bluuebunny/crossref_metadata_2025_split huggingface dataset:
White matter DNA methylation profiling reveals deregulation of HIP1, LMAN2, MOBP, and other loci in multiple system atrophy
Authors: Bettencourt Conceição , Foti Sandrine C. , Miki Yasuo , Botia Juan , Chatterjee Aparajita , Warner Thomas T. , Revesz Tamas , Lashley Tammaryn , Balazs Robert , Viré Emmanuelle , Holton Janice L. 
Published: September 2019

Abstract
Multiple system atrophy (MSA) is a fatal late-onset neurodegenerative disease. Although presenting with distinct pathological hallmarks, which in MSA consist of glial cytoplasmic inclusions (GCIs) containing fibrillar α-synuclein in oligodendrocytes, both MSA and Parkinson’s disease are α-synucleinopathies. Pathologically, MSA can be categorized into striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) or mixed subtypes. Despite extensive research, the regional vulnerability of the brain to MSA pathology remains poorly understood. Genetic, epigenetic and environmental factors have been proposed to explain which brain regions are affected by MSA, and to what extent. Here, we explored for the first time epigenetic changes in post-mortem brain tissue from MSA cases. We conducted a case–control study, and profiled DNA methylation in white mater from three brain regions characterized by severe-to-mild GCIs burden in the MSA mixed subtype (cerebellum, frontal lobe and occipital lobe). Our genome-wide approach using Illumina MethylationEPIC arrays and a powerful cross-region analysis identified 157 CpG sites and 79 genomic regions where DNA methylation was significantly altered in the MSA mixed-subtype cases. HIP1, LMAN2 and MOBP were amongst the most differentially methylated loci. We replicated these findings in an independent cohort and further demonstrated that DNA methylation profiles were perturbed in MSA mixed subtype, and also to variable degrees in the other pathological subtypes (OPCA and SND). Finally, our co-methylation network analysis revealed several molecular signatures (modules) significantly associated with MSA (disease status and pathological subtypes), and with neurodegeneration in the cerebellum. Importantly, the co-methylation module having the strongest association with MSA included a CpG in SNCA, the gene encoding α-synuclein. Altogether, our results provide the first evidence for DNA methylation changes contributing to the molecular processes altered in MSA, some of which are shared with other neurodegenerative diseases, and highlight potential novel routes for diagnosis and therapeutic interventions.
Sensitivity analysis based multi-scale methods of coupled path-dependent problems
Authors: Zupan Nina , Korelc Jože 
Published: September 2019

Abstract
In the paper, a generalized essential boundary condition sensitivity analysis based implementation of $$\text {FE}^2$$FE2 and mesh-in-element (MIEL) multi-scale methods is derived as an alternative to standard implementations of multi-scale analysis, where the calculation of Schur complement of the microscopic tangent matrix is needed for bridging the scales. The paper presents a unified approach to the development of an arbitrary MIEL or $$\text {FE}^2$$FE2 computational scheme for an arbitrary path-dependent material model. Implementation is based on efficient first and second order analytical sensitivity analysis, for which automatic-differentiation-based formulation of essential boundary condition sensitivity analysis is derived. A fully consistently linearized two-level path-following algorithm is introduced as a solution algorithm for the multi-scale modeling. Sensitivity analysis allows each macro step to be followed by an arbitrary number of micro substeps while retaining quadratic convergence of the overall solution algorithm.
Establishing an online physical exercise program for people with hemophilia
Authors: Wagner Barbara , Seuser Axel , Krüger Steffen , Herzig Marie Luca , Hilberg Thomas , Ay Cihan , Hasenöhrl Timothy , Crevenna Richard 
Published: September 2019

SummaryBackgroundHemophilia is a congenital bleeding disorder with an estimated frequency of 1:10,000 births. Repeated joint bleeding is a hallmark of the disorder and leads to painful hemophilic arthropathy. Regular exercise can help improve joint stability and function, reduce the risk of injury and bleeding and improve physical fitness and quality of life. This method paper describes an online training concept aiming to offer access to appropriate exercise instructions for people with hemophilia who are not able to attend regular training at a hemophilia center.MethodsThe online exercise program is accessible through the homepage of the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University Vienna as well as through scanning a QR code printed on information material using a smart phone or tablet.ResultsThe program contains exercises to improve mobility, coordination, muscular strength and flexibility. A brief introduction is given by a hematologist, a pediatrician and a physiatrist. An introductory video informs about contraindications and essential precautions, such as medical attendance and sufficient factor therapy to consider before starting the training. Another video gives advice on the exercise composition. The demonstrated exercises are explained by a physician and are available for adults and children. To individualize training recommendations and offer further diagnostic tools and physical treatment options as necessary, the Department of Physical Medicine, Rehabilitation and Occupational Medicine of the Medical University of Vienna will establish consultation hours for people with hemophilia.ConclusionAs hemophilia is an orphan disease, patients are mainly treated in specialized centers. For patients who live far from these centers or have limited access to a training there for other reasons, the physical medicine consultation hour and the implementation of online exercise instructions offer individually adapted exercise information for a regular home-based training to benefit from increased physical fitness and joint stability.
Influence of chitosan addition on the mechanical and antibacterial properties of carrot cellulose nanofibre film
Authors: Szymańska-Chargot Monika , Chylińska Monika , Pertile Giorgia , Pieczywek Piotr M. , Cieślak Krystian J. , Zdunek Artur , Frąc Magdalena 
Published: September 2019

Abstract
Films of carrot cellulose nanofibrils (CCNFs) with the addition of low-viscosity chitosan (CHIT) were prepared by the vacuum filtration. The chitosan content in the films varied from 9 to 33% (dry wt. basis). The surface morphology of the films was investigated by scanning electron microscopy, and it was found that chitosan was dispersed in the CCNF matrix. The interaction between CCNFs and CHIT was evaluated in terms of Fourier transform infrared spectroscopy (FTIR). The obtained results suggested physical interactions rather than hydrogen bonding between CCNFs and CHIT. This finding also supports the results of the water wettability experiment. The addition of chitosan to the nanocellulose matrix causes an increase in the water contact angle, i.e., the surface of the composites becomes more hydrophobic. This increase is probably connected to an interaction between nanocellulose and chitosan forming a denser structure. Analyses of thermal properties showed that the composites are stable under high temperature, and the degradation occurred above 300 °C. It was found that the addition of CHIT to CCNF matrices caused a decrease in the Young’s modulus—the higher that the concentration of chitosan in the composite was, the lower the Young’s modulus (decreased from 14.71 GPa for CCNFs to 8.76 GPa for CCNF/CHIT_5). Additionally, the tensile strength of composites, i.e., the maximum force that causes a fracture decreased after the addition of chitosan (decreased from 145.83 MPa for CCNFs to 129.43 MPa for CCNF/CHIT_5). The results indicated the highest inhibitory effect of the investigated composites against E. coli and S. epidermidis. Whereas M. luteus was inhibited only by the higher concentration of chitosan in the tested composites, inhibition was not found against C. krissii and all tested filamentous fungi.

Graphic abstract
Photosystem II core quenching in desiccated Leptolyngbya ohadii
Authors: Ranjbar Choubeh Reza , Bar-Eyal Leeat , Paltiel Yossi , Keren Nir , Struik Paul C. , van Amerongen Herbert 
Published: September 2019

Abstract
Cyanobacteria living in the harsh environment of the desert have to protect themselves against high light intensity and prevent photodamage. These cyanobacteria are in a desiccated state during the largest part of the day when both temperature and light intensity are high. In the desiccated state, their photosynthetic activity is stopped, whereas upon rehydration the ability to perform photosynthesis is regained. Earlier reports indicate that light-induced excitations in Leptolyngbya ohadii are heavily quenched in the desiccated state, because of a loss of structural order of the light-harvesting phycobilisome structures (Bar Eyal et al. in Proc Natl Acad Sci 114:9481, 2017) and via the stably oxidized primary electron donor in photosystem I, namely P700+ (Bar Eyal et al. in Biochim Biophys Acta Bioenergy 1847:1267–1273, 2015). In this study, we use picosecond fluorescence experiments to demonstrate that a third protection mechanism exists, in which the core of photosystem II is quenched independently.
Construction of Electrocatalytic and Heat-Resistant Self-Supporting Electrodes for High-Performance Lithium–Sulfur Batteries
Authors: Zhang Xuemei , Wei Yunhong , Wang Boya , Wang Mei , Zhang Yun , Wang Qian , Wu Hao 
Published: September 2019

Abstract
Boosting the utilization efficiency of sulfur electrodes and suppressing the “shuttle effect” of intermediate polysulfides remain the critical challenge for high-performance lithium–sulfur batteries (LSBs). However, most of reported sulfur electrodes are not competent to realize the fast conversion of polysulfides into insoluble lithium sulfides when applied with high sulfur loading, as well as to mitigate the more serious shuttle effect of polysulfides, especially when worked at an elevated temperature. Herein, we reported a unique structural engineering strategy of crafting a unique hierarchical multifunctional electrode architecture constructed by rooting MOF-derived CoS2/carbon nanoleaf arrays (CoS2–CNA) into a nitrogen-rich 3D conductive scaffold (CTNF@CoS2–CNA) for LSBs. An accelerated electrocatalytic effect and improved polysulfide redox kinetics arising from CoS2–CNA were investigated. Besides, the strong capillarity effect and chemisorption of CTNF@CoS2–CNA to polysulfides enable high loading and efficient utilization of sulfur, thus leading to high-performance LIBs performed not only at room temperature but also up to an elevated temperature (55 °C). Even with the ultrahigh sulfur loading of 7.19 mg cm−2, the CTNF@CoS2–CNA/S cathode still exhibits high rate capacity at 55 °C.
The relationship between depressive symptoms and negative symptoms in people with non-affective psychosis: a meta-analysis
Authors: Edwards Clementine Jane , Garety Philippa , Hardy Amy 
Published: September 2019

AbstractThe negative symptoms of psychosis and depressive symptomatology share several features, e.g. low motivation, apathy and reduced activity. Understanding the associations between these two sets of symptoms will support improved assessment and the development of interventions targeting these difficulties in people with psychosis. This is the first large systematic review and meta-analysis to quantify the relationship between these two categories of symptoms, as measured in studies to date. PsycInfo, Embase and Medline were systematically searched to identify eligible studies. Inclusion criteria ensured the studies measured both depression and negative symptoms using validated measures in a sample of over 8000 participants with non-affective psychosis diagnoses. The search led to 2020 records being screened and 56 included in the meta-analysis and review. Both meta-analyses and meta-regressions were conducted to explore the main effect and potential moderating variables. A clear pattern emerges showing that higher ratings of negative symptoms are associated with higher levels of depressive symptoms, with a small effect [standardised effect size = 0.19,p< 0.05). This did not vary greatly with the measures used (SES = 0.19–0.26) and was not moderated by demographic variables or quality ratings. Interestingly, higher depressive symptoms predict a significant relationship with co-occurring negative symptoms. However, higher negative symptoms predict that it is less likely there will be a relationship with co-occurring depressive symptoms. Heterogeneity was high across these analyses. The findings support the adoption of a symptom-specific approach to understanding the interplay between negative and depressive symptoms in psychosis, to improve assessment and intervention.
Genetic heterogeneity in self-reported depressive symptoms identified through genetic analyses of the PHQ-9
Authors: Thorp Jackson G. , Marees Andries T. , Ong Jue-Sheng , An Jiyuan , MacGregor Stuart , Derks Eske M. 
Published: September 2019

AbstractBackgroundDepression is a clinically heterogeneous disorder. Previous large-scale genetic studies of depression have explored genetic risk factors of depression case–control status or aggregated sums of depressive symptoms, ignoring possible clinical or genetic heterogeneity.MethodsWe analyse data from 148 752 subjects of white British ancestry in the UK Biobank who completed nine items of a self-rated measure of current depressive symptoms: the Patient Health Questionnaire (PHQ-9). Genome-Wide Association analyses were conducted for nine symptoms and two composite measures. LD Score Regression was used to calculate SNP-based heritability (h2SNP) and genetic correlations (rg) across symptoms and to investigate genetic correlations with 25 external phenotypes. Genomic structural equation modelling was used to test the genetic factor structure across the nine symptoms.ResultsWe identified nine genome-wide significant genomic loci (8 novel), with no overlap in loci across symptoms. h2SNP ranged from 6% (concentration problems) to 9% (appetite changes). Genetic correlations ranged from 0.54 to 0.96 (all p < 1.39 × 10−3) with 30 of 36 correlations being significantly smaller than one. A two-factor model provided the best fit to the genetic covariance matrix, with factors representing ‘psychological’ and ‘somatic’ symptoms. The genetic correlations with external phenotypes showed large variation across the nine symptoms.ConclusionsPatterns of SNP associations and genetic correlations differ across the nine symptoms, suggesting that current depressive symptoms are genetically heterogeneous. Our study highlights the value of symptom-level analyses in understanding the genetic architecture of a psychiatric trait. Future studies should investigate whether genetic heterogeneity is recapitulated in clinical symptoms of major depression.
On value frameworks and opportunity costs in health technology assessment
Authors: Booth Neill 
Published: September 2019

AbstractObjectivesProceeding from a basic concept underpinning economic evaluation, opportunity cost, this study aims to explain how different approaches to economics diverge quite dramatically in their ideas of what constitutes appropriate valuation, both in principle and practice. Because the concept of opportunity cost does not inherently specify how valuation should be undertaken or specify how appropriate any economic value framework (EVF) might be, the three main economics-based approaches to providing evidence about value for health technology assessment are described.MethodsThis paper describes how the three main EVFs—namely, the extra-welfarist, welfarist, and classical—are most typically understood, applied, and promoted. It then provides clarification and assessment of related concepts and terminology.ResultsAlthough EVFs differ, certain underlying characteristics of valuation were identified as fundamental to all approaches to economic evaluation in practice. The study also suggests that some of the rhetoric and terms employed in relation to the extra-welfarist approach are not wholly justified and, further, that only the welfarist approach ensures adherence to welfare-economic principles. Finally, deliberative analysis, especially when connected with a classical economic approach, can serve as a useful supplement to other analytical approaches.ConclusionsAll three approaches to economic evaluation have something to offer assessment processes, but they all display limitations too. Therefore, the author concludes that the language of economic evaluation should be used with sufficient humility to prevent overselling of EVFs, especially with regard to the qualities of evidence they provide for priority setting processes.
Neo-Expressivism: (Self-)Knowledge, Meaning, and Truth
Authors: Bar-On Dorit 
Published: September 2019

AbstractPhilosophers are often interested in explaining significant contrasts between ordinary descriptive discourses, on the one hand, and discourses – such as ethics, mathematics, or mentalistic discourse – that are thought to be more problematic in various ways. But certain strategies for ‘saving the differences’ can make it too difficult to preserve notable similarities across discourses. My own preference is for strategies that ‘save the differences’ without sacrificing logico-semantic continuities or committing to deflationism about truth, but also without embracing either truth-pluralism or global expressivism.I motivate my preference by examining, as a test case, mentalistic discourse. I begin by reconstructing three philosophical puzzles that have led philosophers to think of mentalistic discourse as problematic (Section 2). These puzzles concern the semantic, epistemological, and metaphysical status of contrasts between first-person present-tense attributions – ‘avowals’ – and all other ordinary contingent attributions. I then briefly present my own,neo-expressiviststrategy for addressing the puzzles (Section 3). Unlike traditional ‘simple expressivism’ (which is the analogue in the mentalistic realm of ethical emotivism), neo-expressivism is not committed to avowals’ being non-truth-apt or having non-propositional meanings. And yet it does not require embracing either deflationism about truth or global expressivism. It preserves continuities between mentalistic and other discourses while allowing us to capture discontinuities. Moreover, it is possible to apply the neo-expressivist framework in other areas where the notion of expression is deemed explanatorily useful, as illustrated by consideringethical neo-expressivism(Section 4). In the final section (5), I make more general comments on truth and meaning and tease out some of the commitments of the approach I advocate.
Palliative care in primary care: European Forum for Primary Care position paper
Authors: Rotar Pavlič Danica , Aarendonk Diederik , Wens Johan , Rodrigues Simões José Augusto , Lynch Marie , Murray Scott 
Published: September 2019

AbstractAim:The aim of this position paper is to assist primary health care (PHC) providers, policymakers, and researchers by discussing the current context in which palliative health care functions within PHC in Europe. The position paper gives examples for improvements to palliative care models from studies and international discussions at European Forum for Primary Care (EFPC) workshops and conferences.Background:Palliative care is a holistic approach that improves the quality of life of patients and their families facing problems associated with terminal illness, through the prevention and relief of suffering by means of early identification and diligent assessment and treatment of pain and other problems, whether physical, psychosocial, or spiritual. Unfortunately, some Europeans, unless they have cancer, still do not have access to generalist or specialist palliative care.Methods:A draft of this position paper was distributed electronically through the EFPC network in 2015, 2016, and 2017. Active collaboration with the representatives of the International Primary Palliative Care Network was established from the very beginning and more recently with the EAPC Primary Care Reference Group. Barriers, opportunities, and examples of good and bad practices were discussed at workshops focusing on palliative care at the international conferences of Southeastern European countries in Ljubljana (2015) and Budva (2017), at regular conferences in Amsterdam (2015) and Riga (2016), at the WONCA Europe conferences in Istanbul (2015), Copenhagen (2016), and Prague (2017), and at the EAPC conference in Madrid (2017).Findings:There is great diversity in the extent and type of palliative care provided in primary care by European countries. Primary care teams (PCTs) are well placed to encourage timely palliative care. We collected examples from different countries. We found numerous barriers influencing PCTs in preparing care plans with patients. We identified many facilitators to improve the organization of palliative care.
Results from a multicenter, noninterventional registry study for multiple myeloma patients who received stem cell mobilization regimens with and without plerixafor
Authors: Morris Curly , Chabannon Christian , Masszi Tamas , Russell Nigel , Nahi Hareth , Kobbe Guido , Krejci Marta , Auner Holger W. , Pohlreich David , Hayden Patrick , Basak Grzegorz W. , Lenhoff Stig , Schaap Nicolaas , van Biezen Anja , Knol Cora , Iacobelli Simona , Liu Qianying , Celanovic Marina , Garderet Laurent , Kröger Nicolaus 
Published: September 2019

Abstract
Plerixafor plus granulocyte-colony stimulating factor (G-CSF) enhances the mobilization of hematopoietic stem cells (HSCs) for collection and subsequent autologous hematopoietic stem cell transplantation (HSCT) in patients with multiple myeloma (MM). This international, multicenter, noninterventional registry study (NCT01362972), evaluated long-term outcomes for MM patients who received plerixafor versus other mobilization regimens. The comparisons were: G-CSF + plerixafor (G-CSF + P) versus G-CSF-; G-CSF + P versus G-CSF + chemotherapy (G-CSF + C); and G-CSF + P + C versus G-CSF + C. Propensity score matching was used to balance groups. Primary outcome measures were progression free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR) after transplantation. After propensity matching, 77 versus 41 patients in the G-CSF + P versus G-CSF cohorts, 129 versus 129 in the G-CSF + P versus G-CSF + C cohorts, and 117 versus 117 in the G-CSF + P + C versus G-CSF + C cohorts were matched, respectively. Propensity score matching resulted in a smaller sample size and imbalances were not completely overcome. For both PFS and OS, the upper limits of the hazard ratio 95% confidence intervals exceeded prespecified boundaries; noninferiority was not demonstrated. CIR rates were higher in the plerixafor cohorts. G-CSF + P remains an option for the mobilization of HSCs in poor mobilizers with MM with no substantial differences in PFS, OS, and CIR in comparison with other regimens.