bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of antidote stocking, availability, and administration practices for a large multihospital organization
Authors: Antoniello Angela A , Pauls Patrick , Awad Nadia I , Sobolewski Kristine , Fernández Denise , Bridgeman Patrick 
Published: July 2022

AbstractPurposeInadequate hospital antidote inventory is a widely documented international issue due to high medication costs, lack of emphasis on antidote importance, variable international standards, hospital size, and drug availability. A large health system underwent process and policy implementation for antidote stocking, availability tracking, and administration strategies to ensure appropriate inventory and improve patient safety.SummaryProcess and policy implementation occurred over a 12-month period across the health system’s 11 acute care hospitals with emergency department services. Opportunities for optimization were identified following data capture surrounding institution-specific antidote inventory and usage across the health system. Specifically, minimum par levels at each institution were determined from 2018 expert recommendations for both the central pharmacy and automated dispensing machines within the emergency department. These quantities ensured the availability of an antidote within a specific timeframe contingent on the acquisition acuity for at least one 100-kg patient. Entries for order sets, order statements, and smart pump drug libraries were modified or formulated to facilitate standardized practices and minimize safety errors before a system-wide electronic health record transition.ConclusionIt is prudent for all institutions, independent or within a health system, to identify areas of improvement for antidote inventory and management. Implementation of a similar process for antidote stocking, sharing, and delivery at other institutions is feasible and necessary to mitigate issues with drug acquisition and timely administration.
Concatenator, a user-friendly program to concatenate DNA sequences, implementing graphical user interfaces for MAFFT and FastTree
Authors: Vences Miguel , Patmanidis Stefanos , Kharchev Vladimir , Renner Susanne S 
Published: July 2022

Abstract

Motivation
Phylogenetic and phylogenomic analyses require multi-gene input files in different formats, but there are few user-friendly programs facilitating the workflow of combining, concatenating or separating, aligning and exploring multi-gene datasets.

Results
We present Concatenator, a user-friendly GUI-driven program that accepts single-marker and multi-marker DNA sequences in different input formats, including Fasta, Phylip and Nexus, and that outputs concatenated sequences as single-marker or multi-marker Fasta, interleaved nexus or Phylip files, including command files for downstream model selection in IQ-TREE. It includes the option to (re)align markers with MAFFT and produces exploratory trees with FastTree. Although tailored for medium-sized phylogenetic projects, Concatenator is able to process phylogenomic datasets of up to 30 000 markers.

Availability and implementation
Concatenator is written in Python, with C extensions for MAFFT and FastTree. Compiled stand-alone executables of Concatenator for MS Windows and Mac OS along with a detailed manual can be downloaded from www.itaxotools.org; the source code is openly available on GitHub (https://github.com/iTaxoTools/ConcatenatorGui).
Predicting and explaining the impact of genetic disruptions and interactions on organismal viability
Authors: Al-Anzi Bader F , Khajah Mohammad , Fakhraldeen Saja A 
Published: July 2022

AbstractMotivationExisting computational models can predict single- and double-mutant fitness but they do have limitations. First, they are often tested via evaluation metrics that are inappropriate for imbalanced datasets. Second, all of them only predict a binary outcome (viable or not, and negatively interacting or not). Third, most are uninterpretable black box machine learning models.ResultsBudding yeast datasets were used to develop high-performance Multinomial Regression (MN) models capable of predicting the impact of single, double and triple genetic disruptions on viability. These models are interpretable and give realistic non-binary predictions and can predict negative genetic interactions (GIs) in triple-gene knockouts. They are based on a limited set of gene features and their predictions are influenced by the probability of target gene participating in molecular complexes or pathways. Furthermore, the MN models have utility in other organisms such as fission yeast, fruit flies and humans, with the single gene fitness MN model being able to distinguish essential genes necessary for cell-autonomous viability from those required for multicellular survival. Finally, our models exceed the performance of previous models, without sacrificing interpretability.Availability and implementationAll code and processed datasets used to generate results and figures in this manuscript are available at our Github repository at https://github.com/KISRDevelopment/cell_viability_paper. The repository also contains a link to the GI prediction website that lets users search for GIs using the MN models.Supplementary informationSupplementary data are available at Bioinformatics online.
REALGAR: a web app of integrated respiratory omics data
Authors: Kan Mengyuan , Diwadkar Avantika R , Saxena Supriya , Shuai Haoyue , Joo Jaehyun , Himes Blanca E 
Published: July 2022

AbstractMotivationIn the post genome-wide association study (GWAS) era, omics techniques have characterized information beyond genomic variants to include cell and tissue type-specific gene transcription, transcription factor binding sites, expression quantitative trait loci (eQTL) and many other biological layers. Analysis of omics data and its integration has in turn improved the functional interpretation of disease-associated genetic variants. Over 170 000 transcriptomic and epigenomic datasets corresponding to studies of various cell and tissue types under specific disease, treatment and exposure conditions are available in the Gene Expression Omnibus resource. Although these datasets are valuable to guide the design of experimental validation studies to understand the function of disease-associated genetic loci, in their raw form, they are not helpful to experimental researchers who lack adequate computational resources or experience analyzing omics data. We sought to create an integrated re-source of tissue-specific results from omics studies that is guided by disease-specific knowledge to facilitate the design of experiments that can provide biologically meaningful insights into genetic associations.ResultsWe designed the Reducing Associations by Linking Genes and omics Results web app to provide multi-layered omics information based on results from GWAS, transcriptomic, epigenomic and eQTL studies for gene-centric analysis and visualization. With a focus on asthma datasets, the integrated omics results it contains facilitate the formulation of hypotheses related to airways disease-associated genes and can be addressed with experimental validation studies.Availability and implementationThe REALGAR web app is available at: http://realgar.org/. The source code is available at: https://github.com/HimesGroup/realgar.Supplementary informationSupplementary data are available at Bioinformatics online.
Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue
Authors: Monogue Brendan , Chen Yixi , Sparks Hadrian , Behbehani Ranya , Chai Andrew , Rajic Alexander J , Massey Aaron , Kleinschmidt-Demasters B K , Vermeren Matthieu , Kunath Tilo , Beckham J David 
Published: July 2022

Abstract
The protein alpha-synuclein is predominantly expressed in neurons and is associated with neurodegenerative diseases like Parkinson’s disease and dementia with Lewy bodies. However, the normal function of alpha-synuclein in neurons is not clearly defined. We have previously shown that mice lacking alpha-synuclein expression exhibit markedly increased viral growth in the brain, increased mortality and increased neuronal cell death, implicating alpha-synuclein in the neuronal innate immune response.
To investigate the mechanism of alpha-synuclein-induced immune responses to viral infections in the brain, we challenged alpha-synuclein knockout mice and human alpha-synuclein knockout dopaminergic neurons with RNA virus infection and discovered that alpha-synuclein is required for neuronal expression of interferon-stimulated genes. Furthermore, human alpha-synuclein knockout neurons treated with type 1 interferon failed to induce a broad range of interferon stimulated genes, implying that alpha-synuclein interacts with type 1 interferon signalling. We next found that alpha-synuclein accumulates in the nucleus of interferon-treated human neurons after interferon treatment and we demonstrated that interferon-mediated phosphorylation of STAT2 is dependent on alpha-synuclein expression in human neurons. Next, we found that activated STAT2 co-localizes with alpha-synuclein following type 1 interferon stimulation in neurons. Finally, we found that brain tissue from patients with viral encephalitis expresses increased levels of phospho-serine129 alpha-synuclein in neurons.
Taken together, our results show that alpha-synuclein expression supports neuron-specific interferon responses by localizing to the nucleus, supporting STAT2 activation, co-localizing with phosphorylated STAT2 in neurons and supporting expression of interferon-stimulated genes. These data provide a novel mechanism that links interferon activation and alpha-synuclein function in neurons.
Disentangling the effects of Alzheimer’s and small vessel disease on white matter fibre tracts
Authors: Dewenter Anna , Jacob Mina A , Cai Mengfei , Gesierich Benno , Hager Paul , Kopczak Anna , Biel Davina , Ewers Michael , Tuladhar Anil M , de Leeuw Frank-Erik , Dichgans Martin , Franzmeier Nicolai , Duering Marco ,   for the SVDs@target Consortium and Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: July 2022

AbstractAlzheimer’s disease and cerebral small vessel disease are the two leading causes of cognitive decline and dementia and coexist in most memory clinic patients. White matter damage as assessed by diffusion MRI is a key feature in both Alzheimer’s and cerebral small vessel disease. However, disease-specific biomarkers of white matter alterations are missing. Recent advances in diffusion MRI operating on the fixel level (fibre population within a voxel) promise to advance our understanding of disease-related white matter alterations. Fixel-based analysis allows derivation of measures of both white matter microstructure, measured by fibre density, and macrostructure, measured by fibre-bundle cross-section. Here, we evaluated the capacity of these state-of-the-art fixel metrics to disentangle the effects of cerebral small vessel disease and Alzheimer’s disease on white matter integrity.We included three independent samples (total n = 387) covering genetically defined cerebral small vessel disease and age-matched controls, the full spectrum of biomarker-confirmed Alzheimer’s disease including amyloid- and tau-PET negative controls and a validation sample with presumed mixed pathology. In this cross-sectional analysis, we performed group comparisons between patients and controls and assessed associations between fixel metrics within main white matter tracts and imaging hallmarks of cerebral small vessel disease (white matter hyperintensity volume, lacune and cerebral microbleed count) and Alzheimer’s disease (amyloid- and tau-PET), age and a measure of neurodegeneration (brain volume).Our results showed that (i) fibre density was reduced in genetically defined cerebral small vessel disease and strongly associated with cerebral small vessel disease imaging hallmarks; (ii) fibre-bundle cross-section was mainly associated with brain volume; and (iii) both fibre density and fibre-bundle cross-section were reduced in the presence of amyloid, but not further exacerbated by abnormal tau deposition. Fixel metrics were only weakly associated with amyloid- and tau-PET.Taken together, our results in three independent samples suggest that fibre density captures the effect of cerebral small vessel disease, while fibre-bundle cross-section is largely determined by neurodegeneration. The ability of fixel-based imaging markers to capture distinct effects on white matter integrity can propel future applications in the context of precision medicine.
A right to memory and communication policy: safeguarding the capability of remembrance
Authors: Tirosh Noam , Schejter Amit M 
Published: July 2022

Abstract
Can a right to memory be counted among the rights society needs to safeguard, if so, what are its theoretical and conceptual foundations, and how do they relate to communications? We answer these questions by offering a new perspective regarding the right’s components, origin and justifications, the mechanisms needed to realize it and the legal framework required for such realization. We begin by first recognizing the fundamental role of memory in human life, in particular as it pertains to the creation, preservation, and endowment of identity, which justifies the need to protect it. We then discuss memory’s four elements—remembering, forgetting, being remembered, and being forgotten—and their dependence on communications. We follow by describing the nature of rights and the distinction between different types of rights. This helps us claim that recognizing the right to memory requires ensuring the capability to communicate by designing appropriate communication policies.
Cooperative National Regulation to Secure Transnational Public Goods: A Reply to Nico Krisch
Authors: O’Keefe Roger 
Published: July 2022

Abstract
There is no doubt, as vividly highlighted in Nico Krisch’s ‘Jurisdiction Unbound: (Extra)territorial Regulation as Global Governance’, that in certain sectors some economically weighty states seek to take advantage of the international law of jurisdiction with a view to determining unilaterally how particular transnational economic activities are conducted. This same law, however, particularly the jurisdictional obligations provided for among states parties by multilateral treaties, is not only capable of serving cooperative national regulation to secure transnational public goods but in respect of a wide range of activities is already doing so. Rather than a fundamental ‘reorientation of jurisdiction towards the solution of common problems and the protection of global interests’, what is needed is political will and diplomatic agreement to use even further the existing law, especially the treaty-based possibilities that it offers, to these ends.
Alternative Modes of Introgression-Mediated Selection Shaped Crop Adaptation to Novel Climates
Authors: Blanco-Pastor José Luis 
Published: July 2022

AbstractRecent plant genomic studies provide fine-grained details on the evolutionary consequences of adaptive introgression during crop domestication. Modern genomic approaches and analytical methods now make it possible to better separate the introgression signal from the demographic signal thus providing a more comprehensive and complex picture of the role of introgression in local adaptation. Adaptive introgression has been fundamental for crop expansion and has involved complex patterns of gene flow. In addition to providing new and more favorable alleles of large effect, introgression during the early stages of domestication also increased allelic diversity at adaptive loci. Previous studies have largely underestimated the effect of such increased diversity following introgression. Recent genomic studies in wheat, potato, maize, grapevine, and ryegrass show that introgression of multiple genes, of as yet unknown effect, increased the effectiveness of purifying selection, and promoted disruptive or fluctuating selection in early cultivars and landraces. Historical selection processes associated with introgression from crop wild relatives provide an instructive analog for adaptation to current climate change and offer new avenues for crop breeding research that are expected to be instrumental for strengthening food security in the coming years.
Peering in: youth perspectives on Health Promoting Schools and youth engagement in Nova Scotia, Canada
Authors: Kontak Julia C , Caldwell Hilary A T , Kay-Arora Margaret , Hancock Friesen Camille L , Kirk Sara F L 
Published: July 2022

Abstract
Health Promoting Schools (HPS) is a whole-school approach that shapes the conditions necessary to support student health and well-being. Youth engagement is recognized as key to HPS implementation, yet research related to the involvement of youth voice in school health promotion initiatives is limited. The purpose of this study was to understand youth perspectives on HPS and school youth engagement. Ten youth (grades 9–10, ages 14–16) were trained as peer researchers using a Youth Participatory Action Research approach. The peer researchers interviewed 23 of their peers (grades 7–10, ages 12–16) on perspectives related to HPS and school youth engagement. All interviews were audio-recorded, transcribed and data were analysed using inductive ‘codebook’ thematic analysis. Themes related to a healthy school community were mapped onto the pillars of HPS: (i) Social and Physical Environment, (ii) Teaching and Learning, (iii) Partnerships and Services and (iv) School Policies. Participants placed more importance on the social and physical environment of the school including respect, inclusivity, supportive relationships and the design of spaces. Key factors for youth engagement were: (i) safe and supportive spaces, (ii) passion and interest, (iii) using their voice, (iv) power dynamics, (v) accessibility and (vi) awareness. With recognition that youth engagement is a crucial part of HPS, this work provides relevant and applicable information on areas of the healthy school community that are important to youth, and if/how they are meaningfully engaged in school decision-making.
A Mendelian randomization study to assess the genetic liability of gastroesophageal reflux disease for cardiovascular diseases and risk factors
Authors: Sun Xingang , Chen Lu , Zheng Liangrong 
Published: July 2022

Abstract
Observational studies have reported that gastroesophageal reflux disease (GERD) is a risk factor for cardiovascular diseases (CVD); however, the causal inferences between them remain unknown. We conducted a Mendelian randomization (MR) study to estimate the causal associations between GERD and 10 CVD outcomes, as well as 14 cardiovascular risk factors. We used summary statistics from genome-wide association studies for GERD and the FinnGen consortium for CVD. We further investigated whether GERD correlated with cardiovascular risk factors and performed multivariable MR and mediation analyses to estimate the mediating effects of these risk factors on GERD–CVD progression. Sensitivity analyses and replication analyses were also performed. Our results indicated that GERD was positively associated with seven CVD outcomes with odds ratios of 1.26 [95% confidence interval (CI), 1.15, 1.37] for coronary artery disease, 1.41 (95% CI, 1.28, 1.57) for myocardial infarction, 1.34 (95% CI, 1.19, 1.51) for atrial fibrillation, 1.34 (95% CI, 1.21, 1.50) for heart failure, 1.30 (95% CI, 1.18, 1.43) for any stroke, 1.19 (95% CI, 1.06, 1.34) for ischemic stroke and 1.29 (95% CI, 1.16, 1.44) for venous thromboembolism. Furthermore, GERD was associated with nine cardiovascular risk factors and major depressive disorder demonstrated significant mediation effects on the causal pathway linking GERD and any stroke. This study demonstrates that GERD is associated with seven CVD outcomes and nine cardiovascular risk factors. Importantly, GERD treatment may help prevent common CVD events.
Behavioral impulsivity is associated with pupillary alterations and hyperactivity in CDKL5 mutant mice
Authors: Viglione Aurelia , Sagona Giulia , Carrara Fabio , Amato Giuseppe , Totaro Valentino , Lupori Leonardo , Putignano Elena , Pizzorusso Tommaso , Mazziotti Raffaele 
Published: July 2022

Abstract
Cyclin-dependent kinase-like 5 (Cdkl5) deficiency disorder (CDD) is a severe neurodevelopmental condition caused by mutations in the X-linked Cdkl5 gene. CDD is characterized by early-onset seizures in the first month of life, intellectual disability, motor and social impairment. No effective treatment is currently available and medical management is only symptomatic and supportive. Recently, mouse models of Cdkl5 disorder have demonstrated that mice lacking Cdkl5 exhibit autism-like phenotypes, hyperactivity and dysregulations of the arousal system, suggesting the possibility to use these features as translational biomarkers. In this study, we tested Cdkl5 male and female mutant mice in an appetitive operant conditioning chamber to assess cognitive and motor abilities, and performed pupillometry to assess the integrity of the arousal system. Then, we evaluated the performance of artificial intelligence models to classify the genotype of the animals from the behavioral and physiological phenotype. The behavioral results show that CDD mice display impulsivity, together with low levels of cognitive flexibility and perseverative behaviors. We assessed arousal levels by simultaneously recording pupil size and locomotor activity. Pupillometry reveals in CDD mice a smaller pupil size and an impaired response to unexpected stimuli associated with hyperlocomotion, demonstrating a global defect in arousal modulation. Finally, machine learning reveals that both behavioral and pupillometry parameters can be considered good predictors of CDD. Since early diagnosis is essential to evaluate treatment outcomes and pupillary measures can be performed easily, we proposed the monitoring of pupil size as a promising biomarker for CDD.