Miracle-dz/UniFAR-FTUs huggingface dataset:
The population cost-effectiveness of delivering universal and indicated school-based interventions to prevent the onset of major depression among youth in Australia

Aims. School-based psychological interventions encompass: universal interventions targeting youth in the general population; and indicated interventions targeting youth with subthreshold depression. This study aimed to: (1) examine the population cost-effectiveness of delivering universal and indicated prevention interventions to youth in the population aged 11–17 years via primary and secondary schools in Australia; and (2) compare the comparative cost-effectiveness of delivering these interventions using face-to-face and internet-based delivery mechanisms. Methods. We reviewed literature on the prevention of depression to identify all interventions targeting youth that would be suitable for implementation in Australia and had evidence of efficacy to support analysis. From this, we found evidence of effectiveness for the following intervention types: universal prevention involving group-based psychological interventions delivered to all participating school students; and indicated prevention involving group-based psychological interventions delivered to students with subthreshold depression. We constructed a Markov model to assess the cost-effectiveness of delivering universal and indicated interventions in the population relative to a ‘no intervention’ comparator over a 10-year time horizon. A disease model was used to simulate epidemiological transitions between three health states (i.e., healthy, diseased and dead). Intervention effect sizes were based on meta-analyses of randomised control trial data identified in the aforementioned review; while health benefits were measured as Disability-adjusted Life Years (DALYs) averted attributable to reductions in depression incidence. Net costs of delivering interventions were calculated using relevant Australian data. Uncertainty and sensitivity analyses were conducted to test model assumptions. Incremental cost-effectiveness ratios (ICERs) were measured in 2013 Australian dollars per DALY averted; with costs and benefits discounted at 3%. Results. Universal and indicated psychological interventions delivered through face-to-face modalities had ICERs below a threshold of $50 000 per DALY averted. That is, $7350 per DALY averted (95% uncertainty interval (UI): dominates – 23 070) for universal prevention, and $19 550 per DALY averted (95% UI: 3081–56 713) for indicated prevention. Baseline ICERs were generally robust to changes in model assumptions. We conducted a sensitivity analysis which found that internet-delivered prevention interventions were highly cost-effective when assuming intervention effect sizes of 100 and 50% relative to effect sizes observed for face-to-face delivered interventions. These results should, however, be interpreted with caution due to the paucity of data. Conclusions. School-based psychological interventions appear to be cost-effective. However, realising efficiency gains in the population is ultimately dependent on ensuring successful system-level implementation.
Ultrasonic nebulisation extraction: extraction column coupled with liquid phase microextraction for analysis of the volatile organic compounds in Foeniculum vulgare Mill. as a model.

INTRODUCTION As the concentrations of the volatile organic compounds are always low and their matrix is complex, it is necessary to pre-concentrate the volatile organic compounds before analysis. Ultrasonic nebulisation extraction with a self-made extraction column coupled with liquid phase microextraction is developed for the extraction of active constituents from spices. OBJECTIVE To develop an environmentally compatible extraction technique for the preparation and analysis of the volatile organic compounds from spices. METHOD The sample is placed into the nebulisation vessel of a nebulisation humidifier and a purging gas is blown through the vessel continuously. When the nebuliser is switched on, a ultrasonic fountain is formed by ultrasonic vibration and the target analytes are transferred from the sample solution to the vapour phase and then concentrated on the extraction solvent in the extraction column. After extraction for 3 min and allowed to stand upright for 5 min, the extract is analysed by GC and GC-MS. Different methods of comparison can then be carried out. RESULTS Optimum conditions were found to be: 30 μL of n-tetradecane as the extraction solvent, a flow rate for the purging gas of 40 mL/min, a purging time of 3 min and a standing time was 5 min. The contents of constituents in the extract obtained by the proposed method were close to those obtained by hydrodistillation (HD). Moreover, the proposed method achieves higher enrichment efficiency. CONCLUSION A method was developed for the extraction of volatile organic compounds from spices. The study has shown that it is a fast and environmentally sustainable technique.
Pycellerator: an arrow-based reaction-like modelling language for biological simulations

MOTIVATION We introduce Pycellerator, a Python library for reading Cellerator arrow notation from standard text files, conversion to differential equations, generating stand-alone Python solvers, and optionally running and plotting the solutions. All of the original Cellerator arrows, which represent reactions ranging from mass action, Michales-Menten-Henri (MMH) and Gene-Regulation (GRN) to Monod-Wyman-Changeaux (MWC), user defined reactions and enzymatic expansions (KMech), were previously represented with the Mathematica extended character set. These are now typed as reaction-like commands in ASCII text files that are read by Pycellerator, which includes a Python command line interface (CLI), a Python application programming interface (API) and an iPython notebook interface. RESULTS Cellerator reaction arrows are now input in text files. The arrows are parsed by Pycellerator and translated into differential equations in Python, and Python code is automatically generated to solve the system. Time courses are produced by executing the auto-generated Python code. Users have full freedom to modify the solver and utilize the complete set of standard Python tools. The new libraries are completely independent of the old Cellerator software and do not require Mathematica. AVAILABILITY AND IMPLEMENTATION All software is available (GPL) from the github repository at https://github.com/biomathman/pycellerator/releases. Details, including installation instructions and a glossary of acronyms and terms, are given in the Supplementary information.
RVFam: an R package for rare variant association analysis with family data

UNLABELLED Family-based designs offer unique advantage for identifying rare risk variants in genetic association studies. There are existing tools for analyzing rare variants in families but lacking components to handle binary traits properly and survival traits. In this report, we introduce an R software package RVFam (Rare Variant association analysis with Family data) designed to analyze continuous, binary and survival traits against rare and common sequencing variants in genome-wide association studies (GWAS) involving family data. Single and multiple variant association tests were implemented while accounting for arbitrary family structures. Extensive simulation studies were performed to evaluate all the approaches implemented in RVFam. AVAILABILITY AND IMPLEMENTATION http://cran.r-project.org/web/packages/RVFam/.
Prognostic significance of social network, social support and loneliness for course of major depressive disorder in adulthood and old age

Aims. Poor recovery from depressive disorder has been shown to be related to low perceived social support and loneliness, but not to social network size or frequency of social interactions. Some studies suggest that the significance of social relationships for depression course may be greater in younger than in older patients, and may differ between men and women. None of the studies examined to what extent the different aspects of social relationships have unique or overlapping predictive values for depression course. It is the aim of the present study to examine the differential predictive values of social network characteristics, social support and loneliness for the course of depressive disorder, and to test whether these predictive associations are modified by gender or age. Methods. Two naturalistic cohort studies with the same design and overlapping instruments were combined to obtain a study sample of 1474 patients with a major depressive disorder, of whom 1181 (80.1%) could be studied over a 2-year period. Social relational variables were assessed at baseline. Two aspects of depression course were studied: remission at 2-year follow-up and change in depression severity over the follow-up period. By means of logistic regression and random coefficient analysis, the individual and combined predictive values of the different social relational variables for depression course were studied, controlling for potential confounders and checking for effect modification by age (below 60 v. 60 years or older) and gender. Results. Multiple aspects of the social network, social support and loneliness were related to depression course, independent of potential confounders – including depression severity – but when combined, their predictive values were found to overlap to a large extent. Only the social network characteristic of living in a larger household, the social support characteristic of few negative experiences with the support from a partner or close friend, and limited feelings of loneliness proved to have unique predictive value for a favourable course of depression. Little evidence was found for effect modification by gender or age. Conclusions. If depressed persons experience difficulties in their social relationships, this may impede their recovery. Special attention for interpersonal problems, social isolation and feelings of loneliness seems warranted in depression treatment and relapse prevention. It will be of great interest to test whether social relational interventions can contribute to better recovery and relapse prevention of depressive disorder.
Targeting of Photoreceptor Genes in Chlamydomonas reinhardtii via Zinc-Finger Nucleases and CRISPR/Cas9

Using optimized protocols, nuclear photoreceptor genes were successfully modified or inactivated in the alga Chlamydomonas via directed gene targeting using zinc-finger nucleases or the nuclease Cas9. The fast-growing biflagellated single-celled chlorophyte Chlamydomonas reinhardtii is the most widely used alga in basic research. The physiological functions of the 18 sensory photoreceptors are of particular interest with respect to Chlamydomonas development and behavior. Despite the demonstration of gene editing in Chlamydomonas in 1995, the isolation of mutants lacking easily ascertained newly acquired phenotypes remains problematic due to low DNA recombination efficiency. We optimized gene-editing protocols for several Chlamydomonas strains (including wild-type CC-125) using zinc-finger nucleases (ZFNs), genetically encoded CRISPR/associated protein 9 (Cas9) from Staphylococcus aureus and Streptococcus pyogenes, and recombinant Cas9 and developed protocols for rapidly isolating nonselectable gene mutants. Using this technique, we disrupted the photoreceptor genes COP1/2, COP3 (encoding channelrhodopsin 1 [ChR1]), COP4 (encoding ChR2), COP5, PHOT, UVR8, VGCC, MAT3, and aCRY and created the chr1 chr2 and uvr8 phot double mutants. Characterization of the chr1, chr2, and mat3 mutants confirmed the value of photoreceptor mutants for physiological studies. Genes of interest were disrupted in 5 to 15% of preselected clones (∼1 out of 4000 initial cells). Using ZFNs, genes were edited in a reliable, predictable manner via homologous recombination, whereas Cas9 primarily caused gene disruption via the insertion of cotransformed DNA. These methods should be widely applicable to research involving green algae.
contamDE: differential expression analysis of RNA-seq data for contaminated tumor samples

MOTIVATION Accurate detection of differentially expressed genes between tumor and normal samples is a primary approach of cancer-related biomarker identification. Due to the infiltration of tumor surrounding normal cells, the expression data derived from tumor samples would always be contaminated with normal cells. Ignoring such cellular contamination would deflate the power of detecting DE genes and further confound the biological interpretation of the analysis results. For the time being, there does not exists any differential expression analysis approach for RNA-seq data in literature that can properly account for the contamination of tumor samples. RESULTS Without appealing to any extra information, we develop a new method 'contamDE' based on a novel statistical model that associates RNA-seq expression levels with cell types. It is demonstrated through simulation studies that contamDE could be much more powerful than the existing methods that ignore the contamination. In the application to two cancer studies, contamDE uniquely found several potential therapy and prognostic biomarkers of prostate cancer and non-small cell lung cancer. AVAILABILITY AND IMPLEMENTATION An R package contamDE is freely available at http://homepage.fudan.edu.cn/zhangh/softwares/ CONTACT zhanghfd@fudan.edu.cn SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
MAC3A and MAC3B, Two Core Subunits of the MOS4-Associated Complex, Positively Influence miRNA Biogenesis

The MOS4-associated complex promotes miRNA accumulation by positively modulating pri-miRNA transcription, stability, and processing. MAC3A and MAC3B are conserved U-box-containing proteins in eukaryotes. They are subunits of the MOS4-associated complex (MAC) that plays essential roles in plant immunity and development in Arabidopsis thaliana. However, their functional mechanisms remain elusive. Here, we show that Arabidopsis MAC3A and MAC3B act redundantly in microRNA (miRNA) biogenesis. Lack of both MAC3A and MAC3B in the mac3b mac3b double mutant reduces the accumulation of miRNAs, causing elevated transcript levels of miRNA targets. mac3a mac3b also decreases the levels of primary miRNA transcripts (pri-miRNAs). However, MAC3A and MAC3B do not affect the promoter activity of genes encoding miRNAs (MIR genes), suggesting that they may not affect MIR transcription. This result, together with the fact that MAC3A associates with pri-miRNAs in vivo, indicates that MAC3A and MAC3B may stabilize pri-miRNAs. Furthermore, we find that MAC3A and MAC3B interact with the DCL1 complex that catalyzes miRNA maturation, promote DCL1 activity, and are required for the localization of HYL1, a component of the DCL1 complex. Besides MAC3A and MAC3B, two other MAC subunits, CDC5 and PRL1, also function in miRNA biogenesis. Based on these results, we propose that MAC functions as a complex to control miRNA levels through modulating pri-miRNA transcription, processing, and stability.
An overview of plant volatile metabolomics, sample treatment and reporting considerations with emphasis on mechanical damage and biological control of weeds.

INTRODUCTION The technology for the collection and analysis of plant-emitted volatiles for understanding chemical cues of plant-plant, plant-insect or plant-microbe interactions has increased over the years. Consequently, the in situ collection, analysis and identification of volatiles are considered integral to elucidation of complex plant communications. Due to the complexity and range of emissions the conditions for consistent emission of volatiles are difficult to standardise. OBJECTIVE To discuss: evaluation of emitted volatile metabolites as a means of screening potential target- and non-target weeds/plants for insect biological control agents; plant volatile metabolomics to analyse resultant data; importance of considering volatiles from damaged plants; and use of a database for reporting experimental conditions and results. METHOD Recent literature relating to plant volatiles and plant volatile metabolomics are summarised to provide a basic understanding of how metabolomics can be applied to the study of plant volatiles. RESULTS An overview of plant secondary metabolites, plant volatile metabolomics, analysis of plant volatile metabolomics data and the subsequent input into a database, the roles of plant volatiles, volatile emission as a function of treatment, and the application of plant volatile metabolomics to biological control of invasive weeds. CONCLUSION It is recommended that in addition to a non-damaged treatment, plants be damaged prior to collecting volatiles to provide the greatest diversity of odours. For the model system provided, optimal volatile emission occurred when the leaf was punctured with a needle. Results stored in a database should include basic environmental conditions or treatments.
Tomato MYB 21 Acts in Ovules to Mediate Jasmonate-regulated 3 Fertility

29 The function of the plant hormone jasmonic acid (JA) in the development of tomato (Solanum 30 lycopersicum) flowers was analyzed with a mutant defective in JA perception (jasmonate31 insensitive1-1, jai1-1). In contrast to Arabidopsis thaliana JA-insensitive plants, which are 32 male sterile, the tomato jai1-1 mutant is female sterile, with major defects in female 33 development. To identify putative JA-dependent regulatory components, we performed 34 transcriptomics on ovules from flowers at three developmental stages from wild type and 35 jai1-1 mutants. One of the strongly down-regulated genes in jai1-1 encodes the MYB 36 transcription factor SlMYB21. Its Arabidopsis orthologue plays a crucial role in JA-regulated 37 stamen development. SlMYB21 was shown here to exhibit transcription factor activity in 38 yeast, to interact with SlJAZ9 in yeast and in planta, and to complement Arabidopsis myb2139 5. To analyze SlMYB21 function, we generated CRISPR/Cas9 mutants and identified a 40 TILLING mutant. These mutants showed female sterility, corroborating a function of MYB21 41 in tomato ovule development. Transcriptomics analysis of wild type, jai1-1 and myb21-2 42 carpels revealed processes that might be controlled by SlMYB21. The data suggest positive 43 regulation of JA biosynthesis by SlMYB21, but negative regulation of auxin and gibberellins. 44 Plant Cell Advance Publication. Published on March 20, 2019, doi:10.1105/tpc.18. 00978 ©2019 American Society of Plant Biologists. All Rights Reserved 2 The results demonstrate that SlMYB21 mediates at least partially the action of JA and might 45 control the flower to fruit transition. 46
Utilizing the Jaccard index to reveal population stratification in sequencing data: a simulation study and an application to the 1000 Genomes Project

MOTIVATION Population stratification is one of the major sources of confounding in genetic association studies, potentially causing false-positive and false-negative results. Here, we present a novel approach for the identification of population substructure in high-density genotyping data/next generation sequencing data. The approach exploits the co-appearances of rare genetic variants in individuals. The method can be applied to all available genetic loci and is computationally fast. Using sequencing data from the 1000 Genomes Project, the features of the approach are illustrated and compared to existing methodology (i.e. EIGENSTRAT). We examine the effects of different cutoffs for the minor allele frequency on the performance of the approach. We find that our approach works particularly well for genetic loci with very small minor allele frequencies. The results suggest that the inclusion of rare-variant data/sequencing data in our approach provides a much higher resolution picture of population substructure than it can be obtained with existing methodology. Furthermore, in simulation studies, we find scenarios where our method was able to control the type 1 error more precisely and showed higher power. AVAILABILITY AND IMPLEMENTATION CONTACT dmitry.prokopenko@uni-bonn.de SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Structural Bioinformatics Computational Approaches to Define a Human Milk Metaglycome

Motivation: The goal of deciphering the human glycome has been hindered by the lack of highthroughput sequencing methods for glycans. While mass spectrometry (MS) is a key technology in glycan sequencing, MS alone provides limited information about the identification of monosaccharide constituents, their anomericity and their linkages. These features of individual, purified glycans can be partly identified using well-defined glycan-binding proteins, such as lectins and antibodies that recognize specific determinants within glycan structures. Results: We present a novel computational approach to automate the sequencing of glycans using metadata-assisted glycan sequencing (MAGS), which combines MS analyses with glycan structural information from glycan microarray technology. Success in this approach was aided by the generation of a “virtual glycome” to represent all potential glycan structures that might exist within a metaglycomes based on a set of biosynthetic assumptions using known structural information. We exploited this approach to deduce the structures of soluble glycans within the human milk glycome by matching predicted structures based on experimental data against the virtual glycome. This represents the first meta-glycome to be defined using this method and we provide a publically available web-based application to aid in sequencing milk glycans. Availability: http://glycomeseq.emory. edu Contact: sagravat@bidmc.harvard. edu Supplementary information: Supplementary data are available at Bioinformatics online.
Spanish Version of the New Ecological Paradigm Scale for Children

Abstract The New Ecological Paradigm (NEP) scale has been extensively used to measure adults’ environmental attitudes. However, it has only recently been adapted for use with children. This paper presents a Spanish version of the NEP Scale for Children, examines children’s ecological beliefs according to socio-demographic variables as well as the relationship between children’s ecological beliefs and pro-environmental behavior. Exploratory factor analysis was conducted, followed by confirmatory factor analysis. In addition, the instrument’s internal consistency was studied and links between environmental attitudes, age, and ecological behavior in children were examined through correlation analyses. The results show that children’s ecological worldviews can be described by a dimension called “overall ecocentrism”. Analysis of variance demonstrated that children from rural areas exhibit a more ecocentric worldview than those from urban areas. The results also denote gender differences.
Increasing incidence of melanoma after solid organ transplantation: a retrospective epidemiological study

The risk of melanoma in organ transplant recipients (OTR) is increased compared with the general population. This retrospective study registered all cases of post‐transplant melanoma in kidney, heart, lung, and liver transplant recipients followed in our specialized post‐transplant Dermatology Clinic since 1991. The yearly prevalence of melanoma and skin carcinoma between 2000 and 2015 was computed and compared in this population. Based on another cohort of kidney transplant recipients grafted since 2005, adjusted age‐ and sex‐standardized incidence ratio (SIR) was calculated using a renal transplantation registry. In our overall OTR cohort, between 1991 and 2000, five melanomas occurred in 1800 OTRs (0.28%), whereas between 1991 and 2015, 53 melanomas were diagnosed in 49 of 4510 OTR (1.09%), representing a 3.9‐fold increase in prevalence after 2000. Remarkably, the prevalence of nonmelanoma skin cancers remained unchanged over this period. Two deaths related to melanoma were recorded with an overall follow‐up of 62 months. In our cohort of 1102 renal transplant recipients, the SIR of melanoma was 4.52. Our data suggest that contrasting with nonmelanoma skin cancer, the risk of post‐transplant melanoma has considerably increased over the last decade.