bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of AIDS-Related Kaposi Sarcoma in All 50 United States From 2000 to 2014
Authors: White Donna L. , Oluyomi Abiodun , Royse Kathryn , Dong Yongquan , Nguyen Harrison , Chang Elaine , Richardson Peter , Jiao Li , Garcia Jose M. , Kramer Jennifer R. , Thrift Aaron P. , Chiao Elizabeth 
Published: June 2019

Background:
Although declining rates of incident AIDS-related Kaposi sarcoma (KS) have been reported, KS incidence rates have noted race/ethnic, age, and geographic diversity. We performed a comprehensive assessment of recent secular trends in AIDS-related KS incidence in the United States.

Methods:
We identified incident KS diagnosed in men aged 20–54 years (who comprise most AIDS-related KS in the United States) using the US Cancer Statistics registry data. Joinpoint analysis assessed for trends in age-adjusted incidence rates between 2000 and 2014 calculating average annual percentage changes (AAPCs) with 95% confidence intervals. Heat maps were generated to compare age-adjusted HIV incidence rates with KS incidence rates.

Results:
Age-adjusted KS incidence rates nationwide decreased from 1.44/100,000 to 0.95/100,000 between 2000 and 2014. Observed rate changes varied across subgroups; eg, there were significant decreases in 30–44 years (AAPC = −5.4%), particularly in Whites and Blacks, significant increases among 20–29 years (AAPC = 2.7), primarily in Blacks, and stable rates among 45–54 years (AAPC = −0.03). In Southern United States, the incidence rates among Blacks did not significantly change. The states with highest average age-adjusted rates over the study period were Georgia (2.71/100,000), New York (2.16/100,000), California (2.02/100,000), Florida (1.90/100,000), and Texas (1.39/100,000), with significantly decreasing trends over time, except Georgia where rates increased (AAPC = 1.8).

Conclusions:
Although KS incidence rates have decreased nationally, age, racial, and geographic disparities persist, including increasing risk among younger Black men and particularly elevated rates in some southern states and urban areas. Further research is needed to address racial and geographic AIDS-related KS disparities.
Internalized HIV Stigma Is Associated With Concurrent Viremia and Poor Retention in a Cohort of US Patients in HIV Care
Authors: Christopoulos Katerina A. , Neilands Torsten B. , Hartogensis Wendy , Geng Elvin H. , Sauceda John , Mugavero Michael J. , Crane Heidi M. , Fredericksen Rob J. , Moore Richard D. , Mathews William Christopher , Mayer Kenneth H. , Chander Geetanjali , Hurt Christopher B. , Johnson Mallory O. 
Published: June 2019

Background:
The relationship of internalized HIV stigma to key care cascade metrics in the United States is not well established using large-scale, geographically diverse data.

Setting:
Center for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study.

Methods:
Beginning in February 2016, we administered a yearly, validated 4-item internalized HIV stigma scale (response scale 1 = strongly disagree to 5 = strongly agree, Cronbach's alpha 0.91) at 7 CNICS sites and obtained cohort data through November 2017. We compared mean stigma levels by sociodemographic characteristics and used multivariable logistic regression, controlling for the same sociodemographic covariates, to evaluate the association between mean stigma and (1) concurrent viremia; (2) missed visits; and (3) poor visit constancy. We used inverse probability weighting (IPW) to account for differences between patients who did and did not undergo stigma assessment.

Results:
Of 13,183 CNICS patients, 6448 (49%) underwent stigma assessment. Mean stigma was 1.99 (SD 1.07), and 28.6% agreed/strongly agreed with at least 1 stigma question. Patients younger than 50 years, racial/ethnic minorities, cis-women, and heterosexuals had higher mean stigma. Mean stigma score was associated with concurrent viremia [adjusted odds ratio (AOR) 1.13, 95% confidence interval (CI): 1.02 to 1.25, P 0.02], missed visits (AOR 1.10, 95% CI: 1.02 to 1.19, P 0.01), and poor visit constancy, although the effect on visit constancy was attenuated in the IPW model (AOR 1.05, 95% CI: 0.98 to 1.13, P 0.17).

Conclusions:
Higher internalized HIV stigma had a modest but statistically significant association with concurrent viremia and poor retention in care. Further inquiry with prospective analyses is warranted.
Marijuana Use and Its Associations With Pain, Opioid Dose, and HIV Viral Suppression Among Persons Living With HIV on Chronic Opioid Therapy
Authors: Merlin Jessica S. , Samet Jeffrey H. , Cheng Debbie M. , Lira Marlene C. , Tsui Judith I. , Forman Leah S. , Colasanti Jonathan , Walley Alexander Y. , Del Rio Carlos , Liebschutz Jane M. 
Published: June 2019

Background:
Medical marijuana is legal in 29 US states and the District of Columbia: both HIV and chronic pain are “approved conditions” for receipt. Chronic pain is common among people living with HIV (PLWH). We anticipate PLWH will question their providers about medical marijuana for chronic pain. We examined marijuana use and its associations with pain, opioid dose, and HIV viral suppression among PLWH receiving chronic opioid therapy.

Methods:
PLWH prescribed chronic opioid therapy were recruited into the Targeting Effective Analgesia in Clinics for HIV cohort. The main exposure variable was any past 12-month marijuana use. The primary outcomes were (1) opioid misuse (≥9 on the Current Opioid Misuse Measure) and (2) opioid dose (morphine equivalent daily dose). HIV viral load (VL) suppression (<200 copies/μL) and pain severity and interference using the Brief Pain Inventory were exploratory outcomes.

Results:
Participants (n = 166) were men (65%), Black (72%), and had an undetectable VL (89%). We found no significant association between current marijuana use and opioid misuse, opioid dose, or pain. Current marijuana use was associated with 3.03 times the odds of having a detectable VL (95% odds ratio: 1.11–8.31, P = 0.03) while controlling for depressive symptoms and other substance use.

Discussion:
We did not detect an association between marijuana use and opioid misuse behaviors, opioid dose, or pain. In an exploratory analysis, current marijuana use was associated with 3× greater odds of having a detectable VL. This study provides insights into potential consequences of marijuana use among PLWH with chronic pain.
Perlin Noise Generation of Physiologically Realistic Patterns of Fibrosis
Authors: Jakes David , Burrage Kevin , Drovandi Christopher C. , Burrage Pamela , Bueno-Orovio Alfonso , Santos Rodrigo Weber dos , Rodriguez Blanca , Lawson Brodie A. J. 
Published: June 2019

AbstractFibrosis, the pathological excess of fibroblast activity, is a significant health issue that hinders the function of many organs in the body, in some cases fatally. However, the severity of fibrosis-derived conditions depends on both the positioning of fibrotic affliction, and the microscopic patterning of fibroblast-deposited matrix proteins within afflicted regions. Variability in an individual’s manifestation of a type of fibrosis is an important factor in explaining differences in symptoms, optimum treatment and prognosis, but a need forex vivoprocedures and a lack of experimental control over conflating factors has meant this variability remains poorly understood. In this work, we present a computational methodology for the generation of patterns of fibrosis microstructure, demonstrating the technique using histological images of four types of cardiac fibrosis. Our generator and automated tuning method prove flexible enough to capture each of these very distinct patterns, allowing for rapid generation of new realisations for high-throughput computational studies. We also demonstrate via simulation, using the generated fibrotic patterns, the importance of micro-scale variability by showing significant differences in electrophysiological impact even within a single class of fibrosis.
BiSCoT: Improving large eukaryotic genome assemblies with optical maps
Authors: Istace Benjamin , Belser Caroline , Aury Jean-Marc 
Published: June 2019

ABSTRACTMotivationLong read sequencing and Bionano Genomics optical maps are two techniques that, when used together, make it possible to reconstruct entire chromosome or chromosome arms structure. However, the existing tools are often too conservative and organization of contigs into scaffolds is not always optimal.ResultsWe developed BiSCoT (Bionano SCaffolding COrrection Tool), a tool that post-processes files generated during a Bionano scaffolding in order to produce an assembly of greater contiguity and quality. BiSCoT was tested on a human genome and four publicly available plant genomes sequenced with Nanopore long reads and improved significantly the contiguity and quality of the assemblies. BiSCoT generates a fasta file of the assembly as well as an AGP file which describes the new organization of the input assembly.AvailabilityBiSCoT and improved assemblies are freely available on Github at http://www.genoscope.cns.fr/biscot and Pypi at https://pypi.org/project/biscot/.
A classification framework forBacillus anthracisdefined by global genomic structure
Authors: Bruce Spencer A. , Schiraldi Nicholas J. , Kamath Pauline L. , Easterday W. Ryan , Turner Wendy C. 
Published: June 2019

ABSTRACTBacillus anthracis, the causative agent of anthrax, is a considerable global health threat affecting wildlife, livestock, and the general public. In this study whole-genome sequence analysis of over 350B. anthracisisolates was used to establish a new high-resolution global genotyping framework that is both biogeographically informative, and compatible with multiple genomic assays. The data presented in this study shed new light on the diverse global dissemination of this species and indicate that many lineages may be uniquely suited to the geographic regions in which they are found. In addition, we demonstrate that plasmid genomic structure for this species is largely consistent with chromosomal population structure, suggesting vertical inheritance in this bacterium has contributed to its evolutionary persistence. This classification methodology is the first based on population genomic structure for this species and has potential use for local and broader institutions seeking to understand both disease outbreak origins and recent introductions. In addition, we provide access to a newly developed genotyping script as well as the full whole genome sequence analyses output for this study, allowing future studies to rapidly employ and append their data in the context of this global collection. This framework may act as a powerful tool for public health agencies, wildlife disease laboratories, and researchers seeking to utilize and expand this classification scheme for further investigations intoB. anthracisevolution.
Does alpha phase modulate visual target detection? Three experiments with tACS phase-based stimulus presentation
Authors: de Graaf Tom A. , Thomson Alix , Janssens Shanice E.W. , van Bree Sander , ten Oever Sanne , Sack Alexander T. 
Published: June 2019

AbstractIn recent years the influence of alpha (7-13 Hz) phase on visual processing has received a lot of attention. Magneto-/encephalography (M/EEG) studies showed that alpha phase indexes visual excitability and task performance. If occipital alpha phase is functionally relevant, the phase of occipital alpha-frequency transcranial alternating current stimulation (tACS) could modulate visual processing. Visual stimuli presented at different pre-determined, experimentally controlled, phases of the entraining tACS signal should then result in an oscillatory pattern of visual performance. We studied this in a series of experiments. In experiment one, we applied 10 Hz tACS to right occipital cortex (O2) and used independent psychophysical staircases to obtain contrast thresholds for detection of visual gratings in left or right hemifield, in six equidistant tACS phase conditions. In experiments two and three, tACS was at EEG-based individual peak alpha frequency. In experiment two, we measured detection rates for gratings with (pseudo-)fixed contrast levels. In experiment three, participants detected brief luminance changes in a custom-built LED device, at eight equidistant alpha phases. In none of the experiments did the primary outcome measure over phase conditions consistently reflect a one-cycle sinusoid as predicted. However, post-hoc analyses of reaction times (RT) suggested that tACS alpha phase did modulate RT in both experiments 1 and 2 (not measured in experiment 3). This observation is in line with the idea that alpha phase causally gates visual inputs through cortical excitability modulation.
Precise transcription timing by a second-messenger drives a bacterial G1/S cell cycle transition
Authors: Kaczmarczyk Andreas , Hempel Antje M. , von Arx Christoph , Böhm Raphael , Dubey Badri N. , Nesper Jutta , Schirmer Tilman , Hiller Sebastian , Jenal Urs 
Published: June 2019

ABSTRACTBacteria adapt their growth rate to their metabolic status and environmental conditions by modulating the length of their quiescent G1 period. But the molecular mechanisms controlling G1 length and exit from G1 are poorly understood. Here we identify a key role for the second messenger c-di-GMP, and demonstrate that a gradual increase in c-di-GMP concentration determines precise gene expression during G1/S inCaulobacter crescentus. We show that c-di-GMP strongly stimulates the kinase ShkA, activates the TacA transcription factor, and initiates a G1/S-specific transcription program leading to cell morphogenesis and S-phase entry. C-di-GMP activates ShkA by binding to its central pseudo-receiver domain uncovering this wide-spread domain as a novel signal input module of bacterial kinases. Activation of the ShkA-dependent genetic program also causes c-di-GMP to reach peak levels, which triggers S-phase entry and, in parallel, promotes proteolysis of ShkA and TacA. Thus, a gradual increase of c-di-GMP results in a precisely tuned ShkA-TacA activity window enabling G1/S specific gene expression before cells commit to replication initiation. By defining a regulatory mechanism for G1/S control, this study contributes to understanding bacterial growth control at the molecular level.GRAPHICAL ABSTRACT
Tailoring cryo-electron microscopy grids by photo-micropatterning for in-cell structural studies
Authors: Toro-Nahuelpan Mauricio , Zagoriy Ievgeniia , Senger Fabrice , Blanchoin Laurent , Théry Manuel , Mahamid Julia 
Published: June 2019

AbstractSpatially-controlled cell adhesion on electron microscopy (EM) supports remains a bottleneck in specimen preparation for cellular cryo-electron tomography. Here, we describe contactless and mask-free photo-micropatterning of EM grids for site-specific deposition of extracellular matrix-related proteins. We attained refined cell positioning for micromachining by cryo-focused ion beam milling. Complex patterns generated predictable intracellular organization, allowing direct correlation between cell architecture and in-cell 3D-structural characterization of the underlying molecular machinery.
Multimodal fusion of structural and functional brain imaging in depression using linked independent component analysis
Authors: Maglanoc Luigi A. , Kaufmann Tobias , Jonassen Rune , Hilland Eva , Beck Dani , Landrø Nils Inge , Westlye Lars T. 
Published: June 2019

AbstractBackgroundPrevious structural and functional neuroimaging studies have implicated distributed brain regions and networks in depression. However, there are no robust imaging biomarkers that are specific to depression, which may be due to clinical heterogeneity and neurobiological complexity. A dimensional approach and fusion of imaging modalities may yield a more coherent view of the neuronal correlates of depression.MethodsWe used linked independent component analysis to fuse cortical macrostructure (thickness, area, gray matter density), white matter diffusion properties and resting-state fMRI default mode network amplitude in patients with a history of depression (n = 170) and controls (n = 71). We used univariate and machine learning approaches to assess the relationship between age, sex, case-control status, and symptom loads for depression and anxiety with the resulting brain components.ResultsUnivariate analyses revealed strong associations between age and sex with mainly global but also regional specific brain components, with varying degrees of multimodal involvement. In contrast, there were no significant associations with case-control status, nor symptom loads for depression and anxiety with the brain components, nor any interaction effects with age and sex. Machine learning revealed low model performance for classifying patients from controls and predicting symptom loads for depression and anxiety, but high age prediction accuracy.ConclusionMultimodal fusion of brain imaging data alone may not be sufficient for dissecting the clinical and neurobiological heterogeneity of depression. Precise clinical stratification and methods for brain phenotyping at the individual level based on large training samples may be needed to parse the neuroanatomy of depression.
Basal forebrain volume reliably predicts the cortical spread of Alzheimer’s degeneration
Authors: Fernández-Cabello Sara , Kronbichler Martin , Dijk Koene R. A. Van , Goodman James A. , Spreng R. Nathan , Schmitz Taylor W. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2019

AbstractAlzheimer’s disease neuropathology is thought to spread across anatomically and functionally connected brain regions. However, the precise sequence of spread remains ambiguous. The prevailing model posits that Alzheimer’s neurodegeneration starts in the entorhinal cortices, before spreading to temporoparietal cortex. Challenging this model, we previously provided evidence that degeneration within the nucleus basalis of Meynert (NbM), a subregion of the basal forebrain heavily populated by cortically projecting cholinergic neurons, precedes and predicts entorhinal degeneration (Schmitz and Spreng, 2016). There have been few systematic attempts at directly comparing staging models using in vivo longitudinal biomarker data, and determining if these comparisons generalize across independent samples. Here we addressed the sequence of pathological staging in Alzheimer’s disease using two independent samples of the Alzheimer’s Disease Neuroimaging Initiative (N1= 284;N2= 553) with harmonized CSF assays of amyloid (Aβ) and hyperphosphorylated tau (pTau), and longitudinal structural MRI data over two years. We derived measures of gray matter degeneration in a priori NbM and the entorhinal regions of interest. To examine the spreading of degeneration, we used a predictive modelling strategy which tests whether baseline gray matter volume in a seed region accounts for longitudinal change in a target region. We demonstrated that predictive pathological spread favored the NbM→entorhinal over the entorhinal→NbM model. This evidence generalized across the independent samples (N1:r=0.20,p=0.03;N2:r=0.37,p<0.001). We also showed that CSF concentrations of pTau/Aβ moderated the observed predictive relationship, consistent with evidence in rodent models of an underlying trans-synaptic mechanism of pathophysiological spread (t826=2.55,p=0.01). The moderating effect of CSF was robust to additional factors, including clinical diagnosis (t826=1.65,p=0.49). We then applied our predictive modelling strategy to an exploratory whole-brain voxel-wise analysis to examine the spatial specificity of the NbM→entorhinal model. We found that smaller baseline NbM volumes predicted greater degeneration in localized regions of the entorhinal and perirhinal cortices. By contrast, smaller baseline entorhinal volumes predicted degeneration in the medial temporal cortex, recapitulating the prevailing staging model. Our findings suggest that degeneration of the basal forebrain cholinergic projection system is a robust and reliable upstream event of entorhinal and neocortical degeneration, calling into question the prevailing view of Alzheimer’s disease pathogenesis.
Normative cerebral cortical thickness for human visual areas
Authors: Alvarez Ivan , Parker Andrew J. , Bridge Holly 
Published: June 2019

1AbstractStudies of changes in cerebral neocortical thickness often rely on small control samples for comparison with specific populations with abnormal visual systems. We present a normative dataset for FreeSurfer-derived cortical thickness across 25 human visual areas derived from 960 participants in the Human Connectome Project. Cortical thickness varies systematically across visual areas, in broad agreement with canonical visual system hierarchies in the dorsal and ventral pathways. In addition, cortical thickness estimates show consistent within-subject variability and reliability. Importantly, cortical thickness estimates in visual areas are well described by a normal distribution, making them amenable to direct statistical comparison.HighlightsNormative neocortical thickness values for human visual areas measured with FreeSurferA gradient of increasing neocortical thickness with visual area hierarchyConsistent within- and between-subject variability in neocortical thickness across visual areas
Does the neuronal noise in cortex help generalization?
Authors: Hu Brian , Shang Jiaqi , Iyer Ramakrishnan , Siegle Josh , Mihalas Stefan 
Published: June 2019

AbstractOne remarkable feature of neuronal activity in the mammalian cortex is the high level of variability in response to repeated stimuli. First, we used an open dataset, the Allen Brain Observatory, to quantify the distribution of responses to repeated presentations of natural movies. We find that even for their preferred moment in the movie clip, neurons have high variability which cannot be well captured by Gaussian or Poisson distributions. A large fraction of responses are better fit by log-normal or Gaussian mixture models with two components. These distributions are similar to activity distributions during training of deep neural networks using dropout. This poses the interesting hypothesis: is the role of cortical noise to help in generalization during learning?Second, to ensure the robustness of our results we analyzed electrophysiological recordings in the same areas of mouse visual cortex, again using repeated natural movie presentations and found similar response distributions. To make sure that the trial-by-trial variations we observe are not due exclusively to the result of changes in state, we constructed a population coupling model, where each neuron’s activity is coupled to a low-dimension version of the activity of all other simultaneously recorded neurons. The population coupling model can capture global, brain-wide activity fluctuations that are state-dependent. The residuals from this model also show non-Gaussian noise distributions.Third, we ask a more specific question: is the noise in the cortex more likely to move the representation of the stimulus in-class versus out-of-class? To address this question, we analyzed the responses of neurons across trials from multiple sections of different movie clips. We observe that the noise in the cortex better aligns to in-class variations. We argue that a useful noise for learning generalizations is to move from representations of different exemplars in-class, similar to cortical noise.