bluuebunny/crossref_metadata_2025_split huggingface dataset:
The moving-eigenvalue method: hitting time for Itô processes and moving boundaries
Authors: Nilsson Martin N P 
Published: September 2020

Abstract
We present simple solutions of first-passage and first-exit time problems for general moving boundaries and general Itô processes in one dimension, including diffusion processes with convection. The approach uses eigenfunction expansion, despite the boundary time-variability that, until now, has been an obstacle for spectral methods. The eigenfunction expansion enables the analytical reduction of the problem to a set of equivalent ordinary differential equations, which can be input directly to readily available solvers. The method is thus suitable as a basis for efficient numerical computation. We illustrate the technique by application to Wiener and Ornstein–Uhlenbeck processes for a variety of moving boundaries, including cases for which exact results are known.
Yang–Baxter deformations and generalized supergravity—a short summary
Authors: Orlando Domenico , Reffert Susanne , Sakamoto Jun-ichi , Sekiguchi Yuta , Yoshida Kentaroh 
Published: September 2020

Abstract
Integrable deformations of type IIB superstring theory on AdS5 × S5 have played an important role over the last years. The Yang–Baxter deformation is a systematic way of generating such integrable deformations. Since its introduction, this topic has seen important conceptual progress and has among others led to the intriguing discovery generalized supergravity, a new low-energy effective theory. This review endeavors to not only introduce the historical development of the Yang–Baxter deformation, but also its relation to generalized supergravity, non-geometric backgrounds, non-abelian T-duality and preserved Killing spinors. We supplement the general treatment with a wealth of explicit examples.
Joint separable numerical range and bipartite ultrafine entanglement witnessing
Authors: Wu Pan , Tang Runhua 
Published: September 2020

Abstract
The entanglement witness is an important tool to detect entanglement. In 2017 an idea considering a pair of Hermitian operators in product form was published, which is called ultrafine entanglement witnessing. In 2018 some rigorous results were given. Here we improve their work. First we point this idea can be directly derived from an earlier concept named joint separable numerical range and explain how it works as a series of witnesses. Second by a simple method we present a sufficient condition for an effective pair. Finally we prove this condition is necessary for optimization. [M Gachechiladze et al 2018 J. Phys. A: Math. Theor. 51 36].
Physico chemical and phase separation characterization of high molecular PLLA blended with low molecular PCL obtained from solvent cast processes
Authors: Arbeiter Daniela , Eickner Thomas , Oschatz Stefan , Reske Thomas , Specht Olaf , Teske Michael , Senz Volkmar , Schmitz Klaus-Peter , Grabow Niels 
Published: September 2020

Abstract
Blends of PLLA and PCL yielded by solvent casting usually exhibit phase separation and crystallization behavior which have a strong impact on their suitability for certain biomedical applications such as degradable coatings or drug carriers. Therefore, it is important to understand the underlying mechanisms. In this study, high-molecular biodegradable semi-crystalline poly(L-lactide) (PLLA) (Mw = 320 kDa) was blended with low-molecular biodegradable semi-crystalline poly(ε-caprolactone) (PCL) (Mw = 40 kDa) in various combinations (10, 50 and 90 wt.% PCL) by solvent casting. The yielded blends were subjected to annealing at 40 °C, 80 °C and 200 °C and cooled down slowly to maintain thermodynamic equilibrium. Scanning electron microscopy, atomic force microscopy, Raman images and differential scanning calorimetry were used to investigate the structure, morphology and thermal properties of the solvent cast PLLA/PCL blends. It was shown that the physico-chemical properties of PLLA/PCL blends prepared by solvent casting differ substantially compared to those accessed by melt manufacturing processes. In summary, the blends showed a complex phase separation behavior, which is completely dependent on the method of preparation and the adjusted temperature during production process.
Graphene oxide—Polymethyl methacrylate coatings for Corrosion protection of aerospace aluminium alloy 7075—T651 surfaces
Authors: Aravindh S , Karthikeyan B 
Published: September 2020

Abstract
We report a corrosion study on Al 7075—T651 surface. The purpose of the study is to use Graphene oxide—Polymethyl methacrylate (GO—PMMA) coating as corrosion resistant layer on Al 7075—T651, an alloy of aluminium mainly used in aerospace industries. The study is done with and without GO—PMMA coating on Al 7075—T651 respectively, by varying the exposure time of material (24, 48 and 72 h) with HCl in atmospheric condition. The formation of corrosion is resisted by the GO—PMMA coated samples. The effect is studied by material characterization and non-destructive evaluation (NDE) techniques. The formation of aluminium hydroxide in uncoated samples is confirmed by Raman spectroscopy and x-ray diffraction (XRD). Corrosion formation, GO—PMMA coating on plain and coated samples are clearly visible in Scanning Electron Microscope (SEM) study. Shift in current is observed in I–V Characteristics study, due to pitting in plain samples. Material loss is observed, to be low in GO—PMMA coated samples, using pulsed thermography. The work proves that the GO—PMMA coating is very effective in corrosion resistance.
COGENT: evaluating the consistency of gene co-expression networks
Authors: Bozhilova Lyuba V. , Pardo-Diaz Javier , Reinert Gesine , Deane Charlotte M. 
Published: September 2020

Abstract

Summary
Gene co-expression networks can be constructed in multiple different ways, both in the use of different measures of co-expression, and in the thresholds applied to the calculated co-expression values, from any given dataset. It is often not clear which co-expression network construction method should be preferred. COGENT provides a set of tools designed to aid the choice of network construction method without the need for any external validation data.

Availability and implementation
https://github.com/lbozhilova/COGENT.

Supplementary information
Supplementary information is available at Bioinformatics online.
SomaticTARDBPvariants as a cause of semantic dementia
Authors: van Rooij Jeroen , Mol Merel O , Melhem Shamiram , van der Wal Pelle , Arp Pascal , Paron Francesca , Donker Kaat Laura , Seelaar Harro ,   Netherlands Brain Bank, Miedema Suzanne S M , Oshima Takuya , Eggen Bart J L , Uitterlinden André , van Meurs Joyce , van Kesteren Ronald E , Smit August B , Buratti Emanuele , van Swieten John C 
Published: September 2020

AbstractThe aetiology of late-onset neurodegenerative diseases is largely unknown. Here we investigated whether de novo somatic variants for semantic dementia can be detected, thereby arguing for a more general role of somatic variants in neurodegenerative disease. Semantic dementia is characterized by a non-familial occurrence, early onset (&lt;65 years), focal temporal atrophy and TDP-43 pathology. To test whether somatic variants in neural progenitor cells during brain development might lead to semantic dementia, we compared deep exome sequencing data of DNA derived from brain and blood of 16 semantic dementia cases. Somatic variants observed in brain tissue and absent in blood were validated using amplicon sequencing and digital PCR. We identified two variants in exon one of the TARDBP gene (L41F and R42H) at low level (1–3%) in cortical regions and in dentate gyrus in two semantic dementia brains, respectively. The pathogenicity of both variants is supported by demonstrating impaired splicing regulation of TDP-43 and by altered subcellular localization of the mutant TDP-43 protein. These findings indicate that somatic variants may cause semantic dementia as a non-hereditary neurodegenerative disease, which might be exemplary for other late-onset neurodegenerative disorders.
Serotonergic Innervations of the Orbitofrontal and Medial-prefrontal Cortices are Differentially Involved in Visual Discrimination and Reversal Learning in Rats
Authors: Alsiö Johan , Lehmann Olivia , McKenzie Colin , Theobald David E , Searle Lydia , Xia Jing , Dalley Jeffrey W , Robbins Trevor W 
Published: September 2020

Abstract
Cross-species studies have identified an evolutionarily conserved role for serotonin in flexible behavior including reversal learning. The aim of the current study was to investigate the contribution of serotonin within the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) to visual discrimination and reversal learning. Male Lister Hooded rats were trained to discriminate between a rewarded (A+) and a nonrewarded (B−) visual stimulus to receive sucrose rewards in touchscreen operant chambers. Serotonin was depleted using surgical infusions of 5,7-dihydroxytryptamine (5,7-DHT), either globally by intracebroventricular (i.c.v.) infusions or locally by microinfusions into the OFC or mPFC. Rats that received i.c.v. infusions of 5,7-DHT before initial training were significantly impaired during both visual discrimination and subsequent reversal learning during which the stimulus–reward contingencies were changed (A− vs. B+). Local serotonin depletion from the OFC impaired reversal learning without affecting initial discrimination. After mPFC depletion, rats were unimpaired during reversal learning but slower to respond at the stimuli during all the stages; the mPFC group was also slower to learn during discrimination than the OFC group. These findings extend our understanding of serotonin in cognitive flexibility by revealing differential effects within two subregions of the prefrontal cortex in visual discrimination and reversal learning.
Sustained Responses of Neutralizing Antibodies Against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Recovered Patients and Their Therapeutic Applicability
Authors: Kim Yeon-Sook , Aigerim Abdimadiyeva , Park Uni , Kim Yuri , Park Hyoree , Rhee Ji-Young , Choi Jae-Phil , Park Wan Beom , Park Sang Won , Kim Yeonjae , Lim Dong-Gyun , Choi Ji-Yeob , Jeon Yoon Kyung , Yang Jeong-Sun , Lee Joo-Yeon , Shin Hyoung-Shik , Cho Nam-Hyuk 
Published: September 2020

Abstract

Background
Zoonotic coronaviruses have emerged as a global threat by causing fatal respiratory infections. Given the lack of specific antiviral therapies, application of human convalescent plasma retaining neutralizing activity could be a viable therapeutic option that can bridges this gap.

Methods
We traced antibody responses and memory B cells in peripheral blood collected from 70 recovered Middle East respiratory syndrome coronavirus (MERS-CoV) patients for 3 years after the 2015 outbreak in South Korea. We also used a mouse infection model to examine whether the neutralizing activity of collected sera could provide therapeutic benefit in vivo upon lethal MERS-CoV challenge.

Results
Anti-spike-specific IgG responses, including neutralizing activity and antibody-secreting memory B cells, persisted for up to 3 years, especially in MERS patients who suffered from severe pneumonia. Mean antibody titers gradually decreased annually by less than 2-fold. Levels of antibody responses were significantly correlated with fever duration, viral shedding periods, and maximum viral loads observed during infection periods. In a transgenic mice model challenged with lethal doses of MERS-CoV, a significant reduction in viral loads and enhanced survival was observed when therapeutically treated with human plasma retaining a high neutralizing titer (&gt; 1/5000). However, this failed to reduce pulmonary pathogenesis, as revealed by pathological changes in lungs and initial weight loss.

Conclusions
High titers of neutralizing activity are required for suppressive effect on the viral replication but may not be sufficient to reduce inflammatory lesions upon fatal infection. Therefore, immune sera with high neutralizing activity must be carefully selected for plasma therapy of zoonotic coronavirus infection.
External validation of prognostic models: what, why, how, when and where?
Authors: Ramspek Chava L , Jager Kitty J , Dekker Friedo W , Zoccali Carmine , van Diepen Merel 
Published: September 2020

Abstract
Prognostic models that aim to improve the prediction of clinical events, individualized treatment and decision-making are increasingly being developed and published. However, relatively few models are externally validated and validation by independent researchers is rare. External validation is necessary to determine a prediction model’s reproducibility and generalizability to new and different patients. Various methodological considerations are important when assessing or designing an external validation study. In this article, an overview is provided of these considerations, starting with what external validation is, what types of external validation can be distinguished and why such studies are a crucial step towards the clinical implementation of accurate prediction models. Statistical analyses and interpretation of external validation results are reviewed in an intuitive manner and considerations for selecting an appropriate existing prediction model and external validation population are discussed. This study enables clinicians and researchers to gain a deeper understanding of how to interpret model validation results and how to translate these results to their own patient population.
Adoptive transfer of CX3CR1 transduced-T regulatory cells improves homing to the atherosclerotic plaques and dampens atherosclerosis progression
Authors: Bonacina Fabrizia , Martini Elisa , Svecla Monika , Nour Jasmine , Cremonesi Marco , Beretta Giangiacomo , Moregola Annalisa , Pellegatta Fabio , Zampoleri Veronica , Catapano Alberico Luigi , Kallikourdis Marinos , Norata Giuseppe Danilo 
Published: September 2020

Abstract

Aim
Loss of immunosuppressive response supports inflammation during atherosclerosis. We tested whether adoptive cell therapy (ACT) with Tregulatory cells (Tregs), engineered to selectively migrate in the atherosclerotic plaque, would dampen the immune-inflammatory response in the arterial wall in animal models of familial hypercholesterolaemia (FH).

Methods and results
FH patients presented a decreased Treg suppressive function associated to an increased inflammatory burden. A similar phenotype was observed in Ldlr −/− mice accompanied by a selective increased expression of the chemokine CX3CL1 in the aorta but not in other districts (lymph nodes, spleen, and liver). Treg overexpressing CX3CR1 were thus generated (CX3CR1+-Tregs) to drive Tregs selectively to the plaque. CX3CR1+-Tregs were injected (i.v.) in Ldlr −/− fed high-cholesterol diet (western type diet, WTD) for 8 weeks. CX3CR1+-Tregs were detected in the aorta, but not in other tissues, of Ldlr −/− mice 24 h after ACT, corroborating the efficacy of this approach. After 4 additional weeks of WTD, ACT with CX3CR1+-Tregs resulted in reduced plaque progression and lipid deposition, ameliorated plaque stability by increasing collagen and smooth muscle cells content, while decreasing the number of pro-inflammatory macrophages. Shotgun proteomics of the aorta showed a metabolic rewiring in CX3CR1+-Tregs treated Ldlr −/− mice compared to controls that was associated with the improvement of inflammation-resolving pathways and disease progression.

Conclusion
ACT with vasculotropic Tregs appears as a promising strategy to selectively target immune activation in the atherosclerotic plaque.
Clinical, Endoscopic and Histological Outcomes in Induction of Moderate-to-Severe Ulcerative Colitis: A Systematic Review with Meta-Analysis
Authors: Magro Fernando , Estevinho Maria Manuela , Dias Cláudia Camila , Correia Luís , Lago Paula , Ministro Paula , Portela Francisco , Feakins Roger , Danese Silvio , Peyrin-Biroulet Laurent 
Published: September 2020

Abstract

Background and Aims
Interest in histology for ulcerative colitis [UC] has increased recently. This systematic review and meta-analysis aims to assess, for the first time, whether histological outcomes are more informative than endoscopic and clinical outcomes in distinguishing the impact of intervention over placebo in induction trials.

Methods
MEDLINE, ScienceDirect and Cochrane Central Register of Controlled Trials were searched to identify randomized placebo-controlled trials [RCTs] enrolling moderate-to-severe UC patients. Studies were assessed using the Quality Assessment Tool for Studies with Diverse Designs. We analysed the pooled proportion of patients achieving clinical, endoscopic and histological remission and response after a pharmacological intervention and compared the results with those of placebo-treated patients by using a random-effects model.

Results
From 889 identified records, 13 RCTs were included. The odds ratio [OR] for remission was higher in patients receiving intervention than in those under placebo for clinical (OR 2.13, 95% confidence interval [CI] 1.33–3.43), endoscopic [OR 1.46, 95% CI 0.19–11.18] and histological remission [OR 1.85, 95% CI 1.20–2.84]. Significant differences were observed for all response outcomes [clinical: OR 2.27, 95% CI 1.84–2.85; endoscopic: OR 2.16, 95% CI 1.51–3.10; histological: OR 3.63, 95% CI, 1.41–9.36]. No significant heterogeneity existed; no subgroup effects were found for duration of the induction or histological scale [p &gt; 0.05]. Clinical and histological remission and endoscopic response were concordant in discriminating interventions from placebo.

Conclusion
Histological outcomes are informative in trials of moderate-to-severe UC. Further studies analysing histology at the end of induction are needed to confirm its relevance in distinguishing the efficacy of an intervention over placebo in comparison to clinical and endoscopic outcomes and to explore its prognostic value.
The validity, reliability, sensitivity and responsiveness of a modified Patient Enablement Instrument (PEI-2) as a tool for serial measurements of health enablement
Authors: Bedford Laura Elizabeth , Yeung Maegan Hon Yan , Au Chi Ho , Tse Emily Tsui Yee , Yim Wing Yee , Yu Esther Yee Tak , Wong Carlos King Ho , Lam Cindy Lo Kuen 
Published: September 2020

Abstract

Background
Patient enablement is a core tenet of patient-centred and holistic primary care. The Patient Enablement Instrument (PEI) is a transitional measure limited in its ability to measure changes over time. A modified version, PEI-2, has been developed to measure enablement at a given time-point without comparison to a recalled baseline.

Objective
To assess the validity, reliability, sensitivity and responsiveness of PEI-2.

Methods
PEI-2 was modified from the Chinese PEI to assess enablement over 4 weeks in a prospective cohort study nested within a community support programme [Trekkers Family Enhancement Scheme (TFES)] in Hong Kong. Construct validity was assessed by factor analysis and convergent validity by Spearman’s correlations with health-related quality of life and depressive symptoms. Internal reliability was assessed using Cronbach’s alpha. Test–retest reliability was assessed by intraclass correlation (ICC), responsiveness by 12–24-month change in PEI-2 score and sensitivity by differences in change of PEI-2 score between TFES participants and a control group.

Results
PEI-2 demonstrated construct validity with all items loading on one factor (factor loadings &gt;0.7). Convergent validity was confirmed by significant correlations with 12-item Short Form Questionnaire, version 2 (r = 0.1089–0.1919) and Patient Health Questionnaire-9 (r = −0.2030). Internal reliability was high (Cronbach’s alpha = 0.9095) and test–retest reliability moderate (ICC = 0.520, P = 0.506). Significant improvements in PEI-2 scores among the TFES group suggested good responsiveness (P &lt; 0.001). The difference in change of PEI-2 scores between TFES and control was significant (P = 0.008), indicating good sensitivity.

Conclusions
This study supports the validity, reliability, sensitivity and responsiveness of PEI-2 in measuring changes in enablement, making it a promising tool for evaluating enablement in cohort and intervention studies.
General practitioner perceptions of assessment and reporting of absolute cardiovascular disease risk via pathology services: a qualitative study
Authors: Chapman Niamh , McWhirter Rebekah E , Schultz Martin G , Ezzy Douglas , Nelson Mark R , Sharman James E 
Published: September 2020

Abstract

Background
Guidelines for cardiovascular disease (CVD) prevention recommend assessment of absolute CVD risk to guide clinical management. Despite this, use among general practitioners (GPs) remains limited.

Objective
Pathology services may provide an appropriate setting to assess and report absolute CVD risk in patients attending for cholesterol measurement. This study aimed to explore GPs perceptions of such a service.

Methods
A focus group and semi-structured interviews were conducted with GPs (n = 18) in Tasmania, Australia, to identify perceptions of assessment and reporting of absolute CVD risk via pathology services. An example pathology report including absolute CVD risk was provided and discussed. Audio-recordings were transcribed and thematically coded by two researchers.

Results
Almost all GPs identified that absolute CVD risk assessed and reported via pathology services could address deficits in practice. First, by reducing the number of appointments required to collect risk factors. Second, by providing a systematic (rather than opportunistic) approach for assessment of absolute CVD risk. Third, by reducing misclassification of patient CVD risk caused by overreliance on clinical intuition. All GPs reported they would order absolute CVD risk when issuing a cholesterol referral if such a service was offered. GPs recommended improving the service by providing information on methods used to measure risk factors on the pathology report.

Conclusions
Absolute CVD risk assessed and reported via pathology services may address challenges of screening CVD risk experienced by GPs in practice and encourage dedicated follow-up care for CVD prevention.
Aberrant early growth of individual trigeminal sensory and motor axons in a series of mouse genetic models of 22q11.2 deletion syndrome
Authors: Motahari Zahra , Maynard Thomas M , Popratiloff Anastas , Moody Sally A , LaMantia Anthony-S 
Published: September 2020

AbstractWe identified divergent modes of initial axon growth that prefigure disrupted differentiation of the trigeminal nerve (CN V), a cranial nerve essential for suckling, feeding and swallowing (S/F/S), a key innate behavior compromised in multiple genetic developmental disorders including DiGeorge/22q11.2 Deletion Syndrome (22q11.2 DS). We combined rapid in vivo labeling of single CN V axons in LgDel+/− mouse embryos, a genomically accurate 22q11.2DS model, and 3D imaging to identify and quantify phenotypes that could not be resolved using existing methods. We assessed these phenotypes in three 22q11.2-related genotypes to determine whether individual CN V motor and sensory axons wander, branch and sprout aberrantly in register with altered anterior–posterior hindbrain patterning and gross morphological disruption of CN V seen in LgDel+/−. In the additional 22q11.2-related genotypes: Tbx1+/−, Ranbp1−/−, Ranbp1+/− and LgDel+/−:Raldh2+/−; axon phenotypes are seen when hindbrain patterning and CN V gross morphology is altered, but not when it is normal or restored toward WT. This disordered growth of CN V sensory and motor axons, whose appropriate targeting is critical for optimal S/F/S, may be an early, critical determinant of imprecise innervation leading to inefficient oropharyngeal function associated with 22q11.2 deletion from birth onward.