloud collisions in the Galactic and Magellanic Cloud H ii regions. Our new finding in M 33 indicates that cloud–cloud collision is a promising process for triggering high-mass star formation in the Local Group.
Symplasmic Isolation Contributes to Somatic Embryo Induction and Development in the Tree Fern Cyathea delgadii Sternb
Authors: Grzyb Małgorzata , Wróbel-Marek Justyna , Kurczyńska Ewa , Sobczak Mirosław , Mikuła Anna
Published: April 2020

In this report, we describe studies on symplasmic communication and cellular rearrangement during direct somatic embryogenesis (SE) in the tree fern Cyathea delgadii. We analyzed changes in the symplasmic transport of low-molecular-weight fluorochromes, such as 8-hydroxypyrene-1,3,6-trisulfonic acid, trisodium salt (HPTS) and fluorescein (delivered to cells as fluorescein diacetate, FDA), within stipe explants and somatic embryos originating from single epidermal cells and developing during 16-d long culture. Induction of SE is preceded by a restriction in fluorochrome distribution between certain explant cells. Microscopic analysis showed a series of cellular changes like a decrease in vacuole size, increase in vacuole numbers, and increased density of cytoplasm and deposition of electron-dense material in cell walls that may be related with embryogenic transition. In somatic embryos, the limited symplasmic communication between cells was observed first in linear tri-cellular embryos. Further development of the fern embryo was associated with the formation of symplasmic domains corresponding to the four segments of the plant body. Using symplasmic tracers, we provided evidence that the changes in plasmodesmata permeability are corelated with somatic-to-embryogenic transition and somatic embryo development.
On the rotator Hamiltonian for the SU (N) × SU (N) sigma model in the delta regime
Authors: Balog J , Niedermayer F , Weisz P
Published: April 2020

We investigate some properties of the standard rotator approximation of the $\mathrm{SU}(N)\times\mathrm{SU}(N)$ sigma-model in the delta regime. In particular, we show that the isospin susceptibility calculated in this framework agrees with that computed by chiral perturbation theory up to next-to-next-to-leading order in the limit $\ell=L_t/L\to\infty$. The difference between the results involves terms vanishing like $1/\ell$, plus terms vanishing exponentially with $\ell$. As we have previously shown for the O($n$) model, this deviation can be described by a correction to the rotator spectrum proportional to the square of the quadratic Casimir invariant. Here we confront this expectation with analytic nonperturbative results on the spectrum in two dimensions for $N=3$.