bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Syphilis Coinfection Is Not Associated With an Increased Risk of Virologic Failure Among HIV-Positive Men Who Have Sex With Men on Antiretroviral Therapy
Authors: Grewal Ramandip , Allen Vanessa G. , Bayoumi Ahmed M. , Gardner Sandra L. , Kaul Rupert , Mazzulli Tony , Moravan Veronika , O'Neill Tyler , Raboud Janet , Rourke Sean B. , Tan Darrell H. S. , Burchell Ann N. ,   in collaboration with the OHTN Network Cohort Study Research Team
Published: February 2019

Background:
Incidence of syphilis continues to increase among HIV-positive men who have sex with men (MSM) in Ontario. Our objective was to determine the effect of acute syphilis on virologic failure (VF) among virally suppressed HIV-positive MSM taking antiretroviral therapy (ART) and determine if the relationship is confounded by drug use.

Setting:
The OHTN Cohort Study is a voluntary cohort of people receiving HIV care in Ontario. Syphilis and viral load (VL) data were retrieved via linkage with the provincial laboratory.

Methods:
Analyses included 2632 MSM from 2008 to 2015, on ART, with ≥1 questionnaire and 2 consecutive VL of <50 copies per milliliter 6 months apart. VF was defined as (1) VL of ≥1000 copies per milliliter or (2) 2 consecutive VLs of ≥200 copies per milliliter ≥1 month apart. We modeled acute syphilis as a time-varying covariate on VF using Poisson regression. Time-varying drug use was assessed for confounding using an iterative process where potential confounders were removed and then reintroduced into the model. Our model allowed for repeat observations using generalized estimating equations.

Results:
VF incidence was 3.5 per 100 person-years [95% confidence interval (CI): 3.4 to 4.2]. The rate ratio for VF for acute syphilis was 1.5 (95% CI: 0.9 to 2.4) in the unadjusted model; 1.6 (95% CI: 1.0 to 2.4) in the model adjusted for age, education, region, and income; and 1.2 (95% CI: 0.7 to 1.9) in the final model with additional adjustment for drug use.

Conclusions:
Acute syphilis was not associated with VF among virologically suppressed MSM on ART. Consequently, ART may still reduce HIV transmission risk to sexual partners.
Brief Report: Cocaine Use and Pre-exposure Prophylaxis: Adherence, Care Engagement, and Kidney Function
Authors: Hojilla Jose Carlo , Satre Derek D. , Glidden David V. , McMahan Vanessa M. , Gandhi Monica , Defechereux Patricia , Guanira Juan V. , Mehrotra Megha , Grant Robert M. , Carrico Adam W. 
Published: February 2019

Background:
Concomitant use of cocaine and HIV pre-exposure prophylaxis (PrEP) raises important clinical questions around adherence, retention in care, and renal toxicity.

Methods:
We assessed the associations of confirmed cocaine use with PrEP adherence (both ascertained through objective measures), care engagement, and renal function in the iPrEx open-label extension. Cocaine use was measured in scalp hair samples and categorized as light (500–3000 pg/mg) and moderate to heavy (>3000 pg/mg). PrEP adherence in the first 3 months was measured through plasma tenofovir concentrations. Disengagement from PrEP care was defined as a gap in follow-up greater than 4 months. Serum creatinine was assessed at baseline and quarterly visits.

Results:
Of the 400 participants included in this analysis, 90% were men who have sex with men, 10% transgender women, 74% Hispanic/Latino; 21% tested positive for cocaine use in the last 3 months. In adjusted analysis, light cocaine use [adjusted odds ratio 2.10 (95% confidence interval: 1.07 to 4.14)] and moderate to heavy use [adjusted odds ratio 2.32 (1.08 to 5.00)] were associated with greater odds of having plasma tenofovir concentrations below the level of quantitation. Participants with moderate to heavy use had a nearly 3-fold higher rate of disengagement from PrEP care compared with nonusers (adjusted hazard ratio 2.90 [1.48 to 5.66]). We found no statistically or clinically significant differences in creatinine clearance and serum creatinine between participants who tested positive for cocaine and those who did not.

Conclusions:
Cocaine use decreases PrEP adherence and care engagement. Comprehensive approaches are needed to reduce cocaine use and enhance engagement along the PrEP care continuum.
A compilation of and typology for abundance-, phylogenetic- and functional-based diversity metrics
Authors: Scheiner Samuel M. 
Published: February 2019

AbstractEcologists are faced with an over-abundance of ways to measure biodiversity. In this paper, I provide a compilation of and guide through this ticket of diversity metrics. I present a typology for diversity metrics that encompasses the three commonly considered categories of information: abundance, phylogenetic relationships, and traits (i.e., function). I update and expand previous summaries of diversity metrics. The formulas of those 117 metrics are presented in a standard notation and format that makes it easy to see the mathematical similarities and differences among the metrics. Finally, I propose a standard set of symbols for many of the metrics that makes their properties immediately obvious. This compilation will make it easier for researchers to identify the metric(s) most suited to their needs and will help guide future metric development.DisclaimerThis manuscript is based on work done while serving at (and furloughed from) the U.S. National Science Foundation. The views expressed in this paper do not necessarily reflect those of the National Science Foundation or the United States Government.
Improving Proteinuria Screening with Mailed Smartphone Urinalysis Testing in Previously Unscreened Patients with Hypertension: a Randomized Controlled Trial
Authors: Leddy Julia , Green Jamie A. , Yule Christina , Molecavage Juliann , Coresh Josef , Chang Alex R 
Published: February 2019

AbstractBackgroundProteinuria screening is recommended for patients with hypertension to screen for kidney disease and identify those at elevated risk for cardiovascular disease. However, screening rates among hypertensive patients are low. Home testing strategies may be useful in improving proteinuria screening adherence.MethodsWe conducted an individual-level, randomized trial at 55 primary care clinic sites in the Geisinger Health System to evaluate the effectiveness of a strategy using home smartphone urinalysis test (Dip.io) to complete proteinuria screening in previously unscreened non-diabetic patient portal users with hypertension. All patients received an educational letter and a standing urinalysis lab order, and then were randomized to control (usual care) or intervention. Intervention arm participants were invited to complete proteinuria screening with a mailed home smartphone urinalysis test. Co-primary outcomes were completion of proteinuria screening and number of albuminuria cases (albumin/creatinine ratio [ACR] ≥ 30 mg/g or protein/creatinine ratio ≥ 150 mg/g) at the end of 3 months. We also evaluated patient satisfaction with the home test, and compliance with recommendations for patients with newly detected albuminuria.ResultsA total of 999 patients were randomized to intervention or control. Out of 499 patients assigned to the intervention arm, 253 were reached by phone, and 69/97 (71.1%) consented patients completed the home test. Overall, the intervention increased proteinuria screening completion (28.9% vs. 18.0%; p<0.001) with no effect on the number of albuminuria cases (4 vs. 4) although only 6/57 (10.5%) patients with trace or 1+ urine dipstick protein had a follow-up quantitative test. Among the 55 patients who completed a survey after the home test, 89% preferred testing at home rather than the physician’s office.ConclusionsA strategy using a home urinalysis smartphone test increased proteinuria screening rates in previously unscreened patients with hypertension and may be useful in increasing rates of proteinuria screening compliance. Future studies are needed to determine whether improving early detection of kidney disease can improve future kidney health.Trial RegistrationClinical Trial Registry: NCT03470701https://clinicaltrials.gov/ct2/show/NCT03470701
8-OxoG in GC-rich Sp1 binding sites enhances gene transcription during adipose tissue development in juvenile mice
Authors: Park Jong Woo , Han Young In , Kim Tae Min , Yeom Su Cheong , Kang Jaeku , Park Joonghoon 
Published: February 2019

ABSTRACTThe oxidation of guanine to 8-oxoguanine (8-oxoG) is the most common type of oxidative DNA lesion. There is a growing body of evidence indicating that 8-oxoG is not only pre-mutagenic, but also plays an essential role in modulating gene expression along with its cognate repair proteins. In this study, we investigated the relationship between 8-oxoG formed under intrinsic oxidative stress conditions and gene expression in adipose and lung tissues of juvenile mice. We observed that transcriptional activity and the number of active genes were significantly correlated with the distribution of 8-oxoG in gene promoter regions, as determined by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), and 8-oxoG and RNA sequencing. Gene regulation by 8-oxoG was not associated with the degree of 8-oxoG formation. Instead, genes with GC-rich transcription factor binding sites in their promoters became more active with increasing 8-oxoG abundance as also demonstrated by specificity protein 1 (Sp1)- and estrogen response element (ERE)-luciferase assays in human embryonic kidney (HEK293T) cells. These results indicate that the occurrence of 8-oxoG in GC-rich Sp1 binding sites is important for gene regulation during adipose tissue development.
Highly sensitive in situ proteomics with cleavable fluorescent tyramide reveals human neuronal heterogeneity
Authors: Liao Renjie , Mondal Manas , Nazaroff Christopher D. , Mastroeni Diego , Coleman Paul D. , LaBaer Joshua , Guo Jia 
Published: February 2019

ABSTRACTThe ability to comprehensively profile proteins in intact tissues in situ is crucial for our understanding of health and disease. However, the existing methods suffer from low sensitivity and limited sample throughput. To address these issues, here we present a highly sensitive and multiplexed in situ protein analysis approach using cleavable fluorescent tyramide and off-the-shelf antibodies. Compared with the current methods, this approach enhances the detection sensitivity and reduces the imaging time by 1-2 orders of magnitude, and can potentially detect hundreds of proteins in intact tissues at the optical resolution. Applying this approach, we studied protein expression heterogeneity in genetically identical cells, and performed expression correlation analysis to identify coregulated proteins. We also profiled >6000 neurons in human formalin-fixed paraffin-embedded (FFPE) hippocampus. By partitioning these neurons into varied cell clusters based on their protein expression profiles, we observed different subregions of the hippocampus consist of neurons from distinct clusters.
When does spatial diversification usefully maximise the durability of crop disease resistance?
Authors: Watkinson-Powell Benjamin , Gilligan Christopher A. , Cunniffe Nik J. 
Published: February 2019

1AbstractMaximising the durability of crop disease resistance genes in the face of pathogen evolution is a major challenge in modern agricultural epidemiology. Spatial diversification in the deployment of resistance genes, where susceptible and resistant fields are more closely intermixed, is predicted to drive lower epidemic intensities over evolutionary timescales. This is due to an increase in the strength of dilution effects, caused by pathogen inoculum challenging host tissue to which it is not well-specialised. The factors that interact with and determine the magnitude of this spatial effect are not currently well understood however, leading to uncertainty over the pathosystems where such a strategy is most likely to be cost-effective. We model the effect on landscape scale disease dynamics of spatial heterogeneity in the arrangement of fields planted with either susceptible or resistant cultivars, and the way in which this effect depends on the parameters governing the pathosystem of interest. Our multi-season semi-discrete epidemiological model tracks spatial spread of wild-type and resistance breaking pathogen strains, and incorporates a localised reservoir of inoculum, as well as the effects of within and between field transmission. The pathogen dispersal characteristics, any fitness cost(s) of the resistance breaking trait, the efficacy of host resistance, and the length of the timeframe of interest, all influence the strength of the spatial diversification effect. These interactions, which are often complex and non-linear in nature, produce substantial variation in the predicted yield gain from the use of a spatial diversification strategy. This in turn allows us to make general predictions of the types of system for which spatial diversification is most likely to be cost-effective, paving the way for potential economic modelling and pathosystem specific evaluation. These results highlight the importance of studying the effect of genetics on landscape scale spatial dynamics within host-pathogen disease systems.
Microbial biogeography and ecology of the mouth and implications for periodontal diseases
Authors: Proctor Diana M. , Shelef Katie M. , Gonzalez Antonio , Davis Long Clara L. , Dethlefsen Les , Burns Adam , Loomer Peter M. , Armitage Gary C. , Ryder Mark I. , Millman Meredith E. , Knight Rob , Holmes Susan P. , Relman David A. 
Published: February 2019

AbstractHuman-associated microbial communities differ in composition among body sites and between habitats within a site. Patterns of variation in the distribution of organisms across time and space is referred to as ‘biogeography’. The human oral cavity is a critical observatory for exploring microbial biogeography because it is spatially structured, easily accessible, and its microbiota has been linked to the promotion of both health and disease. The biogeographic features of microbial communities residing in spatially distinct but ecologically similar environments on the human body, including the subgingival crevice, have not yet been adequately explored. The purpose of this paper is twofold. First, we seek to provide the dental community with a primer on biogeographic theory, highlighting its relevance to the study of the human oral cavity. For this reason, we summarize what is known about the biogeographic variation of dental caries and periodontitis and postulate as to how this may be driven by spatial patterning in oral microbial community composition and structure. Second, we present a number of methods that investigators can use to test specific hypotheses using biogeographic theory.To anchor our discussion, we apply each method to a case study and examine the spatial variation of the human subgingival microbiota of 2 individuals. Our case study suggests that subgingival communities in the aggregate may conform to an anterior-to-posterior gradient in community composition. The gradient appears to be structured both by deterministic and non-deterministic processes, though additional work is needed to test and confirm specific hypotheses. A better understanding of biogeographic patterns and processes will advance our understanding of ways to optimize the efficacy of dental interventions targeting the oral microbiota.
Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis
Authors: Grandjean Joanes , Canella Carola , Anckaerts Cynthia , Ayrancı Gülebru , Bougacha Salma , Bienert Thomas , Buehlmann David , Coletta Ludovico , Gallino Daniel , Gass Natalia , Garin Clément M. , Nadkarni Nachiket Abhay , Hübner Neele , Karatas Meltem , Komaki Yuji , Kreitz Silke , Mandino Francesca , Mechling Anna E. , Sato Chika , Sauer Katja , Shah Disha , Strobelt Sandra , Takata Norio , Wank Isabel , Wu Tong , Yahata Noriaki , Yeow Ling Yun , Yee Yohan , Aoki Ichio , Chakravarty M. Mallar , Chang Wei-Tang , Dhenain Marc , Elverfeldt Dominik von , Harsan Laura-Adela , Hess Andreas , Jiang Tianzi , Keliris Georgios A. , Lerch Jason P. , Okano Hideyuki , Rudin Markus , Sartorius Alexander , der Linden Annemie Van , Verhoye Marleen , Weber-Fahr Wolfgang , Wenderoth Nicole , Zerbi Valerio , Gozzi Alessandro 
Published: February 2019

AbstractPreclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories world-wide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a murine default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.
Abnormalities in Proinsulin Processing in Islets from Individuals with Longstanding T1D
Authors: Sims Emily K. , Nyalwidhe Julius , Syed Farooq , Bahnson Henry T. , Haataja Leena , Speake Cate , Morris Margaret A. , Mirmira Raghavendra G. , Nadler Jerry , Mastracci Teresa L. , Arvan Peter , Greenbaum Carla J. , Evans-Molina Carmella 
Published: February 2019

ABSTRACTWork by our group and others has suggested that elevations in circulating proinsulin relative to C-peptide is associated with development of Type 1 diabetes (T1D). We recently described the persistence of detectable serum proinsulin in a large majority (95.9%) of individuals with longstanding T1D, including individuals with undetectable serum C-peptide. Here we describe analyses performed on human pancreatic sections from the nPOD collection (n=30) and isolated human islets (n=10) to further explore mechanistic etiologies of persistent proinsulin secretion in T1D. Compared to nondiabetic controls, immunostaining among a subset (4/9) of insulin positive T1D donor islets revealed increased numbers of cells with proinsulin-enriched, insulin-poor staining. Laser capture microdissection followed by mass spectrometry revealed reductions in the proinsulin processing enzymes prohormone convertase 1/3 (PC1/3) and carboxypeptidase E (CPE) in T1D donors. Twenty-four hour treatment of human islets with an inflammatory cytokine cocktail reduced mRNA expression of the processing enzymes PC1/3, PC2, and CPE. Taken together, these data provide new mechanistic insight into altered proinsulin processing in long-duration T1D and suggest that reduced β cell prohormone processing is associated with proinflammatory cytokine-induced reductions in proinsulin processing enzyme expression.
Exploring DCAF15 for reprogrammable targeted protein degradation
Authors: Coomar Seemon , Gillingham Dennis G. 
Published: February 2019

AbstractThe targeted degradation of proteins by reprogramming E3 ligases with bifunctional small molecules is an exciting area of chemical biology because it promises a set of chemical tools for achieving the same task as siRNA or CRISPR/Cas9. Although there are hundreds of E3 ligases in the human proteome only a few have been shown to be reprogrammable to target new proteins. Recently various arylsulfonamides were shown to induce degradation of the splicing factor RBM39 via the RING type E3 ligase CRL4DCAF15. Here we identify the arylsulfonamide most amenable to chemical modifications and demonstrate its behaviour in bifunctional reprogramming.
Chemical-genetic profiling reveals cross-resistance and collateral sensitivity between antimicrobial peptides
Authors: Kintses Bálint , Jangir Pramod K. , Fekete Gergely , Számel Mónika , Méhi Orsolya , Spohn Réka , Daruka Lejla , Martins Ana , Hosseinnia Ali , Gagarinova Alla , Kim Sunyoung , Phanse Sadhna , Csörgő Bálint , Györkei Ádám , Ari Eszter , Lázár Viktória , Faragó Anikó , Bodai László , Nagy István , Babu Mohan , Pál Csaba , Papp Balázs 
Published: February 2019

AbstractAntimicrobial peptides (AMPs) are key effectors of the innate immune system and promising therapeutic agents. Yet, knowledge on how to design AMPs with minimal cross-resistance to human host-defense peptides remains limited. Here, with a chemical-genetic approach, we systematically assessed the resistance determinants of Escherichia coli against 15 different AMPs. Although generalizations about AMP resistance are common in the literature, we found that AMPs with different physicochemical properties and cellular targets vary considerably in their resistance determinants. As a consequence, collateral sensitivity effects were common: numerous genes decreased susceptibility to one AMP while simultaneously sensitized to others. Finally, the chemical-genetic map predicted the cross-resistance spectrum of laboratory-evolved human-B-defensin-3 resistant lineages. Our work substantially broadens the scope of known resistance-modulating genes and explores the pleiotropic effects of AMP resistance. In the future, the chemicalgenetic map could inform efforts to minimize cross-resistance between therapeutic and human host AMPs.
Segregostat: A novel concept to control phenotypic diversification dynamics on the example of Gram-negative bacteria
Authors: Sassi Hosni , Nguyen Thai Minh , Telek Samuel , Gosset Guillermo , Grünberger Alexander , Delvigne Frank 
Published: February 2019

SummaryControlling and managing the degree of phenotypic diversification of microbial populations is a challenging task. This task not only requires detailed knowledge regarding diversification mechanisms but also advances technical setups for the real-time analyses and control of population behavior on single-cell level. In this work, setup, design and operation of the so called segregostat is described which, in contrast to a traditional chemostats, allows the control of phenotypic diversification of microbial populations over time. Two exemplary case studies will be discussed, emphasizing the applicability and versatility of the proposed approach. In detail the phenotypic diversification ofEschericia coliorPseudomonas putidabased on monitoring membrane permeability will be controlled. We show that upon nutrient limitation, cell population tends to diversify into several subpopulations exhibiting distinct phenotypic (non-permeablized and permeablized cells). On-line analysis leads to the determination of the ratio between cells in these two states, which in turn trigger the addition of glucose pulses in order to maintain a pre-defined diversification ratio. These results prove that phenotypic diversification can be controlled by means of defined pulse-frequency modulation within continuously running bioreactor setups. This lays the foundation for systematic studies, not only of phenotypic diversification but also for all processes where dynamics single cell approaches are required, such as synthetic co-culture processes.