bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical evaluation of an in-house panfungal real-time PCR assay for the detection of fungal pathogens
Authors: Camp Iris , Manhart Gabriele , Schabereiter-Gurtner Claudia , Spettel Kathrin , Selitsch Brigitte , Willinger Birgit
Published: February 2020

Purpose

Due to an increasing incidence of invasive fungal infections, the availability of reliable diagnostic tools for the fast detection of a wide spectrum of fungal pathogens is of vital importance. In this study, we aimed to conduct an extensive clinical evaluation of a recently published in-house panfungal PCR assay on samples from suspected invasive fungal infections.

Methods

Overall 265 clinical samples from 232 patients with suspected invasive fungal disease (96 deep airway samples, 60 sterile fluids, 50 tissue biopsies, and 59 blood samples) were included. All samples underwent standard culture-based diagnostics and were additionally analyzed with our panfungal PCR assay.

Results

Overall, 55.1% of agreement between culture and the panfungal PCR was observed; in 17% of all samples partial concordance was noted, while results between culture and our PCR assay were not in agreement in 27.9%. Our panfungal assay performed better in samples from normally sterile sites, while samples from the deep airways yielded the highest rate of discordant (39.6%) results. In two tissue and three blood samples an invasive pathogen was only detected by PCR while cultures remained negative.

Conclusion

In combination with routine methods, our panfungal PCR assay is a valuable diagnostic tool. Patients at risk for invasive fungal infections might profit from the reduced time to pathogen identification.
Cannabidiol treatment in an adolescent with multiple substance abuse, social anxiety and depression
Authors: Laczkovics Clarissa , Kothgassner Oswald D. , Felnhofer Anna , Klier Claudia M.
Published: February 2020

In this report, we present a case of a 16,9-year-old patient with multiple substance use disorder (cannabis, MDMA, cocaine, ecstacy), severe depression, social phobia and narcissistic personality disorder.

We administered Cannabidiol (CBD) capsules in different dosages (starting dosage 100 mg up to 600 mg over 8 weeks) after unsuccessful treatment with antidepressants.

CBD was a safe and well tolerated medication for this patient. Upon treatment with CBD and cessation of the antidepressant medication, the patient improved regarding depressive as well as anxiety symptoms including simple phobias and symptoms of paranoia and dissociation. Furthermore, the patient quit abusing illegal drugs including THC without showing withdrawal symptoms. This is the first report of CBD medication in a patient with multiple substance use disorder with a positive outcome.

Until today it is not clear if CBD holds promise as a therapeutic option in substance use disorder as RCTs are lacking, but in this single case the substance seems to work in various domains.
Intra‐individual associations between intentional self‐regulation and prosocial behavior during adolescence: Evidence for bidirectionality
Authors: Memmott‐Elison Madison , Padilla‐Walker Laura M. , Yorgason Jeremy B. , Coyne Sarah M.
Published: February 2020

Introduction

Couched in Positive Youth Development (PYD) theory and relevant empirical work, this study investigated bidirectional associations between intentional self‐regulation and prosocial behavior toward strangers from age 12 to age 18.

Method

Participants included 500 adolescents (52% female, 77% European American; age Time 1 = 12 years, Time 2 = 14 years, Time 3 = 16 years, Time 4 = 18 years) from the Northwestern United States. Adolescents self‐reported on their intentional self‐regulation and prosocial behavior toward strangers across four time points. A random‐intercept cross‐lagged panel model (RICLPM) was estimated in order to assess bidirectionality while avoiding conflating intra‐ and inter‐individual variability.

Results

Results revealed intentional self‐regulation and prosocial behavior toward strangers were bidirectionally related during early adolescence (i.e., from age 12 to 14). During mid‐to‐late adolescence (i.e. age 14 to 18), prosocial behavior toward strangers facilitated intentional selfregulation, whereas intentional self‐regulation did not drive the development of prosocial behavior toward strangers.

Conclusions

Findings indicate that early adolescence may be a particularly plastic developmental period in terms of PYD. Findings also suggest that investigations of relations between adolescents' personal assets and contribution factors merit further scholarly attention. Several directions for future research are presented.
Mental health disorders and utilization of mental healthcare services in United Nations personnel
Authors: Brown Adam D. , Schultebraucks Katharina , Qian Meng , Li Meng , Horesh Danny , Siegel Carol , Brody Yosef , Amer Abdalla Mansour , Lev-Ari Rony Kapel , Mas Francis , Marmar Charles R. , Farmer Jillann
Published: February 2020

Background

United Nations (UN) personnel address a diverse range of political, social, and cultural crises throughout the world. Compared with other occupations routinely exposed to traumatic stress, there remains a paucity of research on mental health disorders and access to mental healthcare in this population. To fill this gap, personnel from UN agencies were surveyed for mental health disorders and mental healthcare utilization.

Methods

UN personnel (N = 17 363) from 11 UN entities completed online measures of generalized anxiety disorder (GAD), major depressive disorder (MDD), posttraumatic stress disorder (PTSD), trauma exposure, mental healthcare usage, and socio-demographic information.

Results

Exposure to one or more traumatic events was reported by 36.2% of survey responders. Additionally, 17.9% screened positive for GAD, 22.8% for MDD, and 19.9% for PTSD. Employing multivariable logistic regressions, low job satisfaction, younger age (<35 years of age), greater length of employment, and trauma exposure on or off-duty was significantly associated with all the three disorders. Among individuals screening positive for a mental health disorder, 2.05% sought mental health treatment within and 10.01% outside the UN in the past year.

Conclusions

UN personnel appear to be at high risk for trauma exposure and screening positive for a mental health disorder, yet a small percentage screening positive for mental health disorders sought treatment. Despite the mental health gaps observed in this study, additional research is needed, as these data reflect a large sample of convenience and it cannot be determined if the findings are representative of the UN.
Fitness costs associated with thiamethoxam and imidacloprid resistance in three field populations ofDiaphorina citri(Hemiptera: Liviidae) from Florida
Authors: Chen Xue Dong , Ebert Timothy A. , Pelz-Stelinski Kirsten S. , Stelinski Lukasz L.
Published: February 2020

Insecticide resistance is an increasing problem in citrus production. The Asian citrus psyllid,Diaphornia citriKuwayama, is recognized as one of the most important citrus pests worldwide and it has developed resistance in areas where insecticides have been overused. The development of insecticide resistance is often associated with fitness costs that only become apparent in the absence of selection pressure. Here, the fitness costs associated with resistance to thiamethoxam and imidacloprid were investigated in three agricultural populations ofD. citrias compared with susceptible laboratory colonies. Results showed that all field populations had greater resistance than laboratory susceptible colonies. For both thiamethoxam and imidacloprid, aCandidatusLiberibacter asiaticus-positive (CLas+) colony was more susceptible than theCLas−colony. Resistance ratios ranged from 7.65–16.11 for imidacloprid and 26.79–49.09 for thiamethoxam in field populations as compared with a susceptible,CLas−laboratory strain. Among three resistant field populations, a significantly reduced net reproductive rate and finite rate of population increase were observed in a population from Lake Wales, FL as compared to both susceptible strains. The fecundity of field populations from Lake Wales, FL was statistically lower than both laboratory susceptible populations. Certain changes in morphological characteristics were observed among resistant, as compared, with susceptible strains. Our data suggest fitness disadvantages associated with insecticide resistance inD. citriare related to both development and reproduction. The lower fitness ofD. citripopulations that exhibit resistance to neonicotinoid insecticides should promote recovery of sensitivity when those populations are no longer exposed to thiamethoxam and/or imidacloprid in the field. The results are congruent with a strategy of insecticide rotation for resistance management.
Columnar-jointed bentonite below a Doleritic Sill, Tideswell Dale, Derbyshire, UK: formation during prograde contact metamorphism
Authors: Mullineux S , Sparks RSJ , Murphy MD , MacNiocaill C , Barfod D , Njorka J , Schumacher JC
Published: February 2020

Columnar-jointed tuffs (bentonites) are located below the Lower Carboniferous Tideswell Dale Sill, Derbyshire, in an abandoned quarry. There are three zones of prismatic joints, columnar joints (∼60 cm thick and mean column width of 4.1 cm) and massive, conchoidally fractured rock sequentially from the dolerite contact downwards. The rocks are very fine-grained (1–10 µm) and consist mainly of sanidine, interlayered illite/smectite, and hematite, with minor quartz, apatite, montmorillonite, anatase and detrital minerals. High K2O and Fe2O3, low Na2O and low MgO are interpreted as due to alteration of felsic volcanic ash. The bentonite was contact-metamorphosed by the sill to temperatures of c. 300 °C. The progression of fracture geometries, thermal considerations and application of theories of column formation indicate that columns formed downwards away from the sill, due to prograde contact metamorphism of the originally clay-rich bentonite. The formation of columnar fracture networks by shrinkage due to igneous heating may have implications for the effectiveness of bentonite as a barrier for disposal of high-level radioactive waste. Regional dimensions include documenting widespread felsic explosive volcanism and inferring a Triassic oxidation event from palaeomagnetic data.
Rearing Children of the Market in the “You” Decade: Choose Your Own Adventure Books and the Ascent of Free Choice in 1980s America
Authors: COOK ELI
Published: February 2020

Exploring some of the key tenets of neoliberal American culture, this article examines the historical forces behind the meteoric rise of interactive “Choose Your Own Adventure” (CYOA) children's books in the 1980s. Despite selling over 250 million copies worldwide and becoming the fourth most popular children's series of all time, the CYOA phenomenon has yet to be placed in its larger social, economic, historical or cultural context. When explaining the rise of interactive narratives, previous literature has mostly focussed on technological change – namely the invention of video games, computer consoles and hypertext narratives. Moving away from such claims, this article demonstrates how the incredible success of solely text-based CYOA books stemmed largely from the cultural ascent of individual market choice to the heart of American notions of agency, liberty, subjectivity and selfhood in the 1970s and 1980s.
Intangible Capital and Leverage
Authors: Horsch Philipp , Longoni Philip , Oesch David
Published: February 2020

We investigate the causal effect of intangible capital on leverage. To address endogeneity, we exploit patent invalidations by a U.S. court in which judges are randomly assigned to cases. Differences in judge leniency provide exogenous variation in the probability that firms’ patents are invalidated. Using this probability as an instrument for exogenous losses in intangible capital, we find a patent invalidation leads to a 14.1% reduction in leverage, suggesting that intangible capital causally supports leverage. This local average treatment effect is stronger in firms that use patents as loan collateral and in less creditworthy as well as smaller firms.
Infection ofHexametra angusticaecoidesChabaud & Brygoo, 1960 (Nematoda: Ascarididae) in a population of captive crested geckoes,Correlophus ciliatusGuichenot (Reptilia: Diplodactylidae)
Authors: Barton Diane P. , Martelli Paolo , Luk William , Zhu Xiaocheng , Shamsi Shokoofeh
Published: February 2020

Here we report on the infection of captive crested geckosCorrelophus ciliatusGuichenot (Reptilia: Diplodactylidae), with adults of the ascaridoid nematode,Hexametra angusticaecoidesChabaud & Brygoo, 1960 (Ascarididae). A population of captive crested geckoes became ill and died within a short period of time. Nematodes were recovered from the crested geckoes examined from within the coelomic cavity, penetrating various organs and migrating through subcutaneous tissues, as well as emerging through the geckos' skin. One gecko was treated with levamisole following surgical excision of nematodes from under the skin; this gecko survived. The potential source of the nematode infection in the captive geckoes is discussed. It is most likely that wild-caught Madagascan mossy geckoes,Uroplatus sikoraeBoettger (Reptilia: Gekkonidae), introduced the infection to the colony. Molecular sequences of the nematodes are the first produced for the members of this genus. A redescription of the species and its genetic characterization based on the internal transcribed spacer sequence data is provided, suggesting some of the morphological criteria that have been used in the past to distinguish betweenHexametraspp. may have been intraspecific morphological variations.
Feeding performance on a novel host: no adaptation over generations and differential patterns in two flea species
Authors: Khokhlova Irina S. , Fielden Laura J. , Warburton Elizabeth M. , van der Mescht Luther , Krasnov Boris R.
Published: February 2020

To model the colonization of a novel host by fleas,Synosternus cleopatraeandXenopsylla ramesis, we established experimental lines maintained for 15 generations on a principal or a novel host (either co-occurring with a flea or not). We compared the blood meal size and the energy expended for digestion by fleas from the 15thgeneration of each line on these hosts between hosts within a line and between lines within a host asking (a) whether fleas adapt to a novel host (increased blood consumption/decreased energy expended for digestion); (b) if yes, whether this adaptation leads to the loss of ability to exploit an original host, and (c) whether the success of adaptation to a novel host depends on its ecological co-occurrence with a flea. The blood consumption and digestion energetics of fleas fed on the principal host differed from those on other hosts. The effect of the principal host on feeding performance differed between fleas, withS. cleopatraeconsuming less blood and expending more energy for digestion on the principal than on any other host, whereas the opposite was true forX. ramesis. No changes in feeding performance on a novel host over generations were found. We propose several explanations for the lack of adaptation to a novel host over time. We explain the poor performance ofS. cleopatraeon its principal hostviaits immune response mounting pattern. We argue that the principal host of a parasite is not necessarily the host on which the parasite demonstrates the best performance.
ON RELATIVE AGING COMPARISONS OF COHERENT SYSTEMS WITH IDENTICALLY DISTRIBUTED COMPONENTS
Authors: Hazra Nil Kamal , Misra Neeraj
Published: February 2020

The relative aging is an important notion which is useful to measure how a system ages relative to another one. Among the existing stochastic orders, there are two important orders describing the relative aging of two systems, namely, aging faster orders in the cumulative hazard and the cumulative reversed hazard rate functions. In this paper, we give some sufficient conditions under which one coherent system ages faster than another one with respect to the aforementioned stochastic orders. Further, we show that the proposed sufficient conditions are satisfied for k-out-of-n systems. Moreover, some numerical examples are given to illustrate the applications of proposed results.
The Flapping Motion of Mercury's Magnetotail Current Sheet: MESSENGER Observations
Authors: Zhang C. , Rong Z. J. , Gao J. W. , Zhong J. , Chai L. H. , Wei Y. , Shen C. , Wan W. X.
Published: February 2020

The flapping motion of Mercury's magnetotail current sheet is investigated based on the observations of MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER). The typical flapping period in Mercury's magnetotail is much shorter (~13 s), comparing with ~10–20 min at Earth's magnetotail. The magnetic field oscillation amplitude induced by flapping motion is larger near both flanks than that around tail center. Similar to Earth's magnetotail, there are two flapping types existent in Mercury's magnetotail, one is the kink‐like flapping that can propagate as traveling waves, and the other one is the steady flapping that does not propagate. Both flapping types distribute widely in magnetotail. The kink‐like flapping waves propagating either dawnward or duskward can be observed across the entire magnetotail current sheet, which suggests that the energy sources for triggering the kink‐like flapping waves should locate around both tail flanks instead of tail center as is for the Earth's magnetotail.
Distinct Formation and Evolution Characteristics of Outer Radiation Belt Electron Butterfly Pitch Angle Distributions Observed by Van Allen Probes
Authors: Ni Binbin , Yan Ling , Fu Song , Gu Xudong , Cao Xing , Xiang Zheng , Zhang Yuannong
Published: February 2020

Using Van Allen Probes pitch angle‐resolved electron flux data, we report intriguing events of electron butterfly pitch angle distributions (PADs) at L > ~5.5 on the nightside with distinct durations, i.e., about 9 hr for the 28–29 April 2013 event and over 2 days for the 2–5 May 2013 event. The formation and evolution of the short‐duration electron butterfly PADs exhibited insignificant dependence on electron energy, probably resulting from a combination of drift shell splitting, magnetopause shadowing, and wave diffusion, but the long‐duration electron butterfly evolution presented strong energy dependence, likely mainly attributed to interactions with MS waves. Both the short‐duration and long‐duration electron butterfly PADs disappeared closely related to enhanced substorm activities, while the responsible waves could be plasmaspheric hiss or chorus waves. Our results demonstrate that radiation belt electron butterfly PADs are naturally complex in both spatial and temporal scales and well connected to solar wind condition, substorm activity, and magnetospheric wave distribution.
Suprathermal Electron Acceleration Perpendicular to the Magnetic Field in the Topside Ionosphere
Authors: Shen Yangyang , Knudsen David J.
Published: February 2020

We present the first direct observations of suprathermal (tens to hundreds of eV) electron acceleration perpendicular to the magnetic field in the topside (900–1,500 km) ionosphere. Based on measurements from the suprathermal electron imager (SEI) onboard the Enhanced Polar Outflow Probe satellite over several months, we identify 30 events (28 in the dayside cusp) of enhanced suprathermal electron fluxes peaking at
90° pitch angles, with energies spanning from tens of eV to 325 eV, the upper limit of the SEI measurement. These events take place with a time duration of the order of 0.1 s, corresponding to a spatial scale of less than 1 km across the magnetic field. They are associated with parallel suprathermal electron bursts and upward currents. The correlation between perpendicular and parallel suprathermal electrons suggests a scenario in which downward bursts and the associated Alfvén waves that drive them provide a free energy source to destabilize plasma waves at electron frequencies, which in turn heat electrons in the perpendicular direction. This is a new energy dissipation process for cusp suprathermal electron precipitation in the topside ionosphere.
Inner‐Shelf Vertical and Alongshore temperature Variability in the Subtidal, Diurnal, and Semidiurnal Bands Along the central California coastline with headlands
Authors: Feddersen Falk , MacMahan Jamie H. , Freismuth Thomas M. , Gough Matt K. , Kovatch Michael
Published: February 2020

The temporal, vertical, and alongshore variation in inner‐shelf temperature, T, across subtidal (ST), diurnal (DU), and semidiurnal (SD) bands on coastlines with headlands is not understood. Inner‐shelf T was observed with 20 moorings in 9‐ to 16‐m depth with high vertical density during Fall 2017 along 50 km of central California coastline with headlands. The ST‐first empirical orthogonal function is largely barotropic. ST warm water events are associated with northward‐propagating buoyant plumes and onshore advection of offshore water, with headland effects, particularly for stronger events. Previous plume arrival criteria are northward propagation biased. The DU vertical structure was mixed barotropic and linear baroclinic, without surface extrema. Inner‐shelf DU‐band temperature variability was always evident, largest north of and weakest south of two headlands. The DU‐T envelope was not modulated by ST stratification and was not linked to the modeled DU‐wind envelope. North of one headland, the alongshore first complex empirical orthogonal function of DU temperature has a previously unobserved southward 2‐m/s phase propagation, even though DU frequency is subcritical, that is, not wind forced. A frictional subcritical wave mechanism is proposed for the DU propagation. The SD‐T vertical structure varies alongshore, suggesting at different locations linear internal waves and nonlinear cold bores. SD‐T variability was incoherent with barotropic tides and decorrelates alongshore in 7.5 km, contrasting with a few kilometers offshore. The SD depth‐averaged energy varied strongly alongshore particularly north and south of the headlands, and stronger and weaker SD energy was linked to nonlinear and linear baroclinic vertical structures, respectively, which are headland influenced.
Long‐Term Trends of High Aerosol Pollution Events and Their Climatic Impacts in North America Using Multiple Satellite Retrievals and Modern‐Era Retrospective Analysis for Research and Applications version 2
Authors: Jin Qinjian , Pryor S. C.
Published: February 2020

Mean magnitudes and temporal trends in aerosol optical depth (AOD) from satellite observations and an aerosol reanalysis exhibit a negative‐positive east‐northwest dipole across the contiguous United States with large magnitude negative trends over the eastern United States while small magnitude positive trends over the northwestern states. Based on analyses of Modern‐Era Retrospective Analysis for Research and Applications version 2, the AOD reduction over the eastern United States appears to be largely attributable to reductions in aerosol sulfate, while there have been marked increases in aerosol‐organic and elemental carbon over almost all of the contiguous United States and particularly the northwestern states. Long‐term trends of high aerosol pollution events (HAPEs; days with AOD over the long‐term local 90th daily AOD percentile) during 2000–2017 also indicate that over the eastern United States, both the frequency and spatial scale of summer HAPEs exhibit significant negative trends, while those of moderate aerosol events (days with AOD between the local 30th and 70th AOD percentiles) exhibit weak upward trends. Opposing trends, of smaller magnitude, are derived in the northwestern United States and southwestern Canada. Net and shortwave solar radiation show positive trends at the surface and top of atmosphere under clear‐sky conditions over the eastern United States consistent with the reduction in AOD. However, skin temperatures do not indicate significant trends during all days or HAPEs, indicating that the aerosol‐induced radiation trends are not sufficient to manifest trends in surface temperature. Precipitation during HAPEs appears to have increased during 2000–2017 over the eastern and central United States, indicating that the reduction in aerosol may already be enhancing the precipitation through aerosol‐cloud interactions.
Bayesian Update and Method of Distributions: Application to Leak Detection in Transmission Mains
Authors: Alawadhi Abdulrahman , Tartakovsky Daniel M.
Published: February 2020

Water‐hammer equations are used to describe transient flow in pipe networks. Uncertainty in model parameters, initial and boundary conditions, and location and strength of a possible leak renders deterministic predictions of this system untenable. When deployed in conjunction with pressure measurements, probabilistic solutions of the water‐hammer equations serve as a tool for detecting leaks in pipes. We use the method of distributions to obtain a probability density function (PDF) for pressure head, whose dynamics are described by the stochastic water‐hammer equations. This PDF provides a prior distribution for subsequent Bayesian data assimilation, in which data collected by pressure sensors are combined with this prior to obtain a posterior PDF of the leak location and size. We conduct a series of numerical experiments with uncertain initial velocity and measurement noise to ascertain the robustness and accuracy of the proposed approach. The results show the method's ability to identify the leak location and strength in a water transmission main.
Emerging roles for UDP-glucuronosyltransferases in drug resistance and cancer progression
Authors: Allain Eric P. , Rouleau Michèle , Lévesque Eric , Guillemette Chantal
Published: February 2020

The best-known role of UDP-glucuronosyltransferase enzymes (UGTs) in cancer is the metabolic inactivation of drug therapies. By conjugating glucuronic acid to lipophilic drugs, UGTs impair the biological activity and enhance the water solubility of these agents, driving their elimination. Multiple clinical observations support an expanding role for UGTs as modulators of the drug response and in mediating drug resistance in numerous cancer types. However, accumulating evidence also suggests an influence of the UGT pathway on cancer progression. Dysregulation of the expression and activity of UGTs has been associated with the progression of several cancers, arguing for UGTs as possible mediators of oncogenic pathways and/or disease accelerators in a drug-naive context. The consequences of altered UGT activity on tumour biology are incompletely understood. They might be associated with perturbed levels of bioactive endogenous metabolites such as steroids and bioactive lipids that are inactivated by UGTs or through non-enzymatic mechanisms, thereby eliciting oncogenic signalling cascades. This review highlights the evidence supporting dual roles for the UGT pathway, affecting cancer progression and drug resistance. Pharmacogenomic testing of UGT profiles in patients and the development of therapeutic options that impair UGT actions could provide useful prognostic and predictive biomarkers and enhance the efficacy of anti-cancer drugs.
Retraction Note: Aberrant mannosylation profile and FTX/miR-342/ALG3-axis contribute to development of drug resistance in acute myeloid leukemia
Authors: Liu Bing , Ma Xiaolu , Liu Qianqian , Xiao Yang , Pan Shimeng , Jia Li
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Correction: Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells
Authors: Willbold Ramona , Wirth Katharina , Martini Thomas , Sültmann Holger , Bolenz Christian , Wittig Rainer
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
High-resolution tomographic volumetric additive manufacturing
Authors: Loterie Damien , Delrot Paul , Moser Christophe
Published: February 2020

In tomographic volumetric additive manufacturing, an entire three-dimensional object is simultaneously solidified by irradiating a liquid photopolymer volume from multiple angles with dynamic light patterns. Though tomographic additive manufacturing has the potential to produce complex parts with a higher throughput and a wider range of printable materials than layer-by-layer additive manufacturing, its resolution currently remains limited to 300 µm. Here, we show that a low-étendue illumination system enables the production of high-resolution features. We further demonstrate an integrated feedback system to accurately control the photopolymerization kinetics over the entire build volume and improve the geometric fidelity of the object solidification. Hard and soft centimeter-scale parts are produced in less than 30 seconds with 80 µm positive and 500 µm negative features, thus demonstrating that tomographic additive manufacturing is potentially suitable for the ultrafast fabrication of advanced and functional constructs.
Deriving disease modules from the compressed transcriptional space embedded in a deep autoencoder
Authors: Dwivedi Sanjiv K. , Tjärnberg Andreas , Tegnér Jesper , Gustafsson Mika
Published: February 2020

Disease modules in molecular interaction maps have been useful for characterizing diseases. Yet biological networks, that commonly define such modules are incomplete and biased toward some well-studied disease genes. Here we ask whether disease-relevant modules of genes can be discovered without prior knowledge of a biological network, instead training a deep autoencoder from large transcriptional data. We hypothesize that modules could be discovered within the autoencoder representations. We find a statistically significant enrichment of genome-wide association studies (GWAS) relevant genes in the last layer, and to a successively lesser degree in the middle and first layers respectively. In contrast, we find an opposite gradient where a modular protein–protein interaction signal is strongest in the first layer, but then vanishing smoothly deeper in the network. We conclude that a data-driven discovery approach is sufficient to discover groups of disease-related genes.
Thermally activated triplet exciton release for highly efficient tri-mode organic afterglow
Authors: Jin Jibiao , Jiang He , Yang Qingqing , Tang Lele , Tao Ye , Li Yuanyuan , Chen Runfeng , Zheng Chao , Fan Quli , Zhang Kenneth Yin , Zhao Qiang , Huang Wei
Published: February 2020

Developing high-efficient afterglow from metal-free organic molecules remains a formidable challenge due to the intrinsically spin-forbidden phosphorescence emission nature of organic afterglow, and only a few examples exhibit afterglow efficiency over 10%. Here, we demonstrate that the organic afterglow can be enhanced dramatically by thermally activated processes to release the excitons on the stabilized triplet state (T1*) to the lowest triplet state (T1) and to the singlet excited state (S1) for spin-allowed emission. Designed in a twisted donor–acceptor architecture with small singlet-triplet splitting energy and shallow exciton trapping depth, the thermally activated organic afterglow shows an efficiency up to 45%. This afterglow is an extraordinary tri-mode emission at room temperature from the radiative decays of S1, T1, and T1*. With the highest afterglow efficiency reported so far, the tri-mode afterglow represents an important concept advance in designing high-efficient organic afterglow materials through facilitating thermally activated release of stabilized triplet excitons.
Mahan excitons in room-temperature methylammonium lead bromide perovskites
Authors: Palmieri Tania , Baldini Edoardo , Steinhoff Alexander , Akrap Ana , Kollár Márton , Horváth Endre , Forró László , Jahnke Frank , Chergui Majed
Published: February 2020

In a seminal paper, Mahan predicted that excitonic bound states can still exist in a semiconductor at electron-hole densities above the insulator-to-metal Mott transition. However, no clear evidence for this exotic quasiparticle, dubbed Mahan exciton, exists to date at room temperature. In this work, we combine ultrafast broadband optical spectroscopy and advanced many-body calculations to reveal that organic-inorganic lead-bromide perovskites host Mahan excitons at room temperature. Persistence of the Wannier exciton peak and the enhancement of the above-bandgap absorption are observed at all achievable photoexcitation densities, well above the Mott density. This is supported by the solution of the semiconductor Bloch equations, which confirms that no sharp transition between the insulating and conductive phase occurs. Our results demonstrate the robustness of the bound states in a regime where exciton dissociation is otherwise expected, and offer promising perspectives in fundamental physics and in room-temperature applications involving high densities of charge carriers.
Switchable encapsulation of polysulfides in the transition between sulfur and lithium sulfide
Authors: Fu Yongsheng , Wu Zhen , Yuan Yifei , Chen Peng , Yu Lei , Yuan Lei , Han Qiurui , Lan Yingjie , Bai Wuxin , Kan Erjun , Huang Chengxi , Ouyang Xiaoping , Wang Xin , Zhu Junwu , Lu Jun
Published: February 2020

Encapsulation strategies are widely used for alleviating dissolution and diffusion of polysulfides, but they experience nonrecoverable structural failure arising from the repetitive severe volume change during lithium−sulfur battery cycling. Here we report a methodology to construct an electrochemically recoverable protective layer of polysulfides using an electrolyte additive. The additive nitrogen-doped carbon dots maintain their “dissolved” status in the electrolyte at the full charge state, and some of them function as active sites for lithium sulfide growth at the full discharge state. When polysulfides are present amid the transition between sulfur and lithium sulfide, nitrogen-doped carbon dots become highly reactive with polysulfides to form a solid and recoverable polysulfide-encapsulating layer. This design skilfully avoids structural failure and efficiently suppresses polysulfide shuttling. The sulfur cathode delivers a high reversible capacity of 891 mAh g−1 at 0.5 C with 99.5% coulombic efficiency and cycling stability up to 1000 cycles at 2 C.
Crystal structure of Drosophila Piwi
Authors: Yamaguchi Sonomi , Oe Akira , Nishida Kazumichi M. , Yamashita Keitaro , Kajiya Asako , Hirano Seiichi , Matsumoto Naoki , Dohmae Naoshi , Ishitani Ryuichiro , Saito Kuniaki , Siomi Haruhiko , Nishimasu Hiroshi , Siomi Mikiko C. , Nureki Osamu
Published: February 2020

PIWI-clade Argonaute proteins associate with PIWI-interacting RNAs (piRNAs), and silence transposons in animal gonads. Here, we report the crystal structure of the Drosophila PIWI-clade Argonaute Piwi in complex with endogenous piRNAs, at 2.9 Å resolution. A structural comparison of Piwi with other Argonautes highlights the PIWI-specific structural features, such as the overall domain arrangement and metal-dependent piRNA recognition. Our structural and biochemical data reveal that, unlike other Argonautes including silkworm Siwi, Piwi has a non-canonical DVDK tetrad and lacks the RNA-guided RNA cleaving slicer activity. Furthermore, we find that the Piwi mutant with the canonical DEDH catalytic tetrad exhibits the slicer activity and readily dissociates from less complementary RNA targets after the slicer-mediated cleavage, suggesting that the slicer activity could compromise the Piwi-mediated co-transcriptional silencing. We thus propose that Piwi lost the slicer activity during evolution to serve as an RNA-guided RNA-binding platform, thereby ensuring faithful co-transcriptional silencing of transposons.
Maturation of the human striatal dopamine system revealed by PET and quantitative MRI
Authors: Larsen Bart , Olafsson Valur , Calabro Finnegan , Laymon Charles , Tervo-Clemmens Brenden , Campbell Elizabeth , Minhas Davneet , Montez David , Price Julie , Luna Beatriz
Published: February 2020

The development of the striatum dopamine (DA) system through human adolescence, a time of increased sensation seeking and vulnerability to the emergence of psychopathology, has been difficult to study due to pediatric restrictions on direct in vivo assessments of DA. Here, we applied neuroimaging in a longitudinal sample of n = 146 participants aged 12–30. R2′, an MR measure of tissue iron which co-localizes with DA vesicles and is necessary for DA synthesis, was assessed across the sample. In the 18–30 year-olds (n = 79) we also performed PET using [11C]dihydrotetrabenazine (DTBZ), a measure of presynaptic vesicular DA storage, and [11C]raclopride (RAC), an indicator of D2/D3 receptor availability. We observed decreases in D2/D3 receptor availability with age, while presynaptic vesicular DA storage (as measured by DTBZ), which was significantly associated with R2′ (standardized coefficient = 0.29, 95% CI = [0.11, 0.48]), was developmentally stable by age 18. Our results provide new evidence for maturational specialization of the striatal DA system through adolescence.
Clades of huge phages from across Earth’s ecosystems
Authors: Al-Shayeb Basem , Sachdeva Rohan , Chen Lin-Xing , Ward Fred , Munk Patrick , Devoto Audra , Castelle Cindy J. , Olm Matthew R. , Bouma-Gregson Keith , Amano Yuki , He Christine , Méheust Raphaël , Brooks Brandon , Thomas Alex , Lavy Adi , Matheus-Carnevali Paula , Sun Christine , Goltsman Daniela S. A. , Borton Mikayla A. , Sharrar Allison , Jaffe Alexander L. , Nelson Tara C. , Kantor Rose , Keren Ray , Lane Katherine R. , Farag Ibrahim F. , Lei Shufei , Finstad Kari , Amundson Ronald , Anantharaman Karthik , Zhou Jinglie , Probst Alexander J. , Power Mary E. , Tringe Susannah G. , Li Wen-Jun , Wrighton Kelly , Harrison Sue , Morowitz Michael , Relman David A. , Doudna Jennifer A. , Lehours Anne-Catherine , Warren Lesley , Cate Jamie H. D. , Santini Joanne M. , Banfield Jillian F.
Published: February 2020

Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is—to our knowledge—the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR–Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR–Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR–Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth’s ecosystems.
A voltage and current measurement dataset for plug load appliance identification in households
Authors: Medico Roberto , De Baets Leen , Gao Jingkun , Giri Suman , Kara Emre , Dhaene Tom , Develder Chris , Bergés Mario , Deschrijver Dirk
Published: February 2020

This paper presents the Plug-Load Appliance Identification Dataset (PLAID), a labelled dataset containing records of the electrical voltage and current of domestic electrical appliances obtained at a high sampling frequency (30 kHz). The dataset contains 1876 records of individually-metered appliances from 17 different appliance types (e.g., refrigerators, microwave ovens, etc.) comprising 330 different makes and models, and collected at 65 different locations in Pittsburgh, Pennsylvania (USA). Additionally, PLAID contains 1314 records of the combined operation of 13 of these appliance types (i.e., measurements obtained when multiple appliances were active simultaneously). Identifying electrical appliances based on electrical measurements is of importance in demand-side management applications for the electrical power grid including automated load control, load scheduling and non-intrusive load monitoring. This paper provides a systematic description of the measurement setup and dataset so that it can be used to develop and benchmark new methods in these and other applications, and so that extensions to it can be developed and incorporated in a consistent manner.
Application of single-level and multi-level modeling approach to examine geographic and socioeconomic variation in underweight, overweight and obesity in Nepal: findings from NDHS 2016
Authors: Shrestha Nipun , Mishra Shiva Raj , Ghimire Saruna , Gyawali Bishal , Pradhan Pranil Man Singh , Schwarz Dan
Published: February 2020

Nepal’s dual burden of undernutrition and over nutrition warrants further exploration of the population level differences in nutritional status. The study aimed to explore, for the first time in Nepal, potential geographic and socioeconomic variation in underweight and overweight and/or obesity prevalence in the country, adjusted for cluster and sample weight. Data came from 14,937 participants, including 6,172 men and 8,765 women, 15 years or older who participated in the 2016 Nepal Demography and Health Survey (NDHS). Single-level and multilevel multi-nominal logistic regression models and Lorenz curves were used to explore the inequalities in weight status. Urban residents had higher odds of being overweight and/or obese (OR: 1.89, 95% CI: 1.62–2.20) and lower odds of being underweight (OR: 0.81, 95% CI: 0.70–0.93) than rural residents. Participants from Provinces 2, and 7 were less likely to be overweight/obese and more likely to be underweight (referent: province-1). Participants from higher wealth quintile households were associated with higher odds of being overweight and/or obese (P-trend < 0.001) and lower odds of being underweight (P-trend < 0.001). Urban females at the highest wealth quintile were more vulnerable to overweight and/or obesity as 49% of them were overweight and/or obese and nearly 39% at the lowest wealth quintile were underweight.
Large-scale Quality Control of Cardiac Imaging in Population Studies: Application to UK Biobank
Authors: Tarroni Giacomo , Bai Wenjia , Oktay Ozan , Schuh Andreas , Suzuki Hideaki , Glocker Ben , Matthews Paul M. , Rueckert Daniel
Published: February 2020

In large population studies such as the UK Biobank (UKBB), quality control of the acquired images by visual assessment is unfeasible. In this paper, we apply a recently developed fully-automated quality control pipeline for cardiac MR (CMR) images to the first 19,265 short-axis (SA) cine stacks from the UKBB. We present the results for the three estimated quality metrics (heart coverage, inter-slice motion and image contrast in the cardiac region) as well as their potential associations with factors including acquisition details and subject-related phenotypes. Up to 14.2% of the analysed SA stacks had sub-optimal coverage (i.e. missing basal and/or apical slices), however most of them were limited to the first year of acquisition. Up to 16% of the stacks were affected by noticeable inter-slice motion (i.e. average inter-slice misalignment greater than 3.4 mm). Inter-slice motion was positively correlated with weight and body surface area. Only 2.1% of the stacks had an average end-diastolic cardiac image contrast below 30% of the dynamic range. These findings will be highly valuable for both the scientists involved in UKBB CMR acquisition and for the ones who use the dataset for research purposes.
Low-energy extracorporeal shock wave therapy for a model of liver cirrhosis ameliorates liver fibrosis and liver function
Authors: Ujiie Naoto , Nakano Toru , Yamada Masato , Sato Chiaki , Nakanishi Chikashi , Fujishima Fumiyoshi , Ito Kenta , Shindo Tomohiko , Shimokawa Hiroaki , Kamei Takashi
Published: February 2020

Low-energy extracorporeal shock waves (LESW) have been studied as a new treatment for angina pectoris and several ischemic diseases because of its effect on angiogenesis and inhibition of fibrosis of the heart. The effect of LESW on fibrosis in liver cirrhosis has not been studied. The aim of this study was to verify the amelioration of liver fibrosis by LESW and elucidate its mechanisms in a rat model of drug-induced liver cirrhosis. Male Wistar rats aged 7 weeks were injected with carbon tetrachloride intraperitoneally twice a week for 12 weeks. Eight rats underwent LESW therapy (0.25 mJ/mm2, 4 Hz, 1000 shots) under general anesthesia (shock wave group). Seven rats only underwent general anesthesia (control group). Quantitative analysis showed that the area of fibrosis in the shock wave group was significantly reduced compared with the control group (11,899.9 vs. 23,525.3 pixels per field, p < 0.001). In the shock wave group, the mRNA expression of transforming growth factor (TGF)-β1 was significantly suppressed (0.40-fold, p = 0.018) and vascular endothelial growth factor-B was significantly increased (1.77-fold, p = 0.006) compared with the control group. Serum albumin was significantly higher in the shock wave group than in the control group (3.0 vs. 2.4 g/dl, p = 0.025). Aspartate aminotransferase/alanine aminotransferase ratio decreased by LESW compared with the control group (1.49 vs. 2.04, p = 0.013). These results suggest that LESW therapy ameliorates liver fibrosis by reducing the expression of TGF-β1 and increasing the expression of angiogenic factors, and improves hepatic function.
Publisher Correction: Multiple concomitant mechanisms contribute to low platelet count in patients with immune thrombocytopenia
Authors: Grodzielski Matías , Goette Nora P. , Glembotsky Ana C. , Constanza Baroni Pietto M. , Méndez-Huergo Santiago P. , Pierdominici Marta S. , Montero Verónica S. , Rabinovich Gabriel A. , Molinas Felisa C. , Heller Paula G. , Lev Paola R. , Marta Rosana F.
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A predictive model for prostate cancer incorporating PSA molecular forms and age
Authors: Oto Julia , Fernández-Pardo Álvaro , Royo Montserrat , Hervás David , Martos Laura , Vera-Donoso César D. , Martínez Manuel , Heeb Mary J. , España Francisco , Medina Pilar , Navarro Silvia
Published: February 2020

The diagnostic specificity of prostate specific antigen (PSA) is limited. We aimed to characterize eight anti-PSA monoclonal antibodies (mAbs) to assess the prostate cancer (PCa) diagnostic utility of different PSA molecular forms, total (t) and free (f) PSA and PSA complexed to α1-antichymotrypsin (complexed PSA). MAbs were obtained by immunization with PSA and characterized by competition studies, ELISAs and immunoblotting. With them, we developed sensitive and specific ELISAs for these PSA molecular forms and measured them in 301 PCa patients and 764 patients with benign prostate hyperplasia, and analyzed their effectiveness to discriminate both groups using ROC curves. The free-to-total (FPR) and the complexed-to-total PSA (CPR) ratios significantly increased the diagnostic yield of tPSA. Moreover, based on model selection, we constructed a multivariable logistic regression model to predictive PCa that includes tPSA, fPSA, and age as predictors, which reached an optimism-corrected area under the ROC curve (AUC) of 0.86. Our model outperforms the predictive ability of tPSA (AUC 0.71), used in clinical practice. In conclusion, The FPR and CPR showed better diagnostic yield than tPSA. In addition, the PCa predictive model including age, fPSA and complexed PSA, outperformed tPSA detection efficacy. Our model may avoid unnecessary biopsies, preventing harmful side effects and reducing health expenses.