bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Recalibrated Four‐Category Child–Pugh Score Performs Better than the Original Child–Pugh and MELD Scores in Predicting In‐Hospital Mortality in Decompensated Alcoholic Cirrhotic Patients with Acute Variceal Bleeding: a Real‐World Cohort Analysis
Authors: Krige Jake , Spence Richard T. , Jonas Eduard , Hoogerboord Marius , Ellsmere James
Published: October 2019

Background

There currently is no consensus on how to accurately predict early rebleeding and death after a major variceal bleed. This study investigated the relative predictive performances of the original Child–Pugh (CP), model for end‐stage liver disease (MELD) and a four‐category recalibrated Child–Pugh (rCP).

Methods

This prospective study included all adult patients admitted to Groote Schuur Hospital with acute esophageal variceal bleeding secondary to alcoholic cirrhosis, between January 2000 and December 2017. CP and rCP grades and MELD score were calculated on admission, and the predictive ability in discriminating in‐hospital rebleeding and death was compared by area under receiver‐operating characteristic (AUROC) curves.

Results

During the study period, 403 consecutive adult patients were treated for bleeding esophageal varices of whom 225 were secondary to alcoholic cirrhosis. Twenty‐four (10.6%) patients were CP grade A, 88 (39.1%) grade B and 113 (50.2%) grade C on hospital admission. MELD scores ranged from 6 to 40. Thirty‐one (13.8%) patients rebleed, and 41 (18.2%) patients died. There was no difference in the discriminatory capacity of the CP (AUROC 0.59, 95% CI 0.50–0.670) and MELD (AUROC 0.62, 95% CI 0.51–0.73) to predict rebleeding (p = 0.72), or between the Child–Pugh (AUROC 0.75, 95% CI 0.71–0.81) and MELD (AUROC 0.71, 95% CI 0.62–0.80) to predict death (p = 0.35). The rCP classification (A–D) had a significantly improved discriminatory capacity (AUROC 0.83 95% CI 0.77–0.89) compared to the CP score (A–C) and MELD to predict death (p = 0.004).

Conclusion

A recalibrated Child–Pugh score outperforms the original Child–Pugh grade and MELD score in predicting in‐hospital death in patients with bleeding esophageal varices secondary to alcoholic cirrhosis.
Efficient modelling of delamination growth using adaptive isogeometric continuum shell elements
Authors: Adams Camiel , Fagerström Martin , Remmers Joris J. C.
Published: October 2019

The computational efficiency of CAE tools for analysing failure progression in large layered composites is key. In particular, efficient approximation and solution methods for delamination modelling are crucial to meet today’s requirements on virtual development lead times. For that purpose, we present here an adaptive continuum shell element based on the isogeometric analysis framework, suitable for the modelling of arbitrary delamination growth. To achieve an efficient procedure, we utilise that, in isogeometric analysis, the continuity of the approximation field easily can be adapted via so-called knot insertion. As a result, the current continuum shell provides a basis for an accurate but also computationally efficient prediction of delamination growth in laminated composites. Results show that the adaptive modelling framework works well and that, in comparison to a fully resolved model, the adaptive approach gives significant time savings even for simple analyses where major parts of the domain exhibit delamination growth.
Does external reference pricing deliver what it promises? Evidence on its impact at national level
Authors: Kanavos Panos , Fontrier Anna-Maria , Gill Jennifer , Efthymiadou Olina
Published: October 2019

Background

External reference pricing (ERP) is widely used to regulate pharmaceutical prices and help determine reimbursement. Its implementation varies substantially across countries, making it difficult to study and understand its impact on key policy objectives.

Objectives

To assess the evidence on ERP in different settings and its impact on key health policy objectives, notably, cost-containment, pharmaceutical price levels, drug use, equity, efficiency, availability, affordability and industrial policy; and second, to critically assess the quality of evidence on ERP.

Methods

Primary and secondary data collection through a survey of leading experts and a systematic literature review, respectively, over the 2000–2017 period.

Results

Forty five studies were included in the systematic review (January 2000–December 2016). Primary evidence was gathered via survey distribution to experts in 21 countries (January–July 2017). ERP contributes to cost-containment, but this is a short-term effect highly dependent on the way ERP is designed and implemented. Low prices, as a result of ERP, can undermine the availability of medicines and lead to launch delays or product withdrawals. Downward price convergence can hamper investment in innovation. ERP does not seem to promote efficiency in achieving health system goals. As evidence is weak, results need to be interpreted with caution.

Conclusions

ERP has not regulated prices efficiently and has unintended consequences that reduce the benefits arising from it. If ERP is carefully designed with minimal price revisions, prudent selection of basket size and countries, and consideration of transaction prices, it could be a more effective mechanism enhancing welfare, equitable access to medicines within countries and help promote industry innovation.
Isolation and characterization of cellulose nanofibers from aspen wood using derivatizing and non-derivatizing pretreatments
Authors: Jonasson Simon , Bünder Anne , Niittylä Totte , Oksman Kristiina
Published: October 2019

The link between wood and corresponding cellulose nanofiber (CNF) behavior is complex owing the multiple chemical pretreatments required for successful preparation. In this study we apply a few pretreatments on aspen wood and compare the final CNF behavior in order to rationalize quantitative studies of CNFs derived from aspen wood with variable properties. This is relevant for efforts to improve the properties of woody biomass through tree breeding. Three different types of pretreatments were applied prior to disintegration (microfluidizer) after a mild pulping step; derivatizing TEMPO-oxidation, carboxymethylation and non-derivatizing soaking in deep-eutectic solvents. TEMPO-oxidation was also performed directly on the plain wood powder without pulping. Obtained CNFs (44–55% yield) had hemicellulose content between 8 and 26 wt% and were characterized primarily by fine (height ≈ 2 nm) and coarser (2 nm < height < 100 nm) grade CNFs from the derivatizing and non-derivatizing treatments, respectively. Nanopapers from non-derivatized CNFs had higher thermal stability (280 °C) compared to carboxymethylated (260 °C) and TEMPO-oxidized (220 °C). Stiffness of nanopapers made from non-derivatized treatments was higher whilst having less tensile strength and elongation-at-break than those made from derivatized CNFs. The direct TEMPO-oxidized CNFs and nanopapers were furthermore morphologically and mechanically indistinguishable from those that also underwent a pulping step. The results show that utilizing both derivatizing and non-derivatizing pretreatments can facilitate studies of the relationship between wood properties and final CNF behavior. This can be valuable when studying engineered trees for the purpose of decreasing resource consumption when isolation cellulose nanomaterials.

Graphic abstract
Feasibility of a Mindfulness-Based Intervention with Sheltered Youth Experiencing Homelessness
Authors: Santa Maria Diane , Cuccaro Paula , Bender Kimberly , Cron Stanley , Fine Micki , Sibinga Erica
Published: October 2019

Objectives

Evidence of the acceptability and potential efficacy of mindfulness strategies with at-risk youth is mounting. Yet only a few studies have assessed these strategies among youth experiencing homelessness (YEH).

Methods

We conducted a mixed methods feasibility study of an adapted mindfulness-based intervention (MBI) with sheltered YEH. The MBI consisted of five 1.5-h sessions delivered at a youth homeless shelter over 2.5 weeks. A one-group pre/post-test design was utilized to collect quantitative assessments of real-time cognitions followed by qualitative inquiry to assess participants’ experiences and perceptions of the intervention.

Results

Participants (N = 39) were between 18–21 years old with the majority identifying as male (56.4%), heterosexual (74.4%), Black (51.3%) and Hispanic (15.4%). Attendance was challenging for participants (2.2 sessions attended on average) who had varying work and school obligations. However, pre–post session survey data completeness was excellent (92% completion rate). Participants completed self-report surveys prior to and after each session that measured affect. Significant improvement in pre–post session outcomes were found for frustration, restlessness, stress, depression, boredom, and mindlessness. Participants reported high levels of acceptability of the curriculum content and delivery format. However, several substantial adaptations that youth identified may improve feasibility and acceptability among YEH. The results are limited by the small sample size and the use of a curriculum not developed with or for YEH.

Conclusions

This study demonstrates the potential feasibility of using MBIs among YEH although adaptations to existing curricula are necessary to increase relevance, acceptability of, and access to MBIs among YEH.
Semantically Coherent 4D Scene Flow of Dynamic Scenes
Authors: Mustafa Armin , Hilton Adrian
Published: October 2019

Simultaneous semantically coherent object-based long-term 4D scene flow estimation, co-segmentation and reconstruction is proposed exploiting the coherence in semantic class labels both spatially, between views at a single time instant, and temporally, between widely spaced time instants of dynamic objects with similar shape and appearance. In this paper we propose a framework for spatially and temporally coherent semantic 4D scene flow of general dynamic scenes from multiple view videos captured with a network of static or moving cameras. Semantic coherence results in improved 4D scene flow estimation, segmentation and reconstruction for complex dynamic scenes. Semantic tracklets are introduced to robustly initialize the scene flow in the joint estimation and enforce temporal coherence in 4D flow, semantic labelling and reconstruction between widely spaced instances of dynamic objects. Tracklets of dynamic objects enable unsupervised learning of long-term flow, appearance and shape priors that are exploited in semantically coherent 4D scene flow estimation, co-segmentation and reconstruction. Comprehensive performance evaluation against state-of-the-art techniques on challenging indoor and outdoor sequences with hand-held moving cameras shows improved accuracy in 4D scene flow, segmentation, temporally coherent semantic labelling, and reconstruction of dynamic scenes.
Associations of psychosis-risk symptoms with quality of life and
self-rated health in the Community
Authors: Michel Chantal , Schmidt Stefanie J. , Schnyder Nina , Flückiger Rahel , Käufeler Iljana , Schimmelmann Benno G. , Schultze-Lutter Frauke
Published: October 2019

Background:

Understanding factors related to poor quality of life (QoL) and
self-rated health (SRH) in clinical high-risk (CHR) for psychosis is
important for both research and clinical applications. We investigated
the associations of both constructs with CHR symptoms, axis-I disorders,
and sociodemographic variables in a community sample.

Methods:

In total, 2683 (baseline) and 829 (3-year follow-up) individuals of
the Swiss Canton of Bern (age-at-baseline: 16–40 years) were interviewed
by telephone regarding CHR symptoms, using the Schizophrenia Proneness
Instrument for basic symptoms, the Structured Interview for
Psychosis-Risk Syndromes for ultra-high risk (UHR) symptoms, the
Mini-International Neuropsychiatric Interview for current axis-I
disorders, the Brief Multidimensional Life Satisfaction Scale for QoL,
and the 3-level EQ-5D for SRH.

Results:

In cross-sectional structural equation modelling, lower SRH was
exclusively significantly associated with higher age, male gender, lower
education, and somatoform disorders. Poor QoL was exclusively associated
only with eating disorders. In addition, both strongly interrelated
constructs were each associated with affective, and anxiety disorders,
UHR and, more strongly, basic symptoms. Prospectively, lower SRH was
predicted by lower education and anxiety disorders at baseline, while
poorer QoL was predicted by affective disorders at baseline.

Conclusions:

When present, CHR, in particular basic symptoms are already
distressful for individuals of the community and associated with poorer
subjective QoL and health. Therefore, the symptoms are clinically
relevant by themselves, even when criteria for a CHR state are not
fulfilled. Yet, unlike affective and anxiety disorders, CHR symptoms
seem to have no long-term influence on QoL and SRH.
Alzheimer's disease progression and risk factors: A standardized comparison between six large data sets
Authors: Evans Stephanie , McRae‐McKee Kevin , Hadjichrysanthou Christoforos , Wong Mei Mei , Ames David , Lopez Oscar , de Wolf Frank , Anderson Roy M. ,   Alzheimer's Disease Neuroimaging Initiative,   Australian Imaging Biomarkers and Lifestyle flagship study of ageing,   Predictors of Cognitive Decline Among Normal Individuals (BIOCARD) study,   Add Neuro Med Consortium
Published: October 2019

There exist a large number of cohort studies that have been used to identify genetic and biological risk factors for developing Alzheimer's disease (AD). However, there is a disagreement between studies as to how strongly these risk factors affect the rate of progression through diagnostic groups toward AD. We have calculated the probability of transitioning through diagnostic groups in six studies and considered how uncertainty around the strength of the effect of these risk factors affects estimates of the distribution of individuals in each diagnostic group in an AD clinical trial simulator. In this work, we identify the optimal choice of widely collected variables for comparing data sets and calculating probabilities of progression toward AD. We use the estimated transition probabilities to inform stochastic simulations of AD progression that are based on a Markov model and compare predicted incidence rates to those in a community‐based study, the Cardiovascular Health Study.
Between Eastern Africa and Western India, 1500–1650: Slavery, Commerce, and Elite Formation
Authors: Subrahmanyam Sanjay
Published: October 2019

This essay examines relations between eastern Africa and western India in the sixteenth and early seventeenth centuries in respect to two related sets of problems: the changing regimes of commercial circulation, and more particularly the evolution of patterns of human movement, notably via the slave trade from Ethiopia and the Swahili coast to Gujarat and the Deccan. It argues that over the course of the sixteenth century, commercial relations between Deccan ports such as Goa and Chaul, and the Swahili coast, came to be strengthened through the intervention of the Portuguese and their military-commercial system. At the same time, large numbers of African slaves reached the Muslim states in India, especially in the period after 1530, where they played a significant role as military specialists, and eventually as elite political and cultural actors. The shifting geographical dimensions of the African presence in India are emphasized, beginning in western Gujarat and winding up in the Deccan Sultanates. This contrasts markedly with the African experience elsewhere, where the meaning and institutional context of slavery were quite different.
Parent Stress for Patients Followed in a Multidisciplinary Spinal Defects Clinic
Authors: Simpson Tess S. , Kenny Jessica J. , Wilson Pamela E. , Clayton Gerald H. , Peterson Robin L.
Published: October 2019

Objective: The primary aim of this study was to characterize parent-reported stress for parents of children being followed in a multidisciplinary spinal defects clinic. Method: Participants were drawn from clinical cases seen through a multidisciplinary outpatient spinal defects clinic between 2014 and 2017. Participants included 223 youth under 21 years old, diagnosed with spina bifida (SB) or a related neural tube defect, and their parents. Parent stress ratings were obtained for all participants as part of the standard care within the clinic using the Parental Stress Scale. Self-reported internalizing symptoms were measured for patients aged 12 and older ( n = 44) with the 9-item Pediatric Health Questionnaire and the 7-item Generalized Anxiety Disorder scale. Results: Contrary to our prediction, we found low levels of parent and adolescent distress in this population. An important finding was that adolescent internalizing symptoms showed a moderate to large association with parent-reported stress and in fact, predicted parent stress better than did any demographic or health-related variable. Child age was also found to correlate with parent-reported stress, and parents of older children reported on average more stress than did parents of younger children. Conclusions: The current findings mainly highlight resilience in this population but do indicate that parent stress and child internalizing symptoms for children with SB are linked and are likely to be a target for clinical management, similar to the case for children without chronic health conditions.

Implications for Impact Statement

The current study highlights resilience in parents of children with a neural tube defect but does indicate that parent stress and child internalizing symptoms for children with a neural tube defect are linked and are likely to be a target of clinical management in a subset of this population. Additionally, it contributes to research investigating the efficacy of psychosocial screening tools in medical clinics and the benefits of multidisciplinary care for youth with neural tube defect.
Metabolomics analysis of children with autism, idiopathic-developmental delays, and Down syndrome
Authors: Orozco Jennie Sotelo , Hertz-Picciotto Irva , Abbeduto Leonard , Slupsky Carolyn M.
Published: October 2019

Although developmental delays affect learning, language, and behavior, some evidence suggests the presence of disturbances in metabolism are associated with psychiatric disorders. Here, the plasma metabolic phenotype of children with autism spectrum disorder (ASD, n = 167), idiopathic-developmental delay (i-DD, n = 51), and Down syndrome (DS, n = 31), as compared to typically developed (TD, n = 193) controls was investigated in a subset of children from the case–control Childhood Autism Risk from Genetics and the Environment (CHARGE) Study. Metabolome profiles were obtained using nuclear magnetic resonance spectroscopy and analyzed in an untargeted manner. Forty-nine metabolites were identified and quantified in each sample that included amino acids, organic acids, sugars, and other compounds. Multiple linear regression analysis revealed significant associations between 11 plasma metabolites and neurodevelopmental outcome. Despite the varied origins of these developmental disabilities, we observed similar perturbation in one-carbon metabolism pathways among DS and ASD cases. Similarities were also observed in the DS and i-DD cases in the energy-related tricarboxylic acid cycle. Other metabolites and pathways were uniquely associated with DS or ASD. By comparing metabolic signatures between these conditions, the current study expands on extant literature demonstrating metabolic alterations associated with developmental disabilities and provides a better understanding of overlapping vs specific biological perturbations associated with these disorders.
DNA methylation of HPA-axis genes and the onset of major depressive disorder in adolescent girls: a prospective analysis
Authors: Humphreys Kathryn L. , Moore Sarah R. , Davis Elena Goetz , MacIsaac Julie L. , Lin David T. S. , Kobor Michael S. , Gotlib Ian H.
Published: October 2019

The stress response system is disrupted in individuals with major depressive disorder (MDD) as well as in those at elevated risk for developing MDD. We examined whether DNA methylation (DNAm) levels of CpG sites within HPA-axis genes predict the onset of MDD. Seventy-seven girls, approximately half (n = 37) of whom were at familial risk for MDD, were followed longitudinally. Saliva samples were taken in adolescence (M age = 13.06 years [SD = 1.52]) when participants had no current or past MDD diagnosis. Diagnostic interviews were administered approximately every 18 months until the first onset of MDD or early adulthood (M age of last follow-up = 19.23 years [SD = 2.69]). We quantified DNAm in saliva samples using the Illumina EPIC chip and examined CpG sites within six key HPA-axis genes (NR3C1, NR3C2, CRH, CRHR1, CRHR2, FKBP5) alongside 59 genotypes for tagging SNPs capturing cis genetic variability. DNAm levels within CpG sites in NR3C1, CRH, CRHR1, and CRHR2 were associated with risk for MDD across adolescence and young adulthood. To rule out the possibility that findings were merely due to the contribution of genetic variability, we re-analyzed the data controlling for cis genetic variation within these candidate genes. Importantly, methylation levels in these CpG sites continued to significantly predict the onset of MDD, suggesting that variation in the epigenome, independent of proximal genetic variants, prospectively predicts the onset of MDD. These findings suggest that variation in the HPA axis at the level of the methylome may predict the development of MDD.
Lobaplatin promotes 125I-induced apoptosis and inhibition of proliferation in hepatocellular carcinoma by upregulating PERK-eIF2α-ATF4-CHOP pathway
Authors: Li Dong , Wang Wu-jie , Wang Yong-zheng , Wang Yi-biao , Li Yu-liang
Published: October 2019

We investigated the mechanism underlying the effect of a combination treatment of 125I radioactive seed implantation and lobaplatin (LBP) in hepatocellular carcinoma. The effects of administration of HCC cells and subcutaneous tumor model of mice with different doses of 125I or a sensitizing concentration of LBP alone, or in combination, on cellular apoptosis and proliferation were analyzed and it was confirmed that LBP promotes 125I-induced apoptosis and inhibition of proliferation of HCC. Furthermore, isobaric tag for relative and absolute quantification labeling analyses suggested that 125I promoted the apoptosis and inhibition of proliferation of HCC cells by upregulating the expression of PERK-eIF2α-ATF4-CHOP pathway, a well-known apoptosis-related pathway. Moreover, LBP was found to boost the 125I-induced upregulation of this pathway and increase the apoptosis. Our data indicate that LBP promotes the apoptotic and anti-proliferative effects of 125I and provide a firm foundation for better clinical application of this combination therapy.
CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis
Authors: Xie Lin , Huang Weibo , Fang Zhenhua , Ding Fan , Zou Fei , Ma Xiaosheng , Tao Jie , Guo Jingkang , Xia Xinlei , Wang Hongli , Yu Zuochong , Lu Feizhou , Jiang Jianyuan
Published: October 2019

The molecular mechanism of intervertebral disc degeneration (IVDD) remains unclear. This study aimed to investigate the role of circular RNAs (circRNAs) in the pathogenesis of IVDD. We sued nucleus pulposus (NP) tissues of patients, tert-butyl hydroperoxide (TBHP) stimulated NP cells (NPCs), and IVDD rat model to explore the interaction between circERCC2 and miR-182-5p/SIRT1 axis. The results showed that downregulation of circERCC2 increased the level of miR-182-5p and decreased the level of SIRT1 in degenerative NP tissues in vivo as well as in TBHP-stimulated NPCs in vitro. Treatment of SIRT1-si activated apoptosis and inhibited mitophagy. Moreover, miR-182-5p-si could regulate the mitophagy and the apoptosis of NPCs by targeting SIRT1. The effects of circERCC2 on NPCs and IVDD rat model were mediated by miR-182-5p/SIRT1 axis. In conclusion, this study provides the first evidence that circERCC2 could ameliorate IVDD through miR-182-5p/SIRT1 axis by activating mitophagy and inhibiting apoptosis, and suggests that circERCC2 is a potentially effective therapeutic target for IVDD.
Genetic interaction networks mediate individual statin drug response in Saccharomyces cerevisiae
Authors: Busby Bede P. , Niktab Eliatan , Roberts Christina A. , Sheridan Jeffrey P. , Coorey Namal V. , Senanayake Dinindu S. , Connor Lisa M. , Munkacsi Andrew B. , Atkinson Paul H.
Published: October 2019

Eukaryotic genetic interaction networks (GINs) are extensively described in the Saccharomyces cerevisiae S288C model using deletion libraries, yet being limited to this one genetic background, not informative to individual drug response. Here we created deletion libraries in three additional genetic backgrounds. Statin response was probed with five queries against four genetic backgrounds. The 20 resultant GINs representing drug–gene and gene–gene interactions were not conserved by functional enrichment, hierarchical clustering, and topology-based community partitioning. An unfolded protein response (UPR) community exhibited genetic background variation including different betweenness genes that were network bottlenecks, and we experimentally validated this UPR community via measurements of the UPR that were differentially activated and regulated in statin-resistant strains relative to the statin-sensitive S288C background. These network analyses by topology and function provide insight into the complexity of drug response influenced by genetic background.
Defining subpopulations of differential drug response to reveal novel target populations
Authors: Keshava Nirmal , Toh Tzen S. , Yuan Haobin , Yang Bingxun , Menden Michael P. , Wang Dennis
Published: October 2019

Personalised medicine has predominantly focused on genetically altered cancer genes that stratify drug responses, but there is a need to objectively evaluate differential pharmacology patterns at a subpopulation level. Here, we introduce an approach based on unsupervised machine learning to compare the pharmacological response relationships between 327 pairs of cancer therapies. This approach integrated multiple measures of response to identify subpopulations that react differently to inhibitors of the same or different targets to understand mechanisms of resistance and pathway cross-talk. MEK, BRAF, and PI3K inhibitors were shown to be effective as combination therapies for particular BRAF mutant subpopulations. A systematic analysis of preclinical data for a failed phase III trial of selumetinib combined with docetaxel in lung cancer suggests potential indications in pancreatic and colorectal cancers with KRAS mutation. This data-informed study exemplifies a method for stratified medicine to identify novel cancer subpopulations, their genetic biomarkers, and effective drug combinations.
Vulnerability of sea turtles and fishes in response to two catastrophic Caribbean hurricanes, Irma and Maria
Authors: Matley J. K. , Eanes S. , Nemeth R. S. , Jobsis P. D.
Published: October 2019

Extreme weather events (e.g., cyclones, floods, droughts) are capable of changing ecosystems and altering how animals obtain resources. Understanding the behavioural responses of animals being impacted by these natural events can help initiate and ameliorate conservation or management programs. This study investigated short- and long-term space-use of the critically endangered hawksbill sea turtle (Eretmochelys imbricata), as well as five species of fishes and stingrays, in response to two of the most destructive Caribbean hurricanes in known history – Irma and Maria, which were at their peak intensity when they passed the US Virgin Islands in September of 2017. Using passive acoustic telemetry in St. Thomas, US Virgin Islands, we show a variety of short-term behavioural patterns initiated across species to reduce exposure to the strong environmental conditions, such as moving to deeper habitats within the study area. Although short-term expansion of activity space was evident for several sea turtles, long-term impacts on space-use and body condition were limited. In contrast, southern stingrays (Hypanus americanus) left the study area shortly after the hurricanes, suggesting vulnerability stemming from altered habitat, prey availability, or temperature/oxygen profiles. This study shows the strong spatial resilience of several nearshore species despite exposure to two consecutive category 5 hurricanes.
Twist Angle mapping in layered WS2 by Polarization-Resolved Second Harmonic Generation
Authors: Psilodimitrakopoulos Sotiris , Mouchliadis Leonidas , Paradisanos Ioannis , Kourmoulakis George , Lemonis Andreas , Kioseoglou George , Stratakis Emmanuel
Published: October 2019

Stacked atomically thin transition metal dichalcogenides (TMDs) exhibit fundamentally new physical properties compared to those of the individual layers. The twist angle between the layers plays a crucial role in tuning these properties. Having a tool that provides high-resolution, large area mapping of the twist angle, would be of great importance in the characterization of such 2D structures. Here we use polarization-resolved second harmonic generation (P-SHG) imaging microscopy to rapidly map the twist angle in large areas of overlapping WS2 stacked layers. The robustness of our methodology lies in the combination of both intensity and polarization measurements of SHG in the overlapping region. This allows the accurate measurement and consequent pixel-by-pixel mapping of the twist angle in this area. For the specific case of 30° twist angle, P-SHG enables imaging of individual layers.
Stimulator of interferon genes (STING) activation exacerbates experimental colitis in mice
Authors: Martin Gary R. , Blomquist Charlene M. , Henare Kimiora L. , Jirik Frank R.
Published: October 2019

Detection of cytoplasmic DNA by the host’s innate immune system is essential for microbial and endogenous pathogen recognition. In mammalian cells, an important sensor is the stimulator of interferon genes (STING) protein, which upon activation by bacterially-derived cyclic dinucleotides (cDNs) or cytosolic dsDNA (dsDNA), triggers type I interferons and pro-inflammatory cytokine production. Given the abundance of bacterially-derived cDNs in the gut, we determined whether STING deletion, or stimulation, acts to modulate the severity of intestinal inflammation in the dextran sodium sulphate (DSS) model of colitis. DSS was administered to Tmem173gt (STING-mutant) mice and to wild-type mice co-treated with DSS and a STING agonist. Colitis severity was markedly reduced in the DSS-treated Tmem173gt mice and greatly exacerbated in wild-type mice co-treated with the STING agonist. STING expression levels were also assessed in colonic tissues, murine bone marrow derived macrophages (BMDMs), and human THP-1 cells. M1 and M2 polarized THP-1 and murine BMDMs were also stimulated with STING agonists and ligands to assess their responses. STING expression was increased in both murine and human M1 polarized macrophages and a STING agonist repolarized M2 macrophages towards an M1-like subtype. Our results suggest that STING is involved in the host’s response to acutely-induced colitis.
The role of extracellular matrix in mouse and human corneal neovascularization
Authors: Barbariga M. , Vallone F. , Mosca E. , Bignami F. , Magagnotti C. , Fonteyne P. , Chiappori F. , Milanesi L. , Rama P. , Andolfo A. , Ferrari G.
Published: October 2019

Corneal neo-vascularization (CNV) is a highly prevalent medical condition which impairs visual acuity. The role of specific proteins in modulating CNV has been extensively reported, although no studies have described the entire human proteome in CNV corneas. In this paper, we performed a proteomic analysis of vascularizedvshealthy corneal stroma, in a CNV mouse model and in CNV-affected patients, with a specific focus on extracellular matrix (ECM) proteins. We identified and quantified 2315 murine proteins, 691 human proteins and validated 5 proteins which are differentially expressed in vascularized samples and conserved in mice and humans: tenascin-C and fibronectin-1 were upregulated, while decorin, lumican and collagen-VI were downregulated in CNV samples. Interestingly, among CNV patients, those affected with Acanthamoeba keratitis showed the highest levels of fibronectin-1 and tenascin-C, suggesting a specific role of these two proteins in Acanthamoeba driven corneal CNV. On a broader picture, our findings support the hypothesis that the corneal stroma in CNV samples is disorganized and less compact. We are confident that the dissection of the human corneal proteome may shed new light on the complex pathophysiology of human CNV, and finally lead to improved treatments.
Oral selective serotonin reuptake inhibitors activate vagus nerve dependent gut-brain signalling
Authors: McVey Neufeld Karen-Anne , Bienenstock John , Bharwani Aadil , Champagne-Jorgensen Kevin , Mao YuKang , West Christine , Liu Yunpeng , Surette Michael G. , Kunze Wolfgang , Forsythe Paul
Published: October 2019

The vagus nerve can transmit signals to the brain resulting in a reduction in depressive behavior as evidenced by the long-term beneficial effects of electrical stimulation of the vagus in patients with intractable depression. The vagus is the major neural connection between gut and brain, and we have previously shown that ingestion of beneficial bacteria modulates behaviour and brain neurochemistry via this pathway. Given the high levels of serotonin in the gut, we considered if gut-brain signaling, and specifically the vagal pathway, might contribute to the therapeutic effect of oral selective serotonin reuptake inhibitors (SSRI). Mesenteric nerve recordings were conducted in mice after treatment with SSRI to ascertain if this class of drugs resulted in increased vagal excitability. Patch clamp recordings of enteric neurons were carried out to measure activity of primary afferent neurons in the gut in response to SSRI and to assess the importance of gut epithelium in transducing signal. The tail suspension test (TST) was used following 14d feeding of SSRI in vagotomised and surgical sham mice to measure depressive-like behaviour. Brain mRNA expression was examined via PCR and the intestinal microbiome was assessed. Mesenteric nerve recordings in BALB/c mice demonstrated that oral treatment with SSRI leads to a significant increase in vagal activity. This effect was not observed in mice treated with a representative noradrenaline-dopamine reuptake inhibitor. It is known that signals from the gut can be transmitted to the vagus via the enteric nervous system. Exposure of the gut to SSRI increased the excitability of intrinsic primary afferent neurons in the myenteric plexus, through an intestinal epithelium dependent mechanism, and alpha-diversity of gut microbiota was altered. Critically, blocking vagal signaling from gut to brain, via subdiaphragmatic vagotomy, abolished the antidepressive effects of oral SSRI treatment as determined by the tail suspension test. This work suggests that vagus nerve dependent gut-brain signaling contributes to the effects of oral SSRI and further, highlights the potential for pharmacological approaches to treatment of mood disorders that focus on vagal stimulation and may not even require therapeutic agents to enter the circulation.
Relationship between subjective sleep disturbances and glycaemia in Chinese adults with type 2 diabetes: findings from a 1.5-year follow-up study
Authors: Xu Chunrong , Zhang Pan , Xiang Quanyong , Chang Guiqiu , Zhang Ming , Zhang Lei , Li Ting , Qiao Cheng , Qin Yu , Lou Peian
Published: October 2019

We wanted to determine whether subjective sleep disturbance was associated with serum glycated hemoglobin (HbA1c) in people with type 2 diabetes mellitus. In total, 944 randomly-selected people with diabetes completed the Chinese version of the Pittsburgh Sleep Quality Index (PSQI). Participants’ glycaemia was assessed using HbA1c in March 2016 and September 2017. The PSQI score and the change in score(△PSQI), and the HbA1c and its change (△HbAlc) were analysed by sex and age (30–45, 46–60, 61–75, and 76–89 years). Associations between time point PSQI and △PSQI with static HbA1c and △HbA1c were analysed using multiple linear regression. The results showed subjective sleep disturbance among people with diabetes was not correlated with serum HbAlc (β coefficient = 0.032, P = 0.103). However, cross-sectional multiple linear regression showed the relationship was present in women (β coefficient = 0.163, P < 0.01). In multiple linear regression, △PSQI score was correlated with △HbAlc value (β coefficient = 0.142, P < 0.01). The regression coefficient (β) for the relationship between △PSQI score and △HbA1c in men was greater than that in women, and for age was β61–75years < β46–60years < β30–45years. The strongest relationship between △PSQI and △HbA1c was in men aged 30–45 years (β = 0.452, P < 0.01). Subjective sleep disturbance among people with diabetes was not related to glycaemic status in the whole sample, but there was a correlation in women. The change in subjective sleep disturbance correlated with the change in glycaemia, most strongly in younger participants, especially men aged 30–45 years.
Thought and language disturbance in bipolar disorder quantified via process-oriented verbal fluency measures
Authors: Weiner Luisa , Doignon-Camus Nadège , Bertschy Gilles , Giersch Anne
Published: October 2019

Bipolar disorder (BD) is characterized by speech abnormalities, reflected by symptoms such as pressure of speech in mania and poverty of speech in depression. Here we aimed at investigating speech abnormalities in different episodes of BD, including mixed episodes, via process-oriented measures of verbal fluency performance – i.e., word and error count, semantic and phonological clustering measures, and number of switches–, and their relation to neurocognitive mechanisms and clinical symptoms. 93 patients with BD – i.e., 25 manic, 12 mixed manic, 19 mixed depression, 17 depressed, and 20 euthymic–and 31 healthy controls were administered three verbal fluency tasks – free, letter, semantic–and a clinical and neuropsychological assessment. Compared to depression and euthymia, switching and clustering abnormalities were found in manic and mixed states, mimicking symptoms like flight of ideas. Moreover, the neuropsychological results, as well as the fact that error count did not increase whereas phonological associations did, showed that impaired inhibition abilities and distractibility could not account for the results in patients with manic symptoms. Rather, semantic overactivation in patients with manic symptoms, including mixed depression, may compensate for trait-like deficient semantic retrieval/access found in euthymia.

“For those who are manic, or those who have a history of mania, words move about in all directions possible, in a three-dimensional ‘soup’, making retrieval more fluid, less predictable.”Kay Redfield Jamison (2017, p. 279).
Relevant heating of the quiet solar corona by Alfvén waves: a result of adiabaticity breakdown
Authors: Escande D. F. , Gondret V. , Sattin F.
Published: October 2019

Ion heating by Alfvén waves has been considered for long as the mechanism explaining why the solar corona has a temperature several orders of magnitude higher than the photosphere. Unfortunately, as the measured wave frequencies are much smaller than the ion cyclotron frequency, particles were expected to behave adiabatically, impeding a direct wave-particle energy transfer to take place, except through decorrelating stochastic mechanisms related to broadband wave spectra. This paper proposes a new paradigm for this mechanism by showing it is actually much simpler, more general, and very efficient. Indeed, for measured wave amplitudes in the quiet corona, ion orbits are shown to cross quasi-periodically one or several slowly pulsating separatrices in phase space. Now, a separatrix is an orbit with an infinite period, thus much longer than the pulsation one. Therefore, each separatrix crossing cancels adiabatic invariance, and yields a very strong energy transfer from the wave, and thus particle heating. This occurs whatever be the wave spectrum, even a monochromatic one. The proposed mechanism is so efficient that it might lead to a self-organized picture of coronal heating: all Alfvén waves exceeding a threshold are immediately quenched and transfer their energy to the ions.
SR9009 administered for one day after myocardial ischemia-reperfusion prevents heart failure in mice by targeting the cardiac inflammasome
Authors: Reitz Cristine J. , Alibhai Faisal J. , Khatua Tarak N. , Rasouli Mina , Bridle Byram W. , Burris Thomas P. , Martino Tami A.
Published: October 2019

Reperfusion of patients after myocardial infarction (heart attack) triggers cardiac inflammation that leads to infarct expansion and heart failure (HF). We previously showed that the circadian mechanism is a critical regulator of reperfusion injury. However, whether pharmacological targeting using circadian medicine limits reperfusion injury and protects against HF is unknown. Here, we show that short-term targeting of the circadian driver REV-ERB with SR9009 benefits long-term cardiac repair post-myocardial ischemia reperfusion in mice. Gain and loss of function studies demonstrate specificity of targeting REV-ERB in mice. Treatment for just one day abates the cardiac NLRP3 inflammasome, decreasing immunocyte recruitment, and thereby allowing the vulnerable infarct to heal. Therapy is given in vivo, after reperfusion, and promotes efficient repair. This study presents downregulation of the cardiac inflammasome in fibroblasts as a cellular target of SR9009, inviting more targeted therapeutic investigations in the future.
pH-Dependent photoluminescence “switch-on” nanosensors composed of silver nanoparticles and nitrogen and sulphur co-doped carbon dots for discriminative detection of biothiols
Authors: Xiang Feng , Li Jizhou , Liu Zhongde
Published: October 2019

A nanomaterial surface energy transfer (NSET) system composed of silver nanoparticles (AgNPs) and nitrogen and sulphur co-doped carbon dots (N,S-CDs) was established to discriminate biothiols, featuring the pH-promoted distinct PL “switch-on” response.
Increased ion throughput using tristate ion-gate multiplexing
Authors: Kwantwi-Barima Pearl , Reinecke Tobias , Clowers Brian H.
Published: October 2019

For time dispersive ion mobility experiments detail control over the mechanism of ion beam modulation is necessary to establish optimum performance as this parameter greatly influences the temporal width of the ion beam arriving at the detector.
Efficient differentiation of human ES and iPS cells into cardiomyocytes on biomaterials under xeno-free conditions
Authors: Sung Tzu-Cheng , Liu Cheng-Hui , Huang Wei-Lun , Lee Yu-Chun , Kumar S. Suresh , Chang Yung , Ling Qing-Dong , Hsu Shih-Tien , Higuchi Akon
Published: October 2019

Efficient differentiation of human ES and iPS cells into cardiomyocytes was successively developed on biomaterials under xeno-free conditions.
Angiogenesis-promoted bone repair with silicate-shelled hydrogel fiber scaffolds
Authors: Dashnyam Khandmaa , Buitrago Jennifer O. , Bold Tsendmaa , Mandakhbayar Nandin , Perez Roman A. , Knowles Jonathan C. , Lee Jung-Hwan , Kim Hae-Won
Published: October 2019

The silicate-shelled alginate hydrogel fiber scaffold is highly effective for promoting ion-induced angiogenesis and bone bioactivity, ultimately useful for the repair and regeneration of hard tissues.
A robust MOF-based trap with high-density active alkyl thiol for the super-efficient capture of mercury
Authors: Yang Pengfei , Shu Yufang , Zhuang Qixin , Li Yongsheng , Gu Jinlou
Published: October 2019

A robust Zr-MSA MOF trap with high-density active alkyl thiol is successfully constructed for the super-efficient capture of mercury.
Development of 4-oxime-1,8-naphthalimide as a bioorthogonal turn-on probe for fluorogenic protein labeling
Authors: Tian Yulin , Li Xiang , Yin Dali
Published: October 2019

We report 4-oxime-1,8-naphthalimide as a novel bioorthogonal turn-on probe based on cascade 1,3-dipolar cycloaddition and photoisomerization for fluorogenic protein labeling.
Calcium stannyl formation by organostannane dehydrogenation
Authors: Morris Louis J. , Hill Michael S. , Manners Ian , McMullin Claire L. , Mahon Mary F. , Rajabi Nasir A.
Published: October 2019

Reaction of the dimeric calcium hydride, [(BDI)CaH]2(1), with Ph3SnH ensues with elimination of H2to provide [(BDI)Ca-μ2-H-(SnPh3)Ca(BDI)] (3) and [(BDI)Ca(SnPh3)]2(4) alongside dismutation to Ph4Sn, H2and Sn(0).
Supramolecular chirality of coordination polymers of Ag+ with a chiral thiol ligand that bears a β-turn structure
Authors: Yuan Yuan , Xiao Yu-Wei , Yan Xiao-Sheng , Wu Si-Xian , Luo Huan , Lin Jian-Bin , Li Zhao , Jiang Yun-Bao
Published: October 2019

The coordination polymers of Ag+ with a β-turn containing chiral thiol ligand exhibit supramolecular chirality showing simultaneously the majority rules effect (MRE) and racemate rules effect (RRE).
Cocrystal design by network-based link prediction
Authors: Devogelaer Jan-Joris , Brugman Sander J. T. , Meekes Hugo , Tinnemans Paul , Vlieg Elias , de Gelder René
Published: October 2019

Cocrystals are predicted using a network of coformers extracted from the CSD.
The effect of dimerization on the activation and conformational dynamics of adenosine A1 receptor
Authors: Li Yang , Wang Mukuo , Gao Na , Li Dongmei , Lin Jianping
Published: October 2019

A1R homodimer can be activated asymmetrically by one or two agonists occupied in orthosteric pockets in single or both protomers.
Elucidating the formation of Al–NBO bonds, Al–O–Al linkages and clusters in alkaline-earth aluminosilicate glasses based on molecular dynamics simulations
Authors: Ganisetti Sudheer , Gaddam Anuraag , Kumar Rajesh , Balaji Sathravada , Mather Glenn C. , Pascual Maria J. , Fabian Margit , Siegel Renée , Senker Jürgen , Kharton Vladislav V. , Guénolé Julien , Krishnan N. M. Anoop , Ferreira José M. F. , Allu Amarnath R.
Published: October 2019

Exploring the reasons for the initiation of Al–O–Al bond formation in alkali-earth alumino silicate glasses is a key topic in the glass-science community.
Ab initiodynamics of hydrogen abstraction from N2H4by OH radicals: an RRKM-based master equation study
Authors: Mai Tam V.-T. , Nguyen Hieu T. , Huynh Lam K.
Published: October 2019

The detailed kinetic mechanism of the N2H4+ OH reaction is comprehensively reported for a wide condition range of conditions (i.e., 200–3000 K & 1–7600 Torr) using the CCSD(T)/CBS//M06-2X/6-311++G(3df,2p) level and the RRKM-based master equation rate model.
Three-dimensional ordered macroporous Ru-substituted BaZrO3 perovskites: active catalysts for ammonia synthesis under mild conditions
Authors: Li Lingling , Yang Linlin , Zhang Tianhua , Wang Xiuyun , Zhang Xing , Lin Bingyu , Ni Jun , Dai Hongxing , Au Chak-Tong , Jiang Lilong
Published: October 2019

Three-dimensional ordered macroporous (3DOM) BaZr(1−x)RuxO3 perovskites were prepared by a PMMA-templating strategy and applied for ammonia synthesis for the first time.
Large magnetocaloric effect and remarkable single-molecule-magnet behavior in triangle-assembled LnIII6 clusters
Authors: Wang Wen-Min , Yue Rong-Xin , Gao Yu , Wang Mei-Jiao , Hao Sha-Sha , Shi Ying , Kang Xiao-Min , Wu Zhi-Lei
Published: October 2019

Two intriguing triangle-assembled LnIII6 clusters (1 and 2) have been synthesized. The magnetic study reveals that 1 displays a larger cryogenic magnetocaloric effect, while 2 exhibits remarkable SMM behaviors.
Highly sensitive optical thermometers based on unconventional thermometric coupled levels of Tm3+ following a Boltzmann-type distribution in oxyfluoride glass ceramics
Authors: Fu Yuting , Zhao Lijuan , Guo Yuao , Yu Hua
Published: October 2019

Two highly-sensitive innovative coupled levels of 3F2,3/1D2 and 3F2,3/1G4 governed by a Boltzmann-type distribution in Tm3+/Yb3+ co-doped β-PbF2 GCs were proposed.