bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-cohort transcriptomic subtyping of B-cell acute lymphoblastic leukemia
Authors: Mäkinen Ville-Petteri , Rehn Jacqueline , Breen James , Yeung David , White Deborah L 
Published: February 2022

AbstractAcute lymphoblastic leukemia (ALL) is the most common childhood cancer and comprises multiple genetically distinguishable subtypes. To detect subtypes, current pipelines include fusion calling, polymorphisms, candidate gene copy numbers and cytogenetics but these approaches have limitations. RNA-seq provides a functional genome-wide snapshot that enables classification of ALL subtypes, however, typical mRNA-seq clustering analyses lack the rigor of quantitative modelling. Furthermore, high-dimensional gene expression data across cohorts and countries contain biases that previous transcriptomics studies have not addressed. Our aim was to integrate easy-to-interpret reliable transcriptome-wide biomarkers into subtyping pipelines. We analyzed 2,046 samples from two continents, carefully adjusted for biases and applied a rigorous machine learning design with independent replication. Six ALL subtypes that covered 32% of patients were robustly detected by mRNA-seq (PPV ≥ 87%). Five other frequent subtypes were distinguishable in 40% of patients, although overlapping transcriptional profiles led to lower accuracy (52% ≤ PPV ≤ 73%). Based on these findings, we developed the Allspice tool that predicts ALL subtypes and driver genes from unadjusted mRNA-seq read counts as encountered in real-world settings. Allspice also includes quantitative classification and safety metrics to help determine the most plausible genetic drivers for cases where other findings are inconclusive.
Clinical severity of Omicron sub-lineage BA.2 compared to BA.1 in South Africa
Authors: Wolter Nicole , Jassat Waasila ,   DATCOV-Gen author group, von Gottberg Anne , Cohen Cheryl 
Published: February 2022

ABSTRACTEarly data indicated that infection with Omicron BA.1 sub-lineage was associated with a lower risk of hospitalisation and severe illness, compared to Delta infection. Recently, the BA.2 sub-lineage has increased in many areas globally. We aimed to assess the severity of BA.2 infections compared to BA.1 in South Africa. We performed data linkages for (i) national COVID-19 case data, (ii) SARS-CoV-2 laboratory test data, and (iii) COVID-19 hospitalisations data, nationally. For cases identified using TaqPath COVID-19 PCR, infections were designated as S-gene target failure (SGTF, proxy for BA.1) or S-gene positive (proxy for BA.2). Disease severity was assessed using multivariable logistic regression models comparing individuals with S-gene positive infection to SGTF-infected individuals diagnosed between 1 December 2021 to 20 January 2022. From week 49 (starting 5 December 2021) through week 4 (ending 29 January 2022), the proportion of S-gene positive infections increased from 3% (931/31,271) to 80% (2,425/3,031). The odds of being admitted to hospital did not differ between individuals with S-gene positive (BA.2 proxy) infection compared to SGTF (BA.1 proxy) infection (adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.85-1.09). Among hospitalised individuals, after controlling for factors associated with severe disease, the odds of severe disease did not differ for individuals with S-gene positive infection compared to SGTF infection (aOR 0.91, 95%CI 0.68-1.22). These data suggest that while BA.2 may have a competitive advantage over BA.1 in some settings, the clinical profile of illness remains similar.
Should COVID-specific arrangements for abortion continue? The views of women experiencing abortion in Britain during the pandemic
Authors: Lohr Patricia A. , Lewandowska Maria , Meiksin Rebecca , Scott Rachel , Reiter Jennifer , Salaria Natasha , Cameron Sharon , Palmer Melissa , French Rebecca , Wellings Kaye 
Published: February 2022

ABSTRACTBackgroundDuring the COVID-19 pandemic, the British governments issued temporary approvals enabling the use of both pills for medical abortion at home. This permitted the introduction of a fully telemedical model of abortion care with consultations taking place via phone or video call and medications delivered to women’s homes. The approvals in England and Wales will expire at the end of March 2022, while that in Scotland remains under consultation.MethodsWe interviewed 30 women who had undergone an abortion in England, Scotland or Wales between August and December 2021. We explored their views on the changes in abortion service configuration during the pandemic and whether abortion via telemedicine and use of abortion medications at home should continue.ResultsSupport for continuation of the permission to use mifepristone and misoprostol at home was overwhelmingly positive. Reasons cited included convenience, comfort, reduced stigma, privacy, and respect for autonomy. A telemedical model was also highly regarded for similar reasons but for some its necessity was linked to safety measures during the pandemic and an option to have an in-person interaction with a health professional at some point in the care pathway was endorsed.ConclusionsThe approval to use abortion pills at home via telemedicine are supported by women having abortions in Great Britain. The respective governments in England, Scotland, and Wales, should be responsive to the patient voice and move to make permanent these important advances in abortion care.What is already known on this topicDuring the COVID-pandemic, specific permission to use both pills for medical abortion at home was granted in England, Scotland and Wales leading to the widespread implementation of a telemedical model with direct-to-patient delivery of medications. The safety, effectiveness, and acceptability of this model of care had been well-documented prior to and during the pandemic.What this study addsThis study adds the voices of women undergoing abortion during the pandemic regarding the specific changes that led to the transformation of medical abortion care in Britain. Amongst 30 women interviewed, there was endorsement for the continuation of permissions to use medical abortion pills at home via telemedicine.How this study might affect research, practice, or policyThe UK government’s vision of health provision puts patients and the public first, where “no decision about me, without me” is the norm. Our findings support law and policy makers in applying this principle to recent developments in abortion care by making the permissions permanent.
The combination of autism and exceptional cognitive ability increases risk for suicidal ideation
Authors: Casten Lucas G , Thomas Taylor R , Doobay Alissa F , Foley-Nicpon Megan , Kramer Sydney , Nickl-Jockschat Thomas , Abel Ted , Assouline Susan , Michaelson Jacob J 
Published: February 2022

AbstractAutism with co-occurring exceptional cognitive ability is often accompanied by severe internalizing symptoms and feelings of inadequacy. Whether cognitive ability also translates into greater risk for suicidal ideation is unclear. To investigate this urgent question, we examined two samples of high-ability individuals with autism for factors that were predictive of suicidal ideation. In the first sample (N=1,074 individuals seen at a clinic specializing in gifted/talented youth), we observed a striking excess of parent-reported suicidal ideation in autistic individuals with IQ≥120 (OR=5.9,p= 0.0007). In separate sample of N=1,983 SPARK participants, we confirmed higher rates of suicidal thoughts compared to non-autistic children from the ABCD cohort (OR=6.8,p <2.2×10−16), and further that autistic children with suicidal thoughts had significantly higher cognitive ability (p <2.2×10−16) than those without. Elevated polygenic scores (PGS) for cognitive performance were associated with increased suicidal thoughts (Z= 2.16,p= 0.03), with PGS for educational attainment trending in the same direction (Z= 1.4,p= 0.17). Notably, similar results were found in parents of these autistic youth, where higher PGS for educational attainment was associated with increasing thoughts of suicide (Z=2.28, p=0.02). Taken together, these results suggest that on a phenotypic and genetic level, increasing cognitive ability is an unexpected risk factor for suicidal ideation in individuals diagnosed with, or at risk for autism.
Global prevalence of antidepressant utilization in the community: A protocol for a systematic review
Authors: Lunghi Carlotta , Dugas Michèle , Leclerc Jacinthe , Poluzzi Elisabetta , Martineau Cathy , Carnovale Valérie , Stéfan Théo , Blouin Patrick , Lépine Johanie , Jalbert Laura , Espinoza Suarez Nataly R. , Svyntozelska Olha , Dery Marie-Pier , Ekanmian Giraud , Nogueira Daniele Maria , Akinola Pelumi Samuel , Skidmore Becky , LeBlanc Annie 
Published: February 2022

ABSTRACTBackgroundAntidepressant drugs are the most frequently prescribed medication for mental disorders. They are also used off-label and for non-psychiatric indications. Prescriptions of antidepressants have increased in the last decades, but no systematic review exists on the extent of their use in the community.Methods and analysisWe will conduct a systematic review to estimate the prevalence of antidepressant use in the community. We will search for studies published from 2010 in the Embase and MEDLINE databases. Study selection (by title/abstract and full-text screening) and data extraction for included studies will be independently conducted by pairs of reviewers. We will then synthesize the data on the prevalence of antidepressant use in individuals living in the community. If possible, we will perform a meta-analysis to generate prevalence-pooled estimates. If the data allows it, we will conduct subgroup analyses by antidepressant class, age, sex, country or other sociodemographics. We will evaluate the risk of bias for each included study through a quality assessment using the Joanna Briggs Institute Critical Appraisal tool: Checklist for Studies Reporting Prevalence Data. DistillerSR software will be used for the management of this review.Ethics and disseminationEthical approval is not required for this review as it will not involve human or animal subjects. The findings of our systematic review will be disseminated through publications in peer-reviewed journals, the Qualaxia Network (https://qualaxia.org), presentations to international conferences on mental health and pharmacoepidemiology, as well as general public events.PROSPERO registration detailsCRD42021247423
AIscEA: Unsupervised Integration of Single-cell Gene Expression and Chromatin Accessibility via Their Biological Consistency
Authors: Jafari Elham , Johnson Travis , Wang Yue , Liu Yunlong , Huang Kun , Wang Yijie 
Published: February 2022

AbstractSince the integrative analysis of single-cell gene expression and chromatin accessibility measurements is essential for revealing gene regulation at the single-cell resolution, integrating these two measurements becomes one of the key challenges in computational biology. Because gene expression and chromatin accessibility are measurements from different modalities, no common features can be directly used to guide their integration. Current state-of-the-art methods assume that the number of cell types across the measurements is the same. However, when cell-type heterogeneity exists, they might not generate reliable results. Furthermore, current methods do not have an effective way to select the hyper-parameter under the unsupervised setting. Therefore, applying computational methods to integrate single-cell gene expression and chromatin accessibility measurements remains difficult.We introduce AIscEA – Alignment-based Integration of single-cell gene Expression and chromatin Accessibility – a computational method that integrates single-cell gene expression and chromatin accessibility measurements using their biological consistency. AIscEA first defines a ranked similarity score to quantify the biological consistency between cell types across measurements. AIscEA then uses the ranked similarity score and a novel permutation test to identify the cell-type alignment across measurements. For the aligned cell types, AIscEA further utilizes graph alignment to align the cells across measurements. We compared AIscEA with the competing methods on several benchmark datasets and demonstrated that AIscEA is more robust to hyper-parameters and can better handle the cell-type heterogeneity problem. Furthermore, we demonstrate that AIscEA significantly outperforms the state-of-the-art methods when integrating real-world SNARE-seq and scMultiome-seq datasets in terms of integration accuracy.
Rapid thalamocortical network switching mediated by cortical synchronization underlies propofol-induced EEG signatures: a biophysical model
Authors: Soplata Austin E. , Adam Elie , Brown Emery N. , Purdon Patrick L. , McCarthy Michelle M. , Kopell Nancy 
Published: February 2022

AbstractPropofol-mediated unconsciousness elicits strong alpha/low-beta and slow oscillations in the electroencephalogram (EEG) of patients. As anesthetic dose increases, the EEG signal changes in ways that give clues to the level of unconsciousness; the network mechanisms of these changes are only partially understood. Here, we construct a biophysical thalamocortical network involving brainstem influences that reproduces transitions in dynamics seen in the EEG involving the evolution of the power and frequency of alpha/low beta and slow rhythm, as well as their interactions.Our model suggests propofol engages thalamic spindle and cortical sleep mechanisms to elicit persistent alpha/low-beta and slow rhythms, respectively. The thalamocortical network fluctuates between two mutually exclusive states on the timescale of seconds. One state is characterized by continuous alpha/low-beta frequency spiking in thalamus (C-state), while in the other, thalamic alpha spiking is interrupted by periods of co-occurring thalamic and cortical silence (I-state). In the I-state, alpha co-localizes to the peak of the slow; in the C-state, there is a variable relationship between an alpha/beta rhythm and the slow oscillation. The C-state predominates near loss of consciousness; with increasing dose, the proportion of time spent in the I-state increases, recapitulating EEG phenomenology. Cortical synchrony drives the switch to the I-state by changing the nature of the thalamocortical feedback. Brainstem influence on the strength of thalamocortical feedback mediates the amount of cortical synchrony. Our model implicates loss of low-beta, cortical synchrony, and coordinated thalamocortical silent periods as contributing to the unconscious state.New & NoteworthyGABAergic anesthetics induce alpha/low-beta and slow oscillations in the EEG, which interact in dose-dependent ways. We construct a thalamocortical model to investigate how these interdependent oscillations change with propofol dose. We find two dynamic states of thalamocortical coordination, which change on the timescale of seconds and dose-dependently mirror known changes in EEG. Thalamocortical feedback determines the oscillatory coupling and power seen in each state, and this is primarily driven by cortical synchrony and brainstem neuromodulation.
The virtual aging brain: a model-driven explanation for cognitive decline in older subjects
Authors: Lavanga Mario , Stumme Johanna , Yalcinkaya Bahar Hazal , Fousek Jan , Jockwitz Christiane , Sheheitli Hiba , Bittner Nora , Hashemi Meysam , Petkoski Spase , Caspers Svenja , Jirsa Viktor 
Published: February 2022

AbstractHealthy aging is accompanied by heterogeneous decline of cognitive abilities among individuals, especially during senescence. The mechanisms of this variability are not understood, but have been associated with the reorganization of white matter fiber tracts and the functional co-activations of brain regions. Here, we built a causal inference framework to provide mechanistic insight into the link between structural connectivity and brain function, informed by brain imaging data and network modeling. By applying various degrees of interhemispheric degradation of structural connectivity, we were not only able to reproduce the age-related decline in interhemispheric functional communication and the associated dynamical flexibility, but we obtained an increase of global modulation of structural connectivity over the brain function during senescence. Notably, the increase in modulation between structural connectivity and brian function was higher in magnitude and steeper in its increase in older adults with poor cognitive performance. We independently validated the causal hypothesis of our framework via a Bayesian approach based on deep-learning. The current results might be the first mechanistic demonstration of dedifferentiation and scaffolding during aging leading to cognitive decline demonstrated in a large cohort.
The impact of familiarity on cortical taste coding
Authors: Staszko Stephanie M. , Boughter John D. , Fletcher Max L. 
Published: February 2022

AbstractThe role of the gustatory region of the insular cortex in mediating associative taste learning, such as conditioned taste aversion, has been well studied. However, while associative learning plays a role in some taste behaviors, such as avoidance of toxins, taste stimuli are often encountered by animals in their natural environment without explicit consequences. This type of inconsequential experience with sensory stimuli has been studied in other sensory systems, generally with the finding that neuronal responses habituate with repeated sensory exposure. The present study sought to determine the effect of taste familiarity on population taste coding in mouse gustatory cortex (GC). Using microendoscope calcium imaging, we studied the taste responses of visually identifiable neurons over five days of taste experience, during which animals could freely choose to consume taste stimuli. We found that the number of active cells in insular cortex, as well as the number of cells characterized as taste-responsive, significantly decreased as animals became familiar with taste stimuli. Moreover, the magnitude of taste-evoked excited responses increased, and inhibited responses decreased with experience. By tracking individual neurons over time, we focused on taste coding in a subpopulation of “stable” neurons that were present on all days of the taste familiarity paradigm. The population-level response across these stable cells was distinct when taste stimuli were novel but became more intercorrelated among those taste stimuli mice willingly consumed as the stimuli became familiar. Overall, these results highlight the effects of familiarity on taste responses in gustatory cortex.
Reduced sensorimotor beta dynamics could represent a “slowed movement state” in healthy individuals
Authors: Leriche Ryan B. , Jackson Nicholas , Peterson Kathryn , Aspandiar Zeeya , Hufnagel Vanessa , Swann Nicole C. 
Published: February 2022

AbstractBeta oscillations (~13-30 Hz) recorded from the sensorimotor cortex have canonical amplitude changes during movement. Specifically, a movement-related beta decrease (MRBD) occurs before movement, and a post-movement beta rebound (PMBR) follows. We investigated how the MRBD and PMBR vary with movement speed. Individuals performed a task with blocks that generated longer reaction times (RTs) and shorter RTs (Slow and Fast blocks, respectively) while scalp-electroencephalography (EEG) was recorded. The timing of task events before movement was also modulated to generate blocks with certain and uncertain timing (Fixed and Varied blocks, respectively). Beta modulation was reduced in Slow blocks compared to Fast blocks (i.e., a less negative MRBD and less positive PMBR). For the movement certainty manipulation, we saw mixed behavioral and EEG results. Our primary findings align with previous work which has shown reduced movement-related beta modulation in patients with Parkinson’s disease. We propose that a “slowed movement state”, whether it is experimentally induced or a manifestation of Parkinson’s disease bradykinesia, is represented through reduced beta dynamics. Altogether, the MRBD and PMBR may represent motor speed on a continuum with Parkinson’s disease as an extreme example of slowed movement.
Host and microbiome features of secondary infections in lethal covid-19
Authors: Zacharias Martin , Kashofer Karl , Wurm Philipp , Regitnig Peter , Schütte Moritz , Neger Margit , Ehmann Sandra , Marsh Leigh M. , Kwapiszewska Grazyna , Loibner Martina , Birnhuber Anna , Leitner Eva , Thüringer Andrea , Winter Elke , Sauer Stefan , Pollheimer Marion J. , Vagena Fotini R. , Lackner Carolin , Jelusic Barbara , Ogilvie Lesley , Durdevic Marija , Timmermann Bernd , Lehrach Hans , Zatloukal Kurt , Gorkiewicz Gregor 
Published: February 2022

AbstractSecondary infections contribute significantly to covid-19 mortality but host and microbial factors driving this sequel remain poorly understood. We performed an autopsy study of 20 covid-19 cases and 14 controls from the first pandemic wave. Autopsies combined with microbial cultivation and deep RNA sequencing (RNAseq) allowed us to define major organ pathologies and specify secondary infections. Lethal covid-19 segregated into two main death causes separating cases with either dominant diffuse alveolar damage (DAD) or secondary infections of lungs. Lung microbiome changes were profound in covid-19 showing a reduced biodiversity and increased presence of prototypical bacterial and fungal pathogens in cases with secondary infections. Deep RNAseq of lung tissues distinctly mirrored death causes and cellular deconvolution stratified DAD cases into subgroups with different cellular compositions. Myeloid cells, including macrophages, and complement C1q activation were found to be strong stratifying factors suggesting a pathophysiological link possibly leading to tolerance in DAD subgroups. Moreover, several signs of immune-impairment were evident in covid-19 lungs including strong induction of inhibitory immune-checkpoints. Thus, our study highlights profound alterations of the local immunity in covid-19, wherein immune-impairment leads to reduced antimicrobial defense favoring the development of secondary infections on top of SARS-CoV-2 infection.
Characterizing SARS-CoV-2 transcription of subgenomic and genomic RNAs during early human infection using multiplexed ddPCR
Authors: Hwang Hyon S. , Lo Che-Min , Murphy Michael , Grudda Tanner , Gallagher Nicholas , Luo Chun Huai , Robinson Matthew L. , Mirza Agha , Conte Madison , Conte Abigail , Zhou Ruifeng , Brooke Christopher B. , Pekosz Andrew , Mostafa Heba H. , Manabe Yukari C. , Thio Chloe L. , Balagopal Ashwin 
Published: February 2022

AbstractControl of SARS-CoV-2 (SCV-2) transmission is a major priority that requires understanding SCV-2 replication dynamics. We developed and validated novel droplet digital PCR (ddPCR) assays to quantify SCV-2 subgenomic RNAs (sgRNAs), which are only produced during active viral replication, and discriminate them from full-length genomic RNAs (gRNAs) in a multiplexed format. We applied this multiplex ddPCR assay to 144 cross-sectional nasopharyngeal samples. sgRNAs were quantifiable across a range of qPCR cycle threshold (Ct) values and correlated with Ct values. The ratio of sgRNA:gRNA was remarkably stable across a wide range of Ct values, whereas adjusted amounts of N sgRNA to a human housekeeping gene declined with higher Ct values. Interestingly, adjusted sgRNA and gRNA amounts were quantifiable in culture-negative samples, although levels were significantly lower than in culture-positive samples. Longitudinal daily testing of 6 persons for up to 14 days revealed that sgRNA is concordant with culture results during the first week of infection but may be discordant with culture later in infection. Further, sgRNA:gRNA is constant during infection despite changes in viral culture. These data indicate stable viral transcription during infection. More work is needed to understand why cultures are negative despite persistence of viral RNAs.