julilili42/papers huggingface dataset:
Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations
2023-03-03

Abstract Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic data sets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and to the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework &lt;monospace&gt;stdpopsim&lt;/monospace&gt; seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of &lt;monospace&gt;stdpopsim&lt;/monospace&gt; focused on establishing this framework using six well-characterized model species (Adrion et al.,2020). Here, we report on major improvements made in the new release of &lt;monospace&gt;stdpopsim&lt;/monospace&gt; (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than three-fold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to &lt;monospace&gt;stdpopsim&lt;/monospace&gt; aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.
Data from the paper "The landscape of biomedical research"
2023-03-03

Data from the paper "The landscape of biomedical research" (https://www.biorxiv.org/content/10.1101/2023.04.10.536208v1). The paper used the PubMed 2020 baseline (download date: 26.01.2021, not available anymore) supplemented with additional files from the 2021 baseline (download date: 27.04.2022, not available anymore), both originally obtained from https://www.nlm.nih.gov/databases/download/pubmed_medline.html, courtesy of the U.S. National Library of Medicine. The data provided here includes: - from the PubMed database: article title, journal, PMID, and publication year. - produced by us: t-SNE embedding X and Y coordinates, label, and color.
Author Response: Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations
2023-03-03

Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic data sets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and to the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than three-fold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.
Data from the paper "The landscape of biomedical research"
2023-03-03

Data from the paper &amp;quot;The landscape of biomedical research&amp;quot; (https://www.biorxiv.org/content/10.1101/2023.04.10.536208v1).\\n\\n\\nThe paper used the PubMed 2020 baseline (download date: 26.01.2021, not available anymore) supplemented with additional files from the 2021 baseline (download date: 27.04.2022, not available anymore), both originally obtained from https://www.nlm.nih.gov/databases/download/pubmed_medline.html, courtesy of the U.S. National Library of Medicine.\\n\\n\\nThe data provided here includes the following files:\\n\\n\\npubmed_landscape_data.zip, which includes:\\n\\n\\n- from the PubMed database: article title, journal, PMID, and publication year.\\n\\n\\n- produced by us: t-SNE embedding X and Y coordinates, label, and color.\\n\\n\\n&amp;nbsp;\\n\\n\\npubmed_landscape_abstracts.zip, which includes:\\n\\n\\n- from the PubMed database: PMID, and paper abstracts.\\n\\n\\n&amp;nbsp;\\n\\n\\nPubMedBERT_embeddings_float16.npy, which includes:\\n\\n\\n- produced by us: PubMedBERT embeddings of the paper abstracts (numpy.ndarray of shape 20,687,150x768).
Data from the paper "The landscape of biomedical research"
2023-03-03

Data from the paper "The landscape of biomedical research". The paper used the PubMed 2020 baseline (download date: 26.01.2021, not available anymore) supplemented with additional files from the 2021 baseline (download date: 27.04.2022, not available anymore), both originally obtained from https://www.nlm.nih.gov/databases/download/pubmed_medline.html, courtesy of the U.S. National Library of Medicine. This data can be found in v2 of this repository (https://zenodo.org/records/7849020). In the latest version of this repository we provide the PubMed 2024 baseline (download date: 06.02.2024) including all papers until the end of 2023, which is not the main data we analyzed in the paper but an updated version including newer articles. The paper contains two supplementary figures (S9 and S10) with the updated embedding. The latest version provided here includes the following files: pubmed_landscape_data_2024_v2.zip, which includes: - from the PubMed database: article title, journal, PMID, and publication year. - produced by us: t-SNE embedding X and Y coordinates, label, color, whether the paper is retracted or not (combining PubMed and Retraction Watch information), affiliation country ( from the first affiliation of the first author), and inferred gender (of both first and last author). (Note: pubmed_landscape_data_2024_v2.zip is identical to pubmed_landscape_data_2024.zip from v3 of this repository, but includes inferred genders additionally.) pubmed_landscape_abstracts_2024.zip, which includes: - from the PubMed database: PMID, and paper abstracts. PubMedBERT_embeddings_float16_2024.npy, which includes: - produced by us: PubMedBERT embeddings of the paper abstracts (numpy.ndarray of shape 23,389,083x768).
Enhanced Apoptosis and Loss of Cell Viability in Melanoma Cells by Combined Inhibition of ERK and Mcl-1 Is Related to Loss of Mitochondrial Membrane Potential, Caspase Activation and Upregulation of Proapoptotic Bcl-2 Proteins
2023-03-04

Targeting of MAP kinase pathways by BRAF inhibitors has evolved as a key therapy for BRAF-mutated melanoma. However, it cannot be applied for BRAF-WT melanoma, and also, in BRAF-mutated melanoma, tumor relapse often follows after an initial phase of tumor regression. Inhibition of MAP kinase pathways downstream at ERK1/2, or inhibitors of antiapoptotic Bcl-2 proteins, such as Mcl-1, may serve as alternative strategies. As shown here, the BRAF inhibitor vemurafenib and the ERK inhibitor SCH772984 showed only limited efficacy in melanoma cell lines, when applied alone. However, in combination with the Mcl-1 inhibitor S63845, the effects of vemurafenib were strongly enhanced in BRAF-mutated cell lines, and the effects of SCH772984 were enhanced in both BRAF-mutated and BRAF-WT cells. This resulted in up to 90% loss of cell viability and cell proliferation, as well as in induction of apoptosis in up to 60% of cells. The combination of SCH772984/S63845 resulted in caspase activation, processing of poly (ADP-ribose) polymerase (PARP), phosphorylation of histone H2AX, loss of mitochondrial membrane potential, and cytochrome c release. Proving the critical role of caspases, a pan-caspase inhibitor suppressed apoptosis induction, as well as loss of cell viability. As concerning Bcl-2 family proteins, SCH772984 enhanced expression of the proapoptotic Bim and Puma, as well as decreased phosphorylation of Bad. The combination finally resulted in downregulation of antiapoptotic Bcl-2 and enhanced expression of the proapoptotic Noxa. In conclusion, combined inhibition of ERK and Mcl-1 revealed an impressive efficacy both in BRAF-mutated and WT melanoma cells, and may thus represent a new strategy for overcoming drug resistance.
Perfusion Air Culture of Precision-Cut Tumor Slices: An Ex Vivo System to Evaluate Individual Drug Response under Controlled Culture Conditions
2023-03-04

Precision-cut tumor slices (PCTS) maintain tissue heterogeneity concerning different cell types and preserve the tumor microenvironment (TME). Typically, PCTS are cultured statically on a filter support at an air–liquid interface, which gives rise to intra-slice gradients during culture. To overcome this problem, we developed a perfusion air culture (PAC) system that can provide a continuous and controlled oxygen medium, and drug supply. This makes it an adaptable ex vivo system for evaluating drug responses in a tissue-specific microenvironment. PCTS from mouse xenografts (MCF-7, H1437) and primary human ovarian tumors (primary OV) cultured in the PAC system maintained the morphology, proliferation, and TME for more than 7 days, and no intra-slice gradients were observed. Cultured PCTS were analyzed for DNA damage, apoptosis, and transcriptional biomarkers for the cellular stress response. For the primary OV slices, cisplatin treatment induced a diverse increase in the cleavage of caspase-3 and PD-L1 expression, indicating a heterogeneous response to drug treatment between patients. Immune cells were preserved throughout the culturing period, indicating that immune therapy can be analyzed. The novel PAC system is suitable for assessing individual drug responses and can thus be used as a preclinical model to predict in vivo therapy responses.
Relating Objective Complexity, Subjective Complexity and Beauty in Binary Pixel Patterns
2023-03-04

The complexity of images critically influences our assessment of their beauty. However, studies relating assessments of complexity and beauty to potential objective measures are hampered by the use of hand-crafted stimuli which are hard to reproduce and manipulate. To tackle this, we developed a systematic method for generating 2D black-and-white pixel patterns using cellular automata, and collected ratings of complexity and beauty from 80 participants. We developed various computational measures of pattern quantification such as density, entropies, local spatial complexity, Kolmogorov complexity, and asymmetries. We also introduced an “intricacy” measure quantifying the number of components in a pattern using a graph-based approach. We related these objective measures with participant judgements of complexity and beauty to find that a weighted combination of local spatial complexity and intricacy was an effective predictor (R2test = 0.47) of complexity. This implies that people’s complexity ratings depended on the local arrangement of pixels along with the global number of components in the pattern. Furthermore, we found a positive linear influence of complexity ratings on beauty, with a negative linear influence of disorder (asymmetry and entropy), and a negative interaction between the two quantities (R2test = 0.65). This implies that there is beauty in complexity as long as there is sufficient order. Lastly, a moderated mediation analysis showed that subjective complexity mediates the influence of objective complexity on beauty, implying that subjective complexity provides useful information over and above objective complexity. Our data and scripts are available on Github.
The MC1R r allele does not increase melanoma risk in MITF E318K carriers
2023-03-05

Abstract Background Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored. Objectives To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K– individuals. Materials and methods Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/– cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank). Results The cohort comprised 1165 MITF E318K– and 322 E318K+ individuals. In E318K– cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P &amp;lt; 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P &amp;lt; 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67–2.49); P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54–1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20–1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P &amp;lt; 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals. Conclusions RHC alleles/genotypes modify melanoma risk differently in MITF E318K– and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K– individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals.
Equilibrium isotope fractionation factors of H exchange between steam and soil clay fractions
2023-03-05

Rationale Steam equilibration overcomes the problem of the traditional measurements of H isotope compositions, which leave an arbitrary amount of adsorbed water in the sample, by controlling for the entire exchangeable H pool, including adsorbed water and hydroxyl‐H. However, the use of steam equilibration to determine nonexchangeable stable H isotope compositions in environmental media (expressed as δ 2 H n values) by mathematically eliminating the influence of exchangeable H after sample equilibration with waters of known H‐isotopic composition requires the knowledge of the equilibrium isotope fractionation factor between steam‐H and exchangeable H of the sample (α ex‐w ), which is frequently unknown. Methods We developed a new method to determine the α ex‐w values for clay minerals, topsoil clay fractions, and mica by manipulating the contributions of exchangeable H to the total H pool via different degrees of post‐equilibration sample drying. We measured the δ 2 H values of steam‐equilibrated mineral and soil samples using elemental analyzer‐pyrolysis‐isotope ratio mass spectrometry. Results The α ex‐w values of seven clay minerals ranged from 1.071 to 1.140, and those of 19 topsoil clay fractions ranged from 0.885 to 1.216. The α ex‐w value of USGS57 biotite, USGS58 muscovite, and of cellulose was 0.965, 0.871, and 1.175, respectively. The method did not work for kaolinite, because its small exchangeable H pool did not respond to the selected drying conditions. Structurally different mineral groups such as two‐ and three‐layer clay minerals or mica showed systematically different α ex‐w values. The α ex‐w value of the topsoil clay fractions correlated with the soil clay content (r = 0.63, P = 0.004), the local mean annual temperature (r = 0.68, P = 0.001), and the δ 2 H values of local precipitation (r = 0.72, P &lt; 0.001), likely to reflect the different clay mineralogy under different weathering regimes. Conclusions Our new α ex‐w determination method yielded realistic results in line with the few previously published values for cellulose. The determined α ex‐w values were similar to the widely assumed values of 1.00–1.08 in the literature, suggesting that the adoption of one of these values in steam equilibration approaches is appropriate.
Entomotherapeutic Role of Periplaneta americana Extract in Alleviating Aluminum Oxide Nanoparticles-Induced Testicular Oxidative Impairment in Migratory Locusts (Locusta migratoria) as an Ecotoxicological Model
2023-03-06

In this study, we shed light for the first time on the usage of migratory locusts (Locusta migratoria) as an insect model to investigate the nanotoxicological influence of aluminum oxide (Al2O3) nanoparticles at low doses on testes, and evaluate the capacity of a whole-body extract of American cockroaches (Periplaneta americana) (PAE) to attenuate Al2O3 NPs-induced toxicity. Energy dispersive X-ray microanalyzer (EDX) analysis verified the bioaccumulation of Al in testicular tissues due to its liberation from Al2O3 NPs, implying their penetration into the blood–testis barrier. Remarkably, toxicity with Al engendered disorders of antioxidant and stress biomarkers associated with substantial DNA damage and cell apoptosis. Furthermore, histopathological and ultrastructural analyses manifested significant aberrations in the testicular tissues from the group exposed to Al2O3 NPs, indicating the overproduction of reactive oxygen species (ROS). Molecular docking analysis emphasized the antioxidant capacity of some compounds derived from PAE. Thus, pretreatment with PAE counteracted the detrimental effects of Al in the testes, revealing antioxidant properties and thwarting DNA impairment and cell apoptosis. Moreover, histological and ultrastructural examinations revealed no anomalies in the testes. Overall, these findings substantiate the potential applications of PAE in preventing the testicular impairment of L. migratoria and the conceivable utilization of locusts for nanotoxicology studies.
Nickel Catalyzed Cross-Coupling of Aryl and Alkenyl Triflates with Alkyl Thiols
2023-03-06

We report a nickel catalyzed C-S cross-coupling of aryl and alkenyl triflates with alkyl thiols. A variety of the corresponding thioethers were synthesized using an air-stable nickel precatalyst under mild reaction conditions with short reaction times. A broad substrate scope, including pharmaceutically relevant compounds, could be demonstrated.
Predicting functional effects of ion channel variants using new phenotypic machine learning methods
2023-03-06

Missense variants in genes encoding ion channels are associated with a spectrum of severe diseases. Variant effects on biophysical function correlate with clinical features and can be categorized as gain- or loss-of-function. This information enables a timely diagnosis, facilitates precision therapy, and guides prognosis. Functional characterization presents a bottleneck in translational medicine. Machine learning models may be able to rapidly generate supporting evidence by predicting variant functional effects. Here, we describe a multi-task multi-kernel learning framework capable of harmonizing functional results and structural information with clinical phenotypes. This novel approach extends the human phenotype ontology towards kernel-based supervised machine learning. Our gain- or loss-of-function classifier achieves high performance (mean accuracy 0.853 SD 0.016, mean AU-ROC 0.912 SD 0.025), outperforming both conventional baseline and state-of-the-art methods. Performance is robust across different phenotypic similarity measures and largely insensitive to phenotypic noise or sparsity. Localized multi-kernel learning offered biological insight and interpretability by highlighting channels with implicit genotype-phenotype correlations or latent task similarity for downstream analysis.
Metabolic Performance and Fate of Electrons during Nitrate-Reducing Fe(II) Oxidation by the Autotrophic Enrichment Culture KS Grown at Different Initial Fe/N Ratios
2023-03-06

Autotrophic NRFeOx microorganisms that oxidize Fe(II), reduce nitrate, and produce biomass play a key role in carbon, iron, and nitrogen cycles in pH-neutral, anoxic environments. Electrons from Fe(II) oxidation are used for the reduction of both carbon dioxide and nitrate.
Improved estimation of the bulk ice crystal fabric asymmetry from polarimetric phase co-registration
2023-03-06

Abstract. The bulk crystal orientation in ice influences the flow of glaciers and ice streams. The ice c-axes fabric is most reliably derived from ice cores. Because these are sparse, the spatial and vertical distribution of the fabric in the Greenland and Antarctic ice sheets is largely unknown. In recent years, methods have been developed to determine fabric characteristics from polarimetric radar measurements. The aim of this paper is to present an improved method to infer the horizontal fabric asymmetry by precisely determining the travel-time difference using co-polarised phase-sensitive radar data. We applied this method to six radar measurements from the East Greenland Ice-core Project (EastGRIP) drill site on Greenland's largest ice stream to give a proof of concept by comparing the results with the horizontal asymmetry of the bulk crystal anisotropy derived from the ice core. This comparison shows an excellent agreement, which is a large improvement compared to previously used methods. Our approach is particularly useful for determining the vertical profile of the fabric asymmetry in higher resolution and over larger depths than was achievable with previous methods, especially in regions with strong asymmetry.