bluuebunny/crossref_metadata_2025 huggingface dataset:
Cariprazine efficacy in bipolar I depression with and without concurrent manic symptoms: post hoc analysis of 3 randomized,
placebo-controlled studies
Authors: McIntyre Roger S. , Suppes Trisha , Earley Willie , Patel Mehul , Stahl Stephen M.
Published: October 2019

Objective.

Mixed presentations, defined by simultaneous occurrence of depressive and manic symptoms, are difficult to treat. Antidepressants, although commonly used, have weak evidence of efficacy and may increase risk of mood destabilization. The aim of this pooled post hoc analysis was to evaluate the efficacy of cariprazine in the treatment of bipolar depression with or without concurrent manic symptoms.

Methods.

Patients from 3 randomized, double-blind, placebo-controlled studies who met DSM-IV-TR or DSM-5 criteria for bipolar I disorder with a current major depressive episode were identified to have concurrent manic symptoms by baseline Young Mania Rating Scale total score ≥4. Efficacy was assessed in cariprazine 1.5 and 3 mg/day dose groups versus placebo; analyses included the least squares mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score.

Results.

Of 1383 patients randomized to treatment, 808 (58.4%) had concurrent manic symptoms. For patients with manic symptoms, mean reduction in MADRS total score from baseline to week 6 was significantly greater for both cariprazine 1.5 and 3 mg/day compared with placebo, with least squares mean differences (LSMDs) versus placebo of −2.5 (p = .0033) and −2.9 (p = .0010), respectively; for patients without manic symptoms, the LSMD was significant for 1.5 mg/day (−3.3; p = .0008), but not for 3 mg/day (−1.9; p = .0562).

Conclusion.

The results of this post hoc analysis suggest that cariprazine may be an appropriate treatment option for patients with bipolar I depression with or without manic symptoms, with higher doses potentially more effective in patients with manic symptoms.
Overlapping features between social anxiety and obsessive-compulsive spectrum in a clinical sample and in healthy controls: toward an integrative model
Authors: Carpita Barbara , Muti Dario , Petrucci Alessandra , Romeo Francesca , Gesi Camilla , Marazziti Donatella , Carmassi Claudia , Dell’Osso Liliana
Published: October 2019

Background.

While the literature frequently highlighted an association between social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD), few studies investigated the overlapping features of these conditions. The presented work evaluated the relationship between SAD and OCD spectrum in a clinical population and in healthy controls (HC).

Methods.

Fifty-six patients with OCD, 51 with SAD, 43 with major depressive disorder (MDD), and 59 HC (N = 209) were assessed using the Mini International Neuropsychiatric Interview, the Social Phobia Spectrum (SCI-SHY), and the Obsessive-Compulsive Spectrum (SCI-OBS).

Results.

SAD patients scored significantly higher than other groups on all SCI-SHY domains and total score; OCD patients scored significantly higher than HC. MDD patients scored significantly higher than HC on the SCI-SHY total, Behavioral inhibition, andInterpersonal sensitivitydomains. OCD patients scored significantly higher than other groups on all SCI-OBS domains exceptDoubt, for which OCD and SAD scored equally high. SAD patients scored significantly higher than HC on the SCI-OBS total,Childhood/adolescence,Doubt, andHypercontroldomains. MDD patients scored significantly higher than HC on theHypercontroldomain. SCI-OBS and SCI-SHY were widely correlated among groups, although lower correlations were found among OCD patients. Stronger correlations were observed between SCI-SHYInterpersonal sensitivityand SCI-OBSDoubt, Obsessive-compulsive themes,andHypercontrol; between SCI-SHYSpecific anxieties/phobic featuresand SCI-OBSObsessive-compulsive themes;and between SCI-SHYBehavioral inhibitionand SCI-OBSDoubt, with slightly different patterns among groups.

Conclusion.

OCD and SAD spectrums widely overlap in clinical samples and in the general population. Interpersonal sensitivity and obsessive doubts might represent a common cognitive core for these conditions.
Understanding Older Workers’ Decisions to Participate in Voluntary Training Opportunities
Authors: Lopina Erika C. , Rogelberg Steven G. , Woznyj Haley
Published: October 2019

Abstract. Age-related changes in training decisions were examined using a within-subject experimental design presenting training framing cues of topic (generativity vs. non-generativity), goal (direction: approach vs. avoidance; referent: mastery vs. performance), and structure (self-paced vs. instructor-paced). As age increased, age-related cues were hypothesized to be more strongly and positively related to the training decision. One hundred and twenty-nine participants completed a policy-capturing study and self-report survey. Age moderated the relationship between the training topic and the training decision. Contrary to the hypothesis, as age increased, the non-generativity topic (rather than the generativity topic) was more strongly and positively related to the training decision. Age did not moderate the relationship between the other training features and the training decision.
Planetary‐Scale Variations in Winds and UV Brightness at the Venusian Cloud Top: Periodicity and Temporal Evolution
Authors: Imai Masataka , Kouyama Toru , Takahashi Yukihiro , Yamazaki Atsushi , Watanabe Shigeto , Yamada Manabu , Imamura Takeshi , Satoh Takehiko , Nakamura Masato , Murakami Shin‐ya , Ogohara Kazunori , Horinouchi Takeshi
Published: October 2019

Planetary‐scale waves at the Venusian cloud‐top cause periodic variations in both winds and ultraviolet (UV) brightness. While the wave candidates are the 4‐day Kelvin wave and 5‐day Rossby wave with zonal wavenumber 1, their temporal evolutions are poorly understood. Here we conducted a time series analysis of the 365‐nm brightness and cloud‐tracking wind variations, obtained by the UV Imager onboard the Japanese Venus Climate Orbiter Akatsuki from June to October 2017, revealing a dramatic evolution of planetary‐scale waves and corresponding changes in planetary‐scale UV features. We identified a prominent 5‐day periodicity in both the winds and brightness variations, whose phase velocities were slower than the dayside mean zonal winds (or the super‐rotation) by >35 m/s. The reconstructed planetary‐scale vortices were nearly equatorially symmetric and centered at ~35° latitude in both hemispheres, which indicated that they were part of a Rossby wave. The amplitude of wind variation associated with the observed Rossby wave packet was amplified gradually over ~20 days and attenuated over ~50 days. Following the formation of the Rossby wave vortices, brightness variation emerges to form rippling white cloud belts in the 45–60° latitudes of both hemispheres. An ~3.8‐day periodic signals were observed in the zonal wind and brightness variations in the equatorial region before the Rossby wave amplification. Although the amplitude and significance of the 3.8‐day mode were relatively low in the observation season, this feature is consistent with a Kelvin wave, which may be the cause of the dark clusters in the equatorial region.
A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer
Authors: Kim Seon-Kyu , Kim Seon-Young , Kim Chan Wook , Roh Seon Ae , Ha Ye Jin , Lee Jong Lyul , Heo Haejeong , Cho Dong-Hyung , Lee Ju-Seog , Kim Yong Sung , Kim Jin Cheon
Published: October 2019

Approximately half of colorectal cancer (CRC) patients experience disease recurrence and metastasis, and these individuals frequently fail to respond to treatment due to their clinical and biological diversity. Here, we aimed to identify a prognostic signature consisting of a small gene group for precisely predicting CRC heterogeneity. We performed transcriptomic profiling using RNA-seq data generated from the primary tissue samples of 130 CRC patients. A prognostic index (PI) based on recurrence-associated genes was developed and validated in two larger independent CRC patient cohorts (n = 795). The association between the PI and prognosis of CRC patients was evaluated using Kaplan–Meier plots, log-rank tests, a Cox regression analysis and a RT-PCR analysis. Transcriptomic profiling in 130 CRC patients identified two distinct subtypes associated with systemic recurrence. Pathway enrichment and RT-PCR analyses revealed an eleven gene signature incorporated into the PI system, which was a significant prognostic indicator of CRC. Multivariate and subset analyses showed that PI was an independent risk factor (HR = 1.812, 95% CI = 1.342–2.448, P < 0.001) with predictive value to identify low-risk stage II patients who responded the worst to adjuvant chemotherapy. Finally, a comparative analysis with previously reported Consensus Molecular Subgroup (CMS), high-risk patients classified by the PI revealed a distinct molecular property similar to CMS4, associated with a poor prognosis. This novel PI predictor based on an eleven gene signature likely represents a surrogate diagnostic tool for identifying high-risk CRC patients and for predicting the worst responding patients for adjuvant chemotherapy.
Computational cytometer based on magnetically modulated coherent imaging and deep learning
Authors: Zhang Yibo , Ouyang Mengxing , Ray Aniruddha , Liu Tairan , Kong Janay , Bai Bijie , Kim Donghyuk , Guziak Alexander , Luo Yi , Feizi Alborz , Tsai Katherine , Duan Zhuoran , Liu Xuewei , Kim Danny , Cheung Chloe , Yalcin Sener , Ceylan Koydemir Hatice , Garner Omai B. , Di Carlo Dino , Ozcan Aydogan
Published: October 2019

Detecting rare cells within blood has numerous applications in disease diagnostics. Existing rare cell detection techniques are typically hindered by their high cost and low throughput. Here, we present a computational cytometer based on magnetically modulated lensless speckle imaging, which introduces oscillatory motion to the magnetic-bead-conjugated rare cells of interest through a periodic magnetic force and uses lensless time-resolved holographic speckle imaging to rapidly detect the target cells in three dimensions (3D). In addition to using cell-specific antibodies to magnetically label target cells, detection specificity is further enhanced through a deep-learning-based classifier that is based on a densely connected pseudo-3D convolutional neural network (P3D CNN), which automatically detects rare cells of interest based on their spatio-temporal features under a controlled magnetic force. To demonstrate the performance of this technique, we built a high-throughput, compact and cost-effective prototype for detecting MCF7 cancer cells spiked in whole blood samples. Through serial dilution experiments, we quantified the limit of detection (LoD) as 10 cells per millilitre of whole blood, which could be further improved through multiplexing parallel imaging channels within the same instrument. This compact, cost-effective and high-throughput computational cytometer can potentially be used for rare cell detection and quantification in bodily fluids for a variety of biomedical applications.
Short- and long-term impact of hyperoxia on the blood and retinal cells’ transcriptome in a mouse model of oxygen-induced retinopathy
Authors: Zasada Magdalena , Madetko-Talowska Anna , Revhaug Cecilie , Rognlien Anne Gro W. , Baumbusch Lars O. , Książek Teofila , Szewczyk Katarzyna , Grabowska Agnieszka , Bik-Multanowski Miroslaw , Józef Pietrzyk Jacek , Kwinta Przemko , Saugstad Ola Didrik
Published: October 2019

Background

We aimed to identify global blood and retinal gene expression patterns in murine oxygen-induced retinopathy (OIR), a common model of retinopathy of prematurity, which may allow better understanding of the pathogenesis of this severe ocular prematurity complication and identification of potential blood biomarkers.

Methods

A total of 120 C57BL/6J mice were randomly divided into an OIR group, in which 7-day-old pups were maintained in 75% oxygen for 5 days, or a control group. RNA was extracted from the whole-blood mononuclear cells and retinal cells on days 12, 17, and 28. Gene expression in the RNA samples was evaluated with mouse gene expression microarrays.

Results

There were 38, 1370 and 111 genes, the expression of which differed between the OIR and control retinas on days 12, 17, and 28, respectively. Gene expression in the blood mononuclear cells was significantly altered only on day 17. Deptor and Nol4 genes showed reduced expression both in the blood and retinal cells on day 17.

Conclusion

There are sustained marked changes in the global pattern of gene expression in the OIR mice retinas. An altered expression of Deptor and Nol4 genes in the blood mononuclear cells requires further investigation as they may indicate retinal neovascularization.
Lytic bacteriophage have diverse indirect effects in a synthetic cross-feeding community
Authors: Fazzino Lisa , Anisman Jeremy , Chacón Jeremy M , Heineman Richard H , Harcombe William R
Published: October 2019

Bacteriophage shape the composition and function of microbial communities. Yet it remains difficult to predict the effect of phage on microbial interactions. Specifically, little is known about how phage influence mutualisms in networks of cross-feeding bacteria. We mathematically modeled the impacts of phage in a synthetic microbial community in which Escherichia coli and Salmonella enterica exchange essential metabolites. In this model, independent phage attack of either species was sufficient to temporarily inhibit both members of the mutualism; however, the evolution of phage resistance facilitated yields similar to those observed in the absence of phage. In laboratory experiments, attack of S. enterica with P22vir phage followed these modeling expectations of delayed community growth with little change in the final yield of bacteria. In contrast, when E. coli was attacked with T7 phage, S. enterica, the nonhost species, reached higher yields compared with no-phage controls. T7 infection increased nonhost yield by releasing consumable cell debris, and by driving evolution of partially resistant E. coli that secreted more carbon. Our results demonstrate that phage can have extensive indirect effects in microbial communities, that the nature of these indirect effects depends on metabolic and evolutionary mechanisms, and that knowing the degree of evolved resistance leads to qualitatively different predictions of bacterial community dynamics in response to phage attack.
Correction: Defining lower limits of biodegradation: atrazine degradation regulated by mass transfer and maintenance demand in Arthrobacter aurescens TC1
Authors: Kundu Kankana , Marozava Sviatlana , Ehrl Benno , Merl-Pham Juliane , Griebler Christian , Elsner Martin
Published: October 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Endogenous stimulus-powered antibiotic release from nanoreactors for a combination therapy of bacterial infections
Authors: Wu Yang , Song Zhiyong , Wang Huajuan , Han Heyou
Published: October 2019

The use of an endogenous stimulus instead of external trigger has an advantage for targeted and controlled release in drug delivery. Here, we report on cascade nanoreactors for bacterial toxin-triggered antibiotic release by wrapping calcium peroxide (CaO2) and antibiotic in a eutectic mixture of two fatty acids and a liposome coating. When encountering pathogenic bacteria in vivo these nanoreactors capture the toxins, without compromising their structural integrity, and the toxins form pores. Water enters the nanoreactors through the pores to react with CaO2 and produce hydrogen peroxide which decomposes to oxygen and drives antibiotic release. The bound toxins reduce the toxicity and also stimulate the body’s immune response. This works to improve the therapeutic effect in bacterially infected mice. This strategy provides a Domino Effect approach for treating infections caused by bacteria that secrete pore-forming toxins.
Pacific subduction control on Asian continental deformation including Tibetan extension and eastward extrusion tectonics
Authors: Schellart W. P. , Chen Z. , Strak V. , Duarte J. C. , Rosas F. M.
Published: October 2019

The India-Asia collision has formed the highest mountains on Earth and is thought to account for extensive intraplate deformation in Asia. The prevailing explanation considers the role of the Pacific and Sunda subduction zones as passive during deformation. Here we test the hypothesis that subduction played an active role and present geodynamic experiments of continental deformation that model Indian indentation and active subduction rollback. We show that the synchronous activity and interaction of the collision zone and subduction zones explain Asian deformation, and demonstrate that east-west extension in Tibet, eastward continental extrusion and Asian backarc basin formation are controlled by large-scale Pacific and Sunda slab rollback. The models require 1740 ± 300 km of Indian indentation such that backarc basins form and central East Asian extension conforms estimates. Indentation and rollback produce ~260–360 km of eastward extrusion and large-scale clockwise upper mantle circulation from Tibet towards East Asia and back to India.
Fast objective coupled planar illumination microscopy
Authors: Greer Cody J. , Holy Timothy E.
Published: October 2019

Among optical imaging techniques light sheet fluorescence microscopy is one of the most attractive for capturing high-speed biological dynamics unfolding in three dimensions. The technique is potentially millions of times faster than point-scanning techniques such as two-photon microscopy. However light sheet microscopes are limited by volume scanning rate and/or camera speed. We present speed-optimized Objective Coupled Planar Illumination (OCPI) microscopy, a fast light sheet technique that avoids compromising image quality or photon efficiency. Our fast scan system supports 40 Hz imaging of 700 μm-thick volumes if camera speed is sufficient. We also address the camera speed limitation by introducing Distributed Planar Imaging (DPI), a scaleable technique that parallelizes image acquisition across cameras. Finally, we demonstrate fast calcium imaging of the larval zebrafish brain and find a heartbeat-induced artifact, removable when the imaging rate exceeds 15 Hz. These advances extend the reach of fluorescence microscopy for monitoring fast processes in large volumes.
Principles for enhancing virus capsid capacity and stability from a thermophilic virus capsid structure
Authors: Stone Nicholas P. , Demo Gabriel , Agnello Emily , Kelch Brian A.
Published: October 2019

The capsids of double-stranded DNA viruses protect the viral genome from the harsh extracellular environment, while maintaining stability against the high internal pressure of packaged DNA. To elucidate how capsids maintain stability in an extreme environment, we use cryoelectron microscopy to determine the capsid structure of thermostable phage P74-26 to 2.8-Å resolution. We find P74-26 capsids exhibit an overall architecture very similar to those of other tailed bacteriophages, allowing us to directly compare structures to derive the structural basis for enhanced stability. Our structure reveals lasso-like interactions that appear to function like catch bonds. This architecture allows the capsid to expand during genome packaging, yet maintain structural stability. The P74-26 capsid has T = 7 geometry despite being twice as large as mesophilic homologs. Capsid capacity is increased with a larger, flatter major capsid protein. Given these results, we predict decreased icosahedral complexity (i.e. T ≤ 7) leads to a more stable capsid assembly.
Complex DNA knots detected with a nanopore sensor
Authors: Kumar Sharma Rajesh , Agrawal Ishita , Dai Liang , Doyle Patrick S. , Garaj Slaven
Published: October 2019

Equilibrium knots are common in biological polymers—their prevalence, size distribution, structure, and dynamics have been extensively studied, with implications to fundamental biological processes and DNA sequencing technologies. Nanopore microscopy is a high-throughput single-molecule technique capable of detecting the shape of biopolymers, including DNA knots. Here we demonstrate nanopore sensors that map the equilibrium structure of DNA knots, without spurious knot tightening and sliding. We show the occurrence of both tight and loose knots, reconciling previous contradictory results from different experimental techniques. We evidence the occurrence of two quantitatively different modes of knot translocation through the nanopores, involving very different tension forces. With large statistics, we explore the complex knots and, for the first time, reveal the existence of rare composite knots. We use parametrized complexity, in concert with simulations, to test the theoretical assumptions of the models, further asserting the relevance of nanopores in future investigation of knots.
Controlled growth of single-crystalline metal nanowires via thermomigration across a nanoscale junction
Authors: Xie De-Gang , Nie Zhi-Yu , Shinzato Shuhei , Yang Yue-Qing , Liu Feng-Xian , Ogata Shigenobu , Li Ju , Ma Evan , Shan Zhi-Wei
Published: October 2019

Mass transport driven by temperature gradient is commonly seen in fluids. However, here we demonstrate that when drawing a cold nano-tip off a hot solid substrate, thermomigration can be so rampant that it can be exploited for producing single-crystalline aluminum, copper, silver and tin nanowires. This demonstrates that in nanoscale objects, solids can mimic liquids in rapid morphological changes, by virtue of fast surface diffusion across short distances. During uniform growth, a thin neck-shaped ligament containing a grain boundary (GB) usually forms between the hot and the cold ends, sustaining an extremely high temperature gradient that should have driven even larger mass flux, if not counteracted by the relative sluggishness of plating into the GB and the resulting back stress. This GB-containing ligament is quite robust and can adapt to varying drawing directions and velocities, imparting good controllability to the nanowire growth in a manner akin to Czochralski crystal growth.
Deciphering photocarrier dynamics for tuneable high-performance perovskite-organic semiconductor heterojunction phototransistors
Authors: Lin Yen-Hung , Huang Wentao , Pattanasattayavong Pichaya , Lim Jongchul , Li Ruipeng , Sakai Nobuya , Panidi Julianna , Hong Min Ji , Ma Chun , Wei Nini , Wehbe Nimer , Fei Zhuping , Heeney Martin , Labram John G. , Anthopoulos Thomas D. , Snaith Henry J.
Published: October 2019

Looking beyond energy harvesting, metal-halide perovskites offer great opportunities to revolutionise large-area photodetection technologies due to their high absorption coefficients, long diffusion lengths, low trap densities and simple processability. However, successful extraction of photocarriers from perovskites and their conversion to electrical signals remain challenging due to the interdependency of photogain and dark current density. Here we report hybrid hetero-phototransistors by integrating perovskites with organic semiconductor transistor channels to form either “straddling-gap” type-I or “staggered-gap” type-II heterojunctions. Our results show that gradual transforming from type-II to type-I heterojunctions leads to increasing and tuneable photoresponsivity with high photogain. Importantly, with a preferential edge-on molecular orientation, the type-I heterostructure results in efficient photocarrier cycling through the channel. Additionally, we propose the use of a photo-inverter circuitry to assess the phototransistors’ functionality and amplification. Our study provides important insights into photocarrier dynamics and can help realise advanced device designs with “on-demand” optoelectronic properties.
Longitudinal associations between ability in arts activities, behavioural difficulties and self-esteem: analyses from the 1970 British Cohort Study
Authors: Mak Hei Wan , Fancourt Daisy
Published: October 2019

Arts engagement has been shown to have benefits for young people’s psychological and behavioural adjustment. However, it is unknown whether it is frequency of arts engagement or individual ability in arts activities that is associated with these benefits. This study therefore examines the link between arts ability and children’s behavioural difficulties and self-esteem independent of frequency of engagement. We analysed data from the 1970 British Cohort Study with an overall sample size of 7700 for the behavioural difficulties outcome, and of 4991 for the self-esteem outcome. Baseline measures were taken when the children were aged 10 and followed up at age 16. OLS regression analysis adjusted for identified confounders shows that ability in the arts at age 10 was associated with a lower level of behavioural difficulties at age 16 independent of baseline behaviours, identified confounders and frequency of arts engagement. An association between arts ability and self-esteem was only found amongst children who have higher educational ability. These result suggest that there may be a value to encouraging the cultivation of arts skills at the onset of adolescence as a way of helping to foster children’s positive behavioural development.
Palladium Nanoparticles/Graphitic Carbon Nitride Nanosheets-Carbon Nanotubes as a Catalytic Amplification Platform for the Selective Determination of 17α-ethinylestradiol in Feedstuffs
Authors: Zheng Zhi xiang , Wang Mei , Shi Xue zhao , Wang Chun ming
Published: October 2019

A new kind of nanocomposite, graphitic carbon nitride (g-C3N4)-carbon nanotubes (CNTs), has been synthesized via solid grinding, and followed by thermal polymerization process of melamine and CNTs. Pd nanoparticles were loaded on the as-prepared nanocomposite by the self-assembly method. The Pd/g-C3N4-CNTs nanocomposite exhibited excellent electrocatalytic activity toward the oxidation of 17α-ethinylestradiol (EE2), and compared with other detection methods of EE2, such as HPLC, this detection platform does not need the samples for further purification processing. And this detection platform was compared with HPLC, there is no significant difference between two methods, and the accuracy and precision of the determination of EE2 in feedstuff sample by differential pulse voltammetry (DPV) to a satisfactory level. Thus, the Pd/g-C3N4-CNTs nanocomposite can be used as a signal amplification platform for the detection of EE2 in feedstuffs samples. Under the optimum condition, the current response increased linearly with EE2 concentration from 2.0 × 10−6 ~ 1.5 × 10−4M with a detection limit of 5.0 × 10−7M (S/N = 3) by DPV. The Pd/g-C3N4-CNTs showed good reproducibility and excellent anti-interference ability that the relative standard deviation was 3.3% (n = 5). This strategy may find widespread and promising applications in other sensing systems involving EE2.
Chemical proteomics reveals target selectivity of clinical Jak inhibitors in human primary cells
Authors: Eberl H. Christian , Werner Thilo , Reinhard Friedrich B. , Lehmann Stephanie , Thomson Douglas , Chen Peiling , Zhang Cunyu , Rau Christina , Muelbaier Marcel , Drewes Gerard , Drewry David , Bantscheff Marcus
Published: October 2019

Kinobeads are a set of promiscuous kinase inhibitors immobilized on sepharose beads for the comprehensive enrichment of endogenously expressed protein kinases from cell lines and tissues. These beads enable chemoproteomics profiling of kinase inhibitors of interest in dose-dependent competition studies in combination with quantitative mass spectrometry. We present improved bead matrices that capture more than 350 protein kinases and 15 lipid kinases from human cell lysates, respectively. A multiplexing strategy is suggested that enables determination of apparent dissociation constants in a single mass spectrometry experiment. Miniaturization of the procedure enabled determining the target selectivity of the clinical BCR-ABL inhibitor dasatinib in peripheral blood mononuclear cell (PBMC) lysates from individual donors. Profiling of a set of Jak kinase inhibitors revealed kinase off-targets from nearly all kinase families underpinning the need to profile kinase inhibitors against the kinome. Potently bound off-targets of clinical inhibitors suggest polypharmacology, e.g. through MRCK alpha and beta, which bind to decernotinib with nanomolar affinity.
Experimental demonstration of coherent superpositions in an ultrasonic pseudospin
Authors: Calderin Lazaro , Hasan M. Arif , Jenkins Neil G. , Lata Trevor , Lucas Pierre , Runge Keith , Deymier Pierre A.
Published: October 2019

We experimentally demonstrate the existence and control of coherent superpositions of elastic states in the direction of propagation of an ultrasonic pseudospin i.e., a φ-bit. The experimental realization of this mechanical pseudospin consists of an elastic aluminum rod serving as a waveguide sandwiched between two heavy steel plates. The Hertzian contact between the rod and the plates leads to restoring forces which couple the directions of propagation (forward and backward). This coupling generates the coherence of the superposition of elastic states. We also demonstrate φ-bit gate operations on the coherent superposition analogous to those used in quantum computing. In the case of a φ-bit, the coherent superposition of states in the direction of propagation are immune to wave function collapse upon measurement as they result from classical waves.
Effects of mulching on soil CO2 fluxes, hay yield and nutritional yield in a forage maize field in Northwest China
Authors: Fan Ming , Li Qiang , Zhang Enhe , Liu Qinglin , Wang Qi
Published: October 2019

In arid areas of China, water shortage and heavy carbon emissions have been threatening agricultural sustainability and which has become a vital issue. A field experiment was conducted to explore how different mulching affects soil moisture and temperature, CO2 fluxes, forage-maize hay yield and nutritional value during 2 consecutive years: 2014 and 2015. The field experiment showed that mulching materials had distinct effects on soil moisture and temperature and CO2 fluxes. The soil temperature and CO2 fluxes were in order of common plastic film mulching (PFM) > bio-degradable mulch mulching (BMM) > no mulching (CK) > straw mulching (SM), while the soil moisture was in order of PFM > BMM > SM > CK over these two years. Compared with CK, hay yield respectively increased by 23.25%, 22.51% and 5.27% for PFM, BMM and SM, WUE increased by 35.60%, 32.34% and 10.88%, and the total nutrient yields increased by 17.75%, 21.35% and 6.95%, respectively. To sum up, in combination with ecology and environmental protection, bio-degradable mulch could replace common plastic film and bio-degradable mulch should be popular in future. As bio-degradable mulch is green non-pollution, it is conducive to the sustainable development of agricultural ecosystem.
Influence of the distribution of fibrosis within an area of myocardial infarction on wave propagation in ventricular tissue
Authors: Liang Cuiping , Wang Kuanquan , Li Qince , Bai Jieyun , Zhang Henggui
Published: October 2019

The presence of fibrosis in heart tissue is strongly correlated with an incidence of arrhythmia, which is a leading cause of sudden cardiac death (SCD). However, it remains incompletely understood how different distributions, sizes and positions of fibrotic tissues contribute to arrhythmogenesis. In this study, we designed 4 different ventricular models mimicking wave propagation in cardiac tissues under normal, myocardial infarction (MI), MI with random fibrosis and MI with gradient fibrosis conditions. Simulation results of ideal square tissues indicate that vulnerable windows (VWs) of random and gradient fibrosis distributions are similar with low levels of fibrosis. However, with a high level of fibrosis, the VWs significantly increase in random fibrosis tissue but not in gradient fibrosis tissue. In addition, we systematically analyzed the effects of the size and position of fibrosis tissues on VWs. Simulation results show that it is more likely for a reentry wave to appear when the length of the infarcted area is greater than 25% of the perimeter of the ventricle, when the width is approximately half that of the ventricular wall, or when the infarcted area is attached to the inside or outside of the ventricular wall.
Prognostic Significance of Apparent Diffusion Coefficient in Hepatocellular Carcinoma Patients treated with Stereotactic Ablative Radiotherapy
Authors: Lo Cheng-Hsiang , Huang Wen-Yen , Hsiang Chih-Weim , Lee Meei-Shyuan , Lin Chun-Shu , Yang Jen-Fu , Hsu Hsian-He , Chang Wei-Chou
Published: October 2019

The role of diffusion-weighted magnetic resonance imaging (DW MRI) in assessing durable tumor control for patients with hepatocellular carcinoma (HCC) treated with stereotactic ablative radiotherapy (SABR) was not defined. This retrospective study included 34 HCC patients with 45 lesions who had DW MRI data at baseline and within 6 months post-SABR. On the first post-SABR MRI, 13 lesions (28.9%) had a complete response (CR), 12 (26.7%) had a partial response (PR), 17 (37.8%) had stable disease, and 3 (6.7%) had progressive disease by modified Response Evaluation Criteria in Solid Tumors (mRECIST). On subsequent imaging, the response rate improved from 55.6% to 75.6%. The apparent diffusion coefficients (ADCs) (mean ± standard deviation) pre- and post-SABR were 1.43 ± 0.28 and 1.72 ± 0.34 (×10−3 mm2/s), respectively (p < 0.001). An ADC change ≥25% (DW[+]) was identified as a predictor of favorable in-field control (IFC) (1-year IFC, 93.3% vs. 50.0% for DW[−], p = 0.004), but an mRECIST-based positive response (CR and PR) at the first MRI was not (p = 0.130). In conclusion, ADC change on early MRI is closely related to IFC in HCCs treated with SABR. Standardization of the DW MRI protocol, as well as prospective validation studies, are warranted.
Assessing trends of breast cancer and carcinoma in situ to monitor screening policies in developing settings
Authors: Brito Érika de Abreu Costa , Lima Marcela Sampaio , Siqueira Hianga Fayssa Fernandes , Marques Adriane Dórea , Moura Alex Rodrigues , Hora Evânia Curvelo , Lima Carlos Anselmo , Santos Marceli de Oliveira , de Souza Mirian Carvalho , da Silva Angela Maria , Brito Hugo Leite de Farias , Cipolotti Rosana
Published: October 2019

There have been arguments about the role of breast cancer screening at the population level, and some points of controversy have arisen, such the establishment of organized screening policies and the age at which to begin screening. The real benefit of screening has been questioned because the results of this practice may increase the diagnosis of indolent lesions without decreasing mortality due to breast cancer. The authors have proposed a study of incidence and mortality trends for breast cancer in a developing setting in Brazil to monitor the effectiveness of the official recommendations that prioritize the age group from 50 to 69 years. The database of the Cancer Registry and the Mortality Information System was used to calculate age-standardized and age-specific rates, which were then used to calculate incidence and mortality trends using the Joinpoint Regression Program. The results showed stability in trends across all ages and age-specific groups in both incidence and mortality. In conclusion, we found that incidence and mortality rates are compatible with those in regions with similar human development indexes, and trends have demonstrated stabilization. Thus, we do not endorse changes in the official recommendations to conduct screening for ages other than 50 to 69 years, nor should policy makers implement organized screening strategies.
Associations between Peripheral Thromboembolic Vascular Disease and Androgen Deprivation Therapy in Asian Prostate Cancer Patients
Authors: Lu Yu-Chuan , Huang Chao-Yuan , Yeh Huei-Ming , Hong Jian-Hua , Chang Chao-Hsiang , Muo Chih-Hsin , Chung Shiu-Dong , Yang Teng-Kai , Jaw Fu-Shan , Chung Chi-Jung
Published: October 2019

This study aimed to investigate the risks of thromboembolic vascular disease following androgen deprivation therapy (ADT) administered to prostate cancer (PCa) patients. A total of 24,464 men with newly diagnosed PCa during 2000–2008 were recruited through a longitudinal health insurance database in Taiwan. All PCa patients were stratified into two: ADT and non-ADT groups. Patients with ADT treatment were grouped into three: surgical castration, chemical castration, and anti-androgen alone. The risks of pulmonary embolism (PE), peripheral arterial occlusion disease (PAOD), and deep vein thrombosis (DVT) were assessed in multiple Cox proportional-hazards regression with time-dependent covariates. During the 12-year follow-up period, incidence rates per 1000 person-years in ADT and non-ADT groups were 2.87 and 1.62 for DVT, 1.00 and 0.52 for PE, and 1.03 and 0.70 for PAOD, respectively. The DVT and PE risks were significantly increased in patients receiving combined androgen blockade (CAB) compared with the counterpart ADT non-recipients. After adjusting for potential risk factors, PCa patients receiving CAB had the highest PE risk (HR = 3.11), followed by DVT risk (HR = 2.53). The DVT risk remained elevated throughout the entire duration of chemical castration. However, high PE risk was observed in patients with ≤720-day treatment duration. No association was found between ADT and PAOD risks. Overall, the risks of PE and DVT were considerably heightened in Asian men subjected to CAB for PCa, whereas PAOD risk was unrelated to such treatments.
RNA Sequencing revealed differentially expressed genes functionally associated with immunity and tumor suppression during latent phase infection of a vv + MDV in chickens
Authors: Dong Kunzhe , Chang Shuang , Xie Qingmei , Zhao Peng , Zhang Huanmin
Published: October 2019

Very virulent plus Marek’s disease (MD) virus (vv + MDV) induces tumors in relatively resistant lines of chickens and early mortality in highly susceptible lines of chickens. The vv + MDV also triggers a series of cellular responses in both types of chickens. We challenged birds sampled from a highly inbred chicken line (line 63) that is relatively resistant to MD and from another inbred line (line 72) that is highly susceptible to MD with a vv + MDV. RNA-sequencing analysis was performed with samples extracted from spleen tissues taken at 10-day and 21-day post infection (dpi). A total of 64 and 106 differentially expressed genes was identified in response to the vv + MDV challenge at latent phase in the resistant and susceptible lines of chickens, respectively. Direct comparisons between samples of the two lines identified 90 and 126 differentially expressed genes for control and MDV challenged groups, respectively. The differentially expressed gene profiles illustrated that intensive defense responses were significantly induced by vv + MDV at 10 dpi and 21 dpi but with slight changes in the resistant line. In contrast, vv + MDV induced a measurable suppression of gene expression associated with host defense at 10 dpi but followed by an apparent activation of the defense response at 21 dpi in the susceptible line of chickens. The observed difference in gene expression between the two genetic lines of chickens in response to MDV challenge during the latent phase provided a piece of indirect evidence that time points for MDV reactivation differ between the genetic lines of chickens with different levels of genetic resistance to MD. Early MDV reactivation might be necessary and potent to host defense system readiness for damage control of tumorigenesis and disease progression, which consequently results in measurable differences in phenotypic characteristics including early mortality (8 to 20 dpi) and tumor incidence between the resistant and susceptible lines of chickens. Combining differential gene expression patterns with reported GO function terms and quantitative trait loci, a total of 27 top genes was selected as highly promising candidate genes for genetic resistance to MD. These genes are functionally involved with virus process (F13A1 and HSP90AB1), immunity (ABCB1LB, RGS5, C10ORF58, OSF-2, MMP7, CXCL12, GAL1, GAL2, GAL7, HVCN1, PDE4D, IL4I1, PARP9, EOMES, MPEG1, PDK4, CCLI10, K60 and FST), and tumor suppression (ADAMTS2, LXN, ARRDC3, WNT7A, CLDN1 and HPGD). It is anticipated that these findings will facilitate advancement in the fundamental understanding on mechanisms of genetic resistance to MD. In addition, such advancement may also provide insights on tumor virus-induced tumorigenesis in general and help the research community recognize MD study may serve as a good model for oncology study involving tumor viruses.
Genome-wide association study and whole-genome sequencing identify a deletion in LRIT3 associated with canine congenital stationary night blindness
Authors: Das Rueben G. , Becker Doreen , Jagannathan Vidhya , Goldstein Orly , Santana Evelyn , Carlin Kendall , Sudharsan Raghavi , Leeb Tosso , Nishizawa Yuji , Kondo Mineo , Aguirre Gustavo D. , Miyadera Keiko
Published: October 2019

Congenital stationary night blindness (CSNB), in the complete form, is caused by dysfunctions in ON-bipolar cells (ON-BCs) which are secondary neurons of the retina. We describe the first disease causative variant associated with CSNB in the dog. A genome-wide association study using 12 cases and 11 controls from a research colony determined a 4.6 Mb locus on canine chromosome 32. Subsequent whole-genome sequencing identified a 1 bp deletion in LRIT3 segregating with CSNB. The canine mutant LRIT3 gives rise to a truncated protein with unaltered subcellular expression in vitro. Genetic variants in LRIT3 have been associated with CSNB in patients although there is limited evidence regarding its apparently critical function in the mGluR6 pathway in ON-BCs. We determine that in the canine CSNB retina, the mutant LRIT3 is correctly localized to the region correlating with the ON-BC dendritic tips, albeit with reduced immunolabelling. The LRIT3-CSNB canine model has direct translational potential enabling studies to help understand the CSNB pathogenesis as well as to develop new therapies targeting the secondary neurons of the retina.
Validation of a Miniaturized Permeability Assay Compatible with CRISPR-Mediated Genome-Wide Screen
Authors: Simonneau Claire , Yang Junning , Kong Xianguo , Kilker Robert , Edelstein Leonard , Fortina Paolo , Londin Eric , Horowitz Arie
Published: October 2019

The impermeability of the luminal endothelial cell monolayer is crucial for the normal performance of the vascular and lymphatic systems. A key to this function is the integrity of the monolayer’s intercellular junctions. The known repertoire of junction-regulating genes is incomplete. Current permeability assays are incompatible with high-throughput genome-wide screens that could identify these genes. To overcome these limitations, we designed a new permeability assay that consists of cell monolayers grown on ~150 μm microcarriers (MCs). Each MC functions as a miniature individual assay of permeability (MAP). We demonstrate that false-positive results can be minimized, and that MAP sensitivity to thrombin-induced increase in monolayer permeability is similar to the sensitivity of impedance measurement. We validated the assay by showing that the expression of single guide RNAs (sgRNAs) that target genes encoding known thrombin signaling proteins blocks effectively thrombin-induced junction disassembly, and that MAPs carrying such cells can be separated effectively by fluorescence-assisted sorting from those that carry cells expressing non-targeting sgRNAs. These results indicate that MAPs are suitable for high-throughput experimentation and for genome-wide screens for genes that mediate the disruptive effect of thrombin on endothelial cell junctions.
Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group
Authors: Semple Catlin , Choi Ka-Yee Grace , Kroeker Andrea , Denechezhe Lizette , Orr Pamela , Mookherjee Neeloffer , Larcombe Linda
Published: October 2019

Canadian Indigenous peoples (First Nations and Inuit) exhibit a high burden of infectious diseases including tuberculosis influenced by societal factors, and biological determinants. Toll-like receptor (TLR)-mediated innate immune responses are the first line of defence against infections. We examined the production of a panel of 30 cytokines in peripheral blood-derived mononuclear cells (PBMC) isolated from Indigenous and non-Indigenous participants, following stimulation with five different TLR ligands. The levels of TLR-induced pro-inflammatory cytokines such as IL-12/23p40, IL-16, and IFN-γ, and chemokines (MCP-4, MDC and eotaxin) were different between Indigenous compared to non-Indigenous participants. Antimicrobial cationic host defence peptides (CHDP) induced by TLR activation are critical for resolution of infections and modulate the TLR-to-NFκB pathway to alter downstream cytokine responses. Therefore, we examined the expression of human CHDP defensins and cathelicidin in PBMC. mRNA expression of genes encoding fordef-A1anddef-B1were significantly higher following stimulation with TLR ligands in Indigenous compared to non-Indigenous participants. The purinergic receptor P2X7 known to be activated by ATP released following TLR stimulation, is a receptor for CHDP. Therefore, we further examined single nucleotide polymorphisms (SNP) in P2X7. Indigenous participants had a significantly higher percentage of a P2X7 SNP which is associated with reduced function and lower ability to clear infections. These results suggest that a higher frequency of non-functional P2X7 receptors may influence the activity of downstream immune mediators required for resolution of infections such as pro-inflammatory cytokines and CHDP defensins, thus contributing to higher burden of infections in Indigenous population.
The complete chloroplast genome of Stryphnodendron adstringens (Leguminosae - Caesalpinioideae): comparative analysis with related Mimosoid species
Authors: Souza Ueric José Borges de , Nunes Rhewter , Targueta Cíntia Pelegrineti , Diniz-Filho José Alexandre Felizola , Telles Mariana Pires de Campos
Published: October 2019

Stryphnodendron adstringensis a medicinal plant belonging to the Leguminosae family, and it is commonly found in the southeastern savannas, endemic to the Cerrado biome. The goal of this study was to assemble and annotate the chloroplast genome ofS. adstringensand to compare it with previously known genomes of the mimosoid clade within Leguminosae. The chloroplast genome was reconstructed usingde novoand referenced-based assembly of paired-end reads generated by shotgun sequencing of total genomic DNA. The size of theS. adstringenschloroplast genome was 162,169 bp. This genome included a large single-copy (LSC) region of 91,045 bp, a small single-copy (SSC) region of 19,014 bp and a pair of inverted repeats (IRa and IRb) of 26,055 bp each. TheS. adstringenschloroplast genome contains a total of 111 functional genes, including 77 protein-coding genes, 30 transfer RNA genes, and 4 ribosomal RNA genes. A total of 137 SSRs and 42 repeat structures were identified inS. adstringenschloroplast genome, with the highest proportion in the LSC region. A comparison of theS. adstringenschloroplast genome with those from other mimosoid species indicated that gene content and synteny are highly conserved in the clade. The phylogenetic reconstruction using 73 conserved coding-protein genes from 19 Leguminosae species was supported to be paraphyletic. Furthermore, the noncoding and coding regions with high nucleotide diversity may supply valuable markers for molecular evolutionary and phylogenetic studies at different taxonomic levels in this group.