Hybrid Causal Feature Selection for Cancer Biomarker Identification from RNA-seq Data.

The discovery of cancer biomarkers helps to advance medical diagnosis and plays an important role in biomedical applications. Most of the existing data-driven methods identify biomarkers by ranking-based strategies, which generally return a subset or superset of the actual biomarkers, while some other causal-wise feature selection methods are based on Markov Blanket (MB) learning, facing the challenges of high-dimensionality & low-sample. In this work, we propose a novel hybrid causal feature selection method (called CAFES) to support large-scale cancer biomarker discovery from real RNA-seq data. Concretely, CAFES first uses minimal-redundancy & maximal-relevance strategy for dimensionality reduction that returns a set of candidate features. CAFES then learns the causal skeleton w.r.t. those features by CI tests and further obtains an appropriate superset of the MB of the target variable. Finally, CAFES learns the causal structure of this superset by the DAG-GNN algorithm and then obtains the MB of the target variable, which can be treated as the cancer biomarkers. We conduct experiments to evaluate the proposed method on two real well-known RNA-seq datasets that covering both binary and multi-class cases. We compare our method CAFES with seven recent methods including Semi-HITON-MB, STMB, BAMB, FBED, LCS-FS, EEMB, and EAMB. The results show that CAFES can identify dozens of cancer biomarkers, and 1/6  âˆ¼ 1/2 of the discovered biomarkers can be verified by existing works that they are really directly related to the corresponding disease. An advantage of CAFES is that its Recall is significantly higher than those of all the counterparts, indicating that the continuous optimization (DAG-GNN) with the returned causal skeleton after feature selection (that can be treated as a conditional independence-based constraint to the optimization problem) is effective in cancer biomarkers identification under high-dimensional and low-sample RNA-seq data. The source code of CAFES is available at https://github.com/Milkteaww/CFS.

Field Evaluation of Experimental Maize Hybrids for Resistance to the Fall Armyworm (Lepidoptera: Noctuidae) in a Warm Temperate Climate.

The polyphagous fall armyworm (FAW), Spodoptera frugiperda, has become an invasive pest worldwide in recent years. To develop maize germplasm with multiple pest resistance and understand genetic inheritance, 12 experimental hybrids (six pairs of reciprocal crosses) with diverse genetic backgrounds and four commercial checks were examined for FAW resistance in 2013 and 2014. The experiment utilized a randomized complete block design with four replications as the block factor. FAW injury on maize plants was assessed at 7 and 14 d after the artificial infestation at the V6 stage, and predatory arthropod taxa and abundance on maize seedlings were recorded 7 d after the infestation. Spodoptera frugiperda resistance varied significantly among the 16 hybrids. Two reciprocal crosses ('FAW1430' × 'Oh43' and 'CML333' × 'NC358') showed the least FAW injury. Eleven arthropod predators [i.e., six coleopterans, three hemipterans, earwigs (dermapterans), and spiders (or arachnids)] were also recorded; the two most common predators were the pink spotted ladybeetle, Coleomegilla maculata, and the insidious flower (or minute pirate) bug, Orius spp. Predator abundance was not correlated to FAW injury but varied greatly between 2013 and 2014. Principal component analysis demonstrated that, when compared with FAW resistant (or Bt-transgenic) checks ('DKC69-71', 'DKC67-88', and 'P31P42'), five pairs of the reciprocal crosses had moderate FAW resistance, whereas a pair of reciprocal crosses ('NC350' × 'NC358' and NC358 × NC350) showed the same FAW susceptibility as the non-Bt susceptible check 'DKC69-72'. Both parents contributed similarly to FAW resistance, or no maternal/cytoplasmic effect was detected in the experimental hybrids.

A North Atlantic synthetic tropical cyclone track, intensity, and rainfall dataset.

Tropical Cyclones (TCs) cause significant socio-economic damages to the US and Caribbean coastal regions annually, making it important to understand TC risk at the local-to-regional scales. However, the short length of the observed record and the substantial computational expense associated with high-resolution climate models make it difficult to assess TC risk using either approach. To overcome these challenges, we developed a database of synthetic TCs using the Risk Analysis Framework for Tropical Cyclones (RAFT). The database includes 40,000 synthetic TC tracks, along-track intensities and storm-induced precipitation. TC tracks generated in RAFT are in reasonable agreement with the observed spatial distribution of TC tracks and basin-scale TC statistics. Specifically along the coast, spatial variations in TC crossing probability and extreme winds upon landfall are well-reproduced by RAFT with R-squared values of 0.81 and 0.73, respectively. In summary, the synthetic TC database constructed with RAFT provides a reasonable pathway for the robust assessment of North Atlantic TC wind and rainfall risks.

2020-2021 field seasons of Maize GxE project within the Genomes to Fields Initiative.

OBJECTIVES: This release note describes the Maize GxE project datasets within the Genomes to Fields (G2F) Initiative. The Maize GxE project aims to understand genotype by environment (GxE) interactions and use the information collected to improve resource allocation efficiency and increase genotype predictability and stability, particularly in scenarios of variable environmental patterns. Hybrids and inbreds are evaluated across multiple environments and phenotypic, genotypic, environmental, and metadata information are made publicly available. DATA DESCRIPTION: The datasets include phenotypic data of the hybrids and inbreds evaluated in 30 locations across the US and one location in Germany in 2020 and 2021, soil and climatic measurements and metadata information for all environments (combination of year and location), ReadMe, and description files for each data type. A set of common hybrids is present in each environment to connect with previous evaluations. Each environment had a collaborator responsible for collecting and submitting the data, the GxE coordination team combined all the collected information and removed obvious erroneous data. Collaborators received the combined data to use, verify and declare that the data generated in their own environments was accurate. Combined data is released to the public with minimal filtering to maintain fidelity to the original data.

Genomes to Fields 2022 Maize genotype by Environment Prediction Competition.

OBJECTIVES: The Genomes to Fields (G2F) 2022 Maize Genotype by Environment (GxE) Prediction Competition aimed to develop models for predicting grain yield for the 2022 Maize GxE project field trials, leveraging the datasets previously generated by this project and other publicly available data. DATA DESCRIPTION: This resource used data from the Maize GxE project within the G2F Initiative [1]. The dataset included phenotypic and genotypic data of the hybrids evaluated in 45 locations from 2014 to 2022. Also, soil, weather, environmental covariates data and metadata information for all environments (combination of year and location). Competitors also had access to ReadMe files which described all the files provided. The Maize GxE is a collaborative project and all the data generated becomes publicly available [2]. The dataset used in the 2022 Prediction Competition was curated and lightly filtered for quality and to ensure naming uniformity across years.

Magnesium lithospermate B ameliorates diabetic nephropathy by suppressing the uremic toxin formation mediated by gut microbiota.

Diabetic nephropathy (DN) is a major cause of renal failure and urgently necessitates new therapeutic strategies. Magnesium lithospermate B (MLB) showed a good protective effect on kidney injure by oral administration, despite its extremely low bioavailability. The current study aimed to investigate its gut microbiota-targeted mechanism to explain the paradoxical properties of pharmacodynamics and pharmacokinetics. Here we show that MLB alleviated DN by recovering the dysfunction of gut microbiota and their associated metabolites in colon content, such as short-chain fatty acids and amino acids. Moreover, MLB significantly decreased uremic toxin levels in plasma, especially the p-cresyl sulfate. We further discovered that MLB could affect the metabolism of p-cresyl sulfate by suppressing the formation of its intestinal precursors, i.e. the microbiota-mediated conversion from 4-hydroxyphenylacetate to p-cresol. In addition, the inhibition effects of MLB were confirmed. MLB and its metabolite danshensu exhibited inhibitory effects on p-cresol formation mediated by three strains belonging to the genus Clostridium, Bifidobacterium, and Fusobacterium, respectively. Meanwhile, MLB decreased the levels of p-cresyl sulfate in plasma and p-cresol in feces caused by rectal administration of tyrosine in mice. To summarize, the results indicated that MLB ameliorated DN through modulating gut microbiota-associated p-cresyl sulfate metabolism. Together, this study provides new insights on the microbiota-targeted mechanism of MLB in intervening DN and a new strategy in lowering plasma uremic toxins by blocking the formation of their precursors in intestine.

2018-2019 field seasons of the Maize Genomes to Fields (G2F) G x E project.

OBJECTIVES: This report provides information about the public release of the 2018-2019 Maize G X E project of the Genomes to Fields (G2F) Initiative datasets. G2F is an umbrella initiative that evaluates maize hybrids and inbred lines across multiple environments and makes available phenotypic, genotypic, environmental, and metadata information. The initiative understands the necessity to characterize and deploy public sources of genetic diversity to face the challenges for more sustainable agriculture in the context of variable environmental conditions. DATA DESCRIPTION: Datasets include phenotypic, climatic, and soil measurements, metadata information, and inbred genotypic information for each combination of location and year. Collaborators in the G2F initiative collected data for each location and year; members of the group responsible for coordination and data processing combined all the collected information and removed obvious erroneous data. The collaborators received the data before the DOI release to verify and declare that the data generated in their own locations was accurate. ReadMe and description files are available for each dataset. Previous years of evaluation are already publicly available, with common hybrids present to connect across all locations and years evaluated since this project's inception.

Superior Large-Signal Piezoelectric Coefficient in Textured NBT-Based Piezoceramics by Template-Induced Structure and Composition Modulation.

The field-induced-phase transition in (Na1/2Bi1/2)TiO3-based lead-free piezoceramics can be facilitated in the ⟨001⟩-crystallographic orientation, and the templated grain growth is an effective method to align polycrystalline ceramics along with specific directions. However, due to the low texturing degree and undesirable composite effect of the added templates, the textured ceramics using the templated grain growth (TGG) method usually require a higher driving field to trigger the phase transition instead. Here, ⟨001⟩-textured (Na0.5Bi0.5)0.935Ba0.065Ti0.978(Fe0.5Nb0.5)0.022O3 ceramics are prepared through a liquid-phase-assisted TGG process at a low sintering temperature (1000 °C), in which the NaNbO3 (NN) templates induce a strong crystallographic anisotropic structure (a high Lotgering factor of 95%) while dissolving into oriented grains. The dissolution of templates acts as a composition doping and contributes to reducing the driving electric field as proven by the phase-field simulation analysis. Furthermore, electrical and structural characterizations reveal that an increased ionic disorder occurs in the textured ceramic, causing highly dynamic polar nanoregions and a larger reversible phase transition. Thanks to the appropriate structure/composition control, the textured ceramic achieves a large d33* value of 907 pm/V at 40 kV/cm. The high-performance lead-free ceramic under low driving electric field benefits the development of multilayer piezoelectric actuators.

Increased U.S. coastal hurricane risk under climate change.

Several pathways for how climate change may influence the U.S. coastal hurricane risk have been proposed, but the physical mechanisms and possible connections between various pathways remain unclear. Here, future projections of hurricane activity (1980-2100), downscaled from multiple climate models using a synthetic hurricane model, show an enhanced hurricane frequency for the Gulf and lower East coast regions. The increase in coastal hurricane frequency is driven primarily by changes in steering flow, which can be attributed to the development of an upper-level cyclonic circulation over the western Atlantic. The latter is part of the baroclinic stationary Rossby waves forced mainly by increased diabatic heating in the eastern tropical Pacific, a robust signal across the multimodel ensemble. Last, these heating changes also play a key role in decreasing wind shear near the U.S. coast, further aggravating coastal hurricane risk enhanced by the physically connected steering flow changes.

Strain-dependent elastography of cancer cells reveals heterogeneity and stiffening due to attachment.

Because cells vary in thickness and in biomechanical properties, the use of a constant force trigger during atomic force microscopy (AFM) stiffness mapping produces a varied nominal strain that can obfuscate the comparison of local material properties. In this study, we measured the biomechanical spatial heterogeneity of ovarian and breast cancer cells by using an indentation-dependent pointwise Hertzian method. Force curves and surface topography were used together to determine cell stiffness as a function of nominal strain. By recording stiffness at a particular strain, it may be possible to improve comparison of the material properties of cells and produce higher contrast representations of cell mechanical properties. Defining a linear region of elasticity that corresponds to a modest nominal strain, we were able to clearly distinguish the mechanics of the perinuclear region of cells. We observed that, relative to the lamelopodial stiffness, the perinuclear region was softer for metastatic cancer cells than their nonmetastatic counterparts. Moreover, contrast in the strain-dependent elastography in comparison to conventional force mapping with Hertzian model analysis revealed a significant stiffening phenomenon in the thin lamellipodial region in which the modulus scales inversely and exponentially with cell thickness. The observed exponential stiffening is not affected by relaxation of cytoskeletal tension, but finite element modeling indicates it is affected by substrate adhesion. The novel cell mapping technique explores cancer cell mechanical nonlinearity that results from regional heterogeneity, which could help explain how metastatic cancer cells can show soft phenotypes while simultaneously increasing force generation and invasiveness.

Intake, growth performance, carcass traits, and meat quality of feedlot lambs fed novel anthocyanin-rich corn cobs.

Feeding anthocyanin- and antioxidant-rich forages to sheep and dairy cows can improve performance and product quality. The objective of this study was to evaluate the impact of feeding anthocyanin-rich (Hi-A) corn cobs on the growth performance and meat quality of lambs. A total of 30 eight-month-old Rambouillet ewe lambs (body weight 30.7 ± 1.2 kg) were fed for 63 days with three diets consisting of 80% concentrate and 20% roughage: Hi-A corn cobs (Hi-A), regular corn cobs (Low-A), and bermudagrass hay (BGH). A completely randomized design trial with 10 lambs per treatment was used. Data were collected on dry matter intake (DMI), body weight (BW), average daily gain (ADG), gain:feed ratio (G:F), carcass traits, meat color, fatty acid (FA) profile, volatile aroma compounds, and sensory panels. After feeding for 63 days, lambs were harvested, and the carcasses were evaluated. Boneless lamb loin chops were fabricated and submitted to FA, aroma, and sensory analysis. The corn cob diets did not affect BW, ADG, or G:F of the lambs compared to BGH diet, but DMI (P < 0.01) was decreased. The dressing percentage was greater (P < 0.05) in lambs fed BGH than in those fed Hi-A, while lambs fed Low-A did not differ from the other two diets. Loin chop instrumental color characteristics were not influenced by diets, except the hue angle, which was greater (P < 0.05) in lambs fed Hi-A than Low-A, while BGH did not differ from lambs fed either cob diet. There was no significant difference in the meat fatty acid profile. Five volatile compounds were affected by diets. The 2-butanone (P = 0.07) and 2,3-butanedione (P = 0.05) were greater in chops from lambs fed BGH relative to lambs fed Hi-A and neither differed (P > 0.05) from lambs fed Low-A diet. The 2-propanone was greater (P = 0.01) in chops from lambs fed BGH than in those fed either the Low-A or Hi-A diets. Both 3-methyl-butanal and methyl benzene were lower (P = 0.01 and P = 0.02, respectively) in chops from lambs fed the Hi-A diet than in those fed either the BGH or Low-A diet. Replacing 20% bermudagrass hay with corn cobs in the diets of feedlot lambs did not affect sheep growth performance, meat fatty acid profile, sensory traits, and most carcass characteristics and meat color parameters. Hi-A corn diet improved aroma in cooked boneless loin chops, but sensory traits were not affected. This study showed the Hi-A corn cobs can be safely used for roughage and feed for lambs and for improving meat aroma in cooked boneless loin chops.

Environment-specific selection alters flowering-time plasticity and results in pervasive pleiotropic responses in maize.

Crop genetic diversity for climate adaptations is globally partitioned. We performed experimental evolution in maize to understand the response to selection and how plant germplasm can be moved across geographical zones. Initialized with a common population of tropical origin, artificial selection on flowering time was performed for two generations at eight field sites spanning 25° latitude, a 2800 km transect. We then jointly tested all selection lineages across the original sites of selection, for the target trait and 23 other traits. Modeling intergenerational shifts in a physiological reaction norm revealed separate components for flowering-time plasticity. Generalized and local modes of selection altered the plasticity of each lineage, leading to a latitudinal pattern in the responses to selection that were strongly driven by photoperiod. This transformation led to widespread changes in developmental, architectural, and yield traits, expressed collectively in an environment-dependent manner. Furthermore, selection for flowering time alone alleviated a maladaptive syndrome and improved yields for tropical maize in the temperate zone. Our findings show how phenotypic selection can rapidly shift the flowering phenology and plasticity of maize. They also demonstrate that selecting crops to local conditions can accelerate adaptation to climate change.

Acute transient thyroid swelling after fine-needle aspiration biopsy: A case report of a rare complication and a literature review.

Fine-needle aspiration biopsy (FNAB) is a safe and effective thyroid examination method with rare complications. Herein, we report a rare case of acute transient thyroid swelling that occurred after ultrasound-guided FNAB. The patient experienced acute pain with rapid thyroid swelling. Ultrasound imaging revealed a nodule with a linear, hypoechoic, and "patch-like" appearance, indicating edema without hemorrhage. After receiving anti-anaphylaxis and detumescence therapy for 1 day, the swelling regressed. Acute transient thyroid swelling is an extremely rare event that occurs shortly after FNAB and may frighten patients; therefore, clinicians should be aware of this complication in this context.

Accurate prediction of complex traits for individuals and offspring from parents using a simple, rapid, and efficient method for gene-based breeding in cotton and maize.

Accurate, simple, rapid, and inexpensive prediction of complex traits controlled by numerous genes is paramount to enhanced plant breeding, animal breeding, and human medicine. Here we report a novel method that enables accurate, simple, and rapid prediction of complex traits of individuals or offspring from parents based on the number of favorable alleles (NFAs) of the genes controlling the objective traits. The NFAs of 226 cotton fiber length (GFL) genes and nine maize hybrid grain yield related (ZmF1GY) genes were directly used to predict cotton fiber lengths of individual plants and maize grain yields of F1 hybrids from parents, respectively, using prediction model-based methods as controls. The NFAs of the 226 GFL genes predicted cotton fiber lengths at an accuracy of 0.85, as the model methods and outperforming genomic prediction by 82 % - 170 %. The NFAs of the nine ZmF1GY genes predicted grain yields of maize hybrids from parents at an accuracy of 0.80, outperforming genomic prediction by 67 %. Moreover, the prediction accuracies of these traits were consistent across years, environments, and eco-agricultural systems. Importantly, the accurate prediction of these traits directly using the NFAs of the genes allows breeding to be performed in greenhouse, phytotron, or off-season, without the need of the model training and validation steps essential and costly for model-based genomic or genic prediction. Therefore, this new method dramatically outperforms the current model-based genomic methods used for phenotype prediction and streamlines the process of breeding, thus promising to substantially enhance current plant and animal breeding.

Validation and Application of a Low-Cost Sorting Device for Fumonisin Reduction in Maize.

Fumonisin mycotoxins are a persistent challenge to human and livestock health in tropical and sub-tropical maize cropping systems, and more efficient methods are needed to reduce their presence in food systems. We constructed a novel, low-cost device for sorting grain, the "DropSort", and tested its effectiveness on both plastic kernel models and fumonisin-contaminated maize. Sorting plastic kernels of known size and shape enabled us to optimize the sorting performance of the DropSort. The device sorted maize into three distinct fractions as measured by bulk density and 100-kernel weight. The level of fumonisin was lower in the heaviest fractions of maize compared to the unsorted samples. Based on correlations among fumonisin and bulk characteristics of each fraction, we found that light fraction 100-kernel weight could be an inexpensive proxy for unsorted fumonisin concentration. Single kernel analysis revealed significant relationships among kernel fumonisin content and physical characteristics that could prove useful for future sorting efforts. The availability of a low-cost device (materials~USD 300) that can be used to reduce fumonisin in maize could improve food safety in resource-limited contexts in which fumonisin contamination remains a pressing challenge.

[Retracted] In vitro and in vivo anticancer effects of marmesin in U937 human leukemia cells are mediated via mitochondrial­mediated apoptosis, cell cycle arrest, and inhibition of cancer cell migration.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that a pair of tumors in Fig. 10 appeared to have been duplicated, although one of the tumors appeared at a larger size in the figure relative to the first one. Furthermore, the flow cytometric plots shown in Fig. 2B in the above paper appeared to be remarkably similar to data presented in a paper published in Phytomedicine [Sui C­G, Meng F­D and Jiang Y­H: Antiproliferative activity of rosamultic acid is associated with induction of apoptosis, cell cycle arrest, inhibition of cell migration and caspase activation in human gastric cancer (SGC­7901) cells. Phyomedicine 22: 796­806, 2015]. After having conducted an independent investigation in the Editorial Office, the Editor of Oncology Reports has determined that the above paper should be retracted from the Journal on account of a lack of confidence concerning the originality and the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received any reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [the original article was published in Oncology Reports 39: 597­602, 2018; DOI: 10.3892/or.2017.6147].

The importance of dominance and genotype-by-environment interactions on grain yield variation in a large-scale public cooperative maize experiment.

High-dimensional and high-throughput genomic, field performance, and environmental data are becoming increasingly available to crop breeding programs, and their integration can facilitate genomic prediction within and across environments and provide insights into the genetic architecture of complex traits and the nature of genotype-by-environment interactions. To partition trait variation into additive and dominance (main effect) genetic and corresponding genetic-by-environment variances, and to identify specific environmental factors that influence genotype-by-environment interactions, we curated and analyzed genotypic and phenotypic data on 1918 maize (Zea mays L.) hybrids and environmental data from 65 testing environments. For grain yield, dominance variance was similar in magnitude to additive variance, and genetic-by-environment variances were more important than genetic main effect variances. Models involving both additive and dominance relationships best fit the data and modeling unique genetic covariances among all environments provided the best characterization of the genotype-by-environment interaction patterns. Similarity of relative hybrid performance among environments was modeled as a function of underlying weather variables, permitting identification of weather covariates driving correlations of genetic effects across environments. The resulting models can be used for genomic prediction of mean hybrid performance across populations of environments tested or for environment-specific predictions. These results can also guide efforts to incorporate high-throughput environmental data into genomic prediction models and predict values in new environments characterized with the same environmental characteristics.

A phase II randomized trial of sodium oligomannate in Alzheimer's dementia.

BACKGROUND: Sodium oligomannate (GV-971), a marine-derived oligosaccharide, is a novel agent that may improve cognition in AD patients. METHODS: The 24-week multicenter, randomized, double-blind, placebo parallel controlled clinical trial was conducted in AD in China between 24 October 2011 and 10 July 2013. The study included a 4-week screening/washout period, followed by a 24-week treatment period. Patients were randomized in a 1:1:1 ratio to receive GV-971 900 mg, 600 mg, or placebo capsule in treatment period, respectively. The primary outcome was cognitive improvement as assessed by changes in Alzheimer's Disease Assessment Scale-cognitive subscale 12-item (ADAS-cog12) scores from baseline to week 24. The secondary efficacy outcomes included CIBIC-Plus, ADCS-ADL, and NPI at 24 weeks after treatment compared with baseline. A subgroup study was assessment of the change in cerebral glucose metabolism by fluorodeoxyglucose positron emission tomography measurements. RESULTS: Comparing with the placebo group (n = 83, change - 1.45), the ADAS-cog12 score change in the GV-971 600-mg group (n = 76) was - 1.39 (p = 0.89) and the GV-971 900-mg group (n = 83) was - 2.58 (p = 0.30). The treatment responders according to CIBIC-Plus assessment were significantly higher in the GV-971 900-mg group than the placebo group (92.77% vs. 79.52%, p < 0.05). The GV-971 900-mg subgroup showed a lower decline of cerebral metabolic rate for glucose than the placebo subgroup at the left precuneus, right posterior cingulate, bilateral hippocampus, and bilateral inferior orbital frontal at uncorrected p = 0.05. The respective rates of treatment-related AEs were 5.9%, 14.3%, and 3.5%. CONCLUSIONS: GV-971 was safe and well tolerated. GV-971 900 mg was chosen for phase III clinical study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01453569 . Registered on October 18, 2011.