bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender-Confirming Vulvoplasty in Transgender Women in the Netherlands: Incidence, Motivation Analysis, and Surgical Outcomes
Authors: van der Sluis Wouter B. , Steensma Thomas D. , Timmermans Floyd W. , Smit Jan Maerten , de Haseth Kristin , Özer Müjde , Bouman Mark-Bram
Published: May 2020

Background

Penile inversion vaginoplasty is the surgical gold standard for genital gender-affirmative surgery in transgender women. However, there is an increase of attention for gender-confirming vulvoplasty (GCV), in which no neovaginal cavity is created.

Aim

To describe underlying motives and surgical outcomes of GCV in transgender women.

Methods

All transgender women who underwent GCV were retrospectively identified from a departmental database. A retrospective chart study was conducted, recording underlying motives, demographics, perioperative complications, and reoperations.

Outcomes

Underlying motives and perioperative complication rate.

Results

In the period January 1990 to January 2020, 17 transgender women underwent GCV at our center. Most women reported that their motivation to undergo GCV was because they had no wish for postoperative neovaginal penetration (n = 10, 59%). This was due to a sexual preference toward women without the wish for neovaginal penetrative intercourse (n = 6, 35%) or due to a negative sexual experience in the past (n = 4, 24%). Some women desired vaginoplasty with neovaginal cavity creation but were ineligible for this because of their medical history (n = 4, 24%), for example, due to locoregional radiotherapy. The median clinical follow-up was 34 months (range 3-190). The postoperative course was uncomplicated in 11 (65%) women. Postoperative complications comprised the following: meatal stenosis (n = 2, for which surgical correction), remnant corpus spongiosum tissue (n = 1, for which surgical correction), minor wound dehiscence (n = 3, for which conservative management), and postoperative urinary tract infection (n = 1, successfully treated with oral antibiotics). One woman, who developed meatal stenosis, had a history of radiotherapy because of rectal carcinoma and needed 2 surgical procedures under general anesthesia to correct this. Information on self-reported satisfaction was available for 12 women. All were satisfied with the postoperative result and they graded their neovagina an 8.2 ± 0.9 out of 10.

Clinical Implications

GCV may be added to the surgical repertoire of the gender surgeon. Transgender women with a desire for genital gender-affirmative surgery should be counseled on surgical options and its (dis)advantages.

Strengths & Limitations

Strengths of this study comprise that it is from a high-volume center. A weakness of this study is the retrospective design. The absence of a self-reported outcome measure validated for the transgender persons is a well-known problem.

Conclusion

An increase is observed in transgender women who opt for GCV; however, the absolute number undergoing this surgery remains small in our center. Postoperative complications do occur but are generally minor and treatable.
In vitro anthelmintic activity assessment of six medicinal plant aqueous extracts against donkey strongyles
Authors: Buza V. , Cătană L. , Andrei S.M. , Ștefănuț L.C. , Răileanu Ș. , Matei M.C. , Vlasiuc I. , Cernea M.
Published: May 2020

The lack of anthelmintic products licensed for donkeys and the rising number of small donkey milk farms in the countries of Western Europe and Italy have led to an increased interest in the study of reliable and safe plant-derived treatment alternatives. In this study, the aqueous extracts of Achillea millefolium L. (flowers), Artemisia absinthium L. (aerial parts), Centaurium erythraea Rafn. (flowers), Gentiana asclepiadea L. (rhizomes and roots), Inula helenium L. (rhizomes and roots) and Tanacetum vulgare L. (aerial parts), have been tested in vitro for their potential ovicidal and larvicidal activity against donkey nematodes. An egg-hatching assay (EHA) and larval development assay (LDA) were performed for the in vitro study, and median lethal concentration (LC-50) values for both EHA and LDA were calculated using probit analysis. All tested plant extracts showed strong anthelmintic activity against strongyle eggs and larvae at concentrations ranging between 125 and 1.95 mg/ml, except for C. erythraea, which exhibited very little or no effect at all at the tested concentrations. A strong ovicidal effect was observed in A. absinthium, with an LC-50 value of 0.486 mg/ml (95% confidence interval (CI) 0.21–1.09). Gentiana asclepiadea showed high efficacy against strongyle larvae, with an LC-50 value of 0.041 mg/ml (95% CI 0.01–0.16). The most significant (P < 0.01) anthelmintic activity was exhibited by I. helenium, with an LC-50 value of 0.041 mg/ml (95% CI 0.01–0.16) for EHA and 0.41 mg/ml (95% CI 0.27–0.62) for LDA. The results proved the anthelmintic efficacy of the tested plant extracts, highlighting the need for further research into plant bioactive molecules both in vitro and in vivo.
Trajectory Planning of Quadrotor Systems for Various Objective Functions
Authors: Heidari Hamidreza , Saska Martin
Published: May 2020

Quadrotors are unmanned aerial vehicles with many potential applications ranging from mapping to supporting rescue operations. A key feature required for the use of these vehicles under complex conditions is a technique to analytically solve the problem of trajectory planning. Hence, this paper presents a heuristic approach for optimal path planning that the optimization strategy is based on the indirect solution of the open-loop optimal control problem. Firstly, an adequate dynamic system modeling is considered with respect to a configuration of a commercial quadrotor helicopter. The model predicts the effect of the thrust and torques induced by the four propellers on the quadrotor motion. Quadcopter dynamics is described by differential equations that have been derived by using the Newton–Euler method. Then, a path planning algorithm is developed to find the optimal trajectories that meet various objective functions, such as fuel efficiency, and guarantee the flight stability and high-speed operation. Typically, the necessary condition of optimality for a constrained optimal control problem is formulated as a standard form of a two-point boundary-value problem using Pontryagin’s minimum principle. One advantage of the proposed method can solve a wide range of optimal maneuvers for arbitrary initial and final states relevant to every considered cost function. In order to verify the effectiveness of the presented algorithm, several simulation and experiment studies are carried out for finding the optimal path between two points with different objective functions by using MATLAB software. The results clearly show the effect of the proposed approach on the quadrotor systems.
Automatically Building Linking Relations between Lane-Level Map and Commercial Navigation Map Using Topological Networks Matching
Authors: Tao Lu , Zhang Pan , Yan Lixin , Zhu Dunyao
Published: May 2020

The lane-level map, which contains the lane-level information severely lacking in widely used commercial navigation maps, has become an essential data source for autonomous driving systems. The linking relations between lane-level map and commercial navigation map can facilitate an autonomous driving system mapping information between different applications using different maps. In this paper, an approach is proposed to build the linking relations automatically. The different topology networks are first reconstructed into similar structures. Then, to build the linking relations automatically, the adaptive multi-filter algorithm and forward path exploring algorithm are proposed to detect corresponding junctions and paths, respectively. The approach is validated by two real data sets of more than 150 km of roads, mainly highway. The linking relations for nearly 94% of the total road length have been built successfully.
New Nationalisms and Identity Politics: Minorities, Majorities and Universal Emancipation
Authors: Morozov Viacheslav
Published: May 2020

A defining feature of new nationalisms, with their right-wing populist rhetoric, is the way they exploit the regime of truth prevalent in liberal democratic societies. Their use of the language of democracy, human rights and identity is sometimes hard to differentiate from the mainstream convention. Despite being majoritarian in the way it seeks democratic legitimacy, new nationalist discourse consistently advances demands framed in terms of minority protection. This is done by presenting the existence of ‘our’ nation as threatened by overwhelming forces of neo-liberal globalisation (embodied in the EU, the West or even in ‘the Washington establishment’). By using the Pussy Riot case as an empirical example, this article argues that there is no way of preventing the language of minority protection from being hijacked by ‘predatory identities’ unless one foregrounds the universal dimension of equality and emancipation, as opposed to rights and entitlements associated with particular identities. The key political question today, as always, is how to navigate between the totalitarian disregard of the local and the parochialist concentration on the particular.
Pushing partnerships: corporate influence on research and policy via the International Life Sciences Institute
Authors: Steele Sarah , Ruskin Gary , Stuckler David
Published: May 2020

Objective:

There are concerns that some non-profit organisations, financed by the food industry, promote industry positions in research and policy materials. Using Freedom of Information (FOI) requests, we test the proposition that the International Life Sciences Institute (ILSI), one prominent non-for profit in international health and nutrition research, promotes industry positions.

Design:

U.S. Right to Know filed five FOI from 2015 to 2018 covering communications with researchers at four US institutions: Texas A&M, University of Illinois, University of Colorado and North Carolina State University. It received 15 078 pages, which were uploaded to the University of California San Francisco’s Industry Documents Library. We searched the Library exploring it thematically for instances of: (1) funding research activity that supports industry interests; (2) publishing and promoting industry-sponsored positions or literature; (3) disseminating favourable material to decision makers and the public and (4) suppressing views that do not support industry.

Results:

Available emails confirmed that ILSI’s funding by corporate entities leads to industry influence over some of ILSI activities. Emails reveal a pattern of activity in which ILSI sought to exploit the credibility of scientists and academics to bolster industry positions and promote industry-devised content in its meetings, journal and other activities. ILSI also actively seeks to marginalise unfavourable positions.

Conclusions:

We conclude that undue influence of industry through third-party entities like ILSI requires enhanced management of conflicts of interest by researchers. We call for ILSI to be recognised as a private sector entity rather than an independent scientific non-profit, to allow for more appropriate appraisal of its outputs and those it funds.
Feeling Like a Burden
Authors: Wirth James H. , Allen Ashley Batts , Zitek Emily M.
Published: May 2020

Abstract. We examined the negative outcomes, particularly social costs that result when a person harms their group by performing poorly, and whether self-compassion could buffer against these negative outcomes. In Studies 1 and 2, participants performed poorly and harmed their group or performed equal to their group. Harmful poor-performing participants felt more burdensome, experienced more negative affect, felt more ostracized, anticipated more exclusion, and felt lowered self-esteem than equal-performing participants. Studies 3 and 4 disentangled poor performance from harming a group. Poor-performing participants either harmed the group or caused no harm. Harmful poor-performing participants felt more burdensome and anticipated more exclusion, indicating the additional social consequences of a harmful poor performance over a non-harmful performance. Across studies, trait self-compassion was associated with reduced negative effects.
A Post‐2013 Dropoff in Total Ozone at a Third of Global Ozonesonde Stations: Electrochemical Concentration Cell Instrument Artifacts?
Authors: Stauffer Ryan M. , Thompson Anne M. , Kollonige Debra E. , Witte Jacquelyn C. , Tarasick David W. , Davies Jonathan , Vömel Holger , Morris Gary A. , Van Malderen Roeland , Johnson Bryan J. , Querel Richard R. , Selkirk Henry B. , Stübi Rene , Smit Herman G. J.
Published: May 2020

An international effort to improve ozonesonde data quality and to reevaluate historical records has made significant improvements in the accuracy of global network data. However, between 2014 and 2016, ozonesonde total column ozone (TCO; O3) at 14 of 37 regularly reporting stations exhibited a sudden dropoff relative to satellite measurements. The ozonesonde TCO drop is 3–7% compared to satellite and ground‐based TCO, and 5–10% or more compared to satellite stratospheric O3 profiles, compromising the use of recent data for trends, although they remain reliable for other uses. Hardware changes in the ozonesonde instrument are likely a major factor in the O3 dropoff, but no single property of the ozonesonde explains the findings. The bias remains in recent data. Research to understand the dropoff is in progress; this letter is intended as a caution to users of the data. Our findings underscore the importance of regular ozonesonde data evaluation.
Solar Energetic Proton Access to the Near‐Equatorial Inner Magnetosphere
Authors: Filwett Rachael J. , Jaynes Allison N. , Baker Daniel N. , Kanekal Shrikanth G. , Kress Brian , Blake J. Bern
Published: May 2020

In this study we examine the ability of protons of solar origin to access the near‐equatorial inner magnetosphere. Here we examine four distinct solar proton events from 20–200 MeV, concurrent with both quiet time and storm time conditions using proton data from the ACE satellite in the solar wind upstream of Earth and data from the Relativistic Electron Proton Telescope (REPT) instrument aboard Van Allen Probes. We examine the direct flux correspondence between interplanetary space and the inner magnetosphere. Small substructures in interplanetary space are observable in the REPT flux profiles, which can penetrate down to L values of ≤4. Furthermore, there are orbit‐to‐orbit variations in the west‐to‐east anisotropic flux ratios. The anisotropic flux ratios are used as a proxy for cutoff energies and display cutoff variations with L shell and energy. The dependence of the anisotropic flux ratio on Dst values is shown. The results paint a picture of highly dynamic spatial and temporal proton cutoff rigidities in the near‐equatorial inner magnetosphere.
Impact of Higher Spatial Atmospheric Resolution on Precipitation Extremes Over Land in Global Climate Models
Authors: Bador Margot , Boé Julien , Terray Laurent , Alexander Lisa V. , Baker Alexander , Bellucci Alessio , Haarsma Rein , Koenigk Torben , Moine Marie‐Pierre , Lohmann Katja , Putrasahan Dian A. , Roberts Chris , Roberts Malcolm , Scoccimarro Enrico , Schiemann Reinhard , Seddon Jon , Senan Retish , Valcke Sophie , Vanniere Benoit
Published: May 2020

Finer grids in global climate models could lead to an improvement in the simulation of precipitation extremes. We assess the influence on model performance of increasing spatial resolution by evaluating pairs of high‐ and low‐resolution forced atmospheric simulations from six global climate models (generally the latest CMIP6 version) on a common 1° × 1° grid. The differences in tuning between the lower and higher resolution versions are as limited as possible, which allows the influence of higher resolution to be assessed exclusively. We focus on the 1985–2014 climatology of annual extremes of daily precipitation over global land, and models are compared to observations from different sources (i.e., in situ‐based and satellite‐based) to enable consideration of observational uncertainty. Finally, we address regional features of model performance based on four indices characterizing different aspects of precipitation extremes. Our analysis highlights good agreement between models that precipitation extremes are more intense at higher resolution. We find that the spread among observations is substantial and can be as large as intermodel differences, which makes the quantitative evaluation of model performance difficult. However, consistently across the four precipitation extremes indices that we investigate, models often show lower skill at higher resolution compared to their corresponding lower resolution version. Our findings suggest that increasing spatial resolution alone is not sufficient to obtain a systematic improvement in the simulation of precipitation extremes, and other improvements (e.g., physics and tuning) may be required.
Scientists Float a New Theory on the Medusae Fossae Formation
Authors: Redd Nola
Published: May 2020

Pumice-like rafts of lightweight material could have carried volcanic debris across an ancient Martian ocean to build one of the most puzzling features on the Red Planet.
Reply to Comments by N. Sultan on “Sedimentation Controls on Methane‐Hydrate Dynamics Across Glacial/Interglacial Stages: An Example From International Ocean Discovery Program Site U1517, Hikurangi Margin”
Authors: Screaton E. J. , Torres M. E. , Dugan B. , Heeschen K. U. , Mountjoy J. J. , Ayres C. , Rose P. S. , Pecher I. A. , Barnes P. M. , LeVay L. J.
Published: May 2020

Screaton et al. (2019, https://doi.org/10.1029/2019GC008603) examined the role of sedimentation, sea level, and bottom water temperature (BWT) changes due to glaciation as drivers for the downward migration of the base of gas hydrate stability and gas hydrate formation. International Ocean Discovery Program (IODP) Site U1517 in the Hikurangi margin was used as a case study because data at this site document a marked increase in chloride over a broad depth range, which was attributed to recent gas hydrate formation. In a comment on Screaton et al. (2019, https://doi.org/10.1029/2019GC008603), Sultan (2020, https://doi.org/10.1029/2019gc008846) used a linear thermal profile to argue that inferences and characterization of methane hydrate at IODP Site U1517 were incorrect because some occur below his estimated base of gas hydrate stability (BGHS). Based on this apparent discrepancy, Sultan (2020, https://doi.org/10.1029/2019gc008846) further stated that low‐chloride spikes may be unreliable indicators of methane hydrate occurrence. In this reply, we emphasize that unsteady‐state, and thus nonlinear, thermal profiles are likely in areas experiencing active sedimentation and bottom‐water temperature (BWT) changes. The resulting deviation from steady‐state temperature profile shifts the BGHS downward. In addition, sedimentation has the potential to bury methane hydrate more rapidly than it dissociates, helping to explain how methane hydrate could be observed below the BGHS. We also review the supporting evidence for gas‐hydrate occurrence at Site U1517 and the criteria used for Site U1517 site selection.
Simulation of Natural Iron Oxide Alteration in Soil: Conversion of Synthetic Ferrihydrite to Hematite Without Artificial Dopants, Observed With Magnetic Methods
Authors: Bilardello Dario , Banerjee Subir K. , Volk Michael W. R. , Soltis Jennifer A. , Penn R. Lee
Published: May 2020

We present new results on the conversion of pure, undoped synthetic ferrihydrite, wet‐annealed at pH 6.56 and 90°C without stabilizing ligands, to nanophase goethite, hematite, and an intermediate magnetic phase, nanophase maghemite. Our analyses included magnetic field and temperature‐dependent properties and characterization by powder X‐ray diffraction, Mössbauer spectra, and high‐resolution transmission electron microscopy. We sampled alteration products after 0.5 hr, and then in a geometric progression to 32 hr, yielding a detailed examination of the earliest alteration phases. There are many similarities to the latest studies of pure ferrihydrite alteration but with a significant difference: We observe early appearance of oriented nanophase goethite along with a soft magnetic contribution, while rhombohedral hematite crystals form later, as reported in previous studies. Our observations attest to the non‐uniqueness of the magnetic enhancement process and to its strong dependence on environmental conditions, with important implications for use of the hematite/goethite ratio as a paleoprecipitation proxy.
Where Do Cold Air Outbreaks Occur, and How Have They Changed Over Time?
Authors: Smith Erik T. , Sheridan Scott C.
Published: May 2020

Cold air outbreaks (CAOs) occur in many regions of the globe and can be detrimental to the agricultural industry and human health, especially in less prepared regions. A systematic CAO classification was developed using two different climate reanalysis data sets from 1979–2018. Trends in CAOs were calculated for different regions across the globe and the results from each reanalysis data set compared with one another to identify discrepancies. CAOs occur more frequently in the Northern Hemisphere than the Southern Hemisphere with the highest number of CAOs in Europe, Central Eurasia, and North America. CAOs were found to have decreased in spatial extent, frequency, duration, and magnitude across much of the globe, particularly across Alaska, Canada, and the North Atlantic, while an increase in CAOs was observed in Eastern Europe, Central Eurasia, and the Southern Ocean. Early and late winter CAOs have also become much less frequent in most regions.
Anthropogenic Intensification of Surface Ocean Interannual pCO2 Variability
Authors: Gallego M. Angeles , Timmermann Axel , Friedrich Tobias , Zeebe Richard E.
Published: May 2020

We use several global coupled atmosphere‐ocean‐biogeochemistry models from the Coupled Model Intercomparison Project (CMIP5) to show that the global interannual variability of the sea surface pCO2 (calculated as 1σ) will increase by ∼64 ± 20% by 2040–2090 relative to the beginning of the industrial revolution under the RCP8.5 scenario. All models agree that the increase in variability is a consequence of a larger background pCO2 and a lower buffering capacity that enhance the response of pCO2 to the fluctuations of surface temperature (T) and dissolved inorganic carbon (DIC). The most skillful group of models under present‐day conditions shows a future global decrease in DIC fluctuations that will weaken the pCO2 interannual variability (IAV). The remaining uncertainties in the projected evolution of pCO2 variability regionally highlight the need for continuous carbon monitoring programs which will contribute to a better understanding of the oceanic carbon sink's response to increased green house emissions.
Circulation and Tides in a Cooler Upper Atmosphere: Dynamical Effects of CO2 Doubling
Authors: Liu Huixin , Tao Chihiro , Jin Hidekatsu , Nakamoto Yusuke
Published: May 2020

Thermosphere cooling is a known effect of increasing CO2 in the atmosphere. In this study, we explore the changes of thermosphere circulation and tides in the cooled thermosphere via a doubled CO2 numerical experiment using the Ground‐to‐topside Atmosphere Ionosphere model for Aeronomy (GAIA). The results reveal three major features. (1) The thermosphere cools about 10 K more around solstices than equinoxes, more at the summer pole than the winter pole. (2) The meridional circulation shifts downward and strongly accelerates by 5–15 m s−1. (3) The tidal activity experiences dramatic changes, with a 40–60% reduction in the semidiurnal tides (SW2) throughout the thermosphere but an 30–50% enhancement in diurnal tides (DW1) below 200 km altitude. The nonmigrating tide DE3 has only minor changes. These changes in temperature, meridional circulation, and tides are persistent features in all seasons and can profoundly affect the spatial distribution and diurnal cycles of the ionospheric responses to CO2 doubling via atmosphere composition and electrodynamics.
Potential for Early Forecast of Moroccan Wheat Yields Based on Climatic Drivers
Authors: Lehmann J. , Kretschmer M. , Schauberger B. , Wechsung F.
Published: May 2020

Wheat production plays an important role in Morocco. Current wheat forecast systems use weather and vegetation data during the crop growing phase, thus limiting the earliest possible release date to early spring. However, Morocco's wheat production is mostly rainfed and thus strongly tied to fluctuations in rainfall, which in turn depend on slowly evolving climate dynamics. This offers a source of predictability at longer time scales. Using physically guided causal discovery algorithms, we extract climate precursors for wheat yield variability from gridded fields of geopotential height and sea surface temperatures which show potential for accurate yield forecasts already in December, with around 50% explained variance in an out‐of‐sample cross validation. The detected interactions are physically meaningful and consistent with documented ocean‐atmosphere feedbacks. Reliable yield forecasts at such long lead times could provide farmers and policy makers with necessary information for early action and strategic adaptation measurements to support food security.
Poloidal‐ and Toroidal‐Mode Mantle Flows Underneath the Cascadia Subduction Zone
Authors: Zhu Hejun , Li Xueyan , Yang Jidong , Stern Robert J. , Lumley David E.
Published: May 2020

Several hypotheses have been proposed to explain intriguing circular shear wave splitting patterns in the Pacific Northwest, invoking either 2‐D entrained flows or 3‐D return flows. Here, we present some hitherto unidentified, depth‐dependent anisotropic signatures to reconcile different conceptual models. At depths shallower than 200 km, the fast propagation directions of seismic waves to the west of the Rocky Mountain are aligned sub‐parallel to the subduction direction of the Juan de Fuca and Gorda Plates. This pattern is consistent with previous onshore/offshore shear wave splitting measurements and indicates that 2‐D entrained flows dominate at shallower depths. From 300 to 500 km, two large‐scale return flows are revealed, one circulating around Nevada and Colorado and the other running around the edge of the descending Juan de Fuca slab. These observations suggest the development of toroidal‐mode mantle flows, driven by the fast rollback of the narrow, fragmented Juan de Fuca and Gorda slabs.
Empirical Models for Predicting Water and Heat Flow Properties of Permafrost Soils
Authors: O'Connor Michael T. , Cardenas M. Bayani , Ferencz Stephen B. , Wu Yue , Neilson Bethany T. , Chen Jingyi , Kling George W.
Published: May 2020

Warming and thawing in the Arctic are promoting biogeochemical processing and hydrologic transport in carbon‐rich permafrost and soils that transfer carbon to surface waters or the atmosphere. Hydrologic and biogeochemical impacts of thawing are challenging to predict with sparse information on arctic soil hydraulic and thermal properties. We developed empirical and statistical models of soil properties for three main strata in the shallow, seasonally thawed soils above permafrost in a study area of ~7,500 km2 in Alaska. The models show that soil vertical stratification and hydraulic properties are predictable based on vegetation cover and slope. We also show that the distinct hydraulic and thermal properties of each soil stratum can be predicted solely from bulk density. These findings fill the gap for a sparsely mapped region of the Arctic and enable regional interpolation of soil properties critical for determining future hydrologic responses and the fate of carbon in thawing permafrost.
The Groundbreaking Experiment in Earthquake Control at Rangely, Colorado, Revisited
Authors: Byrne H. , Silva J. A. , Plesch A. , Juanes R. , Shaw J. H.
Published: May 2020

Earthquakes caused by human activities are a growing societal concern. A pioneering study of induced seismicity in the 1970s involved cooperation between the U.S. Geological Survey and Chevron, Inc., to adjust operations in the Rangely oil field, Colorado, to initiate and control earthquakes. Here we revisit this experiment using coupled flow and geomechanical modeling to determine the physical mechanisms that caused these earthquakes and investigate the strength and state of stress acting on the fault that sourced them. The controlled nature of the Rangely experiment, combined with data from decades of field operations, presents a unique opportunity to understand the phenomenon of induced seismicity in ways that can be applied to manage these risks.
The Influence of Internal Climate Variability on Projections of Synoptically Driven Beijing Haze
Authors: Callahan Christopher W. , Mankin Justin S.
Published: May 2020

Beijing has suffered a series of poor air quality (“haze”) episodes which have damaged human health and economic growth. Beijing's haze is generally driven by pollutant‐trapping meteorological conditions, but climate model projections differ on how these conditions will evolve under forcing. Such differences are driven in part by (1) disagreements over which meteorological conditions matter most and (2) an undersampling of internal variability in projections. To resolve these differences, we show that Beijing haze is associated with anticyclonic circulation, thereby linking multiple meteorological ingredients to a single process well simulated by models. We use this to inform our assessment of future haze risks in both a multimodel ensemble and a single‐model large ensemble, partitioning model uncertainty and internal variability. We estimate that forcing increases haze‐favorable conditions, but internal variability significantly affects these projections, emphasizing the importance of fully sampling sources of uncertainty to ensure accurate projections of haze risks.
A microfluidically controlled concave–convex membrane lens using an addressing operation system
Authors: Yao Shouju , Zhou Zhou , He Gonghan , Zhang Kunpeng , Huang Xiang , Qiu Bing , Sun Daoheng
Published: May 2020

Electrical control toolkits for microlens arrays are available to some extent, but for applications in environments with strong electromagnetic fields, radiation, or deep water, non-electrical actuation and control strategies are more appropriate. An integrated digital microfluidic zoom actuating unit with a logic addressing unit for a built-in membrane lens array, e.g., a flexible bionic compound eye, is developed and studied in this article. A concave–convex membrane fluidic microvalve, which is the component element of the logic gate, actuator, and microlens, is proposed to replace the traditional solenoid valve. The functions of pressure regulation and decoding can be obtained by incorporating microvalves into fluidic networks according to equivalent circuit designs. The zoom actuating unit contains a pressure regulator to adjust the focal length of lenses with three levels, and the logic addressing unit contains a decoder to choose a typical lens from a hexagonal lens array. The microfluidic chip control system is connected flexibly to the actuating part, a membrane lens array. It is shown from a simulation and experimental demonstration that the designed and fabricated system, which is composed of a whole microfluidic zoom unit, addressing technology, and a microlens array, works well. Because these components are constructed in the same fabrication process and operate with the same work media and driving source, the system can be made highly compatible and lightweight for applications such as human-machine interfaces and soft robots.
An electronic nose using a single graphene FET and machine learning for water, methanol, and ethanol
Authors: Hayasaka Takeshi , Lin Albert , Copa Vernalyn C. , Lopez Lorenzo P. , Loberternos Regine A. , Ballesteros Laureen Ida M. , Kubota Yoshihiro , Liu Yumeng , Salvador Arnel A. , Lin Liwei
Published: May 2020

The poor gas selectivity problem has been a long-standing issue for miniaturized chemical-resistor gas sensors. The electronic nose (e-nose) was proposed in the 1980s to tackle the selectivity issue, but it required top-down chemical functionalization processes to deposit multiple functional materials. Here, we report a novel gas-sensing scheme using a single graphene field-effect transistor (GFET) and machine learning to realize gas selectivity under particular conditions by combining the unique properties of the GFET and e-nose concept. Instead of using multiple functional materials, the gas-sensing conductivity profiles of a GFET are recorded and decoupled into four distinctive physical properties and projected onto a feature space as 4D output vectors and classified to differentiated target gases by using machine-learning analyses. Our single-GFET approach coupled with trained pattern recognition algorithms was able to classify water, methanol, and ethanol vapors with high accuracy quantitatively when they were tested individually. Furthermore, the gas-sensing patterns of methanol were qualitatively distinguished from those of water vapor in a binary mixture condition, suggesting that the proposed scheme is capable of differentiating a gas from the realistic scenario of an ambient environment with background humidity. As such, this work offers a new class of gas-sensing schemes using a single GFET without multiple functional materials toward miniaturized e-noses.
KSHV infection skews macrophage polarisation towards M2-like/TAM and activates Ire1 α-XBP1 axis up-regulating pro-tumorigenic cytokine release and PD-L1 expression
Authors: Gilardini Montani Maria Saveria , Falcinelli Luca , Santarelli Roberta , Granato Marisa , Romeo Maria Anele , Cecere Nives , Gonnella Roberta , D’Orazi Gabriella , Faggioni Alberto , Cirone Mara
Published: May 2020

Background

Kaposi’s Sarcoma Herpesvirus (KSHV) is a gammaherpesvirus strongly linked to human cancer. The virus is also able to induce immune suppression, effect that contributes to onset/progression of the viral-associated malignancies. As KSHV may infect macrophages and these cells abundantly infiltrate Kaposi’s sarcoma lesions, in this study we investigated whether KSHV-infection could affect macrophage polarisation to promote tumorigenesis.

Methods

FACS analysis was used to detect macrophage markers and PD-L1 expression. KSHV infection and the molecular pathways activated were investigated by western blot analysis and by qRT-PCR while cytokine release was assessed by Multi-analyte Kit.

Results

We found that KSHV infection reduced macrophage survival and skewed their polarisation towards M2 like/TAM cells, based on the expression of CD163, on the activation of STAT3 and STAT6 pathways and the release of pro-tumorigenic cytokines such as IL-10, VEGF, IL-6 and IL-8. We also found that KSHV triggered Ire1 α-XBP1 axis activation in infected macrophages to increase the release of pro-tumorigenic cytokines and to up-regulate PD-L1 surface expression.

Conclusions

The findings that KSHV infection of macrophages skews their polarisation towards M2/TAM and that activate Ire1 α-XBP1 to increase the release of pro-tumorigenic cytokines and the expression of PD-L1, suggest that manipulation of UPR could be exploited to prevent or improve the treatment of KSHV-associated malignancies.
miR-622 is a novel potential biomarker of breast carcinoma and impairs motility of breast cancer cells through targeting NUAK1 kinase
Authors: Orlandella Francesca Maria , Mariniello Raffaela Mariarosaria , Mirabelli Peppino , De Stefano Anna Elisa , Iervolino Paola Lucia Chiara , Lasorsa Vito Alessandro , Capasso Mario , Giannatiempo Rosa , Rongo Maria , Incoronato Mariarosaria , Messina Francesco , Salvatore Marco , Soricelli Andrea , Salvatore Giuliana
Published: May 2020

Background

Aberrant expression of microRNAs (miR) has been proposed as non-invasive biomarkers for breast cancers. The aim of this study was to analyse the miR-622 level in the plasma and in tissues of breast cancer patients and to explore the role of miR-622 and its target, the NUAK1 kinase, in this context.

Methods

miR-622 expression was analysed in plasma and in tissues samples of breast cancer patients by q-RT-PCR. Bioinformatics programs, luciferase assay, public dataset analysis and functional experiments were used to uncover the role of miR-622 and its target in breast cancer cells.

Results

miR-622 is downregulated in plasma and in tissues of breast cancer patients respect to healthy controls and its downregulation is significantly associated with advanced grade and high Ki67 level. Modulation of miR-622 affects the motility phenotype of breast cancer cells. NUAK1 kinase is a functional target of miR-622, it is associated with poor clinical outcomes of breast cancer patients and is inversely correlated with miR-622 level.

Conclusions

miR-622/NUAK1 axis is deregulated in breast cancer patients and affects the motility phenotype of breast cancer cells. Importantly, miR-622 and NUAK1 hold promises as biomarkers and as targets for breast cancers.
Identification of EMT-related high-risk stage II colorectal cancer and characterisation of metastasis-related genes
Authors: Wang Kai , Song Kai , Ma Zhigang , Yao Yang , Liu Chao , Yang Jing , Xiao Huiting , Zhang Jiashuai , Zhang Yanqiao , Zhao Wenyuan
Published: May 2020

Background

Our laboratory previously reported an individual-level prognostic signature for patients with stage II colorectal cancer (CRC). However, this signature was not applicable for RNA-sequencing datasets. In this study, we constructed a robust epithelial-to-mesenchymal transition (EMT)- related gene pair prognostic signature.

Methods

Based on EMT-related genes, metastasis-associated gene pairs were identified between metastatic and non-metastatic samples. Then, we selected prognosis-associated gene pairs, which were significantly correlated with disease-free survival of stage II CRC using multivariate Cox regression model, as the EMT-related prognosis signature.

Results

An EMT-related signature composed of fifty-one gene pairs (51-GPS) for prediction-relapse risk of patients with stage II CRC was developed, whose prognostic efficiency was validated in independent datasets. Moreover, 51-GPS achieved better predictive performance than other reported signatures, including a commercial signature Oncotype Dx colon cancer and an immune-related gene pair signature. Besides, EMT-related functional gene sets achieved high enrichment scores in high-risk samples. Especially, loss-of-function antisense approach showed that DEGs between the predicted two clusters were metastasis-related.

Conclusions

The EMT-related gene pair signature can identify the high relapse-risk patients with stage II CRC, which can facilitate individualised management of patients.
Testing the carbohydrate-insulin model of obesity in a 5-month feeding study: the perils of post-hoc participant exclusions
Authors: Ludwig David S. , Greco Kimberly F. , Ma Clement , Ebbeling Cara B.
Published: May 2020

A large feeding study reported that total energy expenditure (TEE) was greater on a low- versus high-carbohydrate diet, supporting the carbohydrate-insulin model of obesity. Recently, the validity of this finding was challenged in a post-hoc analysis excluding participants with putative non-adherence to the study diets. Here, we show why that analysis, based on a post-randomization variable linked to the outcome, introduced severe confounding bias. With control for confounding, the diet effect on TEE remained strong in a reanalysis. Together with sensitivity analyses demonstrating robustness to plausible levels of non-adherence, these data provide experimental support for a potentially novel metabolic effect of macronutrients that might inform the design of more effective obesity treatment.
Publisher Correction: A Fast and Refined Cancer Regions Segmentation Framework in Whole-slide Breast Pathological Images
Authors: Guo Zichao , Liu Hong , Ni Haomiao , Wang Xiangdong , Su Mingming , Guo Wei , Wang Kuansong , Jiang Taijiao , Qian Yueliang
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
ERK Activity in Immature Leukemic Cells Drives Clonal Selection during Induction Therapy for Acute Myeloid Leukemia
Authors: Hayun Michal , Zaatra Maria , Itzkovich Chen , Sahar Dvora , Rosenberg Dina , Filatova Margarita , Ringelstein-Harlev Shimrit , Baris Hagit , Moustafa-Hawash Nivin , Louria-Hayon Igal , Ofran Yishai
Published: May 2020

Selection of resistant clones following intensive chemotherapy is a common obstacle for cure in many cancers, particularly in acute myeloid leukemia (AML). In AML, clone-specific sensitivity to chemotherapy varies even within the same patient. Multiple mutations and genetic aberrations are associated with clones surviving chemotherapy. The current study explored the role of activated signaling pathways in chemoresistance as a function of cell maturation, reflected by CD34 expression. In-vitro, Kasumi-1 leukemic cell line, sorted by CD34 expression, showed increased apoptosis only in the CD34− subpopulation after exposure to cytosine arabinoside (Ara-C) or daunorubicin. The resistant CD34+ subset demonstrated higher expression of ERK1/2 and BCL-2 proteins than CD34− cells. MEK1/2 inhibition elevated Ara-C ability to induce apoptosis in CD34+ cells, suggesting that MEK1/2-ERK1/2 is surviving signaling, which correlates to cell maturation levels and plays a role in chemoresistance. Deep sequencing of sorted CD34+/− populations, both derived from the same patient samples, demonstrated various subclonal distribution of NPM1, DNMT3A and FLT3-ITD mutations. Interestingly, in these samples, p-ERK levels and apoptosis rates following chemotherapy exposure significantly differed between CD34+/− populations. Hence, clones may be selected due to their ability to escape apoptosis rather than a direct effect of chemotherapy on a specific mutated clone.
Administration of apo A-I (Milano) nanoparticles reverses pathological remodelling, cardiac dysfunction, and heart failure in a murine model of HFpEF associated with hypertension
Authors: Mishra Mudit , Muthuramu Ilayaraja , Kempen Herman , De Geest Bart
Published: May 2020

Therapeutic interventions with proven efficacy in heart failure with reduced ejection fraction (HFrEF) have been unsuccessful in heart failure with preserved ejection fraction (HFpEF). The modifiable risk factor with the greatest impact on the development of HFpEF is hypertension. The objectives of this study were to establish a murine model of HFpEF associated with hypertension and to evaluate the effect of apo A-IMilano nanoparticles (MDCO-216) on established HFpEF in this model. Subcutaneous infusion of angiotensin II in combination with 1% NaCl in the drinking water was started at the age of 12 weeks in male C57BL/6 N mice and continued for the entire duration of the experiment. Treatment with MDCO-216 partially reversed established cardiac hypertrophy, cardiomyocyte hypertrophy, capillary rarefaction, and perivascular fibrosis in this model. Pressure-volume loop analysis was consistent with HFpEF in hypertension mice as evidenced by the preserved ejection fraction and a significant reduction of cardiac output (7.78 ± 0.56 ml/min versus 10.5 ± 0.7 ml/min; p < 0.01) and of the peak filling rate (p < 0.05). MDCO-216 completely reversed cardiac dysfunction and abolished heart failure as evidenced by the normal lung weight and normal biomarkers of heart failure. In conclusion, apo A-IMilano nanoparticles constitute an effective treatment for established hypertension-associated HFpEF.
Partial Scanning Transmission Electron Microscopy with Deep Learning
Authors: Ede Jeffrey M. , Beanland Richard
Published: May 2020

Compressed sensing algorithms are used to decrease electron microscope scan time and electron beam exposure with minimal information loss. Following successful applications of deep learning to compressed sensing, we have developed a two-stage multiscale generative adversarial neural network to complete realistic 512 × 512 scanning transmission electron micrographs from spiral, jittered gridlike, and other partial scans. For spiral scans and mean squared error based pre-training, this enables electron beam coverage to be decreased by 17.9× with a 3.8% test set root mean squared intensity error, and by 87.0× with a 6.2% error. Our generator networks are trained on partial scans created from a new dataset of 16227 scanning transmission electron micrographs. High performance is achieved with adaptive learning rate clipping of loss spikes and an auxiliary trainer network. Our source code, new dataset, and pre-trained models are publicly available.
Automated detection of the head-twitch response using wavelet scalograms and a deep convolutional neural network
Authors: Halberstadt Adam L.
Published: May 2020

Hallucinogens induce the head-twitch response (HTR), a rapid reciprocal head movement, in mice. Although head twitches are usually identified by direct observation, they can also be assessed using a head-mounted magnet and a magnetometer. Procedures have been developed to automate the analysis of magnetometer recordings by detecting events that match the frequency, duration, and amplitude of the HTR. However, there is considerable variability in the features of head twitches, and behaviors such as jumping have similar characteristics, reducing the reliability of these methods. We have developed an automated method that can detect head twitches unambiguously, without relying on features in the amplitude-time domain. To detect the behavior, events are transformed into a visual representation in the time-frequency domain (a scalogram), deep features are extracted using the pretrained convolutional neural network (CNN) ResNet-50, and then the images are classified using a Support Vector Machine (SVM) algorithm. These procedures were used to analyze recordings from 237 mice containing 11,312 HTR. After transformation to scalograms, the multistage CNN-SVM approach detected 11,244 (99.4%) of the HTR. The procedures were insensitive to other behaviors, including jumping and seizures. Deep learning based on scalograms can be used to automate HTR detection with robust sensitivity and reliability.
The fornix acts as a permissive corridor for septal neuron migration beyond the diencephalic-telencephalic boundary
Authors: Watanabe Keisuke , Takebayashi Hirohide , Sato Noboru
Published: May 2020

Neuronal migration is essential for constructing functional neural networks. Two posterior septal (PS) nuclei, the triangular septal nucleus and bed nuclei of the anterior commissure, are involved in fear and anxiety. During development, glutamatergic PS neurons undergo long-distance rostrodorsal migration from the thalamic eminence (TE) of the diencephalon, then settle in the caudalmost telencephalon. However, the developmental behavior of PS neurons and the guidance structures facilitating their migration remain unknown. We previously demonstrated the migration of PS neurons along the fornix, a major efferent pathway from the hippocampal formation. Here, we show that the postcommissural fornix is essential for PS neuron migration which is largely confined to its axonal tract, which grows in the opposite direction as PS neuron migration. Fornical axons reach the TE prior to initiation of PS neuron rostrodorsal migration. Ectopic expression of Semaphorin 3 A in the dorsomedial cortex resulted in defective fornix formation. Furthermore, loss of the postcommissural fornix stalled PS neuron migration resulting in abnormal accumulation near their origin. This suggests that PS neurons utilize the postcommissural fornix as a permissive corridor during migration beyond the diencephalic-telencephalic boundary. This axonal support is essential for the functional organization of the heterogeneous septal nuclear complex.
Author Correction: Hot Spots of Carbon and Alkalinity Cycling in the Coastal Oceans
Authors: O’Mara Nicholas A. , Dunne John P.
Published: May 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.