bluuebunny/crossref_metadata_2025 huggingface dataset:
Autistic traits in psychotic disorders: prevalence, familial risk, and impact on social functioning
Authors: Ziermans Tim B. , Schirmbeck Frederike , Oosterwijk Floor , Geurts Hilde M. , de Haan Lieuwe ,   Genetic Risk and Outcome of Psychosis (GROUP) Investigators
Published: March 2020

Background

Prevalence estimates of autistic traits in individuals with psychotic disorders (PD) vary greatly and it is unclear whether individuals with a familial risk (FR) for psychosis have an increased propensity to display autistic traits. Furthermore, it is unknown whether the presence of comorbid autism traits disproportionally affects the cognitive and behavioral aspects of social functioning in PD.

Methods

In total, 504 individuals with PD, 587 unaffected siblings with FR, and 337 typical comparison (TC) individuals (16–50 years) were included. Autistic and psychotic traits were measured with the Autism Spectrum Quotient (AQ) and the Community Assessment of Psychic Experiences (CAPE). Social cognition was assessed with the Picture Sequencing Task (PST) and social behavior with the Social Functioning Scale (SFS).

Results

For PD 6.5% scored above AQ clinical cut-off (⩾32), 1.0% for FR, and 1.2% for TC. After accounting for age, sex, and IQ, the PD group showed significantly more autistic traits and alterations in social behavior and cognition, while FR and TC only displayed marginal differences. Within the PD group autistic traits were a robust predictor of social behavior and there were no interactions with positive psychotic symptoms.

Conclusions

Levels of autistic traits are substantially elevated in PD and have a profoundly negative association with social functioning. In contrast, autistic traits above the clinical cut-off are not elevated in those with FR, and only marginally on a dimensional level. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity to help address their social needs.
Prosody and grammar of other-repetitions in Finnish: Repair initiations, registerings, and affectivity
Authors: Stevanovic Melisa , Hakulinen Auli , Vatanen Anna
Published: March 2020

We examine how other-repetitions in Finnish are used for repairing interactional problems in hearing and understanding and for registering what another has just said, describing how prosody and grammar interact in accomplishing these goals. In the repair-initiating repetitions, the pitch contours build a continuum of different degrees of falling pitch from moderate to steep, the latter being associated with some type of an affective stance. In the registering repetitions, the pitch fall is generally narrower than in the repair-initiations, the pitch span of the repetition turn typically matching that of the original turn. A notable feature of other-repetitions in Finnish is the use of particles (mostlyaiandvai), which deal specifically with the informational aspects of other-repetitions, thus contributing to the design of both repair-initiating and registering repetitions. The article illustrates the complex layering of actions that Finnish as a ‘particle language’ affords. (Conversation analysis, other-repetition, prosody, grammar, Finnish, repair, registering, affectivity, response particle)
A heretical view: rather than a solely placental protective function, placental 11β hydroxysteroid dehydrogenase 2 also provides substrate for fetal peripheral cortisol synthesis in obese pregnant ewes
Authors: Ghnenis Adel B. , Odhiambo John F. , Smith Ashley M. , Pankey Chris L. , Nathanielsz Peter W. , Ford Stephen P.
Published: March 2020

Exposure to glucocorticoid levels higher than appropriate for current developmental stages induces offspring metabolic dysfunction. Overfed/obese (OB) ewes and their fetuses display elevated blood cortisol, while fetal Adrenocorticotropic hormone (ACTH) remains unchanged. We hypothesized that OB pregnancies would show increased placental 11β hydroxysteroid dehydrogenase 2 (11β-HSD2) that converts maternal cortisol to fetal cortisone as it crosses the placenta and increased 11β-HSD system components responsible for peripheral tissue cortisol production, providing a mechanism for ACTH-independent increase in circulating fetal cortisol. Control ewes ate 100% National Research Council recommendations (CON) and OB ewes ate 150% CON diet from 60 days before conception until necropsy at day 135 gestation. At necropsy, maternal jugular and umbilical venous blood, fetal liver, perirenal fat, and cotyledonary tissues were harvested. Maternal plasma cortisol and fetal cortisol and cortisone were measured. Fetal liver, perirenal fat, cotyledonary 11β-HSD1, hexose-6-phosphate dehydrogenase (H6PD), and 11β-HSD2 protein abundance were determined by Western blot. Maternal plasma cortisol, fetal plasma cortisol, and cortisone were higher in OB vs. CON (p < 0.01). 11β-HSD2 protein was greater (p < 0.05) in OB cotyledonary tissue than CON. 11β-HSD1 abundance increased (p < 0.05) in OB vs. CON fetal liver and perirenal fat. Fetal H6PD, an 11β-HSD1 cofactor, also increased (p < 0.05) in OB vs. CON perirenal fat and tended to be elevated in OB liver (p < 0.10). Our data provide evidence for increased 11β-HSD system components responsible for peripheral tissue cortisol production in fetal liver and adipose tissue, thereby providing a mechanism for an ACTH-independent increase in circulating fetal cortisol in OB fetuses.
The Role of Urban Growth in Resilience of Communities Under Flood Risk
Authors: Hemmati Mona , Ellingwood Bruce R. , Mahmoud Hussam N.
Published: March 2020

Flood risk to urban communities is increasing significantly as a result of the integrated effects of climate change and socioeconomic development. The latter effect is one of the main drivers of rising flood risk has received less attention in comparison to climate change. Economic development and population growth are major causes of urban expansion in flood‐prone areas, and a comprehensive understanding of the impact of urban growth on flood risk is an essential ingredient of effective flood risk management. At the same time, planning for community resilience has become a national and worldwide imperative in recent years. Enhancements to community resilience require well‐integrated and enormous long‐term public and private investments. Accordingly, comprehensive urban growth plans should take rising flood risk into account to ensure future resilient communities through careful collaboration between engineers, geologists, socialists, economists, and urban planners within the framework of life‐cycle analysis. This paper highlights the importance of including urban growth in accurate future flood risk assessment and how planning for future urbanization should include measurement science‐based strategies in developing policies to achieve more resilient communities.
Post Middle Miocene Tectonomagmatic and Stratigraphic Evolution of the Victoria Land Basin, West Antarctica
Authors: Wenman Christopher P. , Harry Dennis L. , Jha Sumant
Published: March 2020

Seismic reflection and borehole data are used to create structure maps of four regional and three local unconformities that constrain the post middle Miocene evolution of the Victoria Land Basin (VLB), which is located in the western Ross Sea within the Late Cretaceous through Quaternary West Antarctic Rift System. Isochore maps of the strata between unconformities show that rifting was mostly amagmatic between 12 to 7.6 Ma, with subsidence controlled by faults bordering the northwest margin of the basin and in a tectonic zone along the southern basin axis known as the Terror Rift. Depocenters surrounding volcanic features in strata younger than 4.3 Ma indicate an increasing influence of flexure due to volcanic loading on the subsidence pattern in the southern VLB after this time. The intervening period, from 7.6 to 4.3 Ma, was a transitional period during which both extensional tectonism and magmatism exerted strong influences on basin morphology. Since 4.3 Ma, a series of flexural subbasins formed successively at different times and positions as the different volcanic centers that built Ross Island erupted. In composite, these subbasins form a flexural moat surrounding Ross Island and smaller volcanic centers immediately to the north. The widths of these basins indicate that the flexural rigidity of the lithosphere ranges from 0.20 × 1019 to 12.96 × 1019 N‐m (elastic thickness 0.6 to 2.4 km).
Observed Emergence of the Climate Change Signal: From the Familiar to the Unknown
Authors: Hawkins E. , Frame D. , Harrington L. , Joshi M. , King A. , Rojas M. , Sutton R.
Published: March 2020

Changes in climate are usually considered in terms of trends or differences over time. However, for many impacts requiring adaptation, it is the amplitude of the change relative to the local amplitude of climate variability which is more relevant. Here, we develop the concept of “signal‐to‐noise” in observations of local temperature, highlighting that many regions are already experiencing a climate which would be “unknown” by late 19th century standards. The emergence of observed temperature changes over both land and ocean is clearest in tropical regions, in contrast to the regions of largest change which are in the northern extratropics—broadly consistent with climate model simulations. Significant increases and decreases in rainfall have also already emerged in different regions with the United Kingdom experiencing a shift toward more extreme rainfall events, a signal which is emerging more clearly in some places than the changes in mean rainfall.
A Large Ensemble Approach to Quantifying Internal Model Variability Within the WRF Numerical Model
Authors: Bassett R. , Young P. J. , Blair G. S. , Samreen F. , Simm W.
Published: March 2020

The Weather Research and Forecasting (WRF) community model is widely used to explore cross‐scale atmospheric features. Although WRF uncertainty studies exist, these usually involve ensembles where different physics options are selected (e.g., the boundary layer scheme) or adjusting individual parameters. Uncertainty from perturbing initial conditions, which generates internal model variability (IMV), has rarely been considered. Moreover, many off‐line WRF research studies generate conclusions based on a single model run without addressing any form of uncertainty. To demonstrate the importance of IMV, or noise, we present a 4‐month case study of summer 2018 over London, UK, using a 244‐member initial condition ensemble. Simply by changing the model start time, a median 2‐m temperature range or IMV of 1.2 °C was found (occasionally exceeding 8 °C). During our analysis, episodes of high and low IMV were found for all variables explored, explained by a relationship with the boundary condition data. Periods of slower wind speed input contained increased IMV, and vice versa, which we hypothesis is related to how strongly the boundary conditions influence the nested region. We also show the importance of IMV effects for the uncertainty of derived variables like the urban heat island, whose median variation in magnitude is 1 °C. Finally, a realistic ensemble size to capture the majority of WRF IMV is also estimated, essential considering the high computational overheads (244 members equaled 140,000 CPU hours). We envisage that highlighting considerable IMV in this repeatable manner will help advance best practices for the WRF and wider regional climate modeling community.
Cloud and Precipitation Properties of MCSs Along the Meiyu Frontal Zone in Central and Southern China and Their Associated Large‐Scale Environments
Authors: Cui Wenjun , Dong Xiquan , Xi Baike , Liu Min
Published: March 2020

This study focuses on investigating the cloud and precipitation features of Meiyu mesoscale convective systems (MCSs) and their relation to the large‐scale environments in central and southern China using satellite observations and reanalysis data during the period 2014–2018. MCSs from two different locations, the Yangtze River Basin (YRB) and Southern China (SC), are examined separately. The Meiyu MCSs have a mean precipitation rate of 3.6 mm/hr and contribute 20% to 60% of the total precipitation during the Meiyu period. The diurnal cycle of Meiyu MCSs shows a maximum precipitation amount in the morning, which is associated with the enhanced nocturnal low‐level jet (LLJ) overnight. Although the synoptic setups in YRB and SC are found to be similar when normalized around the MCS initiation locations, MCSs exhibit some differences in terms of the cloud top height, precipitation rate, and duration, which are likely by the differences in the local forcing. Large interannual variations are found in MCSs' number, cloud size, lifetime, and rainfall intensity, which is found to be associated with the interannual variabilities in the large‐scale environments. By comparing the large‐scale environments with climatological mean states, we find that the year with the most intense MCS activity during the study period is characterized by an intensified southwesterly LLJ, which increases the moisture transport from the Indian Ocean and an enhancement of the midtropospheric westerly jet, which induces adiabatic ascent along the Meiyu front, creating more favorable conditions for convection.
Dust Deposited on Snow Cover in the San Juan Mountains, Colorado, 2011–2016: Compositional Variability Bearing on Snow‐Melt Effects
Authors: Reynolds Richard L. , Goldstein Harland L. , Moskowitz Bruce M. , Kokaly Raymond F. , Munson Seth M. , Solheid Peat , Breit George N. , Lawrence Corey R. , Derry Jeff
Published: March 2020

Light‐absorbing particles in atmospheric dust deposited on snow cover (dust‐on‐snow, DOS) diminish albedo and accelerate the timing and rate of snow melt. Identification of these particles and their effects is relevant to snow‐radiation modeling and water‐resource management. Laboratory‐measured reflectance of DOS samples from the San Juan Mountains (USA) were compared with DOS mass loading, particle sizes, iron mineralogy, carbonaceous matter type and content, and chemical compositions. Samples were collected each spring for water years 2011–2016, when individual dust layers had merged into one (all layers merged) at the snow surface. Average reflectance values of the six samples were 0.2153 (sd, 0.0331) across the visible wavelength region (0.4–0.7 μm) and 0.3570 (sd, 0.0498) over the full‐measurement range (0.4–2.50 μm). Reflectance values correlated inversely to concentrations of ferric oxide, organic carbon (1.4–10 wt.%), magnetite (0.05–0.13 wt.%), and silt (PM63‐3.9; median grain sizes averaged 21.4 μm) but lacked correspondence to total iron and PM10 contents. Measurements of reflectance and Mössbauer spectra and magnetic properties indicated that microcrystalline hematite and nano‐size goethite were primarily responsible for diminished visible reflectance. Positive correlations between organic carbon and metals attributed to fossil‐fuel combustion, with observations from electron microscopy, indicated that some carbonaceous matter occurred as black carbon. Magnetite was a surrogate for related light‐absorbing minerals, dark rock particles, and contaminants. Similar analyses of DOS from other areas would help evaluate the influences of varied dust sources, wind‐storm patterns, and anthropogenic inputs on snow melt and water resources in and beyond the Colorado River Basin.
A Lacustrine Paleoenvironment Recorded at Vera RubinRidge, Gale Crater: Overview of the Sedimentology and Stratigraphy Observed by the Mars ScienceLaboratory Curiosity Rover
Authors: Edgar L. A. , Fedo C. M. , Gupta S. , Banham S. G. , Fraeman A. A. , Grotzinger J. P. , Stack K. M. , Stein N. T. , Bennett K. A. , Rivera‐Hernández F. , Sun V.Z. , Edgett K. S. , Rubin D. M. , House C. , Van Beek J.
Published: March 2020

For ~500 Martian solar days (sols), the Mars Science Laboratory team explored Vera Rubin ridge (VRR), a topographic feature on the northwest slope of Aeolis Mons. Here we review the sedimentary facies and stratigraphy observed during sols 1,800–2,300, covering more than 100 m of stratigraphic thickness. Curiosity's traverse includes two transects across the ridge, which enables investigation of lateral variability over a distance of ~300 m. Three informally named stratigraphic members of the Murray formation are described: Blunts Point, Pettegrove Point, and Jura, with the latter two exposed on VRR. The Blunts Point member, exposed just below the ridge, is characterized by a recessive, fine‐grained facies that exhibits extensive planar lamination and is crosscut by abundant curvi‐planar veins. The Pettegrove Point member is more resistant, fine‐grained, thinly planar laminated, and contains a higher abundance of diagenetic concretions. Conformable above the Pettegrove Point member is the Jura member, which is also fine‐grained and parallel stratified, but is marked by a distinct step in topography, which coincides with localized meter‐scale inclined strata, a thinly and thickly laminated facies, and occasional crystal molds. All members record low‐energy lacustrine deposition, consistent with prior observations of the Murray formation. Uncommon outcrops of low‐angle stratification suggest possible subaqueous currents, and steeply inclined beds may be the result of slumping. Collectively, the rocks exposed at VRR provide additional evidence for a long‐lived lacustrine environment (in excess of 106 years via comparison to terrestrial records of sedimentation), which extends our understanding of the duration of habitable conditions in Gale crater.
Evaluation of Rain Microphysics Using a Radar Simulator and Numerical Models: Comparison of Two‐Moment Bulk and Spectral Bin Cloud Microphysics Schemes
Authors: Kuba Naomi , Seiki Tatsuya , Suzuki Kentaroh , Roh Woosub , Satoh Masaki
Published: March 2020

This study extended a method to evaluate rain microphysics in a shallow cumulus regime using space‐borne radar observational data with a forward simulator of satellite measurements. We compared a two‐moment bulk scheme with a two‐moment bin scheme. A dynamic‐kinematic model was used to isolate cloud microphysics processes from their interactions with dynamics. The relationship between horizontally averaged reflectivity Zm and optical depth from the cloud top τd, that is, the Zm‐τd relationship, was similar between the bulk and the bin schemes for clouds with large updraft velocity and clean cloud condensation nuclei (CCN). However, the differences in the Zm‐τd relationship between the two schemes became more apparent for clouds with smaller updraft velocity or polluted CCN. For these clouds, the differences resulted from differences in the autoconversion rate. We increased the autoconversion rate by decreasing the shape parameter of the cloud droplet size distribution in the bulk scheme. This reduced the differences in the Zm‐τd relationship between the two schemes, indicating that for these clouds, the autoconversion rate of a cloud microphysics scheme can be evaluated by the Zm‐τd relationship derived from satellite observations. Although the clouds with the smaller updraft velocity or the polluted CCN did not contribute to the rainfall amount significantly, the lifetime of these clouds greatly affected the radiation budget. Thus, the improvement in the autoconversion rate for such weak cumulus clouds provides a better representation of precipitation efficiency and is important for global climate evaluations.
History of Subduction Polarity Reversal During Arc‐Continent Collision: Constraints From the Andaman Ophiolite and its Metamorphic Sole
Authors: Plunder Alexis , Bandyopadhyay Debaditya , Ganerød Morgan , Advokaat Eldert L. , Ghosh Biswajit , Bandopadhyay Pinaki , van Hinsbergen Douwe J. J.
Published: March 2020

Subduction polarity reversal during arc‐continent collision has been proposed as a key mechanism to initiate new subduction zones. Despite often interpreted, well‐exposed geological record that document the reversal is sparse. The ophiolitic lithounits of the Andaman and Nicobar Islands have been proposed to have formed during the initiation of a new subduction zone following the collision of the Woyla Arc of Sumatra with Sundaland (Eurasia). We here present new field, petrological and geochronological data to evaluate the timing of the initiation of Andaman subduction. We targeted the previously inferred but unstudied metamorphic sole of the Andaman ophiolites that witnessed juvenile subduction. Thermodynamic modeling reveals that the exposed amphibolites of the sole formed at around 0.9 GPa and 675 °C. We dated two samples of the metamorphic sole using the Ar/Ar method on amphibole, giving cooling ages of 106.4 ± 2.1 and 105.3 ± 1.6 Ma. This is similar to published ages from plagioclase xenocrysts in recent Barren Island volcanics and in zircons from a gabbro sample from the Andaman ophiolite, which we interpret as the age of the original ophiolite formation. The Ar/Ar ages are considerably older than arc magmatic gabbros and plagiogranites of the overlying ophiolite previously dated at 99–93 Ma and thought to reflect the ophiolite age but recently reinterpreted as a volcanic arc built on the ophiolite. Combined with the ages of Woyla‐Sundaland collision, we argue that subduction polarity reversal occurred in a transient period of perhaps some 10 Myr, similar to recent settings.
Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial–mesenchymal transitions and facilitates early metastasis
Authors: Francart Marie-Emilie , Vanwynsberghe Aline M. , Lambert Justine , Bourcy Morgane , Genna Anthony , Ancel Julien , Perez-Boza Jennifer , Noël Agnès , Birembaut Philippe , Struman Ingrid , Polette Myriam , Gilles Christine
Published: March 2020

Epithelial–mesenchymal transitions (EMTs) are high-profile in the field of circulating tumor cells (CTCs). EMT-shifted CTCs are considered to encompass pre-metastatic subpopulations though underlying molecular mechanisms remain elusive. Our previous work identified tissue factor (TF) as an EMT-induced gene providing tumor cells with coagulant properties and supporting metastatic colonization by CTCs. We here report that vimentin, the type III intermediate filament considered a canonical EMT marker, contributes to TF regulation and positively supports coagulant properties and early metastasis. Different evidence further pointed to a new post-transcriptional regulatory mechanism of TF mRNA by vimentin: (1) vimentin silencing accelerated TF mRNA decay after actinomycin D treatment, reflecting TF mRNA stabilization, (2) RNA immunoprecipitation revealed enriched levels of TF mRNA in vimentin immunoprecipitate, (3) TF 3′-UTR-luciferase reporter vector assays implicated the 3′-UTR of TF mRNA in vimentin-dependent TF regulation, and (4) using different TF 3′UTR-luciferase reporter vectors mutated for potential miR binding sites and specific Target Site Blockers identified a key miR binding site in vimentin-dependent TF mRNA regulation. All together, these data support a novel mechanism by which vimentin interferes with a miR-dependent negative regulation of TF mRNA, thereby promoting coagulant activity and early metastasis of vimentin-expressing CTCs.
High-intensity interval training produces a significant improvement in fitness in less than 31 days before surgery for urological cancer: a randomised control trial
Authors: Blackwell J. E. M. , Doleman B. , Boereboom C. L , Morton A. , Williams S. , Atherton P. , Smith K. , Williams J. P. , Phillips B. E. , Lund J. N.
Published: March 2020

Objectives

To assess the efficacy of high-intensity interval training (HIIT) for improving cardiorespiratory fitness (CRF) in patients awaiting resection for urological malignancy within four weeks.

Subjects/patients and methods

A randomised control trial of consecutive patients aged (>65 years) scheduled for major urological surgery in a large secondary referral centre in a UK hospital. The primary outcome is change in anaerobic threshold (VO2AT) following HIIT vs. standard care.

Results

Forty patients were recruited (mean age 72 years, male (39): female (1)) with 34 completing the protocol. Intention to treat analysis showed significant improvements in anaerobic threshold (VO2AT; mean difference (MD) 2.26 ml/kg/min (95% CI 1.25–3.26)) following HIIT. Blood pressure (BP) also significantly reduced in following: HIIT (SBP: −8.2 mmHg (95% CI −16.09 to −0.29) and DBP: −6.47 mmHg (95% CI −12.56 to −0.38)). No reportable adverse safety events occurred during HIIT and all participants achieved >85% predicted maximum heart rate during sessions, with protocol adherence of 84%.

Conclusions

HIIT can improve CRF and cardiovascular health, representing clinically meaningful and achievable pre-operative improvements. Larger randomised trials are required to investigate the efficacy of prehabilitation HIIT upon different cancer types, post-operative complications, socio-economic impact and long-term survival.
Anti-glypican-1 antibody–drug conjugate is a potential therapy against pancreatic cancer
Authors: Nishigaki Takahiko , Takahashi Tsuyoshi , Serada Satoshi , Fujimoto Minoru , Ohkawara Tomoharu , Hara Hisashi , Sugase Takahito , Otsuru Toru , Saito Yurina , Tsujii Shigehiro , Nomura Taisei , Tanaka Koji , Miyazaki Yasuhiro , Makino Tomoki , Kurokawa Yukinori , Nakajima Kiyokazu , Eguchi Hidetoshi , Yamasaki Makoto , Mori Masaki , Doki Yuichiro , Naka Tetsuji
Published: March 2020

Background

Pancreatic cancer (PDAC) is the most lethal malignancy. New treatment options for it are urgently required. The aim was to develop an antibody–drug conjugate (ADC) targeting glypican-1 (GPC-1) as a new therapy for PDAC.

Methods

We evaluated GPC-1 expression in resected PDAC specimens and PDAC cell lines. We then measured the antitumour effect of anti-GPC-1 monoclonal antibody conjugated with the cytotoxic agent monomethyl auristatin F (MMAF) in vitro and in vivo.

Results

GPC-1 was overexpressed in most primary PDAC cells and tissues. The PDAC cell lines BxPC-3 and T3M-4 strongly expressed GPC-1 relative to SUIT-2 cells. Compared with control ADC, GPC-1-ADC showed a potent antitumour effect against BxPC-3 and T3M-4, but little activity against SUIT-2 cells. In the xenograft and patient-derived tumour models, GPC-1-ADC significantly and potently inhibited tumour growth in a dose-dependent manner. GPC-1-ADC-mediated G2/M-phase cell cycle arrest was detected in the tumour tissues of GPC-1-ADC-treated mice relative to those of control-ADC-treated mice.

Conclusions

GPC-1-ADC showed significant tumour growth inhibition against GPC-1-positive pancreatic cell lines and patient-derived, GPC-1-positive pancreatic cancer tissues. Our preclinical data demonstrated that targeting GPC-1 with ADC is a promising therapy for patients with GPC-1-positive pancreatic cancer.
Cytochrome P450 metabolic resistance (CYP6P9a) to pyrethroids imposes a fitness cost in the major African malaria vector Anopheles funestus
Authors: Tchouakui Magellan , Riveron Miranda Jacob , Mugenzi Leon M. J. , Djonabaye Doumani , Wondji Murielle J. , Tchoupo Micareme , Tchapga Williams , Njiokou Flobert , Wondji Charles S.
Published: March 2020

Metabolic resistance threatens the sustainability of pyrethroid-based malaria control interventions. Elucidating the fitness cost and potential reversal of metabolic resistance is crucial to design suitable resistance management strategies. Here, we deciphered the fitness cost associated with theCYP6P9a(P450-mediated metabolic resistance) in the major African malaria vectorAnopheles funestus. Reciprocal crosses were performed between a pyrethroid susceptible (FANG) and resistant (FUMOZ-R) laboratory strains and the hybrid strains showed intermediate resistance. Genotyping the CYP6P9a-R resistance allele in oviposited females revealed thatCYP6P9anegatively impacts the fecundity as homozygote susceptible mosquitoes (CYP6P9a-SS) lay more eggs than heterozygote (OR = 2.04:P = 0.01) and homozygote resistant mosquitoes.CYP6P9aalso imposes a significant fitness cost on the larval development as homozygote resistant larvae (CYP6P9a-RR) developed significantly slower than heterozygote and homozygote susceptible mosquitoes (χ2 = 11.2;P = 0.0008). This fitness cost was further supported by the late pupation of homozygote resistant than susceptible mosquitoes (OR = 2.50;P < 0.01). However,CYP6P9adoes not impact the longevity as no difference was observed in the life span of mosquitoes with different genotypes (χ2 = 1.6;P = 0.9). In this hybrid strain, a significant decrease of the resistant CYP6P9a-RR genotype was observed after ten generations (χ2 = 6.6;P = 0.01) suggesting a reversal of P450-based resistance in the absence of selection. This study shows that the P450-mediated metabolic resistance imposes a high fitness cost in malaria vectors supporting that a resistance management strategy based on rotation could help mitigate the impact of such resistance.
Whole slide images reflect DNA methylation patterns of human tumors
Authors: Zheng Hong , Momeni Alexandre , Cedoz Pierre-Louis , Vogel Hannes , Gevaert Olivier
Published: March 2020

DNA methylation is an important epigenetic mechanism regulating gene expression and its role in carcinogenesis has been extensively studied. High-throughput DNA methylation assays have been used broadly in cancer research. Histopathology images are commonly obtained in cancer treatment, given that tissue sampling remains the clinical gold-standard for diagnosis. In this work, we investigate the interaction between cancer histopathology images and DNA methylation profiles to provide a better understanding of tumor pathobiology at the epigenetic level. We demonstrate that classical machine learning algorithms can associate the DNA methylation profiles of cancer samples with morphometric features extracted from whole slide images. Furthermore, grouping the genes into methylation clusters greatly improves the performance of the models. The well-predicted genes are enriched in key pathways in carcinogenesis including hypoxia in glioma and angiogenesis in renal cell carcinoma. Our results provide new insights into the link between histopathological and molecular data.
Author Correction: Small Molecule Accurate Recognition Technology (SMART) to Enhance Natural Products Research
Authors: Zhang Chen , Idelbayev Yerlan , Roberts Nicholas , Tao Yiwen , Nannapaneni Yashwanth , Duggan Brendan M. , Min Jie , Lin Eugene C. , Gerwick Erik C. , Cottrell Garrison W. , Gerwick William H.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Discovery and quantification of a widespread methane ebullition event in a coastal inlet (Baltic Sea) using a novel sonar strategy
Authors: Lohrberg A. , Schmale O. , Ostrovsky I. , Niemann H. , Held P. , Schneider von Deimling J.
Published: March 2020

How much of the greenhouse gas methane is transported from the seafloor to the atmosphere is unclear. Here, we present data describing an extensive ebullition event that occurred in Eckernförde Bay, a shallow gas-hosting coastal inlet in the Baltic Sea, in the fall of 2014. A weak storm induced hydrostatic pressure fluctuations that in turn stimulated gas ebullition from the seabed. In a finely tuned sonar survey of the bay, we obtained a hydroacoustic dataset with exceptionally high sensitivity for bubble detection. This allowed us to identify 2849 bubble seeps rising within 28 h from the seafloor across the 90 km² study site. Based on our calculations, the estimated bubble-driven episodic methane flux from the seafloor across the bay is 1,900 μMol m−2 d−1. Our study demonstrates that storm-associated fluctuations of hydrostatic pressure induce bulk gas-driven ebullitions. Given the extensive occurrence of shallow gas-hosting sediments in coastal seas, similar ebullition events probably take place in many parts of the Western Baltic Sea. However, these are likely to be missed during field investigations, due to the lack of high-quality data acquisition during storms, such that atmospheric inputs of marine-derived methane will be highly underestimated.
Immuno-OpenPET: a novel approach for early diagnosis and image-guided surgery for small resectable pancreatic cancer
Authors: Yoshii Yukie , Tashima Hideaki , Iwao Yuma , Yoshida Eiji , Wakizaka Hidekatsu , Akamatsu Go , Yamaya Taiga , Matsumoto Hiroki , Yoshimoto Mitsuyoshi , Igarashi Chika , Hihara Fukiko , Tachibana Tomoko , Zhang Ming-Rong , Nagatsu Kotaro , Sugyo Aya , Tsuji Atsushi B. , Higashi Tatsuya
Published: March 2020

Pancreatic cancer (PC) has a poor prognosis owing to difficulties in the diagnosis of resectable PC at early stages. Several clinical studies have indicated that the detection and surgery of small resectable PC (<1 cm) can significantly improve survival; however, imaging diagnosis and accurate resection of small PC remain challenging. Here, we report the feasibility of “immuno-OpenPET” as a novel approach enabling not only early diagnosis but also image-guided surgery, using a small (<1 cm) resectable PC orthotopic xenograft mouse model. For immuno-OpenPET, we utilized our original OpenPET system, which enables high-resolution positron emission tomography (PET) imaging with depth-of-interaction detectors, as well as real-time image-guided surgery, by arranging the detectors to create an open space for surgery and accelerating the image reconstruction process by graphics processing units. For immuno-OpenPET, 64Cu-labeled anti-epidermal growth factor receptor antibody cetuximab was intraperitoneally administered into mice. It clearly identified PC tumors ≥3 mm. In contrast, neither OpenPET with intravenous-administered 64Cu-cetuximab nor intraperitoneal/intravenous-administered 18F-FDG (a traditional PET probe) could detect PC in this model. Immuno-OpenPET-guided surgery accurately resected small PC in mice and achieved significantly prolonged survival. This technology could provide a novel diagnostic and therapeutic strategy for small resectable PC to improve patient survival.
Entropy generation in bioconvection nanofluid flow between two stretchable rotating disks
Authors: Khan Noor Saeed , Shah Qayyum , Bhaumik Amiya , Kumam Poom , Thounthong Phatiphat , Amiri Irajsadegh
Published: March 2020

Buongiorno’s nanofluid model is followed to study the bioconvection in two stretchable rotating disks with entropy generation. Similarity transformations are used to handle the problem equations for non-dimensionality. For the simulation of the modeled equations, Homotopy Analysis Method is applied. The biothermal system is explored for all the embedded parameters whose effects are shown through different graphs. There exists interesting results due to the effects of different parameters on different profiles. Radial velocity decreases with increasing stretching and magnetic field parameters. Temperature increases with Brownian motion and thermophoresis parameters. Nanoparticles concentration decreases on increasing Lewis number and thermophoresis parameter while motile gyrotactic microorganisms profile increases with increasing Lewis and Peclet numbers. Convergence of the solution is found and good agreement is obtained when the results are compared with published work.
A laser pulse impactful on a half-space using the modified TPL G–N models
Authors: Zenkour Ashraf M. , Mashat Daoud S.
Published: March 2020

This article aims to investigate the wave propagation of generalized thermoelastic half-plane under the effect of thermal loading due to laser pulse with and without energy dissipation. The normal mode method is proposed to solve the problem and get numerical results for the field quantities. The outcomes of the physical quantities have been illustrated graphically and reported to compare the simple Green–Naghdi II and III and their modified single-, dual-, and three-phase-lag models. The graphical outcomes indicate that the different types of Green–Naghdi models with thermal relaxations have great effects on the temperature, displacements, dilatation and stresses.
Genetic epidemiology of the Alpine ibex reservoir of persistent and virulent brucellosis outbreak
Authors: Quéméré Erwan , Rossi Sophie , Petit Elodie , Marchand Pascal , Merlet Joël , Game Yvette , Galan Maxime , Gilot-Fromont Emmanuelle
Published: March 2020

While it is now broadly accepted that inter-individual variation in the outcomes of host–pathogen interactions is at least partially genetically controlled, host immunogenetic characteristics are rarely investigated in wildlife epidemiological studies. Furthermore, most immunogenetic studies in the wild focused solely on the major histocompatibility complex (MHC) diversity despite it accounts for only a fraction of the genetic variation in pathogen resistance. Here, we investigated immunogenetic diversity of the Alpine ibex (Capra ibex) population of the Bargy massif, reservoir of a virulent outbreak of brucellosis. We analysed the polymorphism and associations with disease resistance of the MHC Class II Drb gene and several non-MHC genes (Toll-like receptor genes, Slc11A1) involved in the innate immune response to Brucella in domestic ungulates. We found a very low neutral genetic diversity and a unique MHC Drb haplotype in this population founded few decades ago from a small number of individuals. By contrast, other immunity-related genes have maintained polymorphism and some showed significant associations with the brucellosis infection status hence suggesting a predominant role of pathogen-mediated selection in their recent evolutionary trajectory. Our results highlight the need to monitor immunogenetic variation in wildlife epidemiological studies and to look beyond the MHC.
Ensemble modeling highlights importance of understanding parasite-host behavior in preclinical antimalarial drug development
Authors: Burgert Lydia , Rottmann Matthias , Wittlin Sergio , Gobeau Nathalie , Krause Andreas , Dingemanse Jasper , Möhrle Jörg J. , Penny Melissa A.
Published: March 2020

Emerging drug resistance and high-attrition rates in early and late stage drug development necessitate accelerated development of antimalarial compounds. However, systematic and meaningful translation of drug efficacy and host-parasite dynamics between preclinical testing stages is missing. We developed an ensemble of mathematical within-host parasite growth and antimalarial action models, fitted to extensive data from four antimalarials with different modes of action, to assess host-parasite interactions in two preclinical drug testing systems of murine parasite P. berghei in mice, and human parasite P. falciparum in immune-deficient mice. We find properties of the host-parasite system, namely resource availability, parasite maturation and virulence, drive P. berghei dynamics and drug efficacy, whereas experimental constraints primarily influence P. falciparum infection and drug efficacy. Furthermore, uninvestigated parasite behavior such as dormancy influences parasite recrudescence following non-curative treatment and requires further investigation. Taken together, host-parasite interactions should be considered for meaningful translation of pharmacodynamic properties between murine systems and for predicting human efficacious treatment.
Serum microRNA in patients undergoing atrial fibrillation ablation
Authors: Kiliszek Marek , Maciak Karolina , Maciejak Agata , Krzyżanowski Krystian , Wierzbowski Robert , Gora Monika , Burzynska Beata , Segiet Agnieszka , Skrobowski Andrzej
Published: March 2020

MicroRNAs mediate posttranscriptional gene regulation. The aim of the study was to find a microRNA predictor of successful atrial fibrillation (AF) ablation. A total of 109 patients undergoing first-time AF ablation were included. Nineteen patients were selected to undergo serum microRNA sequencing (study group). The sequencing data were used to select several microRNAs that correlated with 12-month recurrences after AF ablation. Those microRNAs were validated by digital droplet PCR in samples from remaining 90 patients. All patients underwent pulmonary vein isolation (RF ablation, contact force catheter, electroanatomical system). The endpoint of the study was the 12-month AF recurrence rate; the overall recurrence rate was 42.5%. In total, levels of 34 miRNAs were significantly different in sera from patients with AF recurrence compared to patients without AF recurrence. Six microRNAs (miR-183-5p, miR-182-5p, miR-32-5p, miR-107, miR-574-3p, and miR-144-3p) were validated in the whole group. Data from the validation group did not confirm the observations from the study group, as no significant differences were found between miRNAs serum levels in patients with and without recurrences 12 months after AF ablation.
Sources of variation in the 3dMDface and Vectra H1 3D facial imaging systems
Authors: White Julie D. , Ortega-Castrillon Alejandra , Virgo Ciara , Indencleef Karlijne , Hoskens Hanne , Shriver Mark D. , Claes Peter
Published: March 2020

As technology advances and collaborations grow, our ability to finely quantify and explore morphological variation in 3D structures can enable important discoveries and insights into clinical, evolutionary, and genetic questions. However, it is critical to explore and understand the relative contribution of potential sources of error to the structures under study. In this study, we isolated the level of error in 3D facial images attributable to four sources, using the 3dMDface and Vectra H1 camera systems. When the two camera systems are used separately to image human participants, this analysis finds an upper bound of error potentially introduced by the use of the 3dMDface or Vectra H1 camera systems, in conjunction with the MeshMonk registration toolbox, at 0.44 mm and 0.40 mm, respectively. For studies using both camera systems, this upper bound increases to 0.85 mm, on average, and there are systematic differences in the representation of the eyelids, nostrils, and mouth by the two camera systems. Our results highlight the need for careful assessment of potential sources of error in 3D images, both in terms of magnitude and position, especially when dealing with very small measurements or performing many tests.
High-fidelity scaling relationships for determining dissipative particle dynamics parameters from atomistic molecular dynamics simulations of polymeric liquids
Authors: Nafar Sefiddashti M. H. , Boudaghi-Khajehnobar M. , Edwards B. J. , Khomami B.
Published: March 2020

An optimized Dissipative Particle Dynamics (DPD) model with simple scaling rules was developed for simulating entangled linear polyethylene melts. The scaling method, which can be used for mapping dimensionless (reduced units) DPD simulation data to physical units, was based on scaling factors for three fundamental physical units; namely, length, time, and viscosity. The scaling factors were obtained as ratios of equilibrium Molecular Dynamics (MD) simulation data in physical units and equivalent DPD simulation data for relevant quantities. Specifically, the time scaling factor was determined as the ratio of longest relaxation times, the length scaling factor was obtained as the ratio of the equilibrium end-to-end distances, and the viscosity scaling factor was calculated as the ratio of zero-shear viscosities, each as obtained from the MD (in physical units) and DPD (reduced units) simulations. The scaling method was verified for three MD/DPD model liquid pairs under several different nonequilibrium conditions, including transient and steady-state simple shear and planar elongational flows. Comparison of the MD simulation results with those of the scaled DPD simulations revealed that the optimized DPD model, expressed in terms of the proposed scaling method, successfully reproduced the computationally expensive MD results using relatively cheaper DPD simulations.
Hidden Hypocalcemia as a Risk Factor for Cardiovascular Events and All-Cause Mortality among Patients Undergoing Incident Hemodialysis
Authors: Yamaguchi Satoshi , Hamano Takayuki , Doi Yohei , Oka Tatsufumi , Kajimoto Sachio , Kubota Keiichi , Yasuda Seiichi , Shimada Karin , Matsumoto Ayumi , Hashimoto Nobuhiro , Sakaguchi Yusuke , Matsui Isao , Isaka Yoshitaka
Published: March 2020

Lower corrected calcium (cCa) levels are associated with a better prognosis among incident dialysis patients. However, cCa frequently overestimates ionized calcium (iCa) levels. The prognostic importance of the true calcium status defined by iCa remains to be revealed. We conducted a retrospective cohort study of incident hemodialysis patients. We collected data of iCa levels immediately before the first dialysis. We divided patients into three categories: apparent hypocalcemia (low iCa; <1.15 mmol/L and low cCa; <8.4 mg/dL), hidden hypocalcemia (low iCa despite normal or high cCa), and normocalcemia (normal iCa). The primary outcome was the composite of all-cause death and cardiovascular diseases after hospital discharge. Among the enrolled 332 patients, 75% of the patients showed true hypocalcemia, defined as iCa <1.15 mmol/L, 61% of whom showed hidden hypocalcemia. In multivariate Cox models including other potential risk factors, true hypocalcemia was a significant risk factor (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.03–5.34), whereas hypocalcemia defined as corrected calcium <8.4 mg/dL was not. Furthermore, hidden hypocalcemia was significantly associated with an increased risk of the outcome compared with normocalcemia (HR, 2.56; 95% CI, 1.11–5.94), while apparent hypocalcemia was not. Patients with hidden hypocalcemia were less likely to receive interventions to correct hypocalcemia, such as increased doses of active vitamin D or administration of calcium carbonate, than patients with apparent hypocalcemia (odds ratio, 0.45; 95% CI, 0.23–0.89). Hidden hypocalcemia was a strong predictor of death and cardiovascular events, suggesting the importance of measuring iCa.
Surgery for synchronous and metachronous single-organ metastasis of pancreatic cancer: a SEER database analysis and systematic literature review
Authors: Liu Qiaofei , Zhang Ronghua , Michalski Christoph W. , Liu Bing , Liao Quan , Kleeff Jorg
Published: March 2020

Surgery for metastatic pancreatic cancer remains controversial as the survival benefit is questionable. The aim of the present study was to analyze the survival of these patients using data extracted from the surveillance, epidemiology, and end results (SEER) program database. Further, studies on resection for metastatic disease to the lung were systematically reviewed. A total of 11,541 cases with synchronous distant metastasis were analyzed. The median survival of single-organ metastasis was better than of multi-organ metastasis (single-organ 4.0 ± 0.07 months, two-organs 3.0 ± 0.13 months, three/four-organs 2.0 ± 0.19 months; p < 0.0001). Single organ lung metastasis had longer median survival times compared to the other sites (lung 6.0 ± 0.32 months, HR 0.87, 95% CI 0.78–0.97; p = 0.013). Resection of the primary tumor was associated with longer survival in synchronous single-organ metastasis to the lung compared to no resection (14.0 ± 1.93 months vs 6.0 ± 0.31 months, p < 0.0001). A systematic literature review identified 79 cases of metachronous lung metastasis with a survival of 120.0 ± 6.32 months and 83.0 ± 24.84 months following resection of the primary tumor and metastasis, respectively. Lower TNM staging, longer interval to metastasis, and single metastatic lesion correlated with better survival. Resection in highly selected pancreatic cancer patients with synchronous and metachronous lung only metastasis might confer a survival benefit and should be considered on an individual basis.
Author Correction: Interspecific competition among catch crops modifies vertical root biomass distribution and nitrate scavenging in soils
Authors: Heuermann Diana , Gentsch Norman , Boy Jens , Schweneker Dörte , Feuerstein Ulf , Groß Jonas , Bauer Bernhard , Guggenberger Georg , von Wirén Nicolaus
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Morphological and biomechanical characterization of immature and mature nasoseptal cartilage
Authors: Jessop Zita M. , Zhang Yadan , Simoes Irina N. , Al-Sabah Ayesha , Badiei Nafiseh , Gazze Salvatore A. , Francis Lewis , Whitaker Iain S.
Published: March 2020

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