bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges Across the HIV Care Continuum for Patients With HIV/TB Co-infection in Atlanta, GA
Authors: Schechter Marcos C , Bizune Destani , Kagei Michelle , Holland David P , del Rio Carlos , Yamin Aliya , Mohamed Omar , Oladele Alawode , Wang Yun F , Rebolledo Paulina A , Ray Susan M , Kempker Russell R 
Published: April 2018

Abstract

Background
Antiretroviral therapy (ART) for persons with HIV infection prevents tuberculosis (TB) disease. Additionally, sequential ART after initiation of TB treatment improves outcomes. We examined ART use, retention in care, and viral suppression (VS) before, during, and 3 years following TB treatment for an inner-city cohort in the United States.

Methods
Retrospective cohort study among persons treated for culture-confirmed TB between 2008 and 2015 at an inner-city hospital.

Results
Among 274 persons with culture-confirmed TB, 96 (35%) had HIV co-infection, including 23 (24%) new HIV diagnoses and 73 (76%) previous diagnoses. Among those with known HIV prior to TB, the median time of known HIV was 6 years, and only 10 (14%) were on ART at the time of TB diagnosis. The median CD4 at TB diagnosis was 87 cells/uL. Seventy-four (81%) patients received ART during treatment for TB, and 47 (52%) has VS at the end of TB treatment. Only 32% of patients had continuous VS 3 years after completing TB treatment. There were 3 TB recurrences and 3 deaths post–TB treatment; none of these patients had retention or VS after TB treatment.

Conclusions
Among persons with active TB co-infected with HIV, we found that the majority had known HIV and were not on ART prior to TB diagnosis, and retention in care and VS post–TB treatment were very low. Strengthening the HIV care continuum is needed to improve HIV outcomes and further reduce rates of active TB/HIV co-infection in our and similar settings.
Asymptomatic Prenatal Zika Virus Infection and Congenital Zika Syndrome
Authors: Paixao Enny S , Leong Wei-Yee , Rodrigues Laura C , Wilder-Smith Annelies 
Published: April 2018

Abstract
To investigate to what extent asymptomatic vs symptomatic prenatal Zika virus infections contribute to birth defects, we identified 3 prospective and 8 retrospective studies. The ratio varied greatly in the retrospective studies, most likely due to recruitment and recall bias. The prospective studies revealed a ratio of 1:1 for asymptomatic vs symptomatic maternal Zika infections resulting in adverse fetal outcomes.
Folate Receptor Near-Infrared Optical Imaging Provides Sensitive and Specific Intraoperative Visualization of Nonfunctional Pituitary Adenomas
Authors: Cho Steve S , Zeh Ryan , Pierce John T , Jeon Jun , Nasrallah MacLean , Adappa Nithin D , Palmer James N , Newman Jason G , White Caitlin , Kharlip Julia , Snyder Peter , Low Philip , Singhal Sunil , Grady M Sean , Lee John Y K 
Published: April 2018

Abstract

BACKGROUND
Surgical resection is the primary treatment for nonfunctional (NF) pituitary adenomas, but gross-total resection is difficult to achieve in all cases. NF adenomas overexpress folate receptor alpha (FRα).

OBJECTIVE
To test the hypothesis that we could target FRα for highly sensitive and specific intraoperative detection of NF adenomas using near-infrared (NIR) imaging.

METHODS
Fourteen patients with NF pituitary adenoma were infused with the folate analog NIR dye OTL38 preoperatively. NIR fluorescence signal-to-background ratio (SBR) was recorded for each tumor during resection of the adenomas. Extent of surgery was not modified based on the presence or absence of fluorescence. Immunohistochemistry was performed to assess FRα expression in all specimens. Magnetic resonance imaging (MRI) was performed postoperatively to assess residual neoplasm.

RESULTS
Nine adenomas overexpressed FRα and fluoresced with a NIR SBR of 3.2 ± 0.52, whereas the 5 non-FRα-overexpressing adenomas fluoresced with an SBR of 1.5 ± 0.21. Linear regression demonstrated a significant correlation between intraoperative SBR and the FRα expression (P-value < .001). Analysis of 14 margin samples revealed that the surgeon's impression of the tissue had 83% sensitivity, 100% specificity, 100% positive predictive value, and 89% negative predictive value, while NIR fluorescence had 100% for all values. NIR fluorescence accurately predicted postoperative MRI results in 78% of FRα-overexpressing patients.

CONCLUSION
Preoperative injection of folate-tagged NIR dye provides strong signal and visualization of NF pituitary adenomas. It is 100% sensitive and specific for detecting margin neoplasm and can predict postoperative MRI findings. Our results suggest that NIR fluorescence may be superior to white-light visualization alone and may improve resection rates in NF pituitary adenomas.
Blue-wing enhancement of the chromospheric Mg ii h and k lines in a solar flare
Authors: Tei Akiko , Sakaue Takahito , Okamoto Takenori J , Kawate Tomoko , Heinzel Petr , UeNo Satoru , Asai Ayumi , Ichimoto Kiyoshi , Shibata Kazunari 
Published: April 2018

Abstract
We performed coordinated observations of AR 12205, which showed a C-class flare on 2014 November 11, with the Interface Region Imaging Spectrograph (IRIS) and the Domeless Solar Telescope (DST) at Hida Observatory. Using spectral data in the Si iv 1403 Å, C ii 1335 Å, and Mg ii h and k lines from IRIS and the Ca ii K, Ca ii 8542 Å, and Hα lines from DST, we investigated a moving flare kernel during the flare. In the Mg ii h line, the leading edge of the flare kernel showed an intensity enhancement in the blue wing and a smaller intensity of the blue-side peak (h2v) than that of the red-side one (h2r). The blueshift lasted for 9–48 s with a typical speed of 10.1 ±  2.6 km s−1, which was followed by a high intensity and a large redshift with a speed of up to 51 km s−1 detected in the Mg ii h line. The large redshift was a common property for all six lines, but the blueshift prior to it was found only in the Mg ii lines. Cloud modeling of the Mg ii h line suggests that the blue-wing enhancement with such a peak difference could have been caused by a chromospheric-temperature (cool) upflow. We discuss a scenario in which an upflow of cool plasma is lifted up by expanding hot plasma owing to the deep penetration of non-thermal electrons into the chromosphere. Furthermore, we found that the blueshift persisted without any subsequent redshift in the leading edge of the flare kernel during its decaying phase. The cause of such a long-lasting blueshift is also discussed.
Distinct RanBP1 nuclear export and cargo dissociation mechanisms between fungi and animals
Authors: Li Yuling , Zhou Jinhan , Zhang Yuqing , Zhou Qiao , Shen Xiaofei , Jia Da , Han Junhong , Sun Qingxiang 
Published: April 2018

AbstractRan binding protein 1 (RanBP1), the primary effector of nuclear GTPase Ran, is a cytoplasmic-enriched and nuclear-cytoplasmic shuttling protein, playing important roles in nuclear transport through preventing RanGTP from being trapped with karyopherin proteins and dissociating cargoes from nuclear export factor CRM1. Much of what we know about RanBP1 is learned from fungi. Here we show that animal RanBP1 has distinct cargo dissociation and nuclear export mechanisms. In contrast to CRM1-RanGTP sequestration mechanism of cargo dissociation in fungi, animal RanBP1 solely sequesters RanGTP from nuclear export complexes. In fungi, RanBP1, CRM1 and RanGTP form a 1:1:1 nuclear export complex; in contrast, animal RanBP1, CRM1 and RanGTP form a 1:1:2 nuclear export complex. The key feature for the two mechanistic changes from fungi to animals is the loss of affinity between RanBP1-RanGTP and CRM1, since residues mediating their interaction in fungi are not conserved in animals. The biological significances of these different mechanisms in fungi and animals are also studied and discussed. Our study illustrates how orthologous proteins may play conserved functions through distinct routes, and may provide directions for design of antifungal medicines.
Analyzing Vaccine Trials in Epidemics with Mild and Asymptomatic Infection
Authors: Kahn Rebecca , Hitchings Matt , Wang Rui , Bellan Steven , Lipsitch Marc 
Published: April 2018

ABSTRACTVaccine efficacy against susceptibility to infection (VES), regardless of symptoms, is an important endpoint of vaccine trials for pathogens with a high proportion of asymptomatic infection, as such infections may contribute to onward transmission and outcomes such as Congenital Zika Syndrome. However, estimating VESis resource-intensive. We aim to identify methods to accurately estimate VEswhen limited information is available and resources are constrained. We model an individually randomized vaccine trial by generating a network of individuals and simulating an epidemic. The disease natural history follows a Susceptible, Exposed, Infectious and Symptomatic or Infectious and Asymptomatic, Recovered model. We then use seven approaches to estimate VES, and we also estimate vaccine efficacy against progression to symptoms (VEP). A corrected relative risk and an interval censored Cox model accurately estimate VESand only require serologic testing of participants once, while a Cox model using only symptomatic infections returns biased estimates. Only acquiring serological endpoints in a 10% sample and imputing the remaining infection statuses yields unbiased VESestimates across values of R0and accurate estimates of VEPfor higher values. Identifying resource-preserving methods for accurately estimating VESis important in designing trials for diseases with a high proportion of asymptomatic infection.
Economic evaluation of a healthy lifestyle intervention for chronic low back pain: a randomised controlled trial
Authors: Williams A , van Dongen JM , Kamper SJ , O’Brien KM , Wolfenden L , Yoong SL , Hodder RK , Lee H , Robson EK , Haskins R , Rissel C , Wiggers J , Williams CM 
Published: April 2018

AbstractWe performed an economic evaluation of a healthy lifestyle intervention targeting weight loss, physical activity and diet for patients with chronic low back pain, who are overweight or obese. Eligible patients with chronic low back pain (n=160) were randomised to an intervention or usual care control group. The intervention included brief advice, a clinical consultation and referral to a 6-month telephone-based healthy lifestyle coaching service. The primary outcome was quality-adjusted life years (QALYs). Secondary outcomes were pain intensity, disability, weight, and body mass index. Costs included intervention costs, healthcare utilisation costs and work absenteeism costs. An economic analysis was performed from the societal perspective. Mean total costs were lower in the intervention group than the control group (-$614; 95%CI: -3133 to 255). The intervention group had significantly lower healthcare costs (-$292; 95%CI: -872 to -33), medication costs (-$30; 95%CI: -65 to -4) and absenteeism costs (-$1000; 95%CI: -3573 to -210). For all outcomes, the intervention was on average less expensive and more effective than usual care, and the probability of the intervention being cost-effective compared to usual care was relatively high (i.e. 0.81) at a willingness-to-pay of $0/unit of effect. However, the probability of cost-effectiveness was not as favourable among sensitivity analyses. The healthy lifestyle intervention seems to be cost-effective from the societal perspective. However, variability in the sensitivity analyses indicates caution is needed when interpreting these findings.
Active gelation breaks time-reversal-symmetry of mitotic chromosome mechanics
Authors: Mittasch Matthäus , Fritsch Anatol W. , Nestler Michael , Iglesias-Artola Juan M. , Subramanian Kaushikaram , Petzold Heike , Kar Mrityunjoy , Voigt Axel , Kreysing Moritz 
Published: April 2018

AbstractIn cell division, mitosis is the phase in which duplicated sets of chromosomes are mechanically aligned to form the metaphase plate before being segregated in two daughter cells. Irreversibility is a hallmark of this process, despite the fundamental laws of Newtonian mechanics being time symmetric.Here we show experimentally that mitotic chromosomes receive the arrow of time by time-reversal-symmetry breaking of the underlying mechanics in prometaphase. By optically inducing hydrodynamic flows within prophase nuclei, we find that duplicated chromatid pairs initially form a fluid suspension in the nucleoplasm: although showing little motion on their own, condensed chromosomes are free to move through the nucleus in a time-reversible manner. Actively probing chromosome mobility further in time, we find that this viscous suspension of chromatin transitions into a gel after nuclear breakdown. This gel state, in which chromosomes cannot be moved by flows, persists even when chromosomes start moving to form the metaphase plate. Complemented by minimal reconstitution experiments, our active intra-nuclear micro-rheology reveals time-reversal-symmetry breaking of chromosome mechanics to be caused by the transition from a purely fluid suspension into an active gel.Graphical abstractOne sentence summaryFlows induced in living cell nuclei reveal the rheological changes that bring chromosomes under mechanical control during mitosis.
Differences in Pneumococcal Serotype Replacement in Individuals with and without Underlying Medical Conditions
Authors: Weinberger Daniel M. , Warren Joshua L , Dalby Tine , Shapiro Eugene D. , Branth Valentiner , Slotved Hans-Christian , Harboe Zitta Barrella 
Published: April 2018

ABSTRACTBackgroundPneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD) worldwide. However, declines in IPD due to vaccine-targeted serotypes have been partially offset by increases in IPD due to non-vaccine serotypes. The goal of this study was to quantify serotype-specific changes in the incidence of IPD that occurred in different age groups, with or without certain co-morbidities, following the introduction of PCV7 and PCV13 in the childhood vaccination program in Denmark.MethodsWe used nationwide surveillance data for IPD in Denmark and a hierarchical Bayesian regression framework to estimate changes in the incidence of IPD associated with the introduction of PCV7 (2007) and PCV13 (2010) while controlling for serotype-specific epidemic cycles and unrelated secular trends.Results and ConclusionsFollowing the introduction of PCV7 and 13 in children, the net impact of serotype replacement varied considerably by age group and the presence of comorbid conditions. Serotype replacement offset a greater fraction of the decline in vaccine-targeted serotypes following the introduction of PCV7 compared with the period following the introduction of PCV13. Differences in the magnitude of serotype replacement were due to variations in the incidence of non-vaccine serotypes in the different risk groups before the introduction of PCV7 and PCV13. The relative increases in the incidence of IPD caused by non-vaccine serotypes did not differ appreciably in the post-vaccination period. Serotype replacement offset a greater proportion of the benefit of PCVs in strata in which the non-vaccine serotypes comprised a larger proportion of cases prior to the introduction of the vaccines. These findings could help to predict the impact of next-generation conjugate vaccines in specific risk groups.
Autism sensory dysfunction in an evolutionarily conserved system
Authors: Vilidaite Greta , Norcia Anthony M. , West Ryan J. H. , Elliott Christopher J. H. , Pei Francesca , Wade Alex R. , Baker Daniel H. 
Published: April 2018

AbstractThere is increasing evidence for a strong genetic basis for autism, with many genetic models being developed in an attempt to replicate autistic symptoms in animals. However, current animal behaviour paradigms rarely match the social and cognitive behaviours exhibited by autistic individuals. Here we instead assay another functional domain – sensory processing – known to be affected in autism to test a novel genetic autism model in Drosophila melanogaster. We show similar visual response alterations and a similar development trajectory in Nhe3 mutant flies (total N=72) and in autistic human participants (total N=154). We report a dissociation between first- and second-order electrophysiological visual responses to steady-state stimulation in adult mutant fruit flies that is strikingly similar to the response pattern in human adults with ASD as well as that of a large sample of neurotypical individuals with high numbers of autistic traits. We explain this as a genetically driven, selective signalling alteration in transient visual dynamics. In contrast to adults, autistic children show a decrease in the first-order response that is matched by the fruit fly model, suggesting that a compensatory change in processing occurs during development. Our results provide the first animal model of autism comprising a differential developmental phenotype in visual processing.
Pharmacological modulation of AMPA receptor surface diffusion restores hippocampal synaptic plasticity and memory in Huntington’s disease
Authors: Zhang Hongyu , Zhang Chunlei , Vincent Jean , Zala Diana , Benstaali Caroline , Sainlos Matthieu , Grillo-Bosch Dolors , Cho Yoon , David Denis J. , Saudou Frederic , Humeau Yann , Choquet Daniel 
Published: April 2018

AbstractImpaired hippocampal synaptic plasticity is increasingly considered to play an important role in cognitive impairment in Huntington’s disease (HD). However, the molecular basis of synaptic plasticity defects is not fully understood. Combining live-cell nanoparticle tracking and super-resolution imaging, we show that dysregulation of AMPA receptors (AMPARs) surface diffusion represents a molecular basis underlying the aberrant hippocampal synaptic plasticity during HD. AMPARs surface diffusion is increased in various HD neuronal models, which results in the failure of AMPARs surface stabilization after long-term potentiation (LTP) stimuli. This appears to result from a defective brain-derived neurotrophic factor (BDNF) - tyrosine receptor kinase B (TrkB) - Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling pathway that impacts the interaction between the AMPAR auxiliary subunit stargazin and postsynaptic density protein 95 (PSD-95). Notably, the disturbed AMPAR surface diffusion is rescued, via BDNF signaling pathway and by the antidepressant tianeptine. Tianeptine also restores the impaired LTP and hippocampus-dependent memory as well as anxiety/depression-like behavior in different HD mouse models. We thus unveil a mechanistic framework underlying hippocampal synaptic and memory dysfunction and propose a new perspective in HD treatment by targeting AMPAR surface diffusion.
Deterministic splicing ofDscam2is regulated by Muscleblind
Authors: Shun Li Joshua Shing , Millard S.Sean 
Published: April 2018

SummaryAlternative splicing of genes increases the number of distinct proteins in a cell. In the brain it is highly prevalent, presumably because proteome diversity is crucial for establishing the complex circuitry between trillions of neurons. To provide individual cells with different repertoires of protein isoforms, however, this process must be regulated. Previously, we found that the mutually exclusive alternative splicing of a cell surface protein,Dscam2produces two isoforms (exon 10A and 10B) with unique binding properties. This splicing event is tightly regulated and crucial for maintaining axon terminal size, dendritic morphology and synaptic numbers. Here, we show thatDrosophilaMuscleblind (Mbl), a conserved splicing factor implicated in myotonic dystrophy, controlsDscam2alternative splicing. Removingmblfrom cells that normally express isoform B induces the expression of isoform A and eliminates the expression of B, demonstrating that Mbl represses one alternative exon and selects the other.Mblmutants exhibit phenotypes that are also observed in flies engineered to express a single isoform. Consistent with these observations,mblexpression is cell-type-specific and correlates with the expression of isoform B. Our study demonstrates how the regulated expression of a splicing factor is sufficient to provide neurons with unique protein isoforms crucial for development.
powerTCR: a model-based approach to comparative analysis of the clone size distribution of the T cell receptor repertoire
Authors: Koch Hillary , Starenki Dmytro , Cooper Sara J. , Myers Richard M. , Li Qunhua 
Published: April 2018

AbstractSequencing of the T cell receptor repertoire is a powerful tool for deeper study of immune response, but the unique structure of this type of data makes its meaningful quantification challenging. We introduce a new method, the Gamma-GPD spliced threshold model, to address this difficulty. This biologically interpretable model captures the distribution of the TCR repertoire, demonstrates stability across varying sequencing depths, and permits comparative analysis across any number of sampled individuals. We apply our method to several datasets and obtain insights regarding the differentiating features in the T cell receptor repertoire among sampled individuals across conditions. We have implemented our method in the open-source R package powerTCR.Author summaryA more detailed understanding of the immune response can unlock critical information concerning diagnosis and treatment of disease. Here, in particular, we study T cells through T cell receptor sequencing, as T cells play a vital role in immune response. One important feature of T cell receptor sequencing data is the frequencies of each receptor in a given sample. These frequencies harbor global information about the landscape of the immune response. We introduce a flexible method that extracts this information by modeling the distribution of these frequencies, and show that it can be used to quantify differences in samples from individuals of different biological conditions.
Encoding of odor fear memories in the mouse olfactory cortex
Authors: Meissner-Bernard Claire , Dembitskaya Yulia , Venance Laurent , Fleischmann Alexander 
Published: April 2018

AbstractOdor memories are exceptionally robust and essential for animal survival. The olfactory (piriform) cortex has long been hypothesized to encode odor memories, yet the cellular substrates for olfactory learning and memory remain unknown. Here, using intersectional, cFos-based genetic manipulations (“Fos-tagging”), we show that olfactory fear conditioning activates sparse and distributed ensembles of neurons in mouse piriform cortex. We demonstrate that chemogenetic silencing of these Fos-tagged piriform ensembles selectively interferes with odor fear memory retrieval, but does not compromise basic odor detection and discrimination. Furthermore, chemogenetic reactivation of piriform neurons that were Fos-tagged during olfactory fear conditioning causes a decrease in exploratory behavior, mimicking odor-evoked fear memory recall. Together, our experiments identify odor-specific ensembles of piriform neurons as necessary and sufficient for odor fear memory recall.