bluuebunny/crossref_metadata_2025_split huggingface dataset:
The intersection between migration, HIV, and family planning in Uganda: a cross-sectional population-based study
Authors: Namusisi Prossy , Yeh Ping Teresa , Ssekubugu Robert , Chang Larry William , Lutalo Tom , Zimmerman Linnea A. , Grabowski Mary Kathryn 
Published: August 2023

AbstractBackgroundLow use of modern methods of contraception has been linked to HIV seropositivity and to migration, but few studies have evaluated the intersection of both risk factors with contraceptive use.MethodsWe analyzed cross-sectional data from sexually active female participants aged 15 to 49 years in the Rakai Community Cohort Study (RCCS) between 2011 and 2013. The RCCS is an open population-based census and individual survey in south-central Uganda. Recent in-migrants (arrival within approximately 1.5 years) into RCCS communities were identified at time of household census. The primary outcome was unsatisfied demand for a modern contraceptive method (injectable, oral pill, implant, or condom), which was defined as non-use of a modern contraceptive method among female participants who did not want to become pregnant in the next 12 months. Poisson regression models with robust variance estimators were used to identify associations and interactions between recent migration and HIV serostatus on unsatisfied contraceptive demand.ResultsThere were 3,417 sexually active participants with no intention of becoming pregnant in the next year. The mean age was 30 (±8) years, and 17.3% (n=591) were living with HIV. Overall, 43.9% (n=1,500) were not using any modern contraceptive method. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents (adjusted prevalence risk ratio [adjPRR]=1.14; 95% confidence interval [95%CI]: 1.02–1.27), whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-seronegative participants (adjPRR=0.80; 95%CI=0.70-0.90). When stratifying on migration and HIV serostatus, we observed the highest levels of unsatisfied contraceptive demand among in-migrants living with HIV (48.7%); however, in regression analyses, interaction terms between migration and HIV serostatus were not statistically significant.ConclusionsUnsatisfied contraceptive demand was high in this rural Ugandan setting. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand.
Support mechanisms for nurses aspiring to or undertaking clinical academic development globally – protocol for a scoping review
Authors: Jennings Claire , Norman Gill , Marshall Marie , Briggs Michelle 
Published: August 2023

AbstractIntroductionNurse researchers often lack awareness of how to start a clinical academic research career and often lack clear entry routes. This scoping review aims to identify the range and nature of clinical academic opportunities that are available for nurses. This will identify knowledge gaps and provide the basis for future research.Methods and analysisThe review will be conducted using scoping review methodology and reported in accordance with PRISMA-SCR guidelines. We will search CINAHL (EBSCO), Medline (OVID), AMED (OVID) and ProQuest using a search based on the facet’s ‘nurse’ ‘research’ and ‘clinical academic’. Grey literature and a hand search of the reference lists will be conducted for additional publications which meet the inclusion and exclusion criteria. We will include articles with a focus on nurses who are interested in undertaking clinical academic development, or a focus on programmes aimed at supporting clinical academic development for nurses. Following initial screening of titles and abstracts, relevant full text papers will be screened for inclusion. A proportion of all records at each stage will be screened by a second reviewer. We will use a prespecified form to extract data which will be charted and presented in tabular form. Samples of data extraction and charting will be checked by a second reviewer. This will support a narrative summary structured around key identified variables agreed iteratively by the review team.Ethics and disseminationNo ethical or Health Research Authority approval is required to undertake this scoping review. This protocol has been registered with The Open Science Framework (DOI 10.17605/OSF.IO/WVDXH). The findings will inform future research exploring the support mechanisms for nurses aspiring to undertake clinical academic development and be disseminated via presentations at national conferences and publications in peer reviewed journals.Article summaryStrengths and Limitations of this studyThis is the first exploration review of the nature and range of clinical academic opportunities that are available to nurses.The scoping review will be undertaken and reported following established guidelines to ensure transparency and reproducibility.The identification and synthesis of data will include published articles found on the CINAHL, Medline, AMED and ProQuest databases, grey literature available on relevant organisations and professional bodies, and a hand search of reference lists.The scoping review will be focussed on nurses undertaking clinical academic development programmes, as they are the largest group of registered healthcare professionals and are underrepresented as research leaders.Due to limited resources, only a proportion of the screening will be undertaken be 2ndreviewer, and literature not available in English Language will be excluded. We will mitigate these issues by use of additional checks and listing of relevant foreign language studies.
Spatial and temporal control of 3D hydrogel viscoelasticity through phototuning
Authors: Crandell Philip , Stowers Ryan 
Published: August 2023

ABSTRACTThe mechanical properties of the extracellular environment can regulate a variety of cellular functions, such as spreading, migration, proliferation, and even differentiation and phenotypic determination. Much effort has been directed at understanding the effects of the extracellular matrix (ECM) elastic modulus and more recently, stress relaxation, on cellular processes. In physiological contexts like development, wound healing, and fibrotic disease progression, ECM mechanical properties change substantially over time or space. Dynamically tunable hydrogel platforms have been developed to spatiotemporally modulate a gel’s elastic modulus. However, dynamically altering the stress relaxation rate of a hydrogel remains a challenge. Here, we present a strategy to tune hydrogel stress relaxation rates in time or space using a light-triggered tethering of poly(ethylene glycol) (PEG) to alginate. We show that stress relaxation rate can be tuned without altering the elastic modulus of the hydrogel. We found that cells are capable of sensing and responding to dynamic stress relaxation rate changes, both morphologically and through differences in proliferation rates. We also exploited the light-based technique to generate spatial patterns of stress relaxation rates in 3D hydrogels. We anticipate that user-directed control of 3D hydrogel stress relaxation rate will be a powerful tool that enables studies that mimic dynamic ECM contexts, or as a means to guide cell fate in space and time for tissue engineering applications.
A model to analyze age-related differences in human-generated head-tail sequences
Authors: Baena-Mirabete Sergio , García-Viedma Rosario , Fernández-Guinea Sara , Puig Pere 
Published: August 2023

AbstractThe generation of random-like sequences is a common task for assessing high-level cognitive abilities, such as inhibition, sustained attention and working memory. In general, many studies have shown a detrimental effect of aging on pseudo-random productions. The performance of participants in random generation tasks has typically been assessed by measures of randomness such as, among others, entropy and algorithmic complexity that are calculated from the series of responses produced by the subject. We focus on analyzing the mental model of randomness that people implicitly use when producing random series. We propose a novel latent class model based on Markov chains that aims to classify individuals into homogeneous classes according to the way they generate head-tail series. Our results reveal that there are significant age-related differences in the way individuals produce random-like sequences. Specifically, the group of healthy adults implicitly uses a simpler mental mechanism, in terms of memory requirements, compared to the group of younger participants.Author summaryIt is well known that, in general, people deviate from randomness as they attempt to mentally generate head-tail sequences as randomly as possible. The extensive literature on this topic has shown that human-generated head-tail series tend to have more alternations than would be expected by chance. However, it seems unrealistic to suppose that all individuals generate sequences based on the same random mental model. We conducted an experiment in which 331 individuals were asked to mentally simulate a fair coin: 69 healthy older adults with an age ≥ 60 and 262 Biology students with an age between 18 and 20. We found that the way in which random sequences are generated varies between subjects. A similar approach could be used to analyze differences in random generation tasks between subjects with different disorders and healthy subjects.
EagleC Explorer: A desktop application for interactively detecting and visualizing SVs and enhancer hijacking on Hi-C contact maps
Authors: Fu Yihao , Wang Xiaotao , Yue Feng 
Published: August 2023

AbstractIt has been shown that Hi-C can be used as a powerful tool to detect structural variations (SVs) and enhancer hijacking events. However, there has been no existing programs that can directly visualize and detect such events on a personal computer, which hinders the broad adaption of the technology for intuitive discovery in cancer studies. Here, we introduce the EagleC Explorer, a desktop software that is specifically designed for exploring Hi-C and other chromatin contact data in cancer genomes. EagleC Explorer has a set of unique features, including 1) conveniently visualizing global and local Hi-C data; 2) interactively detecting SVs on a Hi-C map for any user-selected region on screen within seconds, using a deep-learning model; 3) reconstructing local Hi-C map surrounding user-provided SVs and generating publication-quality figures; 4) detecting enhancer hijacking events for any user-suggested regions on screen. In addition, EagleC Explorer can also incorporate other genomic tracks such as RNA-Seq or ChIP-Seq to facilitate scientists for integrative data analysis and making novel discoveries.
FRET-guided modeling of nucleic acids
Authors: Steffen Fabio D. , Cunha Richard A. , Sigel Roland K.O. , Börner Richard 
Published: August 2023

AbstractThe functional diversity of RNA is encoded in their innate conformational heterogeneity. The combination of single-molecule spectroscopy and computational modeling offers new, attractive opportunities to map structural transitions within nucleic acid ensembles. Here, we describe a framework to harmonize single-molecule FRET measurements with molecular dynamics simulations andde novostructure prediction. Using either all-atom or implicit fluorophore modeling we recreate FRET experimentsin silico, visualize the underlying structural dynamics and quantify the simulated reaction coordinates. Using multiple accessible-contact volumes (multi-ACV) as apost-hocscoring method for fragment-assembly in Rosetta, we demonstrate that FRET effectively refinesde novoRNA structure prediction without the need of explicit dye labeling. We benchmark our FRET-assisted modeling approach on double-labeled DNA strands and validate it against an intrinsically dynamic manganese(II)-binding riboswitch. We show that a FRET coordinate describing the assembly of a four-way junction allows our pipeline to recapitulate the global fold of the riboswitch with sub-helical accuracy to the crystal structure. We conclude that computational fluorescence spectroscopy facilitates the interpretability of dynamic structural ensembles and improves the mechanistic understanding of nucleic acid interactions.Graphical abstractSchematic workflow of integrative FRET modeling using all-atom fluorophores or an accessible-contact volume dye model. All-atom molecular dynamics track the dye coordinate explicitly as part of the simulation while multi-ACV infer mean dye positionspost hoc.
Development of neonatal connectome dynamics and its prediction for cognitive and language outcomes at age 2
Authors: Xu Yuehua , Liao Xuhong , Lei Tianyuan , Cao Miao , Zhao Jianlong , Zhang Jiaying , Zhao Tengda , Li Qiongling , Jeon Tina , Ouyang Minhui , Chalak Lina , Rollins Nancy , Huang Hao , He Yong 
Published: August 2023

AbstractThe functional connectome of the human brain comprises time-varying network structure that facilitates efficient inter-module communication and support flexible cognitive functions. However, little is known about how the connectome dynamics of the brain emerges and develops at very early stages of human life and whether this dynamics is predictive of neurocognitive outcomes later in life. Here, we employed resting-state functional MRI data from 39 infants (31 to 42 postmenstrual weeks) and a multilayer network model to characterize the development of connectome dynamics during the third trimester and its critical role in predicting future neurocognitive outcomes at 2 years of age. We observed that the modular architecture of baby functional connectomes spontaneously reconfigures over time, with lower network module switching across time primarily in the primary regions and higher module switching mainly in the association areas. With development, the dynamic switching between the brain modules was significantly decreased, primarily located in the lateral precentral gyrus, medial temporal lobe, and subcortical areas. The clustering analysis further revealed that the primary areas displayed a higher developmental rate than the higher-order systems. Using the support vector regression approach, we found that brain connectome dynamics at birth significantly predicted cognitive and language performance at 2 years of age. Our findings highlight the emergence and spatially inhomogeneous maturation of the neonate connectome dynamics, laying a critical neural foundation for the development of cognitive and language skills later in life.
Nuclear Factor Kappa B Over-Activation in the Intervertebral Disc Leads to Macrophage Recruitment and Severe Disc Degeneration
Authors: Burt Kevin G. , Kim Min Kyu M. , Viola Dan C. , Abraham Adam C. , Chahine Nadeen O. 
Published: August 2023

ABSTRACTObjectiveLow back pain (LBP) is the leading cause of global disability and is thought to be driven primarily by intervertebral disc (IVD) degeneration (DD). Persistent upregulation of catabolic enzymes and inflammatory mediators have been associated with severe cases of DD. Nuclear factor kappa B (NF-κB) is a master transcription regulator of immune responses and is over expressed during inflammatory-driven musculoskeletal diseases, including DD. However, its role in triggering DD is unknown. Therefore, this study investigated the effect of NF-κB pathway over-activation on IVD integrity and DD pathology.MethodsUsing skeletally mature mouse model, we genetically targeted IVD cells for canonical NF-κB pathway activation via expression of a constitutively active form of inhibitor of κB kinase B (IKKβ), and assessed changes in IVD cellularity, structural integrity including histology, disc height, and extracellular matrix (ECM) biochemistry, biomechanics, expression of inflammatory, catabolic, and neurotropic mediators, and changes in macrophage subsets, longitudinally up to 6-months post activation.ResultsProlonged NF-κB activation led to severe structural degeneration, with a loss of glycosaminoglycan (GAG) content and complete loss of nucleus pulposus (NP) cellularity. Structural and compositional changes decreased IVD height and compressive mechanical properties with prolonged NF-κB activation. These alterations were accompanied by increases in gene expression of inflammatory molecules (Il1b, Il6, Nos2), chemokines (Mcp1,Mif), catabolic enzymes (Mmp3, Mmp9, Adamts4), and neurotrophic factors (Bdnf,Ngf) within IVD tissue. Increased recruitment of activatedF4/80+macrophages exhibited a greater abundance of pro-inflammatory (CD38+) over inflammatory-resolving (CD206+) macrophage subsets in the IVD, with temporal changes in the relative abundance of macrophage subsets over time, providing evidence for temporal regulation of macrophage polarization in DDin vivo,where macrophages participate in resolving the inflammatory cascade but promote fibrotic transformation of the IVD matrix. We further show that NF-κB driven secretory factors from IVD cells increase macrophage migration and inflammatory activation, and that the secretome of inflammatory-resolving macrophages mitigates effects of NF-κB overactivation.ConclusionOverall the observed results suggest prolonged NF-κB activation can induce severe DD, acting through increases in inflammatory cytokines, chemotactic proteins, catabolic enzymes, and the recruitment and inflammatory activation of a macrophage cell populations, that can be mitigated with inflammatory-resolving macrophage secretome.
Single-cell somatic copy number variants in brain using different amplification methods and reference genomes
Authors: Kalef-Ezra Ester , Turan Zeliha Gozde , Perez-Rodriguez Diego , Bomann Ida , Behera Sairam , Morley Caoimhe , Scholz Sonja W. , Jaunmuktane Zane , Demeulemeester Jonas , Sedlazeck Fritz J , Proukakis Christos 
Published: August 2023

AbstractThe presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. We compared PicoPLEX with two recent adaptations of multiple displacement amplification (MDA): primary template-directed amplification (PTA) and droplet MDA, across 93 human brain cortical nuclei. We demonstrated different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we performed CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We found that 38% of brain cells have at least one Mb-scale CNV, with some supported by bulk sequencing or single-cells from other brain regions. Our study highlights the importance of selecting whole genome amplification method and reference genome for CNV calling, while supporting the existence of somatic CNVs in healthy and diseased human brain.
Predictive Modeling of Evoked Intracranial EEG Response to Medial Temporal Lobe Stimulation in Patients with Epilepsy
Authors: Acharya Gagan , Davis Kathryn A. , Nozari Erfan 
Published: August 2023

AbstractDespite promising advancements, closed-loop neurostimulation for drug-resistant epilepsy (DRE) still relies on manual tuning and produces variable outcomes, while automated predictable algorithms remain an aspiration. As a fundamental step towards addressing this gap, here we study predictive dynamical models of human intracranial EEG (iEEG) response under parametrically rich neurostimulation. Using data from n = 13 DRE patients, we find that stimulation-triggered switched-linear models with ∼300ms of causal historical dependence best explain evoked iEEG dynamics. These models are highly consistent across different stimulation amplitudes and frequencies, allowing for learning a generalizable model from abundant STIM OFF and limited STIM ON data. Further, evoked iEEG in nearly all subjects exhibited a distance-dependent pattern, whereby stimulationdirectlyimpacts the actuation site and nearby regions (≲ 20mm), affects medium-distance regions (20 ∼ 100mm) through network interactions, and hardly reaches more distal areas (≳ 100mm). Peak network interaction occurs at 60∼80mm from the stimulation site. Due to their predictive accuracy and mechanistic interpretability, these models hold significant potential for model-based seizure forecasting and closed-loop neurostimulation design.
Deciphering the orthorhombic crystal structure of a novel NEIL1 nanobody with pseudo-merohedral twinning
Authors: Thompson Marlo K. , Sharma Nidhi , Prakash Aishwarya 
Published: August 2023

AbstractNanobodies or VHHs (Variable Heavy domains of Heavy chain) are single domain antibodies that comprise three antigenic complementary determining regions (CDR). Nanobodies are used in numerous scientific applications including, bio-imaging, diagnosis, therapeutics, and macromolecular crystallography. We obtained crystals of a ∼14 kDa nanobody specific for the NEIL1 DNA glycosylase (hereafter called A5) in 0.5 M ammonium sulfate, 0.1 M sodium citrate tribasic dihydrate pH 5.6, and 1.0 M lithium sulfate monohydrate from the Crystal HT Hampton Research screen that were further optimized. Here, we describe the structure determination and refinement of the A5 crystals to a resolution of 2.1 Å. The data collected were complicated by the presence of anisotropy and twinning, and while initial space group determination pointed to a higher apparent tetragonal crystal system, the data statistics suggested twinning, placing the crystal in an orthorhombic system. Twinning was confirmed by the Padilla and Yeates test, H-test, and Britton test based on local intensity differences with a twin fraction of 0.4. Molecular replacement produced the best solution in the orthorhombic space group P21212 with four molecules in the asymmetric unit and we were able to model over 96% of the residues in the electron density with a final Rworkand Rfreeof 0.1988 and 0.2289 upon refinement.SynopsisThe crystal structure of a specific nanobody against NEIL1 was determined to 2.1 Å. The structure was ultimately solved in an orthorhombic space group after diffraction data analysis revealed mild anisotropy as well as pseudo-merohedral twinning