bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Practical Haplotype Graph, a platform for storing and using pangenomes for imputation
Authors: Bradbury P J , Casstevens T , Jensen S E , Johnson L C , Miller Z R , Monier B , Romay M C , Song B , Buckler E S 
Published: June 2022

AbstractMotivationPangenomes provide novel insights for population and quantitative genetics, genomics and breeding not available from studying a single reference genome. Instead, a species is better represented by a pangenome or collection of genomes. Unfortunately, managing and using pangenomes for genomically diverse species is computationally and practically challenging. We developed a trellis graph representation anchored to the reference genome that represents most pangenomes well and can be used to impute complete genomes from low density sequence or variant data.ResultsThe Practical Haplotype Graph (PHG) is a pangenome pipeline, database (PostGRES & SQLite), data model (Java, Kotlin or R) and Breeding API (BrAPI) web service. The PHG has already been able to accurately represent diversity in four major crops including maize, one of the most genomically diverse species, with up to 1000-fold data compression. Using simulated data, we show that, at even 0.1× coverage, with appropriate reads and sequence alignment, imputation results in extremely accurate haplotype reconstruction. The PHG is a platform and environment for the understanding and application of genomic diversity.Availability and implementationAll resources listed here are freely available. The PHG Docker used to generate the simulation results is https://hub.docker.com/ as maizegenetics/phg:0.0.27. PHG source code is at https://bitbucket.org/bucklerlab/practicalhaplotypegraph/src/master/. The code used for the analysis of simulated data is at https://bitbucket.org/bucklerlab/phg-manuscript/src/master/. The PHG database of NAM parent haplotypes is in the CyVerse data store (https://de.cyverse.org/de/) and named/iplant/home/shared/panzea/panGenome/PHG_db_maize/phg_v5Assemblies_20200608.db.Supplementary informationSupplementary data are available at Bioinformatics online.
EasyGDB: a low-maintenance and highly customizable system to develop genomics portals
Authors: Fernandez-Pozo Noe , Bombarely Aureliano 
Published: June 2022

AbstractSummaryEasyGDB is an easy-to-implement low-maintenance tool developed to create genomic data management web platforms. It can be used for any species, group of species, or multiple genome or annotation versions. EasyGDB provides a framework to develop a web portal that includes the general information about species, projects and members, and bioinformatics tools such as file downloads, BLAST, genome browser, annotation search, gene expression visualization, annotation and sequence download, and gene ids and orthologs lookup. The code of EasyGDB facilitates data maintenance and update for non-experienced bioinformaticians, using BLAST databases to store and retrieve sequence data in gene annotation pages and bioinformatics tools, and JSON files to customize metadata. EasyGDB is a highly customizable tool. Any section and tool can be enabled or disabled like a switch through a single configuration file. This tool aims to simplify the development of genomics portals in non-model species, providing a modern web style with embedded interactive bioinformatics tools to cover all the common needs derived from genomics projects.Availability and implementationThe code and manual to use EasyGDB can be found at https://github.com/noefp/easy_gdb.
XSI—a genotype compression tool for compressive genomics in large biobanks
Authors: Wertenbroek Rick , Rubinacci Simone , Xenarios Ioannis , Thoma Yann , Delaneau Olivier 
Published: June 2022

AbstractMotivationGeneration of genotype data has been growing exponentially over the last decade. With the large size of recent datasets comes a storage and computational burden with ever increasing costs. To reduce this burden, we propose XSI, a file format with reduced storage footprint that also allows computation on the compressed data and we show how this can improve future analyses.ResultsWe show that xSqueezeIt (XSI) allows for a file size reduction of 4-20× compared with compressed BCF and demonstrate its potential for ‘compressive genomics’ on the UK Biobank whole-genome sequencing genotypes with 8× faster loading times, 5× faster run of homozygozity computation, 30× faster dot products computation and 280× faster allele counts.Availability and implementationThe XSI file format specifications, API and command line tool are released under open-source (MIT) license and are available at https://github.com/rwk-unil/xSqueezeItSupplementary informationSupplementary data are available at Bioinformatics online.
MIAMI: mutual information-based analysis of multiplex imaging data
Authors: Seal Souvik , Ghosh Debashis 
Published: June 2022

AbstractMotivationStudying the interaction or co-expression of the proteins or markers in the tumor microenvironment of cancer subjects can be crucial in the assessment of risks, such as death or recurrence. In the conventional approach, the cells need to be declared positive or negative for a marker based on its intensity. For multiple markers, manual thresholds are required for all the markers, which can become cumbersome. The performance of the subsequent analysis relies heavily on this step and thus suffers from subjectivity and lacks robustness.ResultsWe present a new method where different marker intensities are viewed as dependent random variables, and the mutual information (MI) between them is considered to be a metric of co-expression. Estimation of the joint density, as required in the traditional form of MI, becomes increasingly challenging as the number of markers increases. We consider an alternative formulation of MI which is conceptually similar but has an efficient estimation technique for which we develop a new generalization. With the proposed method, we analyzed a lung cancer dataset finding the co-expression of the markers, HLA-DR and CK to be associated with survival. We also analyzed a triple negative breast cancer dataset finding the co-expression of the immuno-regulatory proteins, PD1, PD-L1, Lag3 and IDO, to be associated with disease recurrence. We demonstrated the robustness of our method through different simulation studies.Availability and implementationThe associated R package can be found here, https://github.com/sealx017/MIAMI.Supplementary informationSupplementary data are available at Bioinformatics online.
Deep learning models for RNA secondary structure prediction (probably) do not generalize across families
Authors: Szikszai Marcell , Wise Michael , Datta Amitava , Ward Max , Mathews David H 
Published: June 2022

AbstractMotivationThe secondary structure of RNA is of importance to its function. Over the last few years, several papers attempted to use machine learning to improve de novo RNA secondary structure prediction. Many of these papers report impressive results for intra-family predictions but seldom address the much more difficult (and practical) inter-family problem.ResultsWe demonstrate that it is nearly trivial with convolutional neural networks to generate pseudo-free energy changes, modelled after structure mapping data that improve the accuracy of structure prediction for intra-family cases. We propose a more rigorous method for inter-family cross-validation that can be used to assess the performance of learning-based models. Using this method, we further demonstrate that intra-family performance is insufficient proof of generalization despite the widespread assumption in the literature and provide strong evidence that many existing learning-based models have not generalized inter-family.Availability and implementationSource code and data are available at https://github.com/marcellszi/dl-rna.Supplementary informationSupplementary data are available at Bioinformatics online.
The anaphase-promoting complex/cyclosome co-activator, Cdh1, is a novel target of human papillomavirus 16 E7 oncoprotein in cervical oncogenesis
Authors: Jaiswal Neha , Nandi Deeptashree , Cheema Pradeep Singh , Nag Alo 
Published: June 2022

Abstract
The transforming properties of the high-risk human papillomavirus (HPV) E7 oncoprotein are indispensable for driving the virus life cycle and pathogenesis. Besides inactivation of the retinoblastoma family of tumor suppressors as part of its oncogenic endeavors, E7-mediated perturbations of eminent cell cycle regulators, checkpoint proteins and proto-oncogenes are considered to be the tricks of its transformative traits. However, many such critical interactions are still unknown. In the present study, we have identified the anaphase-promoting complex/cyclosome (APC) co-activator, Cdh1, as a novel interacting partner and a degradation target of E7. We found that HPV16 E7-induced inactivation of Cdh1 promoted abnormal accumulation of multiple Cdh1 substrates. Such a mode of deregulation possibly contributes to HPV-mediated cervical oncogenesis. Our mapping studies recognized the C-terminal zinc-finger motif of E7 to associate with Cdh1 and interfere with the timely degradation of FoxM1, a bona fide Cdh1 substrate and a potent oncogene. Importantly, the E7 mutant with impaired interaction with Cdh1 exhibited defects in its ability for overriding typical cell cycle transition and oncogenic transformation, thereby validating the functional and pathological significance of the E7-Cdh1 axis during cervical carcinoma progression. Altogether, the findings from our study discover a unique nexus between E7 and APC/C-Cdh1, thereby adding to our understanding of the mechanism of E7-induced carcinogenesis and provide a promising target for the management of cervical carcinoma.
Detection of DNA adducts derived from the tobacco carcinogens, benzo[a]pyrene and dibenzo[def,p]chrysene in human oral buccal cells
Authors: Chen Kun-Ming , Sun Yuan-Wan , Krebs Nicolle M , Sun Dongxiao , Krzeminski Jacek , Reinhart Lisa , Gowda Krishne , Amin Shantu , Mallery Susan , Richie John P , El-Bayoumy Karam 
Published: June 2022

Abstract
Polycyclic aromatic hydrocarbons (PAHs) are recognized as potential etiological agents in the development of oral cancer in smokers. In particular, benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DB[a,l]P) are detected in cigarette smoke and the environment and can induce DNA damage, mutagenesis and carcinogenesis in the oral cavity of rodents. Consequently, DNA adducts are regarded as the most direct markers of genotoxicity and can be used as biomarkers of cancer risk. Thus, this study used LC-MS/MS analysis with isotope labeled internal standard to detect and quantify DNA adducts derived from B[a]P and DB[a,l]P in buccal cells of cigarette smokers and non-smokers. Participants in this study include 21 smokers and 16 non-smokers. Our data are the first to report that levels (mean ± SD) of BPDE-N2-dG were significantly (P &lt; 0.001) higher in smokers (20.18 ± 8.40 adducts/108 dG) than in non-smokers (0.84 ± 1.02 adducts/108 dG). Likewise, levels of DBPDE-N6-dA in smokers (5.49 ± 3.41 adducts/108 dA) were significantly higher (P = 0.019) than non-smokers (2.76 ± 2.29 adducts/108 dA). Collectively, the results of this clinical study support that PAHs in tobacco smoke can contribute to the development of oral cancer in humans.
Altered alpha/beta desynchronization during item–context binding contributes to the associative deficit in older age
Authors: Karlsson Anna E , Sander Myriam C 
Published: June 2022

AbstractIt is proposed that older adults have difficulties to bind item and context and to recruit deep, elaborative processing during encoding. Senescent changes in the oscillatory foundations of these processes are currently unclear. We recorded electroencephalography during item–context memory formation in younger (n = 57) and older (n = 55) adults. At test, we assessed memory for the items and the item–context pairs and examined encoding-related activity based on how much information was recovered at retrieval (miss &lt; item–only &lt; pair). Item memory was comparable between age groups while pair memory was reduced in the older adults. Theta synchronization and alpha/beta desynchronization increased linearly with the amount of information available. Single-trial theta power could not predict subsequent item memory, but predicted pair memory in an age-invariant manner, in line with a mechanism supporting associative memory. In contrast, single-trial alpha/beta power predicted both item and pair memory, in line with a mechanism reflecting the depth of information processing, and predicted pair memory less well in the older than the younger adults. Thus, theta and alpha/beta oscillations contribute differently in shaping the contents of memories and reduced processing capacity contributes to episodic memory decline in older age.
Microstates imbalance is associated with a functional dysregulation of the resting-state networks in obsessive–compulsive disorder: a high-density electrical neuroimaging study using the TESS method
Authors: Thirioux Bérangère , Langbour Nicolas , Bokam Prasanth , Renaudin Léa , Wassouf Issa , Harika-Germaneau Ghina , Jaafari Nematollah 
Published: June 2022

AbstractThe dysfunctional patterns of microstates dynamics in obsessive–compulsive disorder (OCD) remain uncertain. Using high-density electrical neuroimaging (EEG) at rest, we explored microstates deterioration in OCD and whether abnormal microstates patterns are associated with a dysregulation of the resting-state networks interplay. We used EEG microstates analyses, TESS method for sources reconstruction, and General Linear Models to test for the effect of disease severity on neural responses. OCD patients exhibited an increased contribution and decreased duration of microstates C and D, respectively. Activity was decreased in the Salience Network (SN), associated with microstate C, but increased in the Default Mode Network (DMN) and Executive Control Network (ECN), respectively, associated with microstates E and D. The hyperactivity of the right angular gyrus in the ECN correlated with the symptoms severity. The imbalance between microstates C and D invalidates the hypothesis that this electrophysiological pattern is specific to psychosis. Demonstrating that the SN-ECN dysregulation manifests as abnormalities in microstates C and D, we confirm that the SN deterioration in OCD is accompanied by a failure of the DMN to deactivate and aberrant compensatory activation mechanisms in the ECN. These abnormalities explain typical OCD clinical features but also detachment from reality, shared with psychosis.
Maturation of large-scale brain systems over the first month of life
Authors: Nielsen Ashley N , Kaplan Sydney , Meyer Dominique , Alexopoulos Dimitrios , Kenley Jeanette K , Smyser Tara A , Wakschlag Lauren S , Norton Elizabeth S , Raghuraman Nandini , Warner Barbara B , Shimony Joshua S , Luby Joan L , Neil Jeffery J , Petersen Steven E , Barch Deanna M , Rogers Cynthia E , Sylvester Chad M , Smyser Christopher D 
Published: June 2022

AbstractThe period immediately after birth is a critical developmental window, capturing rapid maturation of brain structure and a child’s earliest experiences. Large-scale brain systems are present at delivery, but how these brain systems mature during this narrow window (i.e. first weeks of life) marked by heightened neuroplasticity remains uncharted. Using multivariate pattern classification techniques and functional connectivity magnetic resonance imaging, we detected robust differences in brain systems related to age in newborns (n = 262; R2 = 0.51). Development over the first month of life occurred brain-wide, but differed and was more pronounced in brain systems previously characterized as developing early (i.e. sensorimotor networks) than in those characterized as developing late (i.e. association networks). The cingulo-opercular network was the only exception to this organizing principle, illuminating its early role in brain development. This study represents a step towards a normative brain “growth curve” that could be used to identify atypical brain maturation in infancy.
Sex differences in the taste-evoked functional connectivity network
Authors: Ponticorvo Sara , Prinster Anna , Cantone Elena , Di Salle Francesco , Esposito Fabrizio , Canna Antonietta 
Published: June 2022

AbstractThe central gustatory pathway encompasses multiple subcortical and cortical regions whose neural functional connectivity can be modulated by taste stimulation. While gustatory perception has been previously linked to sex, whether and how the gustatory network differently responds to basic tastes between men and women is unclear. Here, we defined the regions of the central gustatory network by a meta-analysis of 35 fMRI taste activation studies and then analyzed the taste-evoked functional connectivity between these regions in 44 subjects (19 women) in a separate 3 Tesla activation study where sweet and bitter solutions, at five concentrations each, were administered during scanning. From the meta-analysis, a network model was set up, including bilateral anterior, middle and inferior insula, thalamus, precentral gyrus, left amygdala, caudate and dorsolateral prefrontal cortex. Higher functional connectivity than in women was observed in men between the right middle insula and bilateral thalami for bitter taste. Men exhibited higher connectivity than women at low bitter concentrations and middle-high sweet concentrations between bilateral thalamus and insula. A graph-based analysis expressed similar results in terms of nodal characteristics of strength and centrality. Our findings add new insights into the mechanisms of taste processing by highlighting sex differences in the functional connectivity of the gustatory network as modulated by the perception of sweet and bitter tastes. These results shed more light on the neural origin of sex-related differences in gustatory perception and may guide future research on the pathophysiology of taste perception in humans.
Normal-Phase TLC and Gradient Reversed-Phase HPLC for the Simultaneous Determination of Enrofloxacin and Bromhexine HCl in Presence of Two of Their Official Impurities
Authors: Tantawy Mahmoud A , Abdulla Shaaban A , Mohamed Ola Y , Abou Al-Alamein Amal M 
Published: June 2022

Abstract
In this work, two chromatographic methods are developed and validated for the determination of enrofloxacin and bromhexine (BRM) HCl in the presence of two of their specified impurities, ciprofloxacin and BRM impurity C. The suggested chromatographic methods included the use of thin layer chromatography (TLC-densitometry) and high-performance liquid chromatography (HPLC). In case of TLC-densitometry, good separation was achieved by using mobile phase of n.butanol:acetone:water:glacial acetic acid:triethylamine (10:3:1:0.5:0.5, by volume) on silica gel stationary phase at 254-nm detection. The developed HPLC method used BDS HYPERSIL C18 column with a mobile phase of water:acetonitrile:methanol:triflouroacetic acid. A linear gradient elution of 75–10%, 20–50% and 5–40% for water, acetonitrile and methanol, respectively, was applied in 13 min at a flow rate of 1.5 mL min−1. These methods were sufficient to separate the four substances simultaneously, and they are validated as per International Conference on Harmonization guidelines.
A New Strategy for the Software-Assisted LC Separations of Ketoconazole and Its Impurities
Authors: Agrawal Roopali , Belemkar Sateesh , Bonde Chandrakant 
Published: June 2022

Abstract
Analytical quality by design and the use of dissimilar chromatographic systems can be employed to accelerate chromatographic separations. Herein, a software (S-Matrix)-assisted platform was used to proficiently screen, optimize and select the optimal parameters for the chromatographic separation of ketoconazole and its related impurities. This approach evaluated the various chromatographic parameters in a stepwise manner based on the statistical tools and provided an in-depth understanding of the critical parameters influencing the peak selectivities and separations. It was demonstrated that dissimilar conditions, such as different stationary phases, mobile phase pH and organic modifiers (i.e., critical method variables), can improve the peak resolution, while the critical quality attributes can provide conditions appropriate for quantification purposes via a quality target analytical method. Furthermore, an orthogonal method was established to support the primary method. The orthogonality between the two methods was defined by the correlation matrix between the two systems using the Pearson correlation coefficient and was found to be 0.12. Using the optimized method, the primary method was validated as per International Council for Harmonization in the range of 0.05–1.0% for impurities and 80.0–120.0% for ketoconazole, thereby indicating the suitability of the method for use in quality control laboratories.
Preparation of Isoquercetin From Toona sinensis by Liquid–Liquid-Refining Extraction And Consecutive Counter-Current Chromatography
Authors: Guo Shuang , Wang Shuai , Yang Yi , Yin Yuxin , Gu Dongyu 
Published: June 2022

Abstract
A high-speed counter-current chromatographic (HSCCC) method using ethyl acetate–water as solvent system was established to separate isoquercetin from Toona sinensis. In an HSCCC single separation, the sample sizes of ethanol extract were optimized from 203 to 1200 mg. The results showed that the yield of the target compound increased from 4 to 26 mg, and the corresponding purity decreased from 93.30 to 81.82%. To further improve the yield and purity, liquid–liquid-refining extraction was introduced to pretreat the ethanol extract and enrich the target compound. The ethanol extract was extracted with n-hexane-ethyl acetate-method-water (1:5:1:5, v/v) and ethyl acetate-water in turn to remove the low-polarity and high-polarity impurities and obtain the crude sample. Under the similar conditions, 85.25 mg of the target compound with the purity of 95.12% was separated from 240 mg of the crude sample. Subsequently, a consecutive HSCCC was developed to obtain 257 mg of the target compound from 720 mg of crude sample, which was equivalent to 14.4 g of ethanol extract. This method improved the purity of the target compound, but more importantly, the sample size can reach 12 times of the maximum sample size of the ethanol extract in a single run.