bluuebunny/crossref_metadata_2025 huggingface dataset:
Global epidemiology of nonpolio enteroviruses causing severe neurological complications: A systematic review and meta‐analysis
Authors: Suresh Sarika , Rawlinson William D. , Andrews Peter Ian , Stelzer‐Braid Sacha
Published: October 2019

Enteroviruses are RNA viruses found as commensals in the human gut and respiratory system, which may cause a wide spectrum of disease. Enteroviruses may cause severe neurologic complications including acute flaccid paralysis (AFP) and encephalitis and are the most commonly diagnosed agents of viral meningitis. Outbreaks of more severe disease are often associated with particular genotypes, such as enterovirus‐A71 causing rhombencephalitis and AFP. There are more than 300 described genotypes of human enterovirus, with overlaps in clinical phenotypes between genotypes, and uncertainty about which genotypes are more prevalent in neurological manifestations.

A systematic review of observational studies was conducted to evaluate the most prevalent enterovirus genotypes causing AFP, encephalitis, and meningitis. The genotyping methods and sampling sites were compiled as secondary outcomes. Sources included MEDLINE, Embase (publications until January 2019), and references selected from included studies. Meta‐analyses using a random effects model were performed to calculate the pooled proportion of enterovirus genotypes in each disease.

Ninety‐six publications met the eligibility criteria, comprising 3779 AFP cases, 1140 encephalitis cases, and 32 810 meningitis cases. Enterovirus‐A71 was most frequently associated with AFP (pooled proportion 0.12, 95% CI, 0.05‐0.20) and encephalitis (0.77, 95% CI, 0.61‐0.91). Echovirus 30 (0.35, 95% CI, 0.27‐0.42) was the most predominant genotype in meningitis cases. Genotypes were most commonly determined using VP1 RT‐ reverse transcription‐polymerase chain reaction, and most samples assessed were cerebrospinal fluid.

With the emergence of enteroviruses as an increasing cause of neurological diseases, surveillance and testing need to increase to identify the aetiology of the most common and most severe disorders.
Lipopeptide‐Based Nanosome‐Mediated Delivery of Hyperaccurate CRISPR/Cas9 Ribonucleoprotein for Gene Editing
Authors: Thach Trung Thanh , Bae Do Hyun , Kim Nam Hyeong , Kang Eun Sung , Lee Bok Soo , Han Kayoung , Kwak Minsuk , Choi Hojae , Nam JiYoung , Bae Taegeun , Suh Minah , Hur Junho K. , Kim Yong Ho
Published: October 2019

A transient cytosolic delivery system for accurate Cas9 ribonucleoprotein is a key factor for target specificity of the CRIPSR/Cas9 toolkit. Owing to the large size of the Cas9 protein and a long negative strand RNA, the development of the delivery system is still a major challenge. Here, a size‐controlled lipopeptide‐based nanosome system is reported, derived from the blood‐brain barrier‐permeable dNP2 peptide which is capable of delivering a hyperaccurate Cas9 ribonucleoprotein complex (HypaRNP) into human cells for gene editing. Each nanosome is capable of encapsulating and delivering ≈2 HypaRNP molecules into the cytoplasm, followed by nuclear localization at 4 h post‐treatment without significant cytotoxicity. The HypaRNP thus efficiently enacts endogenous eGFP silencing and editing in human embryonic kidney cells (up to 27.6%) and glioblastoma (up to 19.7% frequency of modification). The lipopeptide‐based nanosome system shows superior delivery efficiency, high controllability, and simplicity, thus providing biocompatibility and versatile platform approach for CRISPR‐mediated transient gene editing applications.
Designing a Multifunctional Separator for High‐Performance Li–S Batteries at Elevated Temperature
Authors: He Yibo , Wu Shichao , Li Qi , Zhou Haoshen
Published: October 2019

The practical applications of lithium–sulfur (Li–S) batteries are seriously limited by the undesirable polysulfide shuttling and lithium dendrite growth. Herein, a multifunctional membrane is designed and prepared by coating a lithiated Nafion (Li@Nafion) layer and an Al2O3 layer on the two sides of a routine polymer membrane (polypropylene/polyethylene/polypropylene, PEP). The Li@Nafion layer faced to the sulfur cathode builds a “polysulfide‐phobic” surface to restrain the shuttle effect via Coulomb repulsion, while the Al2O3 layer with a uniform porous structure aids in regulating homogeneous Li+ fluxes to achieve stable Li electrodeposition. As a result, the Li//Li symmetric cell with a Li@Nafion/PEP/Al2O3 (LNPA) separator realizes stable Li plating/striping even after 1000 h at a high current density (5 mA cm−2). Moreover, the Li–S batteries incorporating LNPA separators not only can achieve excellent outstanding cyclic stability at an ultrahigh sulfur loading (7.6 mg cm−2), but also exhibit impressive electrochemical performance at an elevated temperature (60 °C). The rational design of the LNPA separator presents new insights to develop high‐performance Li–S batteries.
NiFe Oxalate Nanomesh Array with Homogenous Doping of Fe for Electrocatalytic Water Oxidation
Authors: Gao Xueqing , Chen Dandan , Qi Jing , Li Fang , Song Yanji , Zhang Wei , Cao Rui
Published: October 2019

NiFe‐based materials have shown impressive electrocatalytic activity for the oxygen evolution reaction (OER). The mutual effect between proximate Ni and Fe atoms is essential in regulating the electronic structure of the active site to boost the OER kinetics. Detailed studies confirm that the separated monometal phases in NiFe‐based materials are detrimental to OER. Thus, the high‐level blending of Ni and Fe in NiFe‐based OER electrocatalysts is critical. Herein, an NiFe oxalate nanomesh array based on solid solutions between nickel (II) oxalate and iron (II) oxalate is prepared through a facile surfactant‐free approach in the presence of the reductive oxalate anions. The integrated electrode can efficiently catalyze water oxidation to reach a current density of 50 mA cm−2 with a small overpotential of 203 mV in a 1.0 m KOH aqueous solution. The high efficiency can be attributed to the atomic level mix of Ni and Fe in the solid solutions and the hierarchical porous structure of the nanomesh array. These two aspects bring about fast kinetics, efficient mass diffusion, and quick charge transfer, which are the three major positive factors for a high‐performance heterogenous electrocatalyst.
About adopting a systemic approach to design connected embedded systems: A MOOC promoting systems thinking and systems engineering
Authors: Baron Claude , Daniel‐Allegro Brigitte
Published: October 2019

A connected embedded system is a complex system that integrates hardware and software elements and has real‐time interactions with its environment. Developing such a system requires having a systemic approach, based on systems thinking and systems engineering (SE). Systems thinking demonstrates the need of adopting an interdisciplinary approach (not only technology focused but also considering societal or regulatory commitments), that is essential to explore the whole embedded systems field. SE enables learners acquiring a method which provides the means to set up a consistent design and management plan that fully integrates a product development. This paper describes how a MOOC has been designed and produced to promote the use of a systemic approach when developing connected embedded systems. The MOOC uses different case studies in order to progressively develop system thinker's skills for identifying and solving a variety of problems raised during the design of a connected embedded system. Launched in 2016, it attracted more than 10.800 learners in less than 2 years. What led to such a success is certainly because the team that created the MOOC experienced a collaborative and integrative approach, namely a systemic approach, that also revealed its benefits in this educative project.
Customer value in lean product development: Conceptual model for incremental innovations
Authors: Santos Ana Carolina Oliveira , da Silva Carlos Eduardo Sanches , Braga Rodrigo Aparecido da Silva , Corrêa João Éderson , de Almeida Fabricio Alves
Published: October 2019

As the lean product development (LPD) process is responsible for maximizing the value/waste relation by encouraging different types of innovation, it needs a clear understanding of end customer value. Moreover, lean systems engineering is related to the application of lean thinking (LT) in systems engineering to improve the delivery of value to all stakeholders of the system. Then, faced with this scenario, this research aims to propose a value‐adding conceptual model for incremental product innovations in LPD. A systematic review of the literature from the LT perspective was performed and the conceptions of value were identified and then analyzed and contrasted with the concepts and characteristics of the areas of product development, marketing, and consumer psychology, which made possible the proposition of a conceptual model. The results show that customer value is multidimensional, and it was possible to identify the importance and the need for prioritization of certain dimensions of value for specific markets and customers. The conceptual model named VA2I presented in this study is generic and can be adapted and applied in any type of organization.
Carotenoids as natural functional pigments
Authors: Maoka Takashi
Published: October 2019

Carotenoids are tetraterpene pigments that are distributed in photosynthetic bacteria, some species of archaea and fungi, algae, plants, and animals. About 850 naturally occurring carotenoids had been reported up until 2018. Photosynthetic bacteria, fungi, algae, and plants can synthesize carotenoids de novo. Carotenoids are essential pigments in photosynthetic organs along with chlorophylls. Carotenoids also act as photo-protectors, antioxidants, color attractants, and precursors of plant hormones in non-photosynthetic organs of plants. Animals cannot synthesize carotenoids de novo, and so those found in animals are either directly accumulated from food or partly modified through metabolic reactions. So, animal carotenoids show structural diversity. Carotenoids in animals play important roles such precursors of vitamin A, photo-protectors, antioxidants, enhancers of immunity, and contributors to reproduction. In the present review, I describe the structural diversity, function, biosyntheses, and metabolism of natural carotenoids.
Association between enrollment factors and incident cognitive impairment in Blacks and Whites: Data from the Alzheimer's Disease Center
Authors: Gleason Carey E. , Norton Derek , Zuelsdorff Megan , Benton Susan F. , Wyman Mary F. , Nystrom Naomi , Lambrou Nickolas , Salazar Hector , Koscik Rebecca L. , Jonaitis Erin , Carter Fabu , Harris Brieanna , Gee Alexander , Chin Nathaniel , Ketchum Frederick , Johnson Sterling C. , Edwards Dorothy F. , Carlsson Cynthia M. , Kukull Walter , Asthana Sanjay
Published: October 2019

Introduction

We examined the influence of enrollment factors demonstrated to differ by race on incident mild cognitive impairment and dementia using Alzheimer's Disease Center data.

Methods

Differences in rates of incident impairment between non‐Latino Whites and Blacks (n = 12,242) were examined with age‐at‐progression survival models. Models included race, sex, education, source of recruitment, health factors, and family history of dementia.

Results

No significant race differences in progression were observed in cognitively unimpaired participants. In those with mild cognitive impairment at baseline, Whites evidenced greater risk for progression than Blacks. Enrollment factors, for example, referral source, were significantly related to progression.

Discussion

The finding that Blacks demonstrated lower rate of progression than Whites is contrary to the extant literature. Nested‐regression analyses suggested that selection‐related factors, differing by race, may account for these findings and influence our ability to accurately estimate risk for progression. It is potentially problematic to make racial comparisons using Alzheimer's Disease Center data sets.
Deconvolution of pectin carbonised template silica thin-film: synthesis and characterisation
Authors: Pratiwi Amalia Enggar , Elma Muthia , Rahma Aulia , Rampun Erdina L.A. , Saputro Gesit Satriaji
Published: October 2019

This study shows, for the first time, the synthesis of a carbonised pectin templated silica thin-film material. The aim of this work is to investigate the vibration of carbon groups of pectin–silica xerogels using infrared spectroscopy and curve-fitting software. Thin films were prepared using a two-step acid–base catalysed sol-gel method, employing tetraethyl orthosilicate as the main precursor. Various concentrations of pectin (0.1 wt%, 0.5 wt% and 2.5 wt%) were used as templating agents. These were firstly dissolved in glycerol, and mixed with the silica thin-film material. The sols was then dried in an oven at 60°C for 12 h, and calcined in air using rapid thermal processing at 300°C and 400°C for 1 h. The results show that the concentration of carbon groups for samples calcined under 400°C is higher than that of samples calcined at 300°C – especially in the region of 800 cm−1 for silica-carbon. This clearly shows that the calcination temperature influences the polymerisation of carbon group templates in the silica matrices.
Endperiodic automorphisms of surfaces and foliations
Authors: CANTWELL JOHN , CONLON LAWRENCE , FENLEY SERGIO R.
Published: October 2019

We extend the unpublished work of Handel and Miller on the classification, up to isotopy, of endperiodic automorphisms of surfaces. We give the Handel–Miller construction of the geodesic laminations, give an axiomatic theory for pseudo-geodesic laminations, show that the geodesic laminations satisfy the axioms, and prove that pseudo-geodesic laminations satisfying our axioms are ambiently isotopic to the geodesic laminations. The axiomatic approach allows us to show that the given endperiodic automorphism is isotopic to a smooth endperiodic automorphism preserving smooth laminations ambiently isotopic to the original ones. Using the axioms, we also prove the ‘transfer theorem’ for foliations of 3-manifolds, namely that, if two depth-one foliations${\mathcal{F}}$and${\mathcal{F}}^{\prime }$are transverse to a common one-dimensional foliation${\mathcal{L}}$whose monodromy on the non-compact leaves of${\mathcal{F}}$exhibits the nice dynamics of Handel–Miller theory, then${\mathcal{L}}$also induces monodromy on the non-compact leaves of${\mathcal{F}}^{\prime }$exhibiting the same nice dynamics. Our theory also applies to surfaces with infinitely many ends.
Entropy of transcendental entire functions
Authors: BENINI ANNA MIRIAM , FORNÆSS JOHN ERIK , PETERS HAN
Published: October 2019

We prove that all transcendental entire functions have infinite topological entropy.
Identifying research priorities for psychosocial support programs in humanitarian settings
Authors: Lee C. , Nguyen A. J. , Haroz E. , Tol W. , Aules Y. , Bolton P.
Published: October 2019

Background.

Given the range and reach of psychosocial support (PSS) interventions in humanitarian settings, within the continuum of mental health and psychosocial support services, evaluation of their impact is critical. Understanding stakeholders' perspectives on which PSS interventions of unknown effectiveness warrant rigorous evaluation is essential to identify research priorities. This project aimed to facilitate a process with stakeholders to reach consensus on PSS interventions that are of high priority for further research based on existing evidence and stakeholders' opinions.

Methods.

Interviews with 109 stakeholders working on PSS programming in humanitarian settings served as the foundation for two in-person regional meetings and four webinars. Nominal Group Technique (NGT) was used to develop a priority PSS program list. The top five priorities from each meeting were combined for a final online survey distributed globally.

Results.

Seventy participants across six meetings contributed to the prioritization process. Eighty-seven individuals completed the final online survey. ‘Community based PSS’ was the top-ranked research priority, followed by PSS integrated into basic services, providing PSS to caregivers to improve child wellbeing, PSS-focused gender-based violence programming, and classroom-based PSS interventions.

Conclusions.

NGT and online surveys were effective methods to engage stakeholders in a priority setting exercise to development a research agenda. Information from this stage of the project will be combined with findings from a concurrent systematic review to form the base of a second phase of work, which will include the development and implementation of a research strategy to strengthen the evidence base for those prioritized interventions.
Numerical investigation of shear-flow free-surface turbulence and air entrainment at large Froude and Weber numbers
Authors: Yu Xiangming , Hendrickson Kelli , Campbell Bryce K. , Yue Dick K. P.
Published: October 2019

We investigate two-phase free-surface turbulence (FST) associated with an underlying shear flow under the condition of strong turbulence (SFST) characterized by large Froude ($Fr$) and Weber ($We$) numbers. We perform direct numerical simulations of three-dimensional viscous flows with air and water phases. In contrast to weak FST (WFST) with small free-surface distortions and anisotropic underlying turbulence with distinct inner/outer surface layers, we find SFST to be characterized by large surface deformation and breaking accompanied by substantial air entrainment. The interface inner/outer surface layers disappear under SFST, resulting in nearly isotropic turbulence with ${\sim}k^{-5/3}$ scaling of turbulence kinetic energy near the interface (where $k$ is wavenumber). The SFST air entrainment is observed to occur over a range of scales following a power law of slope $-10/3$. We derive this using a simple energy argument. The bubble size spectrum in the volume follows this power law (and slope) initially, but deviates from this in time due to a combination of ongoing broad-scale entrainment and bubble fragmentation by turbulence. For varying $Fr$ and $We$, we find that air entrainment is suppressed below critical values $Fr_{cr}$ and $We_{cr}$. When $Fr^{2}>Fr_{cr}^{2}$ and $We>We_{cr}$, the entrainment rate scales as $Fr^{2}$ when gravity dominates surface tension in the bubble formation process, while the entrainment rate scales linearly with $We$ when surface tension dominates.
OPEN BOOKS FOR CLOSED NON-ORIENTABLE 3–MANIFOLDS
Authors: GHANWAT ABHIJEET , PANDIT SUHAS , SELVAKUMAR A
Published: October 2019

In this note, we give a new proof of the existence of an open book decomposition for a closed non-orientable 3–manifold. This open book decomposition is analogous to a planar open book decomposition for a closed orientable 3–manifold. More precisely, in this note, we give an open book decomposition of a given closed non-orientable 3–manifold with the pages punctured Möbius bands. We also give an algorithm to determine the monodromy of this open book.
Shorting in Broad Daylight: Short Sales and Venue Choice
Authors: Reed Adam V. , Samadi Mehrdad , Sokobin Jonathan S.
Published: October 2019

Using a novel database on venue short sales and market design characteristics, we ask: Where do short sellers exploit their information advantage? Consistent with the prediction of Zhu (2014), we find that exchange short sales comprise a larger proportion of trading and are more informative about future prices than dark-pool short sales, particularly when there is greater competition among short sellers to trade and in the presence of short-lived information. When examining market design characteristics, we find that dark pools offering volume-weighted average price crossing attract more short sales, whereas those offering block trading attract fewer short sales.
Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect
Authors: Krebs Catharine E. , Ori Anil P.S. , Vreeker Annabel , Wu Timothy , Cantor Rita M. , Boks Marco P. M. , Kahn Rene S. , Olde Loohuis Loes M. , Ophoff Roel A.
Published: October 2019

Background

Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes and difficulty in adequately accounting for confounders like medication use.

Methods

We performed a differential expression analysis in a well-characterized BD case-control sample (Nsubjects= 480) by RNA sequencing of whole blood. We further performed co-expression network analysis, functional enrichment, and cell type decomposition, and integrated differentially expressed genes with genetic risk.

Results

While we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05,Ngenes= 976) rather than BD diagnosis itself (FDR < 0.05,Ngenes= 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD.

Conclusions

These findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but emphasize the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of this study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.
Incubation periods of enteric illnesses in foodborne outbreaks, United States, 1998–2013
Authors: Chai S. J. , Gu W. , O'Connor K. A. , Richardson L. C. , Tauxe R. V.
Published: October 2019

Early in a foodborne disease outbreak investigation, illness incubation periods can help focus case interviews, case definitions, clinical and environmental evaluations and predict an aetiology. Data describing incubation periods are limited. We examined foodborne disease outbreaks from laboratory-confirmed, single aetiology, enteric bacterial and viral pathogens reported to United States foodborne disease outbreak surveillance from 1998–2013. We grouped pathogens by clinical presentation and analysed the reported median incubation period among all illnesses from the implicated pathogen for each outbreak as the outbreak incubation period. Outbreaks from preformed bacterial toxins (Staphylococcus aureus, Bacillus cereusandClostridium perfringens) had the shortest outbreak incubation periods (4–10 h medians), distinct from that ofVibrio parahaemolyticus(17 h median). Norovirus, salmonella and shigella had longer but similar outbreak incubation periods (32–45 h medians); campylobacter and Shiga toxin-producingEscherichia colihad the longest among bacteria (62–87 h medians); hepatitis A had the longest overall (672 h median). Our results can help guide diagnostic and investigative strategies early in an outbreak investigation to suggest or rule out specific etiologies or, when the pathogen is known, the likely timeframe for exposure. They also point to possible differences in pathogenesis among pathogens causing broadly similar syndromes.
Couples’ affect dynamics: Associations with trait hostility and physical intimate partner violence
Authors: Tiberio Stacey S. , Capaldi Deborah M.
Published: October 2019

Whether men's and women's reciprocation of their intimate partners’ negative and positive affect during conflictual topic discussions accounted for the association between their trait hostility and perpetration of physical intimate partner violence (IPV) was examined within a dyadic model, using concurrent measurement. The work builds on that of Dr. Tom Dishion regarding hostile and coercive interactions in key relationships on risk outcomes and the importance of moment-by-moment influences in social interactions. Using dynamic development systems theory and a community sample of at-risk men (N= 156) and their female partners, the hypothesis that quicker negative and slower positive affect reactivity would account for physical IPV perpetration beyond trait hostility was tested. Results suggest that, for women, quicker negative affect reactivity partially explains the hostility IPV association, whereas for men, trait hostility of both partners best explained their perpetration of physical IPV. No support was found for positive affect reactivity as a protective relationship process for IPV involvement. Findings are in line with other studies indicating men were less likely to engage in negative reciprocity relative to women. Furthermore, findings highlight how both partners’ individual characteristics, communication patterns, and emotion regulation processes germane to the romantic relationship impact the likelihood of experiencing physical IPV.
The codevelopment of internalizing symptoms, externalizing symptoms, and cognitive ability across childhood and adolescence
Authors: Papachristou Efstathios , Flouri Eirini
Published: October 2019

Cognitive ability, externalizing symptoms, and internalizing symptoms are correlated in children. However, it is not known why they combine in the general child population over time. To address this, we used data on 17,318 children participating in the UK Millennium Cohort Study and followed-up five times between ages 3 and 14 years. We fitted three parallel-process latent growth curve models to identify the parallel unfolding of children's trajectories of internalizing symptoms, externalizing symptoms, and cognitive ability across this period. We also examined the effects of time-invariant (ethnicity, birth weight, maternal education and age at birth, and breastfeeding status) and time-varying covariates (maternal psychological distress and socioeconomic disadvantage) on the growth parameters of the trajectories. The results showed that the intercepts of the trajectories of cognitive ability and, particularly, externalizing symptoms were inversely correlated. Their linear slopes were also inversely correlated, suggesting parallel development. Internalizing symptoms were correlated positively with externalizing symptoms and inversely (and more modestly) with cognitive ability at baseline, but the slope of internalizing symptoms correlated (positively) only with the slope of externalizing symptoms. The covariates predicted 9% to 41% of the variance in the intercepts and slopes of all domains, suggesting they are important common risk factors. Overall, it appears that externalizing symptoms develop in parallel with both cognitive ability and internalizing symptoms from early childhood through to middle adolescence. Children on an increasing trajectory of externalizing symptoms are likely both increasing in internalizing symptoms and decreasing in cognitive skills as well, and are thus an important group to target for intervention.
Social vulnerability in cost-benefit analysis for flood risk management
Authors: Kind Jarl , Botzen W. J. Wouter , Aerts Jeroen C. J. H.
Published: October 2019

Traditional cost-benefit analyses (CBAs) of flood risk reduction measures usually ignore distributions of damages over populations, which disadvantages the poor. Instead, a CBA based on social welfare includes individual social vulnerability through relative impacts on consumption. If vulnerabilities are high, floods are catastrophic and cause poverty, migration or indirect deaths, and risk reductions have high social welfare values. For non-catastrophic risks, social welfare values of risks are relatively higher for vulnerable low-income households. We present a framework to integrate social vulnerability into CBAs, and show how financial protection reduces social flood vulnerability and provides welfare benefits. A case study illustrates that traditional CBAs underestimate the social welfare value of flood risk reduction measures, up to a factor of 30. Data on financial protection is however scarce, which hampers estimation of the social welfare value in practice. A solution is to increase financial protection of individuals, in addition to offering physical flood protection.
Determinants of early breastfeeding initiation and exclusive breastfeeding in Colombia
Authors: Finnie Sheridan , Peréz-Escamilla Rafael , Buccini Gabriela
Published: October 2019

Objective:

To identify modifiable risk factors associated with early initiation of breastfeeding (EIBF) and exclusive breastfeeding (EBF) in Colombia.

Design:

Cross-sectional study from the 2010 Colombia nationally representative Demographic Health Survey (DHS). Studied exposures were categorized into five hierarchical blocks of increasing proximity to the outcomes: household, maternal, health systems, child, and early feeding characteristics. The two outcomes examined were delayed breastfeeding initiation among infants <24 months and interruption of EBF among infants <6 months. Prevalence ratios were computed using Poisson regression analysis with robust error variance, adjusted for sampling weights, following a hierarchical modelling approach.

Setting:

Nationally representative cross-sectional survey from Colombia.

Participants:

The EIBF analytical sample included 6592 and the EBF sample 1512 women with young children.

Results:

EIBF prevalence was 65·6 % in children under 24 months and EBF was 43 % in infants under 6 months. Modifiable risk factors associated with delayed breastfeeding initiation were: C-section (PR = 2·08, CI 95 % = 1·92, 2·25), maternal overweight/obesity (PR = 1·09, CI 95 % = 1·01, 1·17), lack of skilled attendant at birth (PR = 1·09, CI 95 % = 1·01, 1·18). Modifiable risk factors for EBF interruption were C-section (PR = 1·12, CI 95 % = 1·02, 1·23) and prelacteal feeding (PR = 1·51, CI 95 % = 1·37, 1·68). Non-pregnancy intention was a protective factor for EBF interruption (PR = 0·82, CI 95 % = 0·72, 0·93).

Conclusions:

C-section, lack of skilled attendant at birth, prelacteal feeding, maternal nutritional status, and pregnancy intention were modifiable factors associated with suboptimal breastfeeding practices in Colombia.
Impact of informal cancer caregiving across the cancer experience: A systematic literature review of quality of life
Authors: Ochoa Carol Y. , Buchanan Lunsford Natasha , Lee Smith Judith
Published: October 2019

Objective

Informal caregiving may likely increase as the number of cancer survivors grows. Caregiving responsibilities can impact caregivers’ quality of life (QOL). Understanding the current state of the science regarding caregiving QOL could help inform future research and intervention development.

Methods

A systematic literature review in PubMed/Medline examined research on QOL among informal cancer caregivers and related psychosocial health outcomes. Original research articles in English, published between 2007 and 2017 about caregivers (aged >18 years) of adult cancer patients in the United States were included. Abstracted articles were categorized according to caregiving recipient's phase of survivorship (acute, middle to long-term, end of life/bereavement).

Results

Of 920 articles abstracted, 60 met inclusion criteria. Mean caregiver age ranged from 37 to 68 with the majority being female, non-Hispanic white, with at least a high school degree, and middle income. Almost half of the studies focused on caregivers who provided care for survivors from diagnosis through the end of active treatment. Studies examined physical health, spirituality, psychological distress, and social support. Differences in QOL were noted by caregiver age, sex, and employment status.

Significance of Results

Additional research includes the examination of the needs of diverse cancer caregivers and determines how additional caregiver characteristics (e.g., physical functioning, financial burden, etc.) affect QOL. This includes studies examining caregiver QOL in the phases following the cessation of active treatment and assessments of health systems, support services, and insurance to determine barriers and facilitators needed to meet the immediate and long-term needs of cancer caregivers.
Minimizing competition between glyphosate-resistant volunteer canola (Brassica napus) and glyphosate-resistant soybean: impact of soybean planting date and rate
Authors: Mierau Allyson , Johnson Eric N. , Gulden Robert H. , Weber Jessica D. , May William E. , Willenborg Christian J.
Published: October 2019

In recent years, soybean acreage has increased significantly in western Canada. One of the challenges associated with growing soybean in western Canada is the control of volunteer glyphosate-resistant (GR) canola, because most soybean cultivars are also glyphosate resistant. The objective of this research was to determine the impact of soybean seeding rate and planting date on competition with volunteer canola. We also attempted to determine how high seeding rate could be raised while still being economically feasible for producers. Soybean was seeded at five different seeding rates (targeted 10, 20, 40, 80, and 160 plants m−2) and three planting dates (targeted mid-May, late May, and early June) at four sites across western Canada in 2014 and 2015. Soybean yield consistently increased with higher seeding rates, whereas volunteer canola biomass decreased. Planting date generally produced variable results across site-years. An economic analysis determined that the optimal rate was 40 to 60 plants m−2, depending on market price, and the optimal planting date range was from May 20 to June 1.
Recommandations de Swiss Memory Clinics pour le diagnostic des démences
Authors: Bürge Markus , Bieri Gabriela , Brühlmeier Matthias , Colombo Françoise , Demonet Jean-Francois , Felbecker Ansgar , Georgescu Dan , Gietl Anton , Brioschi Guevara Andrea , Jüngling Freimut , Kirsch Eberhard , Kressig Reto W , Kulic Luka , Monsch Andreas U. , Ott Martin , Pihan Hans , Popp Julius , Rampa Luca , Rüegger-Frey Brigitte , Schneitter Marianne , Unschuld Paul Gerson , von Gunten Armin , Weinheimer Birte , Wiest Roland , Savaskan Egemen
Published: October 2019

Résumé. Le diagnostic précoce des atteintes cognitives, ressenties subjectivement ou rapportées par un tiers, est essentiel pour détecter des maladies neurodégénératives ou exclure des causes traitables telles que des pathologies de médecine interne, neurologiques ou psychiatriques. C’est la seule façon de garantir un traitement anticipé. Dans le cadre du projet 3.1 de la stratégie nationale en matière de démences 2014–2019 («Mise en place et extension d’un réseau de centres de compétences régionaux pour le diagnostic»), l’association Swiss Memory Clinics (SMC) s’est fixé pour objectif d’améliorer les normes de qualité en matière de diagnostic des démences et de soins de proximité dans ce domaine. Ces recommandations contiennent des directives d’ordre général sur le diagnostic et les différentes possibilités d’examens, et proposent des normes pour les procédures à appliquer. Elles expliquent en détail les différents éléments du diagnostic standard, tels que l’anamnèse, l’examen clinique, l’analyse de laboratoire, les tests neuropsychologiques et les procédures neuroradiologiques, et présentent des examens complémentaires pouvant alimenter les réflexions sur le diagnostic différentiel. Les principaux objectifs des recommandations SMC pour le diagnostic des démences sont les suivants: assurer l’accès à un diagnostic de haute qualité à un maximum de personnes atteintes, améliorer le diagnostic précoce de la démence, ainsi que proposer aux médecins de premier recours et aux collaborateurs de Memory Clinics un outil d’investigations diagnostiques utile.
c-Myc transactivates GP73 and promotes metastasis of hepatocellular carcinoma cells through GP73-mediated MMP-7 trafficking in a mildly hypoxic microenvironment
Authors: Liu Yiming , Zhou Sining , Shi Jieyao , Zhang Xiaodi , Shentu Linhui , Chen Zhi , Zhou Linfu
Published: October 2019

Golgi phosphoprotein 73 (GP73), encoded by GOLM1, is a highly expressed factor in hepatocellular carcinoma (HCC) cells and has been regarded for several years as a remarkable serum biomarker for the diagnosis of HCC. Recently, it was found that upregulation of GP73 promotes cancer metastasis, but the mechanism is complex, and it is even unclear how the gene is transactivated in HCC cells. In this study, it was discovered that c-Myc transactivated GP73 in a mildly hypoxic microenvironment and that the activation of c-Myc upregulated the expression of matrix metalloproteinase-7 (MMP-7). Moreover, it is shown that GP73 interacted with intracellular MMP-7 in the region of the cytoplasmic domain and facilitated the trafficking and secretion of MMP-7, resulting in cell metastasis. This study indicates that GP73 is transactivated by c-Myc and serves as a transporter in the trafficking of intracellular MMP-7 in HCC cells. These findings suggest that GP73 is a potential target for combating metastatic HCC.
Loss of CYLD accelerates melanoma development and progression in the Tg(Grm1) melanoma mouse model
Authors: de Jel Miriam Martha , Schott Mandy , Lamm Susanne , Neuhuber Winfried , Kuphal Silke , Bosserhoff Anja-Katrin
Published: October 2019

The deubiquitinase cylindromatosis (CYLD) is a well-known tumor suppressor, found to be down regulated in many cancer types including breast cancer, colon carcinoma and malignant melanoma. CYLD is suppressed in human melanoma cells by the transcriptional repressor SNAIL1 leading to an increase of their proliferative, invasive and migratory potential. To gain additional insights into the distinct function of this tumor suppressor gene a new mouse model Tg(Grm1)Cyld−/− was generated. Herewith, we demonstrate that Cyld-deficiency leads to earlier melanoma onset and accelerated tumor growth and metastasis in the GRM1 melanoma mouse model. First, RNA sequencing data revealed a potential role of CYLD in the regulation of genes involved in proliferation, migration and angiogenesis. Experiments using cell lines generated from both primary and metastatic melanoma tissue of Tg(Grm1) Cyld−/− and Tg(Grm1) Cyld+/+ mice confirmed that loss of CYLD enhances the proliferative and migratory potential, as well as the clonogenicity in vitro. Moreover, we could show that Cyld-knockout leads to increased vasculogenic mimicry and enhanced (lymph-) angiogenesis shown by tube formation assays, immunohistochemistry and mRNA expression analyses. In summary, our findings reveal new functional aspects of CYLD in the process of (lymph-) angiogenesis and demonstrate its importance in the early process of melanoma progression.
Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison
Authors: Sun Yan , Chang Suhua , Wang Fan , Sun Hongqiang , Ni Zhaojun , Yue Weihua , Zhou Hang , Gelernter Joel , Malison Robert T. , Kalayasiri Rasmon , Wu Ping , Lu Lin , Shi Jie
Published: October 2019

Alcohol-related behaviors are moderately heritable and have ethnic-specific characteristics. At present, genetic studies for alcohol dependence (AD) in Chinese populations are underrepresented. We are the first to conduct a genome-wide association study (GWAS) for AD using 533 male alcoholics and 2848 controls of Han Chinese ethnicity and replicate our findings in 146 male alcoholics and 200 male controls. We then assessed genetic effects on AD characteristics (drinking volume/age onset/Michigan Alcoholism Screening Test (MAST)/Barratt Impulsiveness Scale (BIS-11)), and compared the polygenic risk of AD in Han Chinese with other populations (Thai, European American and African American). We found and validated two significant loci, one located in 4q23, with lead SNP rs2075633*ADH1B (Pdiscovery = 6.64 × 10−16) and functional SNP rs1229984*ADH1B (Pdiscovery = 3.93 × 10−13); and the other located in 12q24.12-12q24.13, with lead SNP rs11066001*BRAP (Pdiscovery = 1.63 × 10−9) and functional SNP rs671*ALDH2 (Pdiscovery = 3.44 × 10−9). ADH1B rs1229984 was associated with MAST, BIS_total score and average drinking volume. Polygenic risk scores from the Thai AD and European American AD GWAS were significantly associated with AD in Han Chinese, which were entirely due to the top two loci, however there was no significant prediction from African Americans. This is the first case-control AD GWAS in Han Chinese. Our findings demonstrate that these variants, which were highly linked with ALDH2 rs671 and ADH1B rs1229984, were significant modulators for AD in our Han Chinese cohort. A larger replication cohort is still needed to validate our findings.
Metformin use and risk of gastric adenocarcinoma in a Swedish population-based cohort study
Authors: Zheng Jiaojiao , Xie Shao-Hua , Santoni Giola , Lagergren Jesper
Published: October 2019

Background

Whether or not the use of metformin decreases the risk of gastric adenocarcinoma is unclear.

Methods

This was a population-based cohort study in 2005–2015. Associations between metformin use and gastric non-cardia and cardia adenocarcinomas were examined within two cohorts; a diabetes cohort of participants using anti-diabetes medications, and a matched cohort of common-medication users, where metformin non-users were frequency matched (10:1) with metformin users for sex and age. Multivariable Cox proportional hazard regression analyses provided hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, calendar year, comorbidity, Helicobacter pylori eradication treatment, use of non-steroidal anti-inflammatory drugs or aspirin and use of statins.

Results

During the follow-up for a median of 5.8 years, 892 (0.1%) participants in the diabetes cohort and 6395 (0.1%) participants in the matched cohort of common-medication users developed gastric adenocarcinoma. Metformin users had no significantly decreased risk of gastric non-cardia adenocarcinoma (diabetes cohort: HR 0.93, 95% CI 0.78–1.12; matched cohort: HR 1.30, 95% CI 1.18–1.42) or cardia adenocarcinoma (diabetes cohort: HR 1.49, 95% CI 1.09–2.02; matched cohort: HR 1.58, 95% CI 1.38–1.81) compared with non-users in both cohorts.

Conclusions

This cohort study with <10 years of follow-up suggests metformin use may not prevent gastric adenocarcinoma.
ACT001, a novel PAI-1 inhibitor, exerts synergistic effects in combination with cisplatin by inhibiting PI3K/AKT pathway in glioma
Authors: Xi Xiaonan , Liu Ning , Wang Qianqian , Chu Yahui , Yin Zheng , Ding Yahui , Lu Yaxin
Published: October 2019

PAI-1 plays significant roles in cancer occurrence, relapse and multidrug resistance and is highly expressed in tumours. ACT001, which is currently in phase I clinical trials for the treatment of glioblastoma (GBM). However, the detailed molecular mechanism of ACT001 is still unclear. In this study, we investigated the effects of ACT001 on glioma cell proliferation and clarified its mechanism. We discovered that PAI-1 was the direct target of ACT001 by a cellular thermal shift assay. Then, the interaction between ACT001 and PAI-1 was verified by Biacore assays, thermal stability assays and ACT001 probe assays. Furthermore, from the proteomic analysis, we found that ACT001 directly binds PAI-1 to inhibit the PI3K/AKT pathway, which induces the inhibition of glioma cell proliferation, invasion and migration. Moreover, the combination of ACT001 and cisplatin showed a synergistic effect on the inhibition of glioma in vitro and in vivo. In conclusion, our findings demonstrate that PAI-1 is a new target of ACT001, the inhibition of PAI-1 induces glioma inhibition, and ACT001 has a synergistic effect with cisplatin through the inhibition of the PAI-1/PI3K/AKT pathway.
Progranulin attenuates liver fibrosis by downregulating the inflammatory response
Authors: Yoo Wonbeak , Lee Jaemin , Noh Kyung Hee , Lee Sangmin , Jung Dana , Kabir Mohammad Humayun , Park Dongmin , Lee Cheolju , Kwon Ki-Sun , Kim Ji-Su , Kim Seokho
Published: October 2019

Progranulin (PGRN) is a cysteine-rich secreted protein expressed in endothelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties, being implicated in tissue remodeling, development, inflammation, and protein homeostasis. However, these findings are controversial, and the role of PGRN in liver disease remains unknown. In the current study, we examined the effect of PGRN in two different models of chronic liver disease, methionine‐choline‐deficient diet (MCD)-induced non-alcoholic steatohepatitis (NASH) and carbon tetrachloride (CCl4)-induced liver fibrosis. To induce long-term expression of PGRN, PGRN-expressing adenovirus was delivered via injection into the tibialis anterior. In the CCl4-induced fibrosis model, PGRN showed protective effects against hepatic injury, inflammation, and fibrosis via inhibition of nuclear transcription factor kappa B (NF-κB) phosphorylation. PGRN also decreased lipid accumulation and inhibited pro-inflammatory cytokine production and fibrosis in the MCD-induced NASH model. In vitro treatment of primary macrophages and Raw 264.7 cells with conditioned media from hepatocytes pre-treated with PGRN prior to stimulation with tumor necrosis factor (TNF)-α or palmitate decreased their expression of pro-inflammatory genes. Furthermore, PGRN suppressed inflammatory and fibrotic gene expression in a cell culture model of hepatocyte injury and primary stellate cell activation. These observations increase our understanding of the role of PGRN in liver injury and suggest PGRN delivery as a potential therapeutic strategy in chronic inflammatory liver disease.
c-Myc shuttled by tumour-derived extracellular vesicles promotes lung bronchial cell proliferation through miR-19b and miR-92a
Authors: Borzi Cristina , Calzolari Linda , Ferretti Anna M. , Caleca Laura , Pastorino Ugo , Sozzi Gabriella , Fortunato Orazio
Published: October 2019

Lung cancer causes approximately one fifth of all cancer deaths. Tumour cells actively communicate with the surrounding microenvironment to support malignant progression. Extracellular vesicles (EVs) play a pivotal role in intercellular communication and modulate recipient cells by delivering their contents, including proteins and nucleic acids such as microRNAs (miRNAs). We isolated EVs from the conditioned medium (CM) of human lung cancer cell lines and plasma of lung cancer patients and cancer-free smokers using an ultracentrifugation method. A significant increase in bronchial HBEC-KRASV12high cell proliferation, confirmed by cell cycle analysis, was observed after treatment with cancer-derived EVs. Lung cancer-derived EVs induced transcription of the pri-miR-92a gene, resulting in the overexpression of mature miR-19b and miR-92a in recipient bronchial cells. Modulation of these two miRNAs using miRNA mimics or inhibitors confirmed their ability to promote proliferation. In silico analysis and experimental validation showed that miR-19b and miR-92a impaired the TGF-beta (TGFB) pathway and identified TGFBRI and TGFBRII as target genes involved in EV-mediated bronchial cell proliferation. Interestingly, the oncoprotein c-Myc, a well-known miR-17-92 cluster activator, was detected only in the EVs derived from lung cancer patients and cell lines and was able to modulate the proliferation of HBEC-KRASV12high recipient cells. These data support the role of c-Myc shuttling in lung cancer-derived EVs in inducing the upregulation of onco-miR-19b and miR-92a expression with concomitant impairment of the TGFB signalling pathway in recipient cells.