bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract

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

Abstract
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

Abstract

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

Abstract

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 &gt;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

Abstract

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

Abstract

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

Abstract

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
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractRoot 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

ABSTRACT
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.