bluuebunny/crossref_metadata_2025 huggingface dataset:
Work tool-related eye injuries: Helsinki Ocular Trauma Study
Authors: Sahraravand Ahmad , Haavisto Anna-Kaisa , Puska Päivi , Leivo Tiina
Published: December 2019

Purpose

To quantify and characterize the epidemiology, treatments, long-term outcome, and use of resources for work tool-related eye injuries and their severity.

Methods

We included all new patients with a work tool-related eye injury treated at the Helsinki University Eye Hospital in 1 year. The data were from hospital records, examinations, and patient questionnaires. The follow-ups were at 3 months and 6 years.

Results

Work tools caused 3% (37/1151) of all eye injuries. The mean age was 37 and 84% were men. Most injuries (84%) occurred at work (17) or at home (15). There were 14 minor injuries, 12 contusions, 9 open globe injuries (OGI), and 2 eyelid wounds. The annual incidence of work tool-related eye injuries was 2.4/100,000 and hospitalization 0.6/100,000. At 6-year follow-up, we re-examined 18 patients and 17 were interviewed by phone. Four patients were blinded. We recorded 690 sick leave days and 43 major operations. No traumatic glaucoma was diagnosed. Fifteen patients needed lifelong follow-up. Permanent impairment occurred in 30% (11) of work tool-related eye injuries, from whom, nine were caused by manual tools. Work tools comprised 10% of the permanently impaired, but 2.5% of the non-permanently impaired cases among all eye injuries (1151).

Conclusion

The proportional difference between the permanently impaired and the non-permanently impaired was higher in work tool-related eye injuries than other causes reported in previous Helsinki Ocular Trauma Studies. High-risk injuries were mainly caused by manual tools and nails and resulted in OGI.
Characterizing health state utilities associated with Duchenne muscular dystrophy: a systematic review
Authors: Szabo Shelagh M. , Audhya Ivana F. , Malone Daniel C. , Feeny David , Gooch Katherine L.
Published: December 2019

Background

Preferences for health states for Duchenne muscular dystrophy (DMD) are necessary to assess costs and benefits of novel therapies. Because DMD progression begins in childhood, the impact of DMD on health-related quality-of-life (HRQoL) affects preferences of both DMD patients and their families. The objective of this review was to synthesize published evidence for health state utility from the DMD patient and caregiver perspectives.

Methods

A systematic review was performed using MEDLINE and Embase, according to best practices. Data were extracted from studies reporting DMD patient or caregiver utilities; these included study and patient characteristics, health states considered, and utility estimates. Quality appraisal of studies was performed.

Results

From 888 abstracts, eight publications describing five studies were identified. DMD utility estimates were from preference-based measures presented stratified by ambulatory status, ventilation, and age. Patient (or patient–proxy) utility estimates ranged from 0.75 (early ambulatory DMD) to 0.05 (day-and-night ventilation). Caregiver utilities ranged from 0.87 (for caregivers of adults with DMD) to 0.71 (for caregivers of predominantly childhood patients). Both patient and caregiver utilities trended lower with higher disease severity. Variability in utilities was observed based on instrument, respondent type, and country. Utility estimates for health states within non-ambulatory DMD are under reported; nor were utilities for DMD-related health states such as scoliosis or preserved upper limb function identified.

Conclusion

Published health state utilities document the substantial HRQoL impacts of DMD, particularly with disease progression. Additional research in patient utilities for additional health states, particularly in non-ambulatory DMD patients, is warranted.
Haemodynamic efficacy of microaxial left ventricular assist device in cardiogenic shock: a systematic review and meta-analysis
Authors: van Dort D. I. M. , Peij K. R. A. H. , Manintveld O. C. , Hoeks S. E. , Morshuis W. J. , van Royen N. , Ten Cate T. , Geuzebroek G. S. C
Published: December 2019

The Impella percutaneous mechanical circulatory support device is designed to augment cardiac output and reduce left ventricular wall stress and aims to improve survival in cases of cardiogenic shock. In this meta-analysis we investigated the haemodynamic effects of the Impella device in a clinical setting. We systematically searched all articles in PubMed/Medline and Embase up to July 2019. The primary outcomes were cardiac power (CP) and cardiac power index (CPI). Survival rates and other haemodynamic data were included as secondary outcomes. For the critical appraisal, we used a modified version of the U.S. Department of Health and Human Services quality assessment form. The systematic review included 12 studies with a total of 596 patients. In 258 patients the CP and/or CPI could be extracted. Our meta-analysis showed an increase of 0.39 W [95% confidence interval (CI): 0.24, 0.54], (p = 0.01) and 0.22 W/m2 (95% CI: 0.18, 0.26), (p < 0.01) for the CP and CPI, respectively. The overall survival rate was 56% (95% CI: 0.50, 0.62), (p = 0.09). The quality of the studies was moderate, mostly due to the presence of confounders. Our study suggests that in patients with cardiogenic shock, Impella support seems effective in augmenting CP(I). This study merely investigates the haemodynamic effectiveness of the Impella device and does not reflect the complete clinical impact for the patient.
The contribution of ‘chitoumou’, the edible caterpillar Cirina butyrospermi, to the food security of smallholder farmers in southwestern Burkina Faso
Authors: Payne Charlotte L. R. , Badolo Athanase , Cox Sioned , Sagnon Bakary , Dobermann Darja , Milbank Charlotte , Scarborough Pete , Sanon Antoine , Bationo Fernand , Balmford Andrew
Published: December 2019

Edible insects have been advocated as a means to combat food insecurity, which is prevalent in West Africa. In this study we look at the contribution of the shea caterpillar Cirina butyrospermi, colloquially known as ‘chitoumou’, to the food security of smallholder households in rural southwestern Burkina Faso. We used a mixed methods approach to understand the relationship between caterpillar collection, consumption, and sale by smallholder households, and their seasonal food security status. We found that caterpillars are an important source of food and income for households, significantly increasing the household consumption of animal protein and, with shea nuts, representing the main income source for the majority of women. We also found that food security is higher during caterpillar season, and that household-level food security during this season can be predicted by the amount of caterpillars collected, consumed and sold. However, this relationship holds only during the caterpillar season, suggesting that the positive impact of caterpillars on food security is temporally limited. We conclude that the shea caterpillar is an example of an edible insect that is crucial for seasonal food security in a widespread agricultural system.
In vitro probiotic characterization of high GABA producing strain Lactobacilluas brevis DSM 32386 isolated from traditional “wild” Alpine cheese
Authors: Mancini Andrea , Carafa Ilaria , Franciosi Elena , Nardin Tiziana , Bottari Benedetta , Larcher Roberto , Tuohy Kieran M.
Published: December 2019

Purpose

γ-Aminobutyric acid (GABA) is recognised as a potential metabolic bioactive food ingredient with increasing evidence of its effects on the gut-brain axis and systemic metabolic health. Different lactic acid bacteria are capable of producing GABA, particularly strains of Lactobacillus brevis. In this study, we characterized a Lb. brevis isolated from traditional alpine cheese (Lb. brevis DSM 32386) for its ability to accumulate high levels of GABA in the culture medium and for other important probiotic phenotypic traits.

Methods

In vitro analysis were used to study the Lb. brevis DSM 32386 probiotic traits and the gene expression involved in GABA production

Result

Lactobacillus brevis DSM 32386 converted monosodium glutamate to GABA more efficiently than the type strain Lb. brevis DSM 20054, resulting in more than 200% of GABA produced. This ability seemed to be related to the higher transcriptional activation of the gene encoding for the glutamate (gad) decarboxylase antiporter (gadC) and regulator (gadR). Lactobacillus brevis DSM 32386 performed well in vitro under the stress conditions mimicking the gastro-intestinal tract, being resistant to acid pH (pH 2.5) and growing in simulated pancreatic fluid and 0.3% ox-bile.

Conclusion

These preliminary studies indicate that Lb. brevis DSM 32386 holds promise as a starter for GABA-rich dairy fermented foods and possibly a promising next-generation probiotic microorganism in the context of the gut (microbiota):brain axis.
Geology, Mineralogy, Geochemistry, and Genesis of Bentonite Deposits in Miocene Volcano–Sedimentary Units of the Balikesir Region, Western Anatolia, Turkey
Authors: Kadİr Selahattİn , Külah Tacİt , Erkoyun Hülya , Christidis George E. , Arslanyan Raffİ
Published: December 2019

The widespread Balıkesir bentonite deposits within the Miocene volcano-sedimentary units in western Anatolia have economic potential; they are important raw materials for the paper and bleaching industries in Turkey. No detailed geological, mineralogical, geochemical, or genesis characterizations of these bentonite deposits have been carried out to date. The present study was undertaken to close this gap. The mineralogical characteristics of the bentonites and their parent rocks were examined using polarized-light microscopy, X-ray powder diffractometry (XRD), scanning- and transmission-electron microscopies (SEM–EDX and TEM), and chemical (ICP–AES and –MS) methods. In the bentonite deposits, smectite is associated with smaller amounts of illite, chlorite, quartz, feldspar, dolomite, calcite, opal-CT, and amphibole. The smectite was identified by sharp basal reflections at 14.42–14.93 Å. Plagioclase and sanidine crystals in volcanic units are altered and sericitized. Biotite and hornblende are partly to completely Fe-(oxyhydr)oxidized and chloritized. Smectite flakes occur on altered feldspar and mica grains and devitrified volcanic glass fragments in association with or without calcite ± dolomite crystals. Increasing Al+Fe+Mg/Si ratios with increasing degree of alteration reveal that hydration of volcanogenic grains (feldspar, mica, hornblende, glass shard) favored precipitation of smectite with montmorillonite composition, with an average structural formula: (Ca0.31Na0.05K0.08)(Al2.72Fe0.17Mg1.27Ti0.011Mn0.01)(Si7.94Al0.06)O20(OH)4. The concentration of Al2O3 and MgO and increase of LREE/HREE ratio, and a distinct, negative Eu anomaly show that smectite was probably formed as a result of the decomposition of volcanic feldspar, mica, amphibole, and volcanic glass. Association of carbonate rocks within the smectite-rich material and the absence of chlorite and detrital materials such as rock fragments in the bentonites suggest that the bentonite deposits formed authigenetically as ‘primary bentonites’ from volcanoclastic materials deposited in a calm lacustrine–palustrine environment during an early diagenetic process.
Correlation Between Salivary, Platelet and Central Serotonin Levels in Children
Authors: Egri Csilla , Dunbar Mary , Horvath Gabriella Ana
Published: December 2019

Background:

Serotonin (5-HT) is a neurotransmitter synthesized in both the central nervous system (CNS) and in enterochromaffin cells of the gut. 5-HT biosynthesis is separate between the periphery and the CNS. Any observed correlations between centrally and peripherally measured 5-HT remain to be elucidated. Previous efforts have looked for a noninvasive marker of central serotonin, including serotonin in whole blood, plasma, platelets, saliva, and urine; however, results are conflicting.

Aim:

Finding a noninvasive marker for central serotonin turnover that can be used for diagnosis and therapeutic monitoring in patients with primary neurotransmitter deficiencies.

Methods:

Inclusion criterion was all children presenting with neurological symptoms whose clinical investigations included lumbar puncture (LP) for cerebrospinal fluid (CSF) collection and neurotransmitter metabolite analysis, were recruited. For central serotonin turnover, the serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA) was used. Bivariate correlation between the serotonin levels in CSF (5HIAA), platelets, and saliva was calculated.

Results:

Twenty-six patients (aged 6 months to 15 years) with various neurologic presentations had LP for CSF collection and neurotransmitter metabolite analysis as part of their clinical care. An additional salivary and blood sample was obtained at the same time. Eighteen patients had suitable samples for quantitative measure of serotonin. There was no correlation between platelet serotonin and CSF 5HIAA levels (Pearson’s coefficient of correlation – PCC: 0.010) or between salivary serotonin and CSF 5HIAA (PCC: 0.258). There was a strong negative correlation between salivary and platelet serotonin (PCC: −0.679).

Conclusion:

Our findings suggest that salivary serotonin measurement is not a suitable noninvasive marker for measuring central serotonin turnover.
Darwin’s bureaucrat
Authors: Smith Kevin B. , Renfro Jayme L. N.
Published: December 2019

The study of bureaucratic behavior—focusing on control, decision-making, and institutional arrangements—has historically leaned heavily on theories of rational choice and bounded rationality. Notably absent from this research, however, is attention to the growing literature on biological and especially evolutionary human behavior. This article addresses this gap by closely examining the extant economic and psychological frameworks—which we refer to as “Adam Smith’s bureaucrat” and “Herbert Simon’s bureaucrat”—for their shortcomings in terms of explanatory and predictive theory, and by positing a different framework, which we call “Charles Darwin’s bureaucrat.” This model incorporates new insights from an expanding multidisciplinary research framework and has the potential to address some of the long-noted weaknesses of classic theories of bureaucratic behavior.
Constructing the ‘automatic’ Greenwich time system: George Biddell Airy and the telegraphic distribution of time,c.1852–1880
Authors: ISHIBASHI YUTO
Published: December 2019

In the context of the telegraphic distribution of Greenwich time, while the early experiments, the roles of successive Astronomers Royal in its expansion, and its impacts on the standardization of time in Victorian Britain have all been evaluated, the attempts of George Biddell Airy and his collaborators in constructing the Royal Observatory's time signals as the authoritative source of standard time have been underexplored within the existing historical literature. This paper focuses on the wide-ranging activities of Airy, his assistant astronomers, telegraph engineers, clockmakers and others, which served to increase the reliability of the Royal Observatory's time service between the 1850s and 1870s. Airy and his collaborators aimed to mechanize and automate their telegraphic time distribution system in order to improve its accuracy and reliability. The accomplishment of such technological innovations was disseminated via public lectures, journal articles and correspondence with experts, secondary distributors of standard time and the general public. These communications were used to build public trust in the Greenwich time service. However, the unexplored archival material used in the present paper provides fresh insight into the unstable nature of the Greenwich time system, including its clear limits in terms of its scale of automation and degree of accuracy.
On Reciprocity, Revenge, and Replication: A Rejoinder to Walzer, McMahan, and Keohane
Authors: Sagan Scott D. , Valentino Benjamin A.
Published: December 2019

In their contributions to the symposium “Just War and Unjust Soldiers,” Michael Walzer, Jeff McMahan, and Robert O. Keohane add greatly to our understanding of how best to study and apply just war doctrine to real-world conflicts. We argue, however, that they underestimate both the degree to which the American public seeks revenge, rather than just reciprocity, and the extent of popular acceptance of violations of noncombatant immunity by soldiers perceived to be fighting for a just cause. We call on empirical political scientists, lawyers, psychologists, and historians to engage with moral philosophers and political theorists in debates about the influence of just war theory and the laws of armed conflict.
When Migration Policy Isn't about Migration: Considerations for Implementation of the Global Compact for Migration
Authors: Bloom Tendayi
Published: December 2019

The fluid use of the terminology associated with “migration governance” can obscure its intention and implications. Different meanings of core terminology risks allowing troubling policies that are not really about migration, understood widely as border crossing, or even more broadly as human movement, to be legitimized. UN-level coordination with regard to “migration governance” needs to be part of addressing this concern. For example, this article advocates explicitly engaging with this risk through the implementation of the Global Compact for Safe, Orderly and Regular Migration. It considers this issue from the perspectives of a handful of countries, each of which has its own complex relationship to the compact. It argues that in each of these apparently very different contexts, policies identified as being directed at “migration control” can be found to be directed not at controlling migration but at reconfiguring existing and stable state societies along ethnic, racial, linguistic, and other lines. The development of implementation plans for the Global Compact for Migration provides the opportunity to interrogate the purposes of “migration governance” and to find mechanisms to address its hidden uses.
Privacy, People, and Markets
Authors: Hull Gordon
Published: December 2019

Most current work on privacy understands it according to an economic model: individuals trade personal information for access to desired services and websites. This sounds good in theory. In practice, it has meant that online access to almost anything requires handing over vast amounts of personal information to the service provider with little control over what happens to it next. The two books considered in this essay both work against that economic model. In Privacy as Trust, Ari Ezra Waldman argues for a new model of privacy that starts not with putatively autonomous individuals but with an awareness that managing information flows is part of how people create and navigate social boundaries with one another. Jennifer Rothman's Right of Publicity confronts the explosive growth of publicity rights—the rights of individuals to control and profit from commercial use of their name and public image—and, in so doing, she exposes the poverty of treating information disclosure merely as a matter of economic calculation. Both books emphasize practical and doctrinal solutions to the problems they identify. In this essay, I take a step back and draw out the extent to which they converge on a fundamentally important point: the blunt application of market logic with its tools of property and contracts fails to protect the interests that lead us to turn to privacy in the first place; the tendency to economize privacy is a significant part of why we inadequately protect it.
Association of urinary polycyclic aromatic hydrocarbons and obesity in children aged 3–18: Canadian Health Measures Survey 2009–2015
Authors: Bushnik Tracey , Wong Suzy L. , Holloway Alison C. , Thomson Errol M.
Published: December 2019

Polycyclic aromatic hydrocarbons (PAHs) may contribute to obesity. Childhood obesity is a strong predictor of adult obesity and morbidity; however, the relationship between PAHs and obesity in young children (e.g., aged 3–5) has not been studied. We examined the association between urinary PAH metabolites and measures of obesity in children. We analyzed data from 3667 children aged 3–18 years who participated in the Canadian Health Measures Survey (CHMS, 2009–2015). We ran separate multivariable linear models to estimate the association between quartiles of PAH metabolites and each of body mass index (BMI) percentile, waist circumference (WC), and waist-to-height ratio (WHtR) in the total population, as well as in the age subgroups 3–5, 6–11, and 12–18, adjusting for age, sex, ethnicity, education, income quintile, diet, creatinine, and exposure to environmental tobacco smoke. A multinomial logistic regression model estimated adjusted odds ratios for risk of central obesity. BMI, WC, and WHtR were positively associated with total PAH and naphthalene metabolites in the total population aged 3–18 and in age groups 6–11 and 12–18. In 3–5 year olds, WHtR, but not BMI, was significantly associated with total PAH, naphthalene, and phenanthrene metabolites. Overall, those in the highest quartile for naphthalene or total PAH metabolites had three times greater odds of having central obesity compared with those in the lowest quartile. Urinary PAH metabolites are associated with WHtR, an indicator of central obesity and predictor of health risks associated with obesity, in children as young as 3–5.
Neuropharmacological Interventions and Event File Coding in Gilles de la Tourette Syndrome
Authors: Takacs Adam , Bluschke Annet , Münchau Alexander , Beste Christian
Published: December 2019

Abstract. Alterations in the integration of perception and action have been proposed as a core cognitive characteristic of GTS. However, to date it is unknown how neuropharmacological interventions used to treat GTS affect the neural systems related to perception and action integration. Here, we introduce an integrated neuropsychopharmacological perspective to address this question. Specifically, we consider the relevant abnormalities in cortico-striato-thalamo-cortical circuits. Furthermore, we highlight how GTS medication might affect the integration of perception and action in the context of event file coding.
Developmental Trajectories of Sensorimotor and Cognitive Control in Gilles de la Tourette Syndrome
Authors: Li Shu-Chen , Dilcher Roxane , Münchau Alexander
Published: December 2019

Abstract. The relationship between tics and preceding urges in Tourette syndrome suggests that abnormal internal monitoring is reflected in abnormal perceptual, attentional, and response selection. This article uses the theory of event coding to conceptualize Tourette syndrome as a disorder of the integration of perception and action. Given that Tourette syndrome is a prototypical neurodevelopmental disorder with a characteristic clinical course in childhood and early adolescence, we focus on reviewing developmental trajectories of perception-action binding and their neural correlates in Tourette and healthy controls with a view toward the dopaminergic system. Future cross-sectional and longitudinal research systematically comparing typical development and Tourette-related alterations of neurophysiological correlates underlying perception-action binding may shed light on individual differences in the clinical course in adolescence and adulthood.
The Most Commonly Used Instruments in Research on Functioning in	Schizophrenia
Authors: Barrios Maite , Guilera Georgina , Hidalgo M. Dolores , Cheung Eric C. F. , Chan Raymond C. K. , Gómez-Benito Juana
Published: December 2019

Abstract. A comprehensive assessment of functioning in schizophrenia is essential to plan appropriate interventions for helping individuals with this health condition. The International Classification of Functioning, Disability and Health (ICF) offers a theoretical framework for assessing functioning and disability. Our aim was to identify the most frequently used measurement instruments reported in studies on functioning in schizophrenia, to conduct a content comparison with respect to the ICF, and to compare the categories extracted from these instruments with those covered by the Brief ICF-Core Set for schizophrenia. A structured literature search of studies on functioning in schizophrenia was conducted using Medline, CINAHL, and PsycINFO. The items of the top 20 measurement instruments were then linked to the ICF classification system. The most commonly used instruments were neuropsychological tests (i.e., Wisconsin Card Sorting Test and Trail Making Test) and measures of clinical symptoms (i.e., PANSS) and general functioning (i.e., GAF). The linking process resulted in 45 ICF categories (25 from Body functions, 1 from Body structures, 14 from Activities and Participation, and 5 from the Environmental factors component). Most of the top 20 instruments are not specifically designed for patients with schizophrenia or for assessing functioning, but rather are general standardized tests widely used to measure a broad range of outcome variables in several health conditions. Our results suggest a lack of an internationally accepted, commonly used, specific and comprehensive gold standard to assess functioning in individuals with schizophrenia.
The Distinctive Constitution of Feeling Hurt
Authors: Hardecker David J. K.
Published: December 2019

Abstract. What is the nature of feeling hurt? This question is answered by systematically reviewing and integrating theories and empirical findings on feeling hurt using Lazarus’ theory of emotion. Following this approach, feeling hurt is constituted by a primary appraisal of an illegitimate devaluation and by a secondary appraisal of low controllability. This appraisal pattern activates an action tendency to withdraw from an interaction. This theory leads to several hypotheses for the appraisal (e.g., that an increase in appraisals of controllability should turn hurt into anger) on facial, bodily, and behavioral expressions as well as on the communicative function of feeling hurt. Furthermore, important conceptual distinctions between a broad and a narrow concept of feeling hurt as well as between feeling hurt as an emotion and a long-term emotional episode of hurt are introduced. Finally, feeling hurt is compared with humiliation, shame, guilt, disappointment, sadness, and anger.
The Assessment and Comparison of TMPA and IMERG Products Over the Major Basins of Mainland China
Authors: Su Jianbin , Lü Haishen , Ryu Dongryeol , Zhu Yonghua
Published: December 2019

The Integrated Multi‐satellitE Retrievals for Global Precipitation Measurement mission (IMERG) aims to deliver the “best” precipitation estimation from space and has attracted much attention. The Version 05 of IMERG products including the near‐real‐time “Early” and “Late” run products (IMERG‐E and IMERG‐L, respectively), and the post‐real‐time “Final” run IMERG product (IMERG‐F) are assessed at both national and basin scales against gauge observations over Mainland China for a 4‐year period (from April 2014 to March 2018). As control products for comparison, their predecessor Tropical Rainfall Measurement Mission (TRMM) Multi‐satellite Precipitation Analysis (TMPA) products (i.e., TMPA‐RT and TMPA‐V7) are also employed. Components analysis confirms the best performance of IMERG‐F among the five SPEs in three different categories. All five SPEs feature increasing bias and root mean square difference (RMSD) with increasing daily gauge total precipitation, and such issue is less pronounced for IMERG‐F—as evidenced by the lowest bias and RMSD across all precipitation rates. Besides, compared to TMPA, IMERG products exhibit better accuracy in detecting real precipitation evens, especially for light‐to‐medium rain (<60 mm/day), but they do not demonstrate significant improvement in the assessment of severe over/underestimation. In the basin‐scale comparison, all five SPEs catch the key variation feature of basin‐averaged precipitation time series (except TMPA‐RT over Continental River Basin). Overall, IMERG‐F demonstrates the best performance over all nine basins despite the slight overestimation, followed by TMPA‐V7. IMERG‐E and IMERG‐L show performance close to or even better than TMPA‐V7 in terms of the correlation coefficient and RMSD.
Improving Estimates of Coastal Carbon Sequestration
Authors: Stanley Sarah
Published: December 2019

A new two-model approach could reduce uncertainties in calculated rates of “blue carbon” accumulation within soils of seagrass, tidal marsh, and mangrove habitats.
Nongenic cancer-risk SNPs affect oncogenes, tumour-suppressor genes, and immune function
Authors: Fagny Maud , Platig John , Kuijjer Marieke Lydia , Lin Xihong , Quackenbush John
Published: December 2019

Background

Genome-wide association studies (GWASes) have identified many noncoding germline single-nucleotide polymorphisms (SNPs) that are associated with an increased risk of developing cancer. However, how these SNPs affect cancer risk is still largely unknown.

Methods

We used a systems biology approach to analyse the regulatory role of cancer-risk SNPs in thirteen tissues. By using data from the Genotype-Tissue Expression (GTEx) project, we performed an expression quantitative trait locus (eQTL) analysis. We represented both significant cis- and trans-eQTLs as edges in tissue-specific eQTL bipartite networks.

Results

Each tissue-specific eQTL network is organised into communities that group sets of SNPs and functionally related genes. When mapping cancer-risk SNPs to these networks, we find that in each tissue, these SNPs are significantly overrepresented in communities enriched for immune response processes, as well as tissue-specific functions. Moreover, cancer-risk SNPs are more likely to be ‘cores’ of their communities, influencing the expression of many genes within the same biological processes. Finally, cancer-risk SNPs preferentially target oncogenes and tumour-suppressor genes, suggesting that they may alter the expression of these key cancer genes.

Conclusions

This approach provides a new way of understanding genetic effects on cancer risk and provides a biological context for interpreting the results of GWAS cancer studies.
Spatial proximity between T and PD-L1 expressing cells as a prognostic biomarker for oropharyngeal squamous cell carcinoma
Authors: Tsakiroglou Anna Maria , Fergie Martin , Oguejiofor Ken , Linton Kim , Thomson David , Stern Peter L. , Astley Susan , Byers Richard , West Catharine M. L.
Published: December 2019

Background

Fulfilling the promise of cancer immunotherapy requires novel predictive biomarkers to characterise the host immune microenvironment. Deciphering the complexity of immune cell interactions requires an automated multiplex approach to histological analysis of tumour sections. We tested a new automatic approach to select tissue and quantify the frequencies of cell-cell spatial interactions occurring in the PD1/PD-L1 pathway, hypothesised to reflect immune escape in oropharyngeal squamous cell carcinoma (OPSCC).

Methods

Single sections of diagnostic biopsies from 72 OPSCC patients were stained using multiplex immunofluorescence (CD8, PD1, PD-L1, CD68). Following multispectral scanning and automated regions-of-interest selection, the Hypothesised Interaction Distribution (HID) method quantified spatial proximity between cells. Method applicability was tested by investigating the prognostic significance of co-localised cells (within 30 μm) in patients stratified by HPV status.

Results

High frequencies of proximal CD8+ and PD-L1+ (HR 2.95, p = 0.025) and PD1+ and PD-L1+ (HR 2.64, p = 0.042) cells were prognostic for poor overall survival in patients with HPV negative OPSCC (n = 31).

Conclusion

The HID method can quantify spatial interactions considered to reflect immune escape and generate prognostic information in OPSCC. The new automated approach is ready to test in additional cohorts and its applicability should be explored in research and clinical studies.
Stathmin levels alter PTPN14 expression and impact neuroblastoma cell migration
Authors: Po’uha Sela T. , Le Grand Marion , Brandl Miriam B. , Gifford Andrew J. , Goodall Gregory J. , Khew-Goodall Yeesim , Kavallaris Maria
Published: December 2019

Background

Stathmin mediates cell migration and invasion in vitro, and metastasis in vivo. To investigate stathmin’s role on the metastatic process, we performed integrated mRNA–miRNA expression analysis to identify pathways regulated by stathmin.

Methods

MiRNA and gene arrays followed by miRNA-target-gene integration were performed on stathmin-depleted neuroblastoma cells (CtrlshRNAvs. Stmn Seq2shRNA). The expression of the predicted target PTPN14 was evaluated by RT-qPCR, western blot and immunohistochemistry. Gene-silencing technology was used to assess the role of PTPN14 on proliferation, migration, invasion and signalling pathway.

Results

Stathmin levels modulated the expression of genes and miRNA in neuroblastoma cells, leading to a deregulation of migration and invasion pathways. Consistent with gene array data, PTPN14 mRNA and protein expression were downregulated in stathmin- depleted neuroblastoma cells and xenografts. In two independent neuroblastoma cells, suppression of PTPN14 expression led to an increase in cell migration and invasion. PTPN14 and stathmin expression did not act in a feedback regulatory loop in PTPN14- depleted cells, suggesting a complex interplay of signalling pathways. The effect of PTPN14 on YAP pathway activation was cell-type dependent.

Conclusions

Our findings demonstrate that stathmin levels can regulate PTPN14 expression, which can modulate neuroblastoma cell migration and invasion.
Targeting of apoptosis gene loci by reprogramming factors leads to selective eradication of leukemia cells
Authors: Wang Yajie , Lu Ting , Sun Guohuan , Zheng Yawei , Yang Shangda , Zhang Hongyan , Hao Sha , Liu Yanfeng , Ma Shihui , Zhang Houyu , Ru Yongxin , Gao Shaorong , Yen Kuangyu , Cheng Hui , Cheng Tao
Published: December 2019

Applying somatic cell reprogramming strategies in cancer cell biology is a powerful approach to analyze mechanisms of malignancy and develop new therapeutics. Here, we test whether leukemia cells can be reprogrammed in vivo using the canonical reprogramming transcription factors-Oct4, Sox2, Klf4, and c-Myc (termed as OSKM). Unexpectedly, we discover that OSKM can eradicate leukemia cells and dramatically improve survival of leukemia-bearing mice. By contrast, OSKM minimally impact normal hematopoietic cells. Using ATAC-seq, we find OSKM induce chromatin accessibility near genes encoding apoptotic regulators in leukemia cells. Moreover, this selective effect also involves downregulation of H3K9me3 as an early event. Dissection of the functional effects of OSKM shows that Klf4 and Sox2 play dominant roles compared to c-Myc and Oct4 in elimination of leukemia cells. These results reveal an intriguing paradigm by which OSKM-initiated reprogramming induction can be leveraged and diverged to develop novel anti-cancer strategies.
Resolving the cause of recurrent Plasmodium vivax malaria probabilistically
Authors: Taylor Aimee R. , Watson James A. , Chu Cindy S. , Puaprasert Kanokpich , Duanguppama Jureeporn , Day Nicholas P. J. , Nosten Francois , Neafsey Daniel E. , Buckee Caroline O. , Imwong Mallika , White Nicholas J.
Published: December 2019

Relapses arising from dormant liver-stage Plasmodium vivax parasites (hypnozoites) are a major cause of vivax malaria. However, in endemic areas, a recurrent blood-stage infection following treatment can be hypnozoite-derived (relapse), a blood-stage treatment failure (recrudescence), or a newly acquired infection (reinfection). Each of these requires a different prevention strategy, but it was not previously possible to distinguish between them reliably. We show that individual vivax malaria recurrences can be characterised probabilistically by combined modelling of time-to-event and genetic data within a framework incorporating identity-by-descent. Analysis of pooled patient data on 1441 recurrent P. vivax infections in 1299 patients on the Thailand–Myanmar border observed over 1000 patient follow-up years shows that, without primaquine radical curative treatment, 3 in 4 patients relapse. In contrast, after supervised high-dose primaquine only 1 in 40 relapse. In this region of frequent relapsing P. vivax, failure rates after supervised high-dose primaquine are significantly lower (∼3%) than estimated previously.
Overall electrochemical splitting of water at the heterogeneous interface of nickel and iron oxide
Authors: Suryanto Bryan H. R. , Wang Yun , Hocking Rosalie K. , Adamson William , Zhao Chuan
Published: December 2019

Efficient generation of hydrogen from water-splitting is an underpinning chemistry to realize the hydrogen economy. Low cost, transition metals such as nickel and iron-based oxides/hydroxides have been regarded as promising catalysts for the oxygen evolution reaction in alkaline media with overpotentials as low as ~200 mV to achieve 10 mA cm−2, however, they are generally unsuitable for the hydrogen evolution reaction. Herein, we show a Janus nanoparticle catalyst with a nickel–iron oxide interface and multi-site functionality for a highly efficient hydrogen evolution reaction with a comparable performance to the benchmark platinum on carbon catalyst. Density functional theory calculations reveal that the hydrogen evolution reaction catalytic activity of the nanoparticle is induced by the strong electronic coupling effect between the iron oxide and the nickel at the interface. Remarkably, the catalyst also exhibits extraordinary oxygen evolution reaction activity, enabling an active and stable bi-functional catalyst for whole cell water-splitting with, to the best of our knowledge, the highest energy efficiency (83.7%) reported to date.
Supremely elastic gel polymer electrolyte enables a reliable electrode structure for silicon-based anodes
Authors: Huang Qingquan , Song Jiangxuan , Gao Yue , Wang Daiwei , Liu Shuai , Peng Shufu , Usher Courtney , Goliaszewski Alan , Wang Donghai
Published: December 2019

Silicon-based materials are promising anodes for next-generation lithium-ion batteries, owing to their high specific capacities. However, the huge volume expansion and shrinkage during cycling result in severe displacement of silicon particles and structural collapse of electrodes. Here we report the use of a supremely elastic gel polymer electrolyte to address this problem and realize long-term stable cycling of silicon monoxide anodes. The high elasticity of the gel polymer electrolyte is attributed to the use of a unique copolymer consisting of a soft ether domain and a hard cyclic ring domain. Consequently, the displacement of silicon monoxide particles and volume expansion of the electrode were effectively reduced, and the damage caused by electrode cracking is alleviated. A SiO|LiNi0.5Co0.2Mn0.3O2 cell shows 70.0% capacity retention in 350 cycles with a commercial-level reversible capacity of 3.0 mAh cm−2 and an average Coulombic efficiency of 99.9%.
Mapping lung cancer epithelial-mesenchymal transition states and trajectories with single-cell resolution
Authors: Karacosta Loukia G. , Anchang Benedict , Ignatiadis Nikolaos , Kimmey Samuel C. , Benson Jalen A. , Shrager Joseph B. , Tibshirani Robert , Bendall Sean C. , Plevritis Sylvia K.
Published: December 2019

Elucidating the spectrum of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in clinical samples promises insights on cancer progression and drug resistance. Using mass cytometry time-course analysis, we resolve lung cancer EMT states through TGFβ-treatment and identify, through TGFβ-withdrawal, a distinct MET state. We demonstrate significant differences between EMT and MET trajectories using a computational tool (TRACER) for reconstructing trajectories between cell states. In addition, we construct a lung cancer reference map of EMT and MET states referred to as the EMT-MET PHENOtypic STAte MaP (PHENOSTAMP). Using a neural net algorithm, we project clinical samples onto the EMT-MET PHENOSTAMP to characterize their phenotypic profile with single-cell resolution in terms of our in vitro EMT-MET analysis. In summary, we provide a framework to phenotypically characterize clinical samples in the context of in vitro EMT-MET findings which could help assess clinical relevance of EMT in cancer in future studies.
Demographic amplification is a predictor of invasiveness among plants
Authors: Jelbert Kim , Buss Danielle , McDonald Jenni , Townley Stuart , Franco Miguel , Stott Iain , Jones Owen , Salguero-Gómez Roberto , Buckley Yvonne , Knight Tiffany , Silk Matthew , Sargent Francesca , Rolph Simon , Wilson Phil , Hodgson Dave
Published: December 2019

Invasive plant species threaten native biodiversity, ecosystems, agriculture, industry and human health worldwide, lending urgency to the search for predictors of plant invasiveness outside native ranges. There is much conflicting evidence about which plant characteristics best predict invasiveness. Here we use a global demographic survey for over 500 plant species to show that populations of invasive plants have better potential to recover from disturbance than non-invasives, even when measured in the native range. Invasives have high stable population growth rates in their invaded ranges, but this metric cannot be predicted based on measurements in the native ranges. Recovery from demographic disturbance is a measure of transient population amplification, linked to high levels of reproduction, and shows phylogenetic signal. Our results demonstrate that transient population dynamics and reproductive capacity can help to predict invasiveness across the plant kingdom, and should guide international policy on trade and movement of plants.
Ferroelectric nonlinear anomalous Hall effect in few-layer WTe2
Authors: Wang Hua , Qian Xiaofeng
Published: December 2019

Under broken time reversal symmetry such as in the presence of external magnetic field or internal magnetization, a transverse voltage can be established in materials perpendicular to both longitudinal current and applied magnetic field, known as classical Hall effect. However, this symmetry constraint can be relaxed in the nonlinear regime, thereby enabling nonlinear anomalous Hall current in time-reversal invariant materials – an underexplored realm with exciting new opportunities beyond classical linear Hall effect. Here, using group theory and first-principles theory, we demonstrate a remarkable ferroelectric nonlinear anomalous Hall effect in time-reversal invariant few-layer WTe2 where nonlinear anomalous Hall current switches in odd-layer WTe2 except 1T′ monolayer while remaining invariant in even-layer WTe2 upon ferroelectric transition. This even-odd oscillation of ferroelectric nonlinear anomalous Hall effect was found to originate from the absence and presence of Berry curvature dipole reversal and shift dipole reversal due to distinct ferroelectric transformation in even and odd-layer WTe2. Our work not only treats Berry curvature dipole and shift dipole on an equal footing to account for intraband and interband contributions to nonlinear anomalous Hall effect, but also establishes Berry curvature dipole and shift dipole as new order parameters for noncentrosymmetric materials. The present findings suggest that ferroelectric metals and Weyl semimetals may offer unprecedented opportunities for the development of nonlinear quantum electronics.
Mass Transpiration in Nonlinear MHD Flow Due to Porous Stretching Sheet
Authors: Singh Jitender , Mahabaleshwar U. S. , Bognár Gabriella
Published: December 2019

Motivated from numerous practical applications, the present theoretical and numerical work investigates the nonlinear magnetohydrodynamic (MHD) laminar boundary layer flow of an incompressible, viscous fluid over a porous stretching sheet in the presence of suction/injection (mass transpiration). The flow characteristics are obtained by solving the underlying highly nonlinear ordinary differential equation using homotopy analysis method. The effect of parameters corresponding to suction/injection (mass transpiration), applied magnetic field, and porous stretching sheet parameters on the nonlinear flow is investigated. The asymptotic limits of the parameters regarding the flow characteristics are obtained mathematically, which compare very well with those obtained using the homotopy analysis technique. A detailed numerical study of the laminar boundary layer flow in the vicinity of the porous stretching sheet in MHD and offers a particular choice of the parametric values to be taken in order to practically model a particular type of the event among suction and injection at the sheet surface.
Comparison of Anterior only and Combined Anterior and Posterior Approach in Treating Lumbosacral Tuberculosis
Authors: Sun Dong , Zhang Ze-hua , Mei Gang , Hou Tian-yong , Li Yang , Xu Jian-Zhong , Luo Fei
Published: December 2019

A combined anterior and posterior (AP) surgical approach is a popular treatment modality of lumbosacral tuberculosis, but it is often traumatic and complicated. The present study aims to find whether the anterior only approach with the ARCH plate system is less invasive than the AP approach in treating lumbosacral tuberculosis. The ARCH plate system is an innovative anatomic lumbosacral anterior multi-directional locking plate system which was devised with due consideration to the anatomic features of the lumbosacral spine and irregular destruction of involved vertebral endplates. In this retrospective study, 32 patients with lumbosacral tuberculosis underwent surgeries via either the anterior only approach (ARCH group, 18 patients) using the ARCH system or the conventional combined anterior and posterior approach (AP group, 14 patients). American Spinal Injury Association (ASIA) scores, Visual Analogue Scale (VAS) scores, Oswestry Disability Index (ODI), bone union status, ESR, CRP, intervertebral foraminal height between L5 and S1, the vertical height between the anterior upper edge of L5 and S1 vertebral body, lumbosacral angle, and the physiological lordosis of between L1 and S1 from both groups were recorded and compared. All patients were followed up for at least two years. The average duration of operation, blood loss, and length of hospital admission of the ARCH group (154.6 min, 361.1 ml&18.3days) was significantly smaller and shorter(p < 0.001, p < 0.001 & p = 0.008) that those of the AP group(465.5 min, 814.3 ml & 24.6days). The ODI score(p = 0.08, 0.471, 0.06, 0.07, 0.107), the VAS score(p = 0.099, 0.249, 0.073, 0.103, 0.273), the intervertebral foraminal height between L5 and S1(p = 0.826, 0.073, 0.085), L5-S1 height(p = 0.057, 0.234, 0.094), lumbosacral angle(p = 0.052, 0.242, 0.825), and L5-S1 lordosis(p = 0.146, 0.129, 0.053) of both groups showed no significant difference in any of the time points. The anterior only approach using the ARCH system is as effective as the combined anterior and posterior approach and is less traumatic in treating lumbosacral tuberculosis.