bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of m-learning HiSense APP-ID in enhancing knowledge, empathy, and self-efficacy in caregivers of persons with intellectual disabilities: a randomized controlled trial
Authors: van Wingerden Evelien , Wouda Mirjam , Sterkenburg Paula
Published: September 2019

M-learning is a flexible form of digital education that can benefit professional caregivers. The m-learning intervention ‘HiSense APP-ID’ was developed to support caregivers of persons with intellectual disability (ID). The intervention focuses on improving knowledge about sensitive and responsive caregiving for persons with ID. This randomized controlled trial of 101 professional caregivers of persons with moderate or mild ID evaluated whether m-learning improves practical and theoretical knowledge about secure attachment in persons with ID, and increases empathy and self-efficacy. The ‘HiSense APP-ID’ consists of 120 multiple-choice questions relating to attachment theory and the experience of persons with ID. Participants answer four questions each day for 30 days. In pre-, post-, and follow-up assessments, all participants completed a series of questionnaires concerning social validity, knowledge, self-efficacy, and empathy. Linear mixed effects modeling was then used to assess the effectiveness of the intervention. Users rated the app positively on usefulness, ease of use, design, and development of their own skills. Knowledge improved in the group of participants who followed m-learning. An interaction effect was found for empathic concern, but no significant effect was found for social empathy or self-efficacy. Thus, m-learning is a useful and flexible educational tool for professional caregivers of persons with ID, and the ‘HiSense APP-ID’ was able to improve theoretical knowledge in very short sessions spaced over a longer period of time.
The Crisis of International Criminal Law in Africa: A Regional Regime in Response?
Authors: Omorogbe Eki Yemisi
Published: September 2019

This article considers the African Union’s (AU) proposal for a regional court for international crimes under the Malabo Protocol 2014 (Protocol). It places that within the AU’s rejection of the International Criminal Court’s (ICC) arrest warrants for African Heads of States that are not party to the Rome Statute and a more general protection of incumbents. It argues that the enthusiasm for establishing a regional criminal court, which lacks jurisdiction to prosecute incumbents, has not been sustained and African states remain committed to the ICC. It shows that nevertheless the Protocol’s provisions on genocide, crimes against humanity and war crimes, although imperfect, better address the specific character of armed conflicts in Africa than current international law, including the Rome Statute of the ICC. It concludes that the regional court for international crimes is unlikely to be established unless the ICC takes further action against incumbent leaders but that the Protocol’s provisions could be used in the development of a more Africa-centric international law.
Cooperative Lane-Change Maneuver for Multiple Automated Vehicles on a Highway
Authors: Luo Yugong , Yang Gang , Xu Mingchang , Qin Zhaobo , Li Keqiang
Published: September 2019

With the development of vehicle-to-vehicle (V2V) communication, it is possible to share information among multiple vehicles. However, the existing research on automated lane changes concentrates only on the single-vehicle lane change with self-detective information. Cooperative lane changes are still a new area with more complicated scenarios and can improve safety and lane-change efficiency. Therefore, a multi-vehicle cooperative automated lane-change maneuver based on V2V communication for scenarios of eight vehicles on three lanes was proposed. In these scenarios, same-direction and intersectant-direction cooperative lane changes were defined. The vehicle that made the cooperative decision obtained the information of surrounding vehicles that were used to cooperatively plan the trajectories, which was called cooperative trajectory planning. The cooperative safety spacing model was proposed to guarantee and improve the safety of all vehicles, and it essentially developed constraints for the trajectory-planning task. Trajectory planning was treated as an optimization problem with the objective of maximizing safety, comfort, and lane-change efficiency under the constraints of vehicle dynamics and the aforementioned safety spacing model. Trajectory tracking based on a model predictive control method was designed to minimize tracking errors and control increments. Finally, to verify the validity of the proposed maneuver, an integrated simulation platform combining MATLAB/Simulink with CarSim was established. Moreover, a hardware-in-the-loop test bench was performed for further verification. The results indicated that the proposed multi-vehicle cooperative automated lane-change maneuver can achieve lane changes of multiple vehicles and increase lane-change efficiency while guaranteeing safety and comfort.
Correction to: Investigation of growth mechanism for highly oriented TiO2 nanorods: the role of reaction time and annealing temperature
Authors: Bade Bharat R. , Rondiya Sachin , Bhopale Somnath R. , Dzade Nelson Y. , Kamble Mahesh M. , Rokade Avinash , Nasane Mamta P. , More Mahendra A. , Jadkar Sandesh R. , Funde Adinath M.
Published: September 2019

Please note that this correction article itself should also be fully open access, with © The Author(s), open access grants:
Longitudinal and lateral aerodynamic characterisation of reflex wing Unmanned Aerial Vehicle from flight tests using Maximum Likelihood, Least Square and Neural Gauss Newton methods
Authors: Saderla S. , Dhayalan R. , Singh K. , Kumar N. , Ghosh A. K.
Published: September 2019

In this paper, longitudinal and lateral-directional aerodynamic characterisation of the Cropped Delta Reflex Wing (CDRW) configuration–based unmanned aerial vehicle is carried out by means of full-scale static wind-tunnel tests followed by full-scale flight testing. A predecided set of longitudinal and lateral/directional manoeuvres is performed to acquire the respective flight data, using a dedicated onboard flight data acquisition system. The compatibility of the acquired dynamics is quantified, in terms of scale factors and biases of the measured variables, using Kinematic consistency check. Maximum likelihood (ML), least squares and newly emerging neural Gauss–Newton (NGN) methods were implemented for a wing-alone delta configuration, mainly to capture the dynamic derivatives for both longitudinal and lateral directional cases. Estimated damping and weak dynamic derivatives, which are in general challenging to capture for a wing alone configuration, are consistent using ML and NGN methods. Validation of the estimated parameters with aerodynamic model is performed by proof-of-match exercise and are presented therein.
Menstrual psychosis
Authors: Ahern E. , Cohen D. , Prior C. , Raji E.
Published: September 2019

In this report, we explore a case of symptoms consistent with menstrual psychosis. In order to do this, a review of the literature relating to this topic was conducted and a report was written. This is a case of a previously well adolescent female who experienced psychotic symptoms in the pre-menstrual phase of her cycle and became well soon after her menstrual period began. These episodes were prevented by aripiprazole, but recurred once medication was withdrawn. We conclude that psychosis in some women may have a relationship with the menstrual cycle. In women presenting with psychosis, it may be appropriate to note menstrual variation in symptoms. This could have a potential role in individualisation of treatment for women with psychotic disorders.
First record of a nonpaleotropical intejocerid cephalopod from Darriwilian (Middle Ordovician) strata of central Spain
Authors: Kröger Björn , Gutiérrez-Marco Juan Carlos
Published: September 2019

The order Intejocerida is an enigmatic, short-lived cephalopod taxon known previously only from Early–Middle Ordovician beds of Siberia and the United States. Here we report a new genus,Cabaneroceras, and a new species,C. aznari, from Middle Ordovician strata of central Spain. This finding widens the paleogeographic range of the order toward high-paleolatitudinal areas of peri-Gondwana. A curved conch, characteristic for the new genus, was previously unknown from members of the Intejocerida.

UUID:http://zoobank.org/21f0a09c-5265-4d29-824b-6b105d36b791
Striving for Entrepreneurial Autonomy: A Comparison of Russia and the Netherlands
Authors: Van Gelderen Marco , Shirokova Galina , Shchegolev Vladimir , Beliaeva Tatiana
Published: September 2019

Autonomy is a primary motive, as well as source of satisfaction, for those who start and run their own business. Autonomy is not inherent to business ownership – owner/founders must make concentrated efforts to achieve and maintain autonomy. This study aims to increase our understanding of autonomy by investigating how it is experienced, the factors that affect it, and the actions that business owners take to attain and retain it. We study these topics in the setting of an emerging market – Russia – and compare the outcomes with a similar study conducted in the Netherlands. Our cross-cultural comparison reveals that the way autonomy is experienced and attained can be viewed as an expression of survival values in Russia and of self-expression values in the Netherlands. We posit an underlying structural similarity by theorizing the level of experienced entrepreneurial autonomy to be the outcome of the balance of power and dependencies.
The Asian Anthropocene: Electricity and Fossil Developmentalism
Authors: Chatterjee Elizabeth
Published: September 2019

Much scholarship extrapolates global narratives of the Anthropocene from the “fossil capitalism” of European imperial powers. This analysis deploys the alternative lens of grid electricity—the great macro-technology of the twentieth century—to reevaluate the dynamics of the Anthropocene outside the Anglozone. Histories of Asian electrification refute the notion of any simple relationship between colonialism and fossil capitalism. Instead, they point towards a postcolonial trend of fossil developmentalism. Especially in the context of late development, energy expansion became a state-led moral project. Cutting against fossil capitalism's logic of commodification, electricity provision was increasingly conceptualized as a national good and an entitlement, even if one honored in the breach. This trend transcended the distinction between market and planned economies, and extended beyond formal democracies. The (partial) democratization of consumption brought by fossil developmentalism is the hallmark of the “Great Acceleration” in human impacts on the environment since 1950.
Monitoring green sea turtles in Brazilian feeding areas: relating body condition index to fibropapillomatosis prevalence
Authors: Rossi Silmara , Sánchez-Sarmiento Angélica María , Santos Robson Guimarães dos , Zamana Roberta Ramblas , Prioste Fabiola Eloisa Setim , Gattamorta Marco Aurélio , Ochoa Pablo Felipe Cruz , Grisi-Filho José Henrique Hildebrand , Matushima Eliana Reiko
Published: September 2019

Fibropapillomatosis (FP) can be an important conservation threat to green sea turtles (Chelonia mydas) due to its widespread distribution and complex aetiology. Thus, understanding the impacts of FP in sea turtle populations is a research priority towards conservation efforts. The body condition index (BCI), based on straight carapace length (SCL) and body mass (BM), is an accurate indicator of body-nutritional condition that can be used in routine green turtle health evaluations. This study aimed to compare BCI in FP-free (N = 369) and FP-affected (N = 518) green turtles from Brazilian feeding areas. Body condition indices were evaluated in terms of the South-west Atlantic Fibropapillomatosis Score – FPSSWA(mild, moderate and severe), study sites (five Brazilian states), origin (intentional capture, fishery, stranding and afloat) and sex (when known). Curved and straight carapace lengths, and body mass were recorded in order to calculate BCI. Statistical analysis revealed significant differences in BCI among green turtles from different study areas (P= 0.02), and lower BCI values in FP-free than in FP-positive individuals (P< 0.0001). With regards to origin, the highest BCI was found in the intentional capture group (N = 245; 1.47 ± 0.16), followed by fishery (N = 180; 1.46 ± 0.20). Analysis according to sex revealed a higher mean BCI among females than males (P< 0.017). This study provides relevant data on the health and nutritional status of green turtles along the Brazilian coast, in important feeding areas for this species.
First report of brooding of eggs in the deep-sea genusAnguillosyllis(Annelida: Syllidae)
Authors: Fukuda Marcelo V. , Barroso Rômulo
Published: September 2019

The syllid genusAnguillosyllisis relatively rare and mainly restricted to deep waters. The phylogenetic position of the genus was only recently inferred, while its reproductive mode, an important trait in the classification of the Syllidae, remains unknown. We describe herein our finding of one specimen ofAnguillosyllis lanaiwith fragile egg capsules dorsally attached to some parapodial lobes, the first observation to date providing information about reproductive aspects of animals of the genus, and discuss possible evolutionary and phylogenetic implications of this finding.
Barnacle cover modifies foraging behaviour of the intertidal limpetPatella vulgata
Authors: Santini Giacomo , Thompson Richard C. , Jenkins Stuart R. , Chelazzi Guido , Hartnoll Richard G. , Kay Suzanne M. , Hawkins Stephen J.
Published: September 2019

Limpets and barnacles are important components of intertidal assemblages worldwide. This study examines the effects of barnacles on the foraging behaviour of the limpetPatella vulgata, which is the main algal grazer in the North-west Atlantic. The behaviour of limpets on a vertical seawall on the Isle of Man (UK) was investigated using autonomous radio-telemetry, comparing their activity patterns on plots characterized by dense barnacle cover and plots from which the barnacles had been removed. Limpet behaviour was investigated at mid-shore level, but two different elevations were considered. This experiment revealed a significant effect of barnacle cover on the activity ofP. vulgata. Limpets on smooth surfaces spent a greater proportion of total time active than did limpets on barnacles. Movement activity was also greater in areas that were lower down in the tidal range. In general, limpets were either predominantly active during diurnal high or nocturnal low tides and always avoided nocturnal high tides. Individuals on barnacles at the higher elevation concentrated their activity during nocturnal low water. All the other groups of limpets (smooth surfaces on the upper level and all individuals on the lower shore) had more excursions centred around daylight hours with an equal distribution of activity between periods of low and high water. Inter-individual variability was, however, pronounced.
Do children really acquire dense neighbourhoods?
Authors: JONES Samuel David , BRANDT Silke
Published: September 2019

Children learn high phonological neighbourhood density words more easily than low phonological neighbourhood density words (Storkel, 2004). However, the strength of this effect relative to alternative predictors of word acquisition is unclear. We addressed this issue using communicative inventory data from 300 British English-speaking children aged 12 to 25 months. Using Bayesian regression, we modelled word understanding and production as a function of: (i) phonological neighbourhood density, (ii) frequency, (iii) length, (iv) babiness, (v) concreteness, (vi) valence, (vii) arousal, and (viii) dominance. Phonological neighbourhood density predicted word production but not word comprehension, and this effect was stronger in younger children.
New histories and new laws: Crimes against humanity at the International Criminal Tribunal for Rwanda
Authors: Alexander Amanda
Published: September 2019

This article looks at the development of the concept of crimes against humanity at the International Criminal Tribunal for Rwanda (ICTR). It contends that the ICTR’s interpretation of crimes against humanity is generally seen by international lawyers as a commendable, but unsurprising, step in the historical development of this category. In much the same way, the ICTR’s historical account is considered to be a standard attempt by a war crimes court to relate a liberal history of crimes against humanity in a way that upholds civilized values. Yet, although the historical and legal work of the ICTR appear unexceptional, this article will argue that they do demonstrate a particular conceptual approach towards warfare, history, humanity, and the nature of international law. Moreover, this is a conceptual approach that is quite different to that taken by the International Military Tribunal at Nuremberg. The article suggests that these differences, and the invisibility of the change, are due to the ICTR’s reliance on familiar narrative tropes. These narratives were established through poststructuralist theory but could be expressed in a variety of more or (often) less theoretical forms. By exploring the influence of these narratives on the Tribunal, it is possible to examine some of the ways in which conceptual change is facilitated and knowledge is created in international law. In particular, it shows how theories that are often considered marginal to international law have had a significant impact on some of the central provisions of international humanitarian law.
The Norwegian Twin Registry
Authors: Nilsen Thomas , Brandt Ingunn , Harris Jennifer R.
Published: September 2019

The Norwegian Twin Registry (NTR) is maintained as a research resource that was compiled by merging several panels of twin data that were established for research into physical and mental health, wellbeing and development. NTR is a consent-based registry. Where possible, data that were collected in previous studies are curated for secondary research use. A particularly valuable potential benefit associated with the Norwegian twin data lies in the opportunities to expand and enhance the data through record linkage to nationwide registries that cover a wide array of health data and other information, including socioeconomic factors. This article provides a brief description of the current NTR sample and data collections, information about data access procedures and an overview of the national registries that can be linked to the NTR for research projects.
Control of thiocarbamate-resistant rigid ryegrass (Lolium rigidum) in wheat in southern Australia
Authors: Brunton David J. , Boutsalis Peter , Gill Gurjeet , Preston Christopher
Published: September 2019

Two field experiments were conducted during 2018 at Paskeville and Arthurton, South Australia, to identify effective herbicide options for the control of thiocarbamate-resistant rigid ryegrass in wheat. Dose–response experiments confirmed resistance in both field populations (T1 and A18) of rigid ryegrass to triallate, prosulfocarb, trifluralin, and pyroxasulfone. T1 and A18 were 17.9- and 20-fold more resistant to triallate than susceptible SLR4. The level of resistance detected in T1 to prosulfocarb (5.9-fold) and pyroxasulfone (4-fold) was lower compared to A18, which displayed 12.1- and 7.8-fold resistance to both herbicides, respectively. Despite resistance, the mixture of two different preplant-incorporated (PPI) site-of-action herbicides improved rigid ryegrass control and wheat yield compared to a single PPI herbicide only. Prosulfocarb + triallate and prosulfocarb + S-metolachlor + triallate did not reduce rigid ryegrass seed set when compared to prosulfocarb applied alone at the higher rate (2,400 g ai ha–1). Pyroxasulfone + triallate PPI followed by glyphosate (1,880 g ai ha-1) as a weed seed set control treatment reduced rigid ryegrass seed production by 93% and 95% at both sites, respectively. These herbicides also significantly improved grain yield of wheat at Paskeville (22%) and Arthurton (38%) compared to the untreated.
The Improvement of Turbulent Heat Flux Parameterization for Use in the Tropical Regions Using Low Wind Speed Excess Resistance Parameter
Authors: Akinnubi R.T. , Adeniyi M.O.
Published: September 2019

Reliable simulation of turbulent heat fluxes needed for modeling land‐atmosphere interactions remains a challenge over the humid tropical region. This may be connected with the inadequate parameterization of the roughness lengths for momentum (z0m) and heat (z0h) transfer usually expressed in terms of excess resistance factor (κB−1). This paper assesses the performance of existing κB−1 schemes developed for high wind speed conditions over the humid tropical region. Thereafter, a more appropriate κB−1 suitable for low wind speed condition is developed for use in the aerodynamic resistance parameterization. Based on observed surface heat fluxes and profile measurements of wind speed and temperature from Nigeria Micrometeorological Experimental site, new κB−1 parameterization was derived through the application of the Monin‐Obukhov similarity theory and Brutsaert theoretical model for heat transfer. The derived
, where Re* is the Reynolds number. Turbulent flux parameterization with this new formula provides better estimates of heat fluxes with reference to results from existing κB−1 schemes. The R2 increased by about 85%, while mean bias error and root‐mean‐square error in the parameterized QH based on the derived κB−1 reduced by about 63% and 66.7%, respectively. Similarly, the R2 increased by about 38%, while mean bias error and root‐mean‐square error in the parameterized QE based on the derived κB−1 reduced by about 47.8% and 52.6%, respectively. The derived κB−1 gave better estimates of QH than QE during the daytime. The derived κB−1 scheme corrects a well‐documented, large overestimation of turbulent heat fluxes, and it is therefore recommended for use in regions where low wind speed is prevalent.
The Nappe des Marbres Unit of the Basque‐Cantabrian Basin: The Tectono‐thermal Evolution of a Fossil Hyperextended Rift Basin
Authors: Ducoux M. , Jolivet L. , Callot J.‐P. , Aubourg C. , Masini E. , Lahfid A. , Homonnay E. , Cagnard F. , Gumiaux C. , Baudin T.
Published: September 2019

The architecture of the Pyrenean‐Cantabrian belt results from the inversion of a series of former Cretaceous rift basins. A HT‐LP metamorphic event dated at 105 to 85 Ma ago is commonly associated with an Albo‐Cenomanian episode of hyperextension of the continental crust. This metamorphism is well known in the eastern Basque‐Cantabrian Basin within the Nappe des Marbres Unit (NMU) that is preserved from intense compressional deformation during the Pyrenean orogeny. Based on a structural study at the scale of the eastern Basque‐Cantabrian Basin and on a dense sampling for TRSCM estimates with the Raman spectroscopy of carbonaceous material (RSCM) method (Raman Spectrometry on Carbonaceous Material), we show following results: (1) the NMU has recorded two major phases of deformation, related to a localized extensional ductile foliation (S1) during the Cretaceous rifting and later by the regional N‐S shortening, recorded by a regional cleavage (S2) observed only in shale sediments. (2) The NMU is affected by early salt tectonics related to several diapirs and salt walls fed by the Upper Triassic evaporitic layer. (3) The NMU recorded maximum temperatures exceeding 550°C, which represent some of the highest temperatures along the Pyrenees. These new data demonstrate that there is no E‐W lateral metamorphic gradient across the belt and that hyperextension rifting occurred consistently within a high‐thermal regime; (4) metamorphic isograds are oblique in respect of the main structures, suggesting that the metamorphic event postdates most of the early salt‐related deformations prior to or coeval with early stages of rifting. As it represents one of the best preserved example of preorogenic hyperextended basin, the eastern Basque‐Cantabrian Basin record may be used regionally to better understand the rift to orogen evolution of the Pyrenean Internal Metamorphic Zone but also more generally as an analog of salt‐bearing hyperextended rift record.
Nuclear Bomb or Earthquake? Explosions Reveal the Differences
Authors: Kornei Katherine
Published: September 2019

A series of controlled chemical detonations in the Nevada desert is helping researchers discern between ground shaking caused by nuclear explosions and earthquakes.
Multiple‐Instance Superparameterization: 1. Concept, and Predictability of Precipitation
Authors: Jones Todd R. , Randall David A. , Branson Mark D.
Published: September 2019

We have investigated the predictability of precipitation using a new configuration of the superparameterized Community Atmosphere Model (SP‐CAM). The new configuration, called the multiple‐instance SP‐CAM, or MP‐CAM, uses the average heating and drying rates from 10 independent two‐dimensional cloud‐permitting models (CPMs) in each grid column of the global model, instead of a single CPM. The 10 CPMs start from slightly different initial conditions and simulate alternative realizations of the convective cloud systems. By analyzing the ensemble of possible realizations, we can study the predictability of the cloud systems and identify the weather regimes and physical mechanisms associated with chaotic convection. We explore alternative methods for quantifying the predictability of precipitation. Our results show that unpredictable precipitation occurs when the simulated atmospheric state is close to critical points as defined by Peters and Neelin (2006, https://doi.org/10.1038/nphys314). The predictability of precipitation is also influenced by the convective available potential energy and the degree of mesoscale organization. It is strongly controlled by the large‐scale circulation. A companion paper compares the global atmospheric circulations simulated by SP‐CAM and MP‐CAM.
Imagining Simpler Worlds to Understand the Complexity of Our Own
Authors: Gerber Edwin P. , DallaSanta Kevin , Gupta Aman
Published: September 2019

The atmospheric circulation response to global warming is important for accurate prediction of climate change on regional scales. For the midlatitudes, shifts in the extratropical jet streams have important consequences for precipitation, blocking, and extreme events. It has proven to be a challenge, however, to predict. For example, the North Atlantic jet stream plays a vital role in the climate of eastern North America and Europe; in the last intercomparison of state‐of‐the‐art climate models, the models did not even agree on the sign of its wintertime response to global warming. Perhaps this should not come as a surprise, as we also lack a comprehensive theory for the impact of warming on the midlatitude circulation. In a recent study, Tan et al. (2019, https://doi.org/10.1029/2018MS001492) constructed models of simpler atmospheres to explore the response of the midlatitude jet to global warming. Their idealized atmospheres highlight the difficulty of developing a comprehensive theory for the midlatitude circulation but also provide pathways to improve models of Earth's atmosphere. Models of simpler atmospheres allow one to isolate the impact of specific atmospheric processes and connect theoretical understanding with comprehensive climate prediction systems. Such models can also be used to explore very different atmospheric regimes, from Earth's past to distant planets.
Activation of mitogen-activated protein kinases in satellite glial cells of the trigeminal ganglion contributes to substance P-mediated inflammatory pain
Authors: Zhang Yanyan , Song Ning , Liu Fei , Lin Jiu , Liu Mengke , Huang Chaolan , Liao Daqing , Zhou Cheng , Wang Hang , Shen Jiefei
Published: September 2019

Inflammatory orofacial pain, in which substance P (SP) plays an important role, is closely related to the cross-talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs). SGC activation is emerging as the key mechanism underlying inflammatory pain through different signalling mechanisms, including glial fibrillary acidic protein (GFAP) activation, phosphorylation of mitogen-activated protein kinase (MAPK) signalling pathways, and cytokine upregulation. However, in the TG, the mechanism underlying SP-mediated orofacial pain generated by SGCs is largely unknown. In this study, we investigated whether SP is involved in inflammatory orofacial pain by upregulating interleukin (IL)-1β and tumour necrosis factor (TNF)-α from SGCs, and we explored whether MAPK signalling pathways mediate the pain process. In the present study, complete Freund’s adjuvant (CFA) was injected into the whisker pad of rats to induce an inflammatory model in vivo. SP was administered to SGC cultures in vitro to confirm the effect of SP. Facial expression analysis showed that pre-injection of L703,606 (an NK-1 receptor antagonist), U0126 (an inhibitor of MAPK/extracellular signal-regulated kinase [ERK] kinase [MEK] 1/2), and SB203580 (an inhibitor of P38) into the TG to induce targeted prevention of the activation of the NK-1 receptor and the phosphorylation of MAPKs significantly suppressed CFA-induced inflammatory allodynia. In addition, SP promoted SGC activation, which was proven by increased GFAP, p-MAPKs, IL-1β and TNF-α in SGCs under inflammatory conditions. Moreover, the increase in IL-1β and TNF-α was suppressed by L703, 606, U0126 and SB203580 in vivo and in vitro. These present findings suggested that SP, released from TG neurons, activated SGCs through the ERK1/2 and P38 pathways and promoted the production of IL-1β and TNF-α from SGCs, contributing to inflammatory orofacial pain associated with peripheral sensitization.
Multi-omic biomarker identification and validation for diagnosing warzone-related post-traumatic stress disorder
Authors:   The PTSD Systems Biology Consortium, Dean Kelsey R. , Hammamieh Rasha , Mellon Synthia H. , Abu-Amara Duna , Flory Janine D. , Guffanti Guia , Wang Kai , Daigle Bernie J. , Gautam Aarti , Lee Inyoul , Yang Ruoting , Almli Lynn M. , Bersani F. Saverio , Chakraborty Nabarun , Donohue Duncan , Kerley Kimberly , Kim Taek-Kyun , Laska Eugene , Young Lee Min , Lindqvist Daniel , Lori Adriana , Lu Liangqun , Misganaw Burook , Muhie Seid , Newman Jennifer , Price Nathan D. , Qin Shizhen , Reus Victor I. , Siegel Carole , Somvanshi Pramod R. , Thakur Gunjan S. , Zhou Yong , Hood Leroy , Ressler Kerry J. , Wolkowitz Owen M. , Yehuda Rachel , Jett Marti , Doyle Francis J. , Marmar Charles
Published: September 2019

Post-traumatic stress disorder (PTSD) impacts many veterans and active duty soldiers, but diagnosis can be problematic due to biases in self-disclosure of symptoms, stigma within military populations, and limitations identifying those at risk. Prior studies suggest that PTSD may be a systemic illness, affecting not just the brain, but the entire body. Therefore, disease signals likely span multiple biological domains, including genes, proteins, cells, tissues, and organism-level physiological changes. Identification of these signals could aid in diagnostics, treatment decision-making, and risk evaluation. In the search for PTSD diagnostic biomarkers, we ascertained over one million molecular, cellular, physiological, and clinical features from three cohorts of male veterans. In a discovery cohort of 83 warzone-related PTSD cases and 82 warzone-exposed controls, we identified a set of 343 candidate biomarkers. These candidate biomarkers were selected from an integrated approach using (1) data-driven methods, including Support Vector Machine with Recursive Feature Elimination and other standard or published methodologies, and (2) hypothesis-driven approaches, using previous genetic studies for polygenic risk, or other PTSD-related literature. After reassessment of ~30% of these participants, we refined this set of markers from 343 to 28, based on their performance and ability to track changes in phenotype over time. The final diagnostic panel of 28 features was validated in an independent cohort (26 cases, 26 controls) with good performance (AUC = 0.80, 81% accuracy, 85% sensitivity, and 77% specificity). The identification and validation of this diverse diagnostic panel represents a powerful and novel approach to improve accuracy and reduce bias in diagnosing combat-related PTSD.
Large-scale integrated analysis of ovarian cancer tumors and cell lines identifies an individualized gene expression signature for predicting response to platinum-based chemotherapy
Authors: Sun Jie , Bao Siqi , Xu Dandan , Zhang Yan , Su Jianzhong , Liu Jiaqi , Hao Dapeng , Zhou Meng
Published: September 2019

Heterogeneity in chemotherapeutic response is directly associated with prognosis and disease recurrence in patients with ovarian cancer (OvCa). Despite the significant clinical need, a credible gene signature for predicting response to platinum-based chemotherapy and for guiding the selection of personalized chemotherapy regimens has not yet been identified. The present study used an integrated approach involving both OvCa tumors and cell lines to identify an individualized gene expression signature, denoted as IndividCRS, consisting of 16 robust chemotherapy-responsive genes for predicting intrinsic or acquired chemotherapy response in the meta-discovery dataset. The robust performance of this signature was subsequently validated in 25 independent tumor datasets comprising 2215 patients and one independent cell line dataset, across different technical platforms. The IndividCRS was significantly correlated with the response to platinum therapy and predicted the improved outcome. Moreover, the IndividCRS correlated with homologous recombination deficiency (HRD) and was also capable of discriminating HR-deficient tumors with or without platinum-sensitivity for guiding HRD-targeted clinical trials. Our results reveal the universality and simplicity of the IndividCRS as a promising individualized genomic tool to rapidly monitor response to chemotherapy and predict the outcome of patients with OvCa.
Lactate and pyruvate promote oxidative stress resistance through hormetic ROS signaling
Authors: Tauffenberger Arnaud , Fiumelli Hubert , Almustafa Salam , Magistretti Pierre J.
Published: September 2019

L-lactate was long considered a glycolytic by-product but is now being recognized as a signaling molecule involved in cell survival. In this manuscript, we report the role of L-lactate in stress resistance and cell survival mechanisms using neuroblastoma cells (SH-SY5Y) as well as the C. elegans model. We observed that L-lactate promotes cellular defense mechanisms, including Unfolded Protein Response (UPR) and activation of nuclear factor erythroid 2–related factor 2 (NRF2), by promoting a mild Reactive Oxygen Species (ROS) burst. This increase in ROS triggers antioxidant defenses and pro-survival pathways, such as PI3K/AKT and Endoplasmic Reticulum (ER) chaperones. These results contribute to the understanding of the molecular mechanisms involved in beneficial effects of L-lactate, involving mild ROS burst, leading to activation of unfolded protein responses and detoxification mechanisms. We present evidence that this hormetic mechanism induced by L-lactate protects against oxidative stress in vitro and in vivo. This work contributes to the identification of molecular mechanisms, which could serve as targets for future therapeutic approaches for cell protection and aging-related disorders.
High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma
Authors: Xiong Dan-dan , Feng Zhen-bo , Lai Ze-feng , Qin Yue , Liu Li-min , Fu Hao-xuan , He Rong-quan , Wu Hua-yu , Dang Yi-wu , Chen Gang , Luo Dian-zhong
Published: September 2019

Nitidine chloride (NC) has been demonstrated to have an anticancer effect in hepatocellular carcinoma (HCC). However, the mechanism of action of NC against HCC remains largely unclear. In this study, three pairs of NC-treated and NC-untreated HCC xenograft tumour tissues were collected for circRNA sequencing analysis. In total, 297 circRNAs were differently expressed between the two groups, with 188 upregulated and 109 downregulated, among which hsa_circ_0088364 and hsa_circ_0090049 were validated by real-time quantitative polymerase chain reaction. The in vitro experiments showed that the two circRNAs inhibited the malignant biological behaviour of HCC, suggesting that they may play important roles in the development of HCC. To elucidate whether the two circRNAs function as “miRNA sponges” in HCC, we identified circRNA-miRNA and miRNA-mRNA interactions by using the CircInteractome and miRwalk, respectively. Subsequently, 857 miRNA-associated differently expressed genes in HCC were selected for weighted gene co-expression network analysis. Module Eigengene turquoise with 423 genes was found to be significantly related to the survival time, pathology grade and TNM stage of HCC patients. Gene functional enrichment analysis showed that the 423 genes mainly functioned in DNA replication- and cell cycle-related biological processes and signalling cascades. Eighteen hubgenes (SMARCD1, CBX1, HCFC1, RBM12B, RCC2, NUP205, ECT2, PRIM2, RBM28, COPS7B, PRRC2A, GPR107, ANKRD52, TUBA1B, ATXN7L3, FUS, MCM8 and RACGAP1) associated with clinical outcomes of HCC patients were then identified. These findings showed that the crosstalk between hsa_circ_0088364 and hsa_circ_0090049 and their competing mRNAs may play important roles in HCC, providing interesting clues into the potential of circRNAs as therapeutic targets of NC in HCC.
Degraded neutrophil extracellular traps promote the growth of Actinobacillus pleuropneumoniae
Authors: de Buhr Nicole , Bonilla Marta C. , Pfeiffer Jessica , Akhdar Silke , Schwennen Cornelia , Kahl Barbara C. , Waldmann Karl-Heinz , Valentin-Weigand Peter , Hennig-Pauka Isabel , von Köckritz-Blickwede Maren
Published: September 2019

Actinobacillus pleuropneumoniae (A.pp) causes severe pneumonia associated with enormous economic loss in pigs. Peracute diseased pigs die in <24 h with pneumonia. Neutrophils are the prominent innate immune cell in this infection that massively infiltrate the infected lung. Here we show that neutrophils release neutrophil extracellular traps (NETs) as response to A.pp infection. Numerous NET-markers were identified in bronchoalveolar lavage fluid (BALF) of A.pp-infected piglets in vivo, however, most NET fibers are degraded. Importantly, A.pp is able to enhance its growth rate in the presence of NETs that have been degraded by nucleases efficiently. A.pp itself releases no nuclease, but we identified host nucleases as sources that degrade NETs after A.pp infection. Furthermore, the nucleases of co-infecting pathogens like Streptococcus suis increase growth of A.pp in presence of porcine NETs. Thus, A.pp is not only evading the antimicrobial activity of NETs, A.pp is rather additionally using parts of NETs as growth factor thereby taking advantage of host nucleases as DNase1 or nucleases of co-infecting bacteria, which degrade NETs. This effect can be diminished by inhibiting the bacterial adenosine synthase indicating that degraded NETs serve as a source for NAD, which is required by A.pp for its growth. A similar phenotype was found for the human pathogen Haemophilus (H.) influenzae and its growth in the presence of human neutrophils. H. influenzae benefits from host nucleases in the presence of neutrophils. These data shed light on the detrimental effects of NETs during host immune response against certain bacterial species that require and/or efficiently take advantage of degraded DNA material, which has been provided by host nuclease or nucleases of other co-infecting bacteria, as growth source.
Lung tumorspheres reveal cancer stem cell-like properties and a score with prognostic impact in resected non-small-cell lung cancer
Authors: Herreros-Pomares Alejandro , de-Maya-Girones Juan Diego , Calabuig-Fariñas Silvia , Lucas Rut , Martínez Alicia , Pardo-Sánchez José Miguel , Alonso Sergio , Blasco Ana , Guijarro Ricardo , Martorell Miguel , Escorihuela Eva , Chiara María Dolores , Duréndez Elena , Gandía Carolina , Forteza Jerónimo , Sirera Rafael , Jantus-Lewintre Eloísa , Farràs Rosa , Camps Carlos
Published: September 2019

The high resistance against current therapies found in non-small-cell lung cancer (NSCLC) has been associated to cancer stem-like cells (CSCs), a population for which the identification of targets and biomarkers is still under development. In this study, primary cultures from early-stage NSCLC patients were established, using sphere-forming assays for CSC enrichment and adherent conditions for the control counterparts. Patient-derived tumorspheres showed self-renewal and unlimited exponential growth potentials, resistance against chemotherapeutic agents, invasion and differentiation capacities in vitro, and superior tumorigenic potential in vivo. Using quantitative PCR, gene expression profiles were analyzed and NANOG, NOTCH3, CD44, CDKN1A, SNAI1, and ITGA6 were selected to distinguish tumorspheres from adherent cells. Immunoblot and immunofluorescence analyses confirmed that proteins encoded by these genes were consistently increased in tumorspheres from adenocarcinoma patients and showed differential localization and expression patterns. The prognostic role of genes significantly overexpressed in tumorspheres was evaluated in a NSCLC cohort (N = 661) from The Cancer Genome Atlas. Based on a Cox regression analysis, CDKN1A, SNAI1, and ITGA6 were found to be associated with prognosis and used to calculate a gene expression score, named CSC score. Kaplan–Meier survival analysis showed that patients with high CSC score have shorter overall survival (OS) in the entire cohort [37.7 vs. 60.4 months (mo), p = 0.001] and the adenocarcinoma subcohort [36.6 vs. 53.5 mo, p = 0.003], but not in the squamous cell carcinoma one. Multivariate analysis indicated that this gene expression score is an independent biomarker of prognosis for OS in both the entire cohort [hazard ratio (HR): 1.498; 95% confidence interval (CI), 1.167–1.922; p = 0.001] and the adenocarcinoma subcohort [HR: 1.869; 95% CI, 1.275–2.738; p = 0.001]. This score was also analyzed in an independent cohort of 114 adenocarcinoma patients, confirming its prognostic value [42.90 vs. not reached (NR) mo, p = 0.020]. In conclusion, our findings provide relevant prognostic information for lung adenocarcinoma patients and the basis for developing novel therapies. Further studies are required to identify suitable markers and targets for lung squamous cell carcinoma patients.
The emerging role of IMD 0354 on bone homeostasis by suppressing osteoclastogenesis and bone resorption, but without affecting bone formation
Authors: Chen Wenxiang , Xie Ziang , Tang Pan , Wang Yongli , Jie Zhiwei , Qin An , Jiang Xuesheng , Hu Zhijun , Fan Shunwu
Published: September 2019

Osteoporosis is caused by an imbalance between bone formation and bone resorption. Receptor activator of nuclear factor-κB ligand (RANKL) promotes the activity and differentiation of osteoclasts via activating the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. IMD 0354 is a selective molecular inhibitor of inhibitor of NF-κB kinase subunit beta (IKKβ) and effective for treatment of acute and subacute inflammatory diseases through the suppression of NF-κB activation. However, the effect of IMD 0354 on bone homeostasis is unknown. In this study, we demonstrated that IMD 0354 significantly attenuated ovariectomy-induced bone loss and inhibited osteoclastogenesis in mice, whereas bone formation was not affected. Additionally, IMD 0354 dramatically inhibited osteoclast differentiation and function induced by RANKL and macrophage colony-stimulating factor in bone marrow monocytes as verified by tartrate-resistant acid phosphatase (TRAP) staining as well as bone resorption assay in vitro. Subsequently, we found that activation of NF-κB signaling and the ERK/c-Fos axis were blunted during osteoclast formation induced by RANKL. Transcription factors nuclear factor of activated T cells c1 (NFATc1) and c-Fos were suppressed with the decreased expression of osteoclast-related genes by IMD 0354. Our findings suggest that IMD 0354 could be a potential preventive and therapeutic drug for osteoporosis.
Epidemiology of genitourinary foreign bodies in the united states emergency room setting and its association with mental health disorders
Authors: Rodríguez Dayron , Thirumavalavan Nannan , Pan Shu , Apoj Michel , Butaney Mohit , Gross Martin S. , Munarriz Ricardo
Published: September 2019

The epidemiology of genitourinary foreign bodies (GUFB) has been mainly described through case reports and small series. The aim of this study is to investigate the epidemiologic, medical, and socioeconomic factors associated with GUFB, along with the resultant costs of care in emergency departments (EDs) nationwide. ED visits with the primary diagnosis of a GUFB between 2010 and 2014 were abstracted from the Nationwide Emergency Department Sample database. Between 2010 and 2014, a weighted estimate of 102,333 visits to the ED with GUFB were recorded in the US, representing a national incidence of 7.6 ED visits per 100,000 persons. Of these visits, 4.7% resulted in admission and males were more likely to be admitted (24.8% vs. 2.1%, p < 0.01). A third of patients had low income, 30% had no medical insurance, and a third of patients had Medicaid. Urethra/bladder and penile foreign bodies had a significant association with mental health disorders (35.6%). Vulvar/vaginal foreign bodies had a lower prevalence of mental health disorders (6.1%). Costs of managing patients in the ED averaged $3769. More importantly, penile or urethra/bladder foreign bodies incurred a higher cost ($30,071). This is the largest population-based study investigating the epidemiology of GUFB. GUFB are more common in young women and the majority of them are vulvar/vaginal. Urethral and bladder foreign bodies occurred in older male patients and are associated with longer hospital stays and costs. Over one third of male patients with urethra/bladder had significant mental health disorders.
Deciphering African late middle Pleistocene hominin diversity and the origin of our species
Authors: Mounier Aurélien , Mirazón Lahr Marta
Published: September 2019

The origin of Homo sapiens remains a matter of debate. The extent and geographic patterning of morphological diversity among Late Middle Pleistocene (LMP) African hominins is largely unknown, thus precluding the definition of boundaries of variability in early H. sapiens and the interpretation of individual fossils. Here we use a phylogenetic modelling method to predict possible morphologies of a last common ancestor of all modern humans, which we compare to LMP African fossils (KNM-ES 11693, Florisbad, Irhoud 1, Omo II, and LH18). Our results support a complex process for the evolution of H. sapiens, with the recognition of different, geographically localised, populations and lineages in Africa – not all of which contributed to our species’ origin. Based on the available fossils, H. sapiens appears to have originated from the coalescence of South and, possibly, East-African source populations, while North-African fossils may represent a population which introgressed into Neandertals during the LMP.