bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cannabis Exposure is Associated With a Lower Likelihood of Neurocognitive Impairment in People Living With HIV
Authors: Watson Caitlin Wei-Ming , Paolillo Emily W. , Morgan Erin E. , Umlauf Anya , Sundermann Erin E. , Ellis Ronald J. , Letendre Scott , Marcotte Thomas D. , Heaton Robert K. , Grant Igor 
Published: December 2019

Background:
Aging and HIV have adverse effects on the central nervous system, including increased inflammation and neural injury and confer risk of neurocognitive impairment (NCI). Previous research suggests the nonacute neurocognitive effects of cannabis in the general population are adverse or null. However, in the context of aging and HIV, cannabis use may exert beneficial effects due to its anti-inflammatory properties. In the current study, we examined the independent and interactive effects of HIV and cannabis on NCI and the potential moderation of these effects by age.

Methods:
Participants included 679 people living with HIV (PLHIV) and 273 people living without HIV (HIV−) (18–79 years old) who completed neurocognitive, neuromedical, and substance use assessments. NCI was defined as a demographically corrected global deficit score ≥ 0.5. Logistic regression models examined the effects of age, HIV, cannabis (history of cannabis substance use disorder and cannabis use in past year), and their 2-way and 3-way interactions on NCI.

Results:
In logistic regression models, only a significant interaction of HIV X cannabis was detected (P = 0.02). Among PLHIV, cannabis was associated with a lower proportion of NCI (odds ratio = 0.53, 95% confidence interval = 0.33–0.85) but not among HIV− individuals (P = 0.40). These effects did not vary by age.

Conclusions:
Findings suggest cannabis exposure is linked to a lower odds of NCI in the context of HIV. A possible mechanism of this result is the anti-inflammatory effect of cannabis, which may be particularly important for PLHIV. Further investigations are needed to refine the effects of dose, timing, and cannabis compound on this relationship, which could inform guidelines for cannabis use among populations vulnerable to cognitive decline.
Forecasting Prevalence of HIV-1 Integrase Strand Transfer Inhibitor (INSTI) Drug Resistance: A Modeling Study
Authors: Northrop Alex J. , Pomeroy Laura W. 
Published: December 2019

Background:
Antiretroviral therapy (ART) is a cornerstone of HIV-1 treatment and provides significant health benefits for patients with responsive HIV-1 strains. Integrase strand transfer inhibitors (INSTIs) are the newest class of ART. Although most HIV-1 cases are responsive, a small number are already resistant. Here, we forecast the prevalence of INSTI resistance amid wide-spread use.

Methods:
We developed a stochastic model to simulate HIV-1 dynamics and INSTI resistance for raltegravir, elvitegravir, and dolutegravir. We forecast prevalence of INSTI resistance in adults living with HIV-1 over a 30-year period using parameter values and initial conditions that mimic HIV-1 dynamics Washington DC. We used the model to predict the amount of transmitted drug resistance (TDR) versus regimen-acquired drug resistance.

Results:
We forecast the prevalence of HIV-1 cases resistant to raltegravir as 0.41 (minimum: 0.21; maximum: 0.57), resistant to elvitegravir as 0.44 (minimum: 0.26; maximum: 0.60), and resistant to dolutegravir as 0.44 (minimum: 0.25; maximum: 0.65). Model output was greatly affected by the proportion of those living with HIV-1 on ART and the rate of converting from an INSTI-sensitive strain to an INSTI-resistant strain for chronically infected ART-experienced cases. We forecast that TDR will contribute minimally—if at all—to the overall proportion of resistant HIV-1 cases.

Conclusions:
INSTI drug resistance has the potential to be a public health concern in the next 30 years. Although several parameters influence the predicted prevalence of INSTI drug resistance, TDR is unlikely to contribute substantially to future trends.
Intestinal Dysbiosis and Markers of Systemic Inflammation in Viscerally and Generally Obese Persons Living With HIV
Authors: Gogokhia Lasha , Taur Ying , Juluru Krishna , Yagan Neda , Zhu Yuan-Shan , Pamer Eric , Glesby Marshall J. 
Published: December 2019

Background:
The intestinal microbiota contributes to the pathogenesis of obesity and metabolic disorders. People living with HIV (PLWH) have a higher risk for the development of visceral adiposity with accompanying worsened cardiovascular risk.

Setting:
Convenience sample from an HIV clinic and research unit.

Methods:
To understand the relationship between adiposity and intestinal dysbiosis, we compared the gut microbiota and inflammatory markers in a cross-sectional study of viscerally obese, generally obese, and lean PLWH. Fecal intestinal microbiota was characterized by 16S ribosomal DNA sequencing. Abdominal CTs quantified subcutaneous adipose tissue and visceral adipose tissue (SAT; VAT). Serum high sensitivity C-reactive protein, adiponectin, leptin, IL-6, MCP-1, and sCD14 were assayed.

Results:
We studied 15, 9, and 11 participants with visceral obesity, general obesity, and lean body type, respectively. The generally obese group were all women and 2/3 African American, whereas the visceral obesity and lean groups were predominantly white and men who have sex with men. Markers of systemic inflammation and sCD14 were higher in general obesity compared with lean. sCD14 was positively correlated with VAT, but not SAT. Bacterial diversity was significantly reduced in participants with visceral and general obesity and composition of intestinal microbiota was significantly different from lean body types. Bacterial alpha diversity was negatively correlated with VAT area, waist/hip ratio, and sCD14, but not with SAT area.

Conclusions:
In this exploratory study, obesity in general was associated with dysbiotic intestinal microbiota. The relationships of VAT to bacterial diversity and sCD14 suggest that dysbiosis in viscerally obese PLWH could be associated with heightened inflammatory state.
Semen Extracellular Vesicles From HIV-1–Infected Individuals Inhibit HIV-1 Replication In Vitro, and Extracellular Vesicles Carry Antiretroviral Drugs In Vivo
Authors: Welch Jennifer L. , Kaddour Hussein , Winchester Lee , Fletcher Courtney V. , Stapleton Jack T. , Okeoma Chioma M. 
Published: December 2019

Background:Extracellular vesicles (EVs) are cell-derived vesicles with diverse functions in intercellular communication including disease and infection, and EVs seem to influence HIV-1 pathogenesis. EVs isolated from HIV-1–uninfected semen (SE), but not blood (BE), contain factors that interfere with HIV-1 infection and replication in target cells. The reason for this dichotomy is unknown. Furthermore, the effect of HIV-1 infection and antiretroviral (ARV) drugs on the anti–HIV-1 effects of SE and BE is unknown. Here, we characterize EVs and EV-free plasma isolated from HIV-infected donor semen and blood and their effects on HIV infection.Methods:EVs and EV-free plasma were purified from autologous blood and semen of HIV-negative, HIV-infected antiretroviral therapy (ART)-naïve, and HIV-infected ART-treated participants. HIV infection was assessed in a TZM-bl cell reporter system. ARV concentrations were analyzed using liquid chromatography-mass spectrometry.Results:SE isolated from both HIV-negative and HIV-infected, ART-naïve donors inhibited HIV-1 infection, but BE and semen and blood EV-free plasma did not. By contrast, BE, SE, and EV-free plasma from HIV-infected, ART-treated donors inhibited HIV-1. Importantly, exosomes isolated from ART-treated donors contained concentrations of ARV drugs (ART-EVs) at biologically relevant inhibitory levels.Conclusions:The HIV-1–inhibitory phenotype of SE is independent of donor HIV-1 or ART status, and ARV drugs and their metabolites are SE- and BE-associated in vivo.
Sleep apnea and stroke
Authors: McDermott Mollie , Brown Devin L. 
Published: December 2019

Purpose of review
Stroke and sleep apnea are highly prevalent conditions with a physiologically plausible bidirectional relationship. This review addresses prestroke sleep apnea, wake-up stroke and sleep apnea, and poststroke sleep apnea, with an attempt to highlight research published in the last 18 months.

Recent findings
Sleep apnea is highly prevalent poststroke. Poststroke sleep apnea is associated with worse poststroke functional and cognitive outcomes and a higher risk of recurrent stroke. Physiologic tests are needed to diagnose sleep apnea in poststroke patients as sleep apnea questionnaires do not perform well in this population. The role of CPAP in poststroke management is not yet well established.

Summary
Sleep apnea is a well established independent risk factor for stroke that confers an approximately two-fold increased risk of incident stroke. Sleep apnea is highly prevalent poststroke and is associated with worse outcomes after stroke. Sleep apnea is an attractive target for research addressing secondary stroke prevention and recovery.
RNA expression studies in stroke: what can they tell us about stroke mechanism?
Authors: Falcione Sarina , Kamtchum-Tatuene Joseph , Sykes Gina , Jickling Glen C. 
Published: December 2019

Purpose of review
Diagnosis of stroke and understanding the mechanism of stroke is critical to implement optimal treatment. RNA expressed in peripheral blood cells is emerging as a precision biomarker to aid in stroke diagnosis and prediction of stroke cause. In this review, we summarize available data regarding the role of RNA to predict stroke, the rationale for these changes, and a discussion of novel mechanistic insight and clinical applications.

Recent findings
Differences in RNA gene expression in blood have been identified in patients with stroke, including differences to distinguish ischemic from hemorrhagic stroke, and differences between cardioembolic, large vessel atherosclerotic, and small vessel lacunar stroke cause. Gene expression differences show promise as novel stroke biomarkers to predict stroke of unclear cause (cryptogenic stroke). The differences in RNA expression provide novel insight to stroke mechanism, including the role of immune response and thrombosis in human stroke. Important insight to regulation of gene expression in stroke and its causes are being acquired, including alternative splicing, noncoding RNA, and microRNA.

Summary
Improved diagnosis of stroke and determination of stroke cause will improve stroke treatment and prevention. RNA biomarkers show promise to aid in the diagnosis of stroke and cause determination, as well as providing novel insight to mechanism of stroke in patients. While further study is required, an RNA profile may one day be part of the stroke armamentarium with utility to guide acute stroke therapy and prevention strategies and refine stroke phenotype.
Host genomics of the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment
Authors: Thorball Christian W. , Borghesi Alessandro , Bachmann Nadine , von Siebenthal Chantal , Vongrad Valentina , Turk Teja , Neumann Kathrin , Beerenwinkel Niko , Bogojeska Jasmina , Roth Volker , Kok Yik Lim , Parbhoo Sonali , Wieser Mario , Böni Jürg , Perreau Matthieu , Klimkait Thomas , Yerly Sabine , Battegay Manuel , Rauch Andri , Schmid Patrick , Bernasconi Enos , Cavassini Matthias , Kouyos Roger D. , Günthard Huldrych F. , Metzner Karin J. , Fellay Jacques ,   Swiss HIV Cohort Study
Published: December 2019

ABSTRACTIntroductionA major hurdle to HIV-1 eradication is the establishment of a latent viral reservoir early after primary infection. Several factors are known to influence the HIV-1 reservoir size and decay rate on suppressive antiretroviral treatment (ART), but little is known about the role of human genetic variation.MethodsWe measured the reservoir size at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readouts: the reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants.ResultsGenome- and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive ART.ConclusionsOur results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.
Combining antibiotics with antivirulence compounds can have synergistic effects and reverse selection for antibiotic resistance in Pseudomonas aeruginosa
Authors: Rezzoagli Chiara , Archetti Martina , Mignot Ingrid , Baumgartner Michael , Kümmerli Rolf 
Published: December 2019

AbstractAntibiotics are losing efficacy due to the rapid evolution and spread of resistance. Treatments targeting bacterial virulence factors have been considered as alternatives because they target virulence instead of pathogen viability, and should therefore exert weaker selection for resistance than conventional antibiotics. However, antivirulence treatments rarely clear infections, which compromises their clinical applications. Here, we explore the potential of combining antivirulence drugs with antibiotics against the opportunistic human pathogen Pseudomonas aeruginosa. We combined two antivirulence compounds (gallium, a siderophore-quencher, and furanone C-30, a quorum sensing-inhibitor) together with four clinically relevant antibiotics (ciprofloxacin, colistin, meropenem, tobramycin) in 9×9 drug concentration matrices. We found that drug-interaction patterns were concentration dependent, with promising levels of synergies occurring at intermediate drug concentrations for certain drug pairs. We then tested whether antivirulence compounds are potent adjuvants, especially when treating antibiotic resistant clones. We found that the addition of antivirulence compounds to antibiotics could restore growth inhibition for most antibiotic resistant clones, and even abrogate or reverse selection for resistance in five drug combination cases. Molecular analyses suggest that selection against resistant clones occurs when resistance mechanisms involve restoration of protein synthesis, but not when efflux pumps are upregulated. Altogether, our work provides a first systematic analysis of antivirulence-antibiotic combinatorial treatments and suggests that such combinations have a high potential to be both effective in treating infections and in limiting the spread of antibiotic resistance.
Within-host Mycobacterium tuberculosis evolution: a population genetics perspective
Authors: Morales-Arce Ana Y. , Harris Rebecca B. , Stone Anne C. , Jensen Jeffrey D. 
Published: December 2019

ABSTRACTThe within-host evolutionary dynamics of TB remain unclear, and underlying biological characteristics render standard population genetic approaches based upon the Wright-Fisher model largely inappropriate. In addition, the compact genome combined with an absence of recombination is expected to result in strong purifying selection effects. Thus, it is imperative to establish a biologically-relevant evolutionary framework incorporating these factors in order to enable an accurate study of this important human pathogen. Further, such a model is critical for inferring fundamental evolutionary parameters related to patient treatment, including mutation rates and the severity of infection bottlenecks. We here implement such a model and infer the underlying evolutionary parameters governing within-patient evolutionary dynamics. Results demonstrate that the progeny skew associated with the clonal nature of TB severely reduces genetic diversity and that the neglect of this parameter in previous studies has led to significant mis-inference of mutation rates. As such, our results suggest an underlying de novo mutation rate that is considerably faster than previously inferred, and a progeny distribution differing significantly from Wright-Fisher assumptions. This inference largely reconciles the seemingly contradictory observations of both rapid drug-resistance evolution but extremely low levels of genetic variation in both resistant and non-resistant populations.
Learning cognitive maps as structured graphs for vicarious evaluation
Authors: Rikhye Rajeev V. , Gothoskar Nishad , Guntupalli J. Swaroop , Dedieu Antoine , Lázaro-Gredilla Miguel , George Dileep 
Published: December 2019

AbstractCognitive maps are mental representations of spatial and conceptual relationships in an environment. These maps are critical for flexible behavior as they permit us to navigate vicariously, but their underlying representation learning mechanisms are still unknown. To form these abstract maps, hippocampus has to learn to separate or merge aliased observations appropriately in different contexts in a manner that enables generalization, efficient planning, and handling of uncertainty. Here we introduce a specific higher-order graph structure – clone-structured cognitive graph (CSCG) – which forms different clones of an observation for different contexts as a representation that addresses these problems. CSCGs can be learned efficiently using a novel probabilistic sequence model that is inherently robust to uncertainty. We show that CSCGs can explain a variety cognitive map phenomena such as discovering spatial relations from an aliased sensory stream, transitive inference between disjoint episodes of experiences, formation of transferable structural knowledge, and shortcut-finding in novel environments. By learning different clones for different contexts, CSCGs explain the emergence of splitter cells and route-specific encoding of place cells observed in maze navigation, and event-specific graded representations observed in lap-running experiments. Moreover, learning and inference dynamics of CSCGs offer a coherent explanation for a variety of place cell remapping phenomena. By lifting the aliased observations into a hidden space, CSCGs reveal latent modularity that is then used for hierarchical abstraction and planning. Altogether, learning and inference using a CSCG provides a simple unifying framework for understanding hippocampal function, and could be a pathway for forming relational abstractions in artificial intelligence.
Dinoflagellate symbionts escape vomocytosis by host cell immune suppression
Authors: Jacobovitz Marie R. , Rupp Sebastian , Voss Philipp A. , Gornik Sebastian G. , Guse Annika 
Published: December 2019

AbstractEmergence of the symbiotic lifestyle fostered the immense diversity of all ecosystems on Earth, but symbiosis plays a particularly remarkable role in marine ecosystems. Photosynthetic dinoflagellate endosymbionts power reef ecosystems by transferring vital nutrients to their coral hosts. The mechanisms driving this symbiosis, specifically those which allow hosts to discriminate between beneficial symbionts and pathogens, are not well understood. Here, we uncover that host immune suppression is key for dinoflagellate endosymbionts to avoid elimination by the host using a comparative, model systems approach. Unexpectedly, we find that the clearance of non-symbiotic microalgae occurs by non-lytic expulsion (vomocytosis) and not intracellular digestion, the canonical mechanism used by professional immune cells to destroy foreign invaders. We provide evidence that suppression of TLR signalling by targeting the conserved MyD88 adapter protein has been co-opted for this endosymbiotic lifestyle, suggesting that this is an evolutionarily ancient mechanism exploited to facilitate symbiotic associations ranging from coral endosymbiosis to the microbiome of vertebrate guts.
Grapevine rootstocks affect growth-related scion phenotypes
Authors: Migicovsky Zoë , Cousins Peter , Jordan Lindsay M. , Myles Sean , Striegler Richard Keith , Verdegaal Paul , Chitwood Daniel H. 
Published: December 2019

AbstractGrape growers use rootstocks to provide protection against pests and pathogens and to modulate viticulture performance such as shoot growth. Our study examined two grapevine scion varieties (‘Chardonnay’ and ‘Cabernet Sauvignon’) grafted to 15 different rootstocks and determined the effect of rootstocks on eight traits important to viticulture. We assessed the vines across five years and identified both year and variety as contributing strongly to trait variation. The effect of rootstock was relatively consistent across years and varieties, explaining between 8.99% and 9.78% of the variation in growth-related traits including yield, pruning weight, berry weight, and Ravaz index (yield to pruning weight ratio). Increases in yield due to rootstock were generally the result of increases in berry weight, likely due to increased water uptake by vines grafted to a particular rootstock. We demonstrated a greater than 50% increase in yield, pruning weight, or Ravaz index by choosing the optimal rootstock, indicating that rootstock choice is crucial for grape growers looking to improve vine performance.
Fluorescence-based whole plant imaging and phenomics
Authors: Rigoulot Stephen B. , Schimel Tayler M. , Lee Jun Hyung , Brabazon Holly , Meier Kerry A. , Schmid Manuel J. , Seaberry Erin M. , Poindexter Magen R. , Layton Jessica S. , Brabazon Jared W. , Madajian Jonathan A. , Finander Michael J. , DiBenedetto John , Occhialini Alessandro , Lenaghan Scott C. , Stewart C. Neal 
Published: December 2019

SummaryReverse genetics approaches have revolutionized plant biology and agriculture. Phenomics has the prospect of bridging plant phenotypes with genes, including transgenes, to transform agricultural fields1. Genetically-encoded fluorescent proteins (FPs) have transformed studies in gene expression, protein trafficking, and plant physiology. While the first instance of plant canopy imaging of green fluorescent protein (GFP) was performed over 20 years ago2, modern phenomics has largely ignored fluorescence as a transgene indicator despite the burgeoning FP color palette currently available to biologists3–5. Here we show a new platform for standoff imaging of plant canopies expressing a wide variety of FP genes in leaves. The platform, the fluorescence-inducing laser projector (FILP), uses a low-noise camera to image a scene illuminated by compact diode lasers of various colors and emission filters to phenotype transgenic plants expressing multiple constitutive or inducible FPs. Of the 20 FPs screened, we selected the top performing candidates for standoff phenomics at ≥ 3 m using FILP in a laboratory-based laser range. Included in demonstrated applications is the performance of an osmotic stress-inducible synthetic promoter selected from a high throughput library screen. While FILP has unprecedented versatility as a laboratory platform, we envisage future iterations of the system for use in automated greenhouse or even drone-fielded versions of the platform for crop screening.