bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arylsulfatase A, a genetic modifier of Parkinson’s disease, is an α-synuclein chaperone
Authors: Lee Jun Sung , Kanai Kazuaki , Suzuki Mari , Kim Woojin S , Yoo Han Soo , Fu YuHong , Kim Dong-Kyu , Jung Byung Chul , Choi Minsun , Oh Kyu Won , Li Yuanzhe , Nakatani Mitsuyoshi , Nakazato Tomoko , Sekimoto Satoko , Funayama Manabu , Yoshino Hiroyo , Kubo Shin-ichiro , Nishioka Kenya , Sakai Ryusuke , Ueyama Morio , Mochizuki Hideki , Lee He-Jin , Sardi Sergio Pablo , Halliday Glenda M , Nagai Yoshitaka , Lee Phil Hyu , Hattori Nobutaka , Lee Seung-Jae 
Published: July 2019

AbstractMutations in lysosomal genes increase the risk of neurodegenerative diseases, as is the case for Parkinson’s disease. Here, we found that pathogenic and protective mutations in arylsulfatase A (ARSA), a gene responsible for metachromatic leukodystrophy, a lysosomal storage disorder, are linked to Parkinson’s disease. Plasma ARSA protein levels were changed in Parkinson’s disease patients. ARSA deficiency caused increases in α-synuclein aggregation and secretion, and increases in α-synuclein propagation in cells and nematodes. Despite being a lysosomal protein, ARSA directly interacts with α-synuclein in the cytosol. The interaction was more extensive with protective ARSA variant and less with pathogenic ARSA variant than wild-type. ARSA inhibited the in vitro fibrillation of α-synuclein in a dose-dependent manner. Ectopic expression of ARSA reversed the α-synuclein phenotypes in both cell and fly models of synucleinopathy, the effects correlating with the extent of the physical interaction between these molecules. Collectively, these results suggest that ARSA is a genetic modifier of Parkinson’s disease pathogenesis, acting as a molecular chaperone for α-synuclein.
Why Appoint a Weak Mediator? A Strategic Choice to Reduce Uncertainty in International Mediation
Authors: Chen Yiyi 
Published: July 2019

Abstract
Existing research on mediation finds that mediation by a strong mediator is both more prevalent and more conducive to a negotiated settlement. However, why disputants select a weak mediator remains unclear. From the perspective of the uncertainty mechanism, the nature of mediation is a procedure for sharing private information and reducing disputants’ uncertainty regarding the resolve to continue fighting. Disputants can benefit from mediation through gaining a comparative advantage regarding uncertainty by focusing on either controlling the sharing of their own information or increasing their opponents’ sharing of information. With regard to these two strategic choices, this article argues that the selection of a weak mediator is more likely when disputants prefer controlling the sharing of their information to expanding their opponents’ information sharing. Correspondingly, three potential factors that influence the disputants’ strategic choice of gaining a comparative advantage regarding uncertainty are applied, namely, a previous mediation in the dispute; the dispute’s level of hostility; and the power disparity between the disputants. The author compiles data from the International Crisis Behaviour (ICB, 1918–2015) data set and the International Conflict Management (ICM, 1945–2003) data set for the empirical analysis. The results show that mediation by a weak mediator is more likely when it is the first time that the disputants have submitted to mediation in the dispute and when the dispute’s level of hostility is low. In some cases, a large power disparity between the disputants also makes the selection of a weak mediator more likely.
Inhibition of pro-inflammatory myeloid cell responses by short-term S100A9 blockade improves cardiac function after myocardial infarction
Authors: Marinković Goran , Grauen Larsen Helena , Yndigegn Troels , Szabo Istvan Adorjan , Mares Razvan Gheorghita , de Camp Lisa , Weiland Matthew , Tomas Lukas , Goncalves Isabel , Nilsson Jan , Jovinge Stefan , Schiopu Alexandru 
Published: July 2019

AbstractAimsNeutrophils have both detrimental and beneficial effects in myocardial infarction (MI), but little is known about the underlying pathways. S100A8/A9 is a pro-inflammatory alarmin abundantly expressed in neutrophils that is rapidly released in the myocardium and circulation after myocardial ischaemia. We investigated the role of S100A8/A9 in the innate immune response to MI.Methods and resultsIn 524 patients with acute coronary syndrome (ACS), we found that high plasma S100A8/A9 at the time of the acute event was associated with lower left ventricular ejection fraction (EF) at 1-year and increased hospitalization for heart failure (HF) during follow-up. In wild-type C57BL/6 mice with MI induced by permanent coronary artery ligation, treatment with the S100A9 blocker ABR-238901 during the inflammatory phase of the immune response inhibited haematopoietic stem cell proliferation and myeloid cell egression from the bone marrow. The treatment reduced the numbers of neutrophils and monocytes/macrophages in the myocardium, promoted an anti-inflammatory environment, and significantly improved cardiac function compared with MI controls. To mimic the clinical scenario, we further confirmed the effects of the treatment in a mouse model of ischaemia/reperfusion. Compared with untreated mice, 3-day ABR-238901 treatment significantly improved left ventricular EF (48% vs. 35%, P = 0.002) and cardiac output (15.7 vs. 11.1 mL/min, P = 0.002) by Day 21 post-MI.ConclusionShort-term S100A9 blockade inhibits inflammation and improves cardiac function in murine models of MI. As an excessive S100A8/A9 release is linked to incident HF, S100A9 blockade might represent a feasible strategy to improve prognosis in ACS patients.
Interannual comparison of core taxa and community composition of the blow microbiota from East Australian humpback whales
Authors: Vendl C , Ferrari B C , Thomas T , Slavich E , Zhang E , Nelson T , Rogers T 
Published: July 2019

ABSTRACTCetacean represent vulnerable species impacted by multiple stressors, including reduction in prey species, habitat destruction, whaling and infectious disease. The composition of blow microbiota has been claimed to provide a promising tool for non-invasive health monitoring aiming to inform conservation management. Still, little is known about the temporal stability and composition of blow microbiota in whales. We used East Australian humpback whales (Megaptera novaeangliae) as a model species and collected blow and control samples in August 2016 and 2017 for an interannual comparison. We analysed the blow by barcode tag sequencing of the bacterial 16S rRNA gene. We found that the microbial communities in 2016 and 2017 were statistically similar regarding alpha and beta diversity but distinct to seawater. Zero-radius operational taxonomic units (zOTUs) shared by both groups accounted for about 50% of all zOTUs present. Still, the large individual variability in the blow microbiota resulted in a small number of core taxa (defined as present in at least 60% of whales). We conclude that the blow microbiota of humpback whales is either generally limited and of transient nature or the reduced airway microbiota is the symptom of a compromised physiological state potentially due to the challenges of the whales‘ annual migration.
Is the long-term decline in cardiovascular-disease mortality in high-income countries over? Evidence from national vital statistics
Authors: Lopez Alan D , Adair Tim 
Published: July 2019

Abstract

Background
The substantial decline in cardiovascular-disease (CVD) mortality in high-income countries has underpinned their increasing longevity over the past half-century. However, recent evidence suggests this long-term decline may have stagnated, and even reversed in younger populations. We assess recent CVD-mortality trends in high-income populations and discuss the findings in relation to trends in risk factors.

Methods
We used vital statistics since 2000 for 23 high-income countries published in the World Health Organization Mortality Database. Age-standardized CVD death rates by sex for all ages, and at ages 35–74 years, were calculated and smoothed using LOWESS regression. Findings were contrasted with the Global Burden of Disease (GBD) Study.

Results
The rate of decline in CVD mortality has slowed considerably in most countries in recent years for both males and females, particularly at ages 35–74 years. Based on the latest year of data, the decline in the CVD-mortality rate at ages 35–74 years was &lt;2% (about half the annual average since 2000) for at least one sex in more than half the countries. In North America (US males and females, Canada females), the CVD-mortality rate even increased in the most recent year. The GBD Study estimates, after correcting for misdiagnoses, suggest an even more alarming reversal, with CVD death rates rising in seven countries for at least one sex in 2017. The rate of decline and initial level of CVD mortality appear largely unrelated.

Conclusions
A significant slowdown in CVD-mortality decline is now apparent across high-income countries with diverse epidemiological environments. High and increasing obesity levels, limited potential future gains from further reducing already low smoking prevalence, especially in English-speaking countries, and persistent inequalities in mortality risk pose significant challenges for public policy to promote better cardiovascular health.
Evidence synthesis for constructing directed acyclic graphs (ESC-DAGs): a novel and systematic method for building directed acyclic graphs
Authors: Ferguson Karl D , McCann Mark , Katikireddi Srinivasa Vittal , Thomson Hilary , Green Michael J , Smith Daniel J , Lewsey James D 
Published: July 2019

Abstract

Background
Directed acyclic graphs (DAGs) are popular tools for identifying appropriate adjustment strategies for epidemiological analysis. However, a lack of direction on how to build them is problematic. As a solution, we propose using a combination of evidence synthesis strategies and causal inference principles to integrate the DAG-building exercise within the review stages of research projects. We demonstrate this idea by introducing a novel protocol: ‘Evidence Synthesis for Constructing Directed Acyclic Graphs’ (ESC-DAGs)’.

Methods
ESC-DAGs operates on empirical studies identified by a literature search, ideally a novel systematic review or review of systematic reviews. It involves three key stages: (i) the conclusions of each study are ‘mapped’ into a DAG; (ii) the causal structures in these DAGs are systematically assessed using several causal inference principles and are corrected accordingly; (iii) the resulting DAGs are then synthesised into one or more ‘integrated DAGs’. This demonstration article didactically applies ESC-DAGs to the literature on parental influences on offspring alcohol use during adolescence.

Conclusions
ESC-DAGs is a practical, systematic and transparent approach for developing DAGs from background knowledge. These DAGs can then direct primary data analysis and DAG-based sensitivity analysis. ESC-DAGs has a modular design to allow researchers who are experienced DAG users to both use and improve upon the approach. It is also accessible to researchers with limited experience of DAGs or evidence synthesis.
Bi-Halfspace and Convex Hull Theorems for Translating Solitons
Authors: Chini Francesco , Møller Niels Martin 
Published: July 2019

AbstractWhile it is well known from examples that no interesting “halfspace theorem” holds for properly immersed $n$-dimensional self-translating mean curvature flow solitons in Euclidean space $\mathbb {R}^{n+1}$, we show that they must all obey a general “bi-halfspace theorem” (aka “wedge theorem”): two transverse vertical halfspaces can never contain the same such hypersurface. The same holds for any infinite end. The proofs avoid the typical methods of nonlinear barrier construction for the approach via distance functions and the Omori–Yau maximum principle. As an application we classify the closed convex hulls of all properly immersed (possibly with compact boundary) $n$-dimensional mean curvature flow self-translating solitons $\Sigma ^n$ in ${\mathbb {R}}^{n+1}$ up to an orthogonal projection in the direction of translation. This list is short, coinciding with the one given by Hoffman–Meeks in 1989 for minimal submanifolds: all of ${\mathbb {R}}^{n}$, halfspaces, slabs, hyperplanes, and convex compacts in ${\mathbb {R}}^{n}$.
Seroprevalence, Risk Factors, and Rodent Reservoirs of Leptospirosis in an Urban Community of Puerto Rico, 2015
Authors: Briskin Emily A , Casanovas-Massana Arnau , Ryff Kyle R , Morales-Estrada Shirley , Hamond Camila , Perez-Rodriguez Nicole M , Benavidez Kathryn M , Weinberger Daniel M , Castro-Arellano Iván , Wunder Elsio A , Sharp Tyler M , Rivera-Garcia Brenda , Ko Albert I 
Published: July 2019

Abstract

Background
The burden of leptospirosis in Puerto Rico remains unclear due to underreporting.

Methods
A cross-sectional survey and rodent trapping was performed in a community within San Juan, Puerto Rico to determine the seroprevalence and risk factors for Leptospira infection. The microscopic agglutination test was used to detect anti-Leptospira antibodies as a marker of previous infection. We evaluated Leptospira carriage by quantitative polymerase chain reaction among rodents trapped at the community site.

Results
Of 202 study participants, 55 (27.2%) had Leptospira agglutinating antibodies. Among the 55 seropositive individuals, antibodies were directed most frequently against serogroups Icterohaemorrhagiae (22.0%) and Autumnalis (10.6%). Of 18 captured rodents, 11 (61.1%) carried pathogenic Leptospira (Leptospira borgpetersenii, 7 and Leptospira interrogans, 2). Four participants showed their highest titer against an isolate obtained from a rodent (serogroup Ballum). Increasing household distance to the canal that runs through the community was associated with decreased risk of infection (odds ratio = 0.934 per 10-meter increase; 95% confidence interval, .952–.992).

Conclusions
There are high levels of Leptospira exposure in an urban setting in Puerto Rico, for which rodents may be an important reservoir for transmission. Our findings indicate that prevention should focus on mitigating risk posed by infrastructure deficiencies such as the canal.
Inferring new relations between medical entities using literature curated term co-occurrences
Authors: Spiro Adam , Fernández García Jonatan , Yanover Chen 
Published: July 2019

Abstract

Objectives
Identifying new relations between medical entities, such as drugs, diseases, and side effects, is typically a resource-intensive task, involving experimentation and clinical trials. The increased availability of related data and curated knowledge enables a computational approach to this task, notably by training models to predict likely relations. Such models rely on meaningful representations of the medical entities being studied. We propose a generic features vector representation that leverages co-occurrences of medical terms, linked with PubMed citations.

Materials and Methods
We demonstrate the usefulness of the proposed representation by inferring two types of relations: a drug causes a side effect and a drug treats an indication. To predict these relations and assess their effectiveness, we applied 2 modeling approaches: multi-task modeling using neural networks and single-task modeling based on gradient boosting machines and logistic regression.

Results
These trained models, which predict either side effects or indications, obtained significantly better results than baseline models that use a single direct co-occurrence feature. The results demonstrate the advantage of a comprehensive representation.

Discussion
Selecting the appropriate representation has an immense impact on the predictive performance of machine learning models. Our proposed representation is powerful, as it spans multiple medical domains and can be used to predict a wide range of relation types.

Conclusion
The discovery of new relations between various medical entities can be translated into meaningful insights, for example, related to drug development or disease understanding. Our representation of medical entities can be used to train models that predict such relations, thus accelerating healthcare-related discoveries.
Effect of exogenous fibrolytic enzymes and ammonia fiber expansion on the fermentation of wheat straw in an artificial rumen system (RUSITEC)1
Authors: Saleem Atef M , Ribeiro Gabriel O , Sanderson Haley , Alipour Daryoush , Brand Tassilo , Hünerberg Martin , Yang Wenzhu Z , Santos Laize V , McAllister Tim A 
Published: July 2019

AbstractThis study investigated the effect of treatment of wheat straw using ammonia fiber expansion (AFEX) and exogenous fibrolytic enzymes (Viscozyme) on fiber digestibility, rumen fermentation, microbial protein synthesis, and microbial populations in an artificial rumen system [Rumen Simulation Technique (RUSITEC)]. Four treatments were assigned to 16 vessels (4 per treatment) in 2 RUSITEC apparatuses in a randomized block design. Treatments were arranged as a 2 × 2 factorial using untreated or AFEX-treated wheat straw with or without exogenous fibrolytic enzymes [0 or 500 μg of protein/g straw dry matter (DM)]. Fibrolytic enzymes were applied to straw, prior to sealing in nylon bags. The concentrate mixture was provided in a separate bag within each fermentation vessel. The RUSITECs were adapted for 8 d and disappearance of DM, neutral detergent fiber (NDF), acid detergent fiber (ADF), and crude protein (CP) was measured after 48 h of incubation. Ammonia fiber expansion increased (P < 0.01) the disappearance of wheat straw DM (69.6 vs. 38.3%), NDF (65.6 vs. 36.8%), ADF (61.4 vs. 36.0%), and CP (68.3 vs. 24.0%). Total dietary DM, organic matter (OM), and NDF disappearance was also increased (P ≤ 0.05) by enzymes. Total microbial protein production was greater (P < 0.01) for AFEX-treated (72.9 mg/d) than untreated straw (63.1 mg/d). Total gas and methane (CH4) production (P < 0.01) were also greater for AFEX-treated wheat straw than untreated straw, with a tendency for total gas to increase (P = 0.06) with enzymes. Ammonia fiber expansion increased (P < 0.01) total volatile fatty acid (VFA) production and the molar proportion of propionate, while it decreased (P < 0.01) acetate and the acetate-to-propionate ratio. The AFEX-treated straw had lower relative quantities of fungi, methanogens, and Fibrobacter succinogenes (P < 0.01) and fewer protozoa (P < 0.01) compared to untreated straw. The pH of fermenters fed AFEX-treated straw was lower (P < 0.01) than those fed untreated straw. Both AFEX (P < 0.01) and enzymes (P = 0.02) decreased xylanase activity. There was an enzyme × straw interaction (P = 0.02) for endoglucanase activity. Enzymes increased endoglucanase activity of AFEX-treated wheat straw, but had no effect on untreated straw. The addition of enzymes lowered the relative abundance of Ruminococcus flavefaciens, but increased F. succinogenes. These results indicate that AFEX increased the ruminal disappearance of wheat straw and improved fermentation and microbial protein synthesis in the RUSITEC.
Towards a Coherent Theory of Panel Recommendations for Expired Measures
Authors: Bhardwaj Prakhar 
Published: July 2019

Abstract
Article 19.1 of the Dispute Settlement Understanding provides that if a measure is found to be inconsistent with a WTO Agreement, the Panel or Appellate Body ‘shall recommend that the Member concerned bring the measure into conformity with the agreement’. However, Panels find themselves in a difficult position when the contested measure has expired during the course of proceedings. Since, on the one hand, the measure which would have ordinarily been recommended to be withdrawn is no longer in existence, but on the other hand, they are under an obligation to issue a recommendation as per Article 19.1. Various rationales of the Panels and the Appellate Body for providing recommendations for expired measures (‘EMRs’) have been inconsistent, ad-hoc and even contradictory. Given the different array of approaches adopted, there is no coherent and integrated theory which can be formulated which tells us when and why EMRs should be provided under Article 19.1. This article seeks to bridge this gap. The article also provides a critical analysis of the questionable recommendations issued by the Panel in India – Import of Iron and Steel Products and provides a more coherent framework to guide Panels’ recommendations in relation to expired measures.
Prostate-specific antigen response patterns during cabazitaxel therapy in patients with metastatic castration-resistant prostate cancer
Authors: Kanao Kent , Ito Toshiki , Takahara Kiyoshi , Ando Ryosuke , Yasui Takahiro , Shiroki Ryoichi , Miyake Hideaki , Sumitomo Makoto 
Published: July 2019

Abstract

Background
The objective of this study was to categorize prostate-specific antigen (PSA) response during cabazitaxel therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) into different patterns and to investigate the prognostic impact of the PSA response patterns.

Methods
We reviewed data from patients with mCRPC who had been treated with cabazitaxel therapy at four institutions belonging to Tokai Urologic Oncology Research Seminar. Patients eligible for this study had received at least three cycles of cabazitaxel treatment at three- or four-week intervals. The PSA response patterns were categorized as primary resistance (PR), response (RE), stabilization (ST), and fluctuating (FL). The overall survival (OS) was compared among the patterns.

Results
Data from a total of 50 patients were analyzed in this study. The number of patients exhibiting PR, RE, ST and FL patterns were 18 (36%), 14 (28%), 12 (24%) and 6 (12%), respectively. The median (95% CI) OS of patients with PR and RE patterns was 10.7 (5.6–15.9) and 14.9 (6.8–23.0) months, respectively, and was not reached for patients with ST and FL patterns. The OS of patients with the FL pattern was significantly better than that of patients with PR (P = 0.012) and RE (P = 0.010) patterns.

Conclusion
There were some patients whose PSA were fluctuating during cabazitaxel therapy in patients with mCRPC. Because the prognosis of such patients was relatively good, the judgment to discontinue the cabazitaxel therapy after PSA rise followed by decrease should be made prudently.
Skeletal Mineralization in Association with Type X Collagen Expression Is an Ancestral Feature for Jawed Vertebrates
Authors: Debiais-Thibaud Mélanie , Simion Paul , Ventéo Stéphanie , Muñoz David , Marcellini Sylvain , Mazan Sylvie , Haitina Tatjana 
Published: July 2019

AbstractIn order to characterize the molecular bases of mineralizing cell evolution, we targeted type X collagen, a nonfibrillar network forming collagen encoded by the Col10a1 gene. It is involved in the process of endochondral ossification in ray-finned fishes and tetrapods (Osteichthyes), but until now unknown in cartilaginous fishes (Chondrichthyes). We show that holocephalans and elasmobranchs have respectively five and six tandemly duplicated Col10a1 gene copies that display conserved genomic synteny with osteichthyan Col10a1 genes. All Col10a1 genes in the catshark Scyliorhinus canicula are expressed in ameloblasts and/or odontoblasts of teeth and scales, during the stages of extracellular matrix protein secretion and mineralization. Only one duplicate is expressed in the endoskeletal (vertebral) mineralizing tissues. We also show that the expression of type X collagen is present in teeth of two osteichthyans, the zebrafish Danio rerio and the western clawed frog Xenopus tropicalis, indicating an ancestral jawed vertebrate involvement of type X collagen in odontode formation. Our findings push the origin of Col10a1 gene prior to the divergence of osteichthyans and chondrichthyans, and demonstrate its ancestral association with mineralization of both the odontode skeleton and the endoskeleton.