bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hand-hygiene mitigation strategies against global disease spreading through the air transportation network
Authors: Nicolaides Christos , Avraam Demetris , Cueto-Felgueroso Luis , González Marta C. , Juanes Ruben 
Published: January 2019

ABSTRACTHand hygiene is considered as an efficient and cost-effective way to limit the spread of diseases and, as such, it is recommended by both the World Health Organization (WHO) and the Centres for Disease Control and Prevention (CDC). While the effect of hand washing on individual transmissibility of a disease has been studied through medical and public-health research, its potential as a mitigation strategy against a global pandemic has not been fully explored yet. In this study, we investigate contagion dynamics through the world air transportation network and analyze the impact of hand-hygiene behavioural changes of airport population against the spread of infectious diseases worldwide. Using a granular dataset of the world air transportation traffic, we build a detailed individual mobility model that controls for the correlated and recurrent nature of human travel and the waiting-time distributions of individuals at different locations. We perform a Monte-Carlo simulation study to assess the impact of different hand-washing mitigation strategies at the early stages of a global epidemic. From the simulation results we find that increasing the hand cleanliness homogeneously at all airports in the world can inhibit the impact of a potential pandemic by 24 to 69%. By quantifying and ranking the contribution of the different airports to the mitigation of an epidemic outbreak, we identify ten key airports at the core of a cost-optimal deployment of the hand-washing strategy: increasing the engagement rate at those locations alone could potentially reduce a world pandemic by 8 to 37%. This research provides evidence of the effectiveness of hand hygiene in airports on the global spread of infectious diseases, and has important implications for the way public-health policymakers may design new effective strategies to enhance hand hygiene in airports through behavioral changes.
Werner syndrome helicase is a selective vulnerability of microsatellite instability-high tumor cells
Authors: Lieb Simone , Blaha-Ostermann Silvia , Kamper Elisabeth , Ehrenhöfer-Wölfer Katharina , Schlattl Andreas , Wernitznig Andreas , Lipp Jesse J. , Nagasaka Kota , Bader Gerd , Neumüller Ralph A. , Kraut Norbert , Pearson Mark A. , Petronczki Mark , Wöhrle Simon 
Published: January 2019

AbstractTargeted cancer therapy is based on exploiting selective dependencies of tumor cells. By leveraging recent large-scale genomic profiling and functional screening of cancer cell lines we identified Werner syndrome helicase (WRN) as a novel specific vulnerability of microsatellite instability-high (MSI-H) cancer cells. MSI, caused by defective mismatch repair is frequently detected in human malignancies, in particular in colorectal, endometrial and gastric cancers. We demonstrate that WRN inactivation selectively impairs the viability of MSI-H but not microsatellite stable (MSS) colorectal and endometrial cancer cell lines. In MSI-H cells, WRN loss results in the emergence of chromosome breaks, chromatin bridges and micronuclei highlighting defective genome integrity. WRN variants harboring mutations abrogating the ATPase function of WRN helicase fail to rescue the viability phenotype of WRN-depleted MSI-H colorectal cells. Our study suggests that pharmacological inhibition of WRN helicase function might represent a novel opportunity to develop a targeted therapy for MSI-H cancers.
Cross-reactivity of a rice NLR immune receptor to distinct effectors from the blast pathogen leads to partial disease resistance
Authors: Varden Freya A. , Saitoh Hiromasa , Yoshino Kae , Franceschetti Marina , Kamoun Sophien , Terauchi Ryohei , Banfield Mark J. 
Published: January 2019

ABSTRACTUnconventional integrated domains in plant intracellular immune receptors (NLRs) can directly bind translocated pathogen effector proteins to initiate an immune response. The rice immune receptor pairs Pik-1/Pik-2 and RGA5/RGA4 both use integrated heavy metal-associated (HMA) domains to bind the Magnaporthe oryzae effectors AVR-Pik and AVR-Pia, respectively. These effectors both belong to the MAX effector family and share a core structural fold, despite being divergent in sequence. How integrated domains maintain specificity of recognition, even for structurally similar effectors, has implications for understanding plant immune receptor evolution and function. Here we show that the rice NLR pair Pikp-1/Pikp-2 triggers an immune response leading to partial disease resistance towards the “mismatched” effector AVR-Pia in planta, and that the Pikp-HMA domain binds AVR-Pia in vitro. The HMA domain from another Pik-1 allele, Pikm, is unable to bind AVR-Pia, and does not trigger a response in plants. The crystal structure of Pikp-HMA bound to AVR-Pia reveals a different binding interface compared to AVR-Pik effectors, suggesting plasticity in integrated domain/effector interactions. This work shows how a single NLR can bait multiple pathogen effectors via an integrated domain, and may enable engineering immune receptors with extended disease resistance profiles.
Commonly used insect repellents hide human odors from Anopheles mosquitoes
Authors: Afify Ali , Betz Joshua F. , Riabinina Olena , Potter Christopher J. 
Published: January 2019

AbstractThe mode of action for most mosquito repellents is unknown. This is primarily due to the difficulty in monitoring how the mosquito olfactory system responds to repellent odors. Here, we used the Q-system of binary expression to enable activity-dependent Ca2+ imaging in olfactory neurons of the African malaria mosquito Anopheles coluzzii. This system allows neuronal responses to common insect repellents to be directly visualized in living mosquitoes from all olfactory organs including the antenna. The synthetic repellents DEET and IR3535 did not activate Odorant Receptor Co-Receptor (Orco) expressing olfactory receptor neurons (ORNs) at any concentration, while picaridin weakly activated ORNs only at high concentrations. In contrast, natural repellents (i.e. lemongrass oil and eugenol) strongly activated small numbers of ORNs in the mosquito antennae at low concentrations. We determined that DEET, IR3535, and picaridin decrease the response of Orco expressing ORNs when these repellents are physically mixed with activating human-derived odorants. We present evidence that synthetic repellents may primarily exert their olfactory mode of action by decreasing the amount of activating ligand reaching ORNs. These results suggest that synthetic repellents disruptively change the chemical profile of host scent signatures on the skin surface rendering humans invisible to mosquitoes.
The microstructure of laminin-111 compensates for dystroglycan loss in functional differentiation of mammary epithelial cells
Authors: Kent A , Mayer N , Inman JL , Hochman-Mendez C , Bissell MJ , Robertson C 
Published: January 2019

Abstract:Laminin-111, an extracellular matrix (ECM) glycoprotein found in the basement membrane of mammary gland epithelia, is essential for lactation. In mammary epithelial cells, dystroglycan (Dg) is believed to be necessary for polymerization of laminin-111 into networks, thus we asked whether correct polymerization could compensate for Dg loss. Artificially polymerized laminin-111 and the laminin-glycoprotein mix Matrigel, both formed branching, spread networks with fractal dimensions from 1.7-1.8, whereas laminin-111 in media formed small aggregates without fractal properties (a fractal dimension of 2). In Dg knockout cells, either polymerized laminin-111 or Matrigel readily attached to the cell surface, whereas aggregated laminin-111 did not. In contrast, polymerized and aggregated laminin-111 bound similarly to Dg knock-ins. Both polymerized laminin-111 and Matrigel promoted cell rounding, clustering, formation of tight junctions, and expression of milk proteins, whereas aggregated Ln-1 did not attach to cells or promote functional differentiation.HighlightsLaminin assembles into a fractal network when in presence of either the cell surface receptor dystroglycan or acidic glycoproteins or an acidic buffer.When this microstructure is recreated with an acidic treatment, laminin binds readily to dystroglycan null cells and induces functional differentiation of mammary epithelial cells.
Positive effects of low LDL-C and statins on bone mineral density: an integrated epidemiological observation analysis and Mendelian Randomization study
Authors: Hoi-Yee Li Gloria , Cheung Ching-Lung , Chun-Ming Au Philip , Choon-Beng Tan Kathryn , Chi-Kei Wong Ian , Sham Pak-Chung 
Published: January 2019

AbstractBackgroundLow-density lipoprotein cholesterol (LDL-C) is suggested to play a role in osteoporosis but its association with bone metabolism remains unclear. Effects of LDL-C-lowering drugs on bone are also controversial. We aim to determine whether LDL-C is linked causally to BMD and assess the effects of LDL-C-lowering drugs on BMD.MethodsAssociation between blood lipid levels and BMD was examined by epidemiological observation analyses in US representative cohort NHANES III (N=3,638) and Hong Kong Osteoporosis Study (HKOS; N=1,128). Two-sample Mendelian Randomization (MR), employing genetic data from GWAS of blood lipids (N=188,577), total body BMD (TB-BMD) (N=66,628) and estimated BMD (eBMD) (N=142,487), was performed to infer causality between blood lipids and BMD. Genetic proxies for LDL-C-lowering drugs were used to examine the drugs’ effects on BMD.ResultsIn NHANES III cohort, each SD decrease in LDL-C was associated with 0.045 SD increase in femoral neck BMD (95% CI: 0.009 to 0.081; P=0.015). A similar increase in BMD was observed in HKOS at femoral neck and lumbar spine. In MR analysis, decrease in genetically predicted LDL-C was associated with increase in TB-BMD [estimate per SD decrease, 0.038 (95% CI: 0.002 to 0.074); P=0.038] and eBMD [0.076 (0.042 to 0.111); P=1.20×10−5]. Reduction of TB-BMD was causally associated with increased LDL-C [0.035 (0.033 to 0.066); P=0.034]. Statins’ LDL-C-lowering proxies were associated with increased TB-BMD [0.18 (0.044 to 0.316); P=9.600×10−3] and eBMD [0.143 (0.062 to 0.223); P=5.165×10−4].ConclusionsNegative causal association exists between LDL-C level and BMD. Statins’ LDL-C-lowering effect increases BMD, suggesting its protective effect on bone.
Inter-individual Variability of Functional Connectivity in Awake and Anesthetized Rhesus Monkeys
Authors: Xu Ting , Sturgeon Darrick , Ramirez Julian S.B. , Froudist-Walsh Seán , Margulies Daniel S. , Schroeder Charlie E. , Fair Damien A. , Milham Michael P. 
Published: January 2019

ABSTRACTBackgroundNonhuman primate models (NHP) are commonly used to advance our understanding of brain function and organization. However, to date, they have offered few insights into individual differences among NHPs. In large part, this is due to the logistical challenges of NHP research, which limit most studies to five subjects or fewer.MethodsWe leveraged the availability of a large-scale open NHP imaging resource to provide an initial examination of individual differences in the functional organization of the nonhuman primate brain. Specifically, we selected one awake fMRI dataset (Newcastle: n = 10) and two anesthetized fMRI data sets (Oxford: n = 19; UC-Davis: n = 19) to examine individual differences in functional connectivity characteristics across the cortex, as well as potential state dependencies.ResultsWe noted significant individual variations of functional connectivity across the macaque cortex. Similar to the findings in human, during the awake state, the primary sensory and motor cortices showed lower variability than the high-order association regions. This variability pattern was significantly correlated with T1w/T2w map, the degree of long-distance connectivity, but not short-distance connectivity. However, the inter-individual variability under anesthesia exhibited a very distinct pattern, with lower variability in medial frontal cortex, precuneus and somatomotor regions and higher variability in the lateral ventral frontal and insular cortices.ConclusionsThis work has implications for our understanding of the evolutionary origins of individual variation in the human brain, as well as methodological implications that must be considered in any pursuit to study individual variation in NHP models.
Distribution Pattern and Diversity Maintenance Mechanism of the Denitrifier Community in Alkaline Copper Mine Drainage
Authors: Liu Jinxian , Li Cui , Luo Zhengming , Wang Xue , Bao Jiabing , Chai Baofeng 
Published: January 2019

ABSTRACTDenitrifiers have been shown to vary in abundance and diversity across the environmental gradients; however, the factors that determine the type and magnitude of the response of the denitrifier communities remain unclear. In order to reveal the effects of alkaline mine drainage (AlkMD) on the denitrifier community composition and diversity maintenance mechanism in a tailings reservoir, we examined the diversity patterns and adaptation mechanisms of different denitrifier communities in Shibahe copper tailings water in Zhongtiaoshan, China. The results showed that the α-diversity of Proteobacteria and the nosZI-bearing denitrifier community in downstream seeping water (SDSW) were the highest, while those in the upstream tailings water (STW1) were the lowest. The highest nirS and nirK-bearing denitrifier community α-diversity were measured in STW1, and the lowest in STW3. The community dissimilarity of the denitrifier communities was strongly correlated with environment parameters, but the factors varied in different groups. The Proteobacteria community was correlated strongly with nitrate (NO3-); the nirS and nirK-bearing denitrifier communities were correlated strongly with pH, total carbon (TC), NO3- and ammonia nitrogen (NH4+), and the nosZI-bearing denitrifier community was correlated strongly with total organic carbon (TOC), dissolved oxygen (DO), NO3-, electroconductibility (EC) and spatial distance (PCNM1). Our results indicated that environmental changes were valuable index reflecting variations in denitrifier community composition in AlkMD. Additionally, the findings in this study are helpful in understanding the relationship between the microbial community composition changes and functional adaptation in different ecosystems.IMPORTANCEMetal mine tailings pond is an important site polluted by heavy metals and nitrogen, and excess nitrogen is mainly removed by microorganisms through denitrification. Although many studies have reported that Proteobacteria is the main denitrifying bacteria, and nirS, nirK and nosZ-bearing denitrifiers are three key functional groups in denitrification process. However, less is known of their response to discharge of alkaline copper tailings wastewater (AlkMD). AlkMD exerts an adverse impact on composition and structure of denitrifying bacteria community. The change of nitrogen and carbon concentration along the flow direction of wastewater resulted in the change of denitrifying bacteria community diversity pattern, that is to say, environmental filtering force drove the denitrifier community structure in this highly polluted ecosystem.
ATAC-seq signal processing and recurrent neural networks can identify RNA polymerase activity
Authors: Tripodi Ignacio J. , Chowdhury Murad , Dowell Robin 
Published: January 2019

AbstractNascent transcription assays are the current gold standard for identifying regions of active transcription, including markers for functional transcription factor (TF) binding. Here we present a signal processing-based model to determine regions of active transcription genome-wide using the simpler assay for transposase-accessible chromatin, followed by high-throughput sequencing (ATAC-seq). The focus of this study is twofold: First, we perform a frequency space analysis of the “signal” generated from ATAC-seq experiments’ short reads, at a single-nucleotide resolution, using a discrete wavelet transform. Second, we explore different uses of neural networks to combine this signal with its underlying genome sequence in order to classify ATAC-seq peaks on the presence or absence of bidirectional transcription. We analyze the performance of different data encoding schemes and machine learning architectures, and show how a hybrid signal/sequence representation classified using recurrent neural networks (RNNs) yields the best performance across different cell types.Contactrobin.dowell@colorado.edu
Obesity is a significant risk factor for ileostomy site incisional hernia following reversal
Authors: De Robles Marie Shella , Bakhtiar Arsalan , Young Christopher J. 
Published: January 2019

BackgroundIncisional hernia following ileostomy reversal can cause significant morbidity, impaired quality of life, and burden on the healthcare system. This study aimed to determine the prevalence of ileostomy site incisional hernia following reversal and to identify possible risk factors for its development.MethodsThis was a retrospective cohort study involving consecutive patients who underwent ileostomy reversal between November 1999 to February 2015 by a single surgeon. Primary outcome analysed was incisional hernia occurrence at the previous stoma site.ResultsTwo hundred and twenty‐four ileostomy reversals were identified. The most common indication for ileostomy construction was colorectal cancer, followed by inflammatory bowel disease and diverticulosis. The stomas were either a loop (75%), end‐loop (24%) or end ileostomy (1%). The mean time interval from the stoma creation to reversal was 6.1 months (range 2–69, SD 7.1). After a mean follow‐up of 30.7 months (range 10–89, SD 15.1), 12 patients (5%) developed a hernia at the previous stoma. The mean time for hernia occurrence was 25.2 months (range 3–126, SD 32). Patients who developed ileostomy site incisional hernia were more likely to have a higher body mass index (28.1 versus 26.3, P = 0.007).ConclusionAlthough we found a lower rate of incisional hernias after reversal of ileostomies than reported elsewhere in the literature, it remains a significant clinical problem. Obesity is a significant risk factor for ileostomy‐site incisional hernia.
Factors controlling the variation in organic carbon stocks in agricultural soils of Germany
Authors: Vos Cora , Don Axel , Hobley Eleanor U. , Prietz Roland , Heidkamp Arne , Freibauer Annette 
Published: January 2019

This study gives an overview of soil organic carbon (SOC) stocks in Germany's agricultural soils, and quantifies and explains the influence of explanatory variables such as land use and management, soil type and climate. Over 2500 agricultural sites were sampled and their SOC stocks determined, together with other soil properties. Machine‐learning algorithms were used to identify the most important variables. Land use, land‐use history, clay content and electrical conductivity were the main predictors in the topsoil, whereas bedrock material, relief and electrical conductivity governed the variation in subsoil carbon stocks. We found that 32% of all soil profiles were anthropogenically transformed. The influence of climate variables was surprisingly small, whereas site variables, in particular in the subsoil, explained a large proportion of the variation in soil carbon. The understanding of SOC dynamics at the regional scale requires a thorough description of the spatial variation in soil properties. The effect of agronomic management on SOC stocks was important near the soil surface, but was mainly attributable to land use (grassland or arable and not to other management factors.Highlights

Factors affecting spatial variation of soil organic carbon stocks are largely unknown.
More than 200 possible predictors for this variation were assessed for over 2500 sites.
Land use (history), texture, electrical conductivity, bedrock and relief were main controlling factors of carbon stock variation.
Aggregation and carbon storage capacity of soil determine much of the spatial variation in carbon stocks.
Canine sterile steroid‐responsive lymphadenitis in 49 dogs
Authors: Ribas Latre A. , McPartland A. , Cain D. , Walker D. , Black V. , Van Den Steen N. , Warman S. , Battersby I. , Murtagh K. , Silvestrini P. , Batchelor D. , Tappin S. W. 
Published: January 2019

ObjectivesTo report clinical and laboratory features, treatment responses and outcome in dogs diagnosed with sterile steroid‐responsive lymphadenitis in the United Kingdom.Materials and MethodsMedical records of dogs diagnosed with sterile steroid‐responsive lymphadenitis from 2009 to 2016 at six specialist referral centres were evaluated retrospectively.ResultsThe study included 49 dogs. Springer spaniels appeared to be over‐represented (16 of 49 dogs). Young dogs (median age: 3 years and 9 months) and females (31 of 49) were frequently affected. Clinical presentation was variable, with pyrexia (39 of 49), lethargy (35 of 49) and anorexia (21 of 49) the most commonly reported clinical signs. Lymph node cytology or histopathology demonstrated neutrophilic, pyogranulomatous, granulomatous or necrotising lymphadenitis without a detectable underlying cause in all cases. Because a sterile immune‐mediated aetiology was suspected, all dogs received prednisolone, which was followed by rapid resolution of clinical signs and lymphadenopathy in most cases.Clinical SignificanceSterile steroid‐responsive lymphadenitis should be considered in dogs with pyrexia of unknown origin with inflammatory lymphadenopathy if no underlying cause can be found and often responds well to immunosuppressive corticosteroid therapy.
Insight into the impact of vitamin D on cardiovascular outcomes in chronic kidney disease
Authors: Junarta Joey , Jha Vivekanand , Banerjee Debasish 
Published: January 2019

ABSTRACTPatients with chronic kidney disease (CKD) experience excess cardiovascular morbidity and mortality that is unexplained by traditional cardiovascular risk factors. Vitamin D deficiency is highly prevalent in CKD and is associated with increased cardiovascular mortality in both the general population and in CKD patients. Vitamin D supplementation is a reasonably safe and simple intervention and meta‐analyses of observational studies have suggested that vitamin D supplementation in CKD improves cardiovascular mortality. However, randomized controlled trials examining the impact of vitamin D supplementation in improving surrogate markers of cardiovascular structure and function remain inconclusive. This review investigates the impact of vitamin D supplementation on surrogate end‐points and cardiovascular events from trials in CKD; and discusses why results have been heterogenous, particularly critiquing the effect of different dosing regimens and the failure to take into account the implications of vitamin D supplementation in study participants with differing vitamin D binding protein genotypes.