bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship of pay-for-performance and provider pay
Authors: Shurson Lauren , Gregg S. Renee
Published: December 2019

Background:

Policymakers and health care leaders search for a payment model to balance the interests of providers, patients, and payers. This has shifted reimbursement from a fee-for-service (FFS) to pay-for-performance (P4P) model. The FFS model of reimbursement may lead to provider overuse. The P4P model incentivizes quality, not quantity, of care. However, the payer's reimbursement shift to P4P has not affected compensation of individual providers.

Objectives:

To explore the effects of payment compensation models on provider behavior and employment.

Data sources:

CINAHL, Cochrane, and EBSCO databases were searched. To ensure accuracy, a PRISMA flow diagram was used. A thematic analysis was performed using 52 articles.

Conclusions:

Four themes emerged: health care as an economic anomaly, the ability to incentivize value, ethics, and provider–employer–payer alignment. Basic economic principles are distorted in health care because of payment layers and competing goals. Although payment structure affects health care provider (HCP) performance, the correlation is not understood. There is a lack of knowledge on several key areas: 1) HCP behavioral research, 2) how employment may be influencing existing HCP attitudes and actions, 3) how nurse practitioners (NPs) differ from physicians, and 4) P4P outcome data. There is also a lack of literature involving NP's and reimbursement.

Implications for practice:

Nurse practitioners must be included in compensation model research. Payment reform should address all individual HCP compensation. Reforms will be limited if focus remains on payer–organization reform and ignores HCP compensation. As HCPs, it is imperative to understand how payers reimburse services to establish guiding principles for equitable and ethical compensation negotiations.
Buprenorphine compared with methadone in opioid-dependent pregnant women: How does it affect neonatal abstinence syndrome?
Authors: Bivin Bethany , Waring Ashley , Alves Paul
Published: December 2019

Background:

The growing opioid epidemic in the United States has led to increasingly high rates of neonatal abstinence syndrome (NAS). Preliminary studies have shown that buprenorphine maintenance treatment (BMT) may lead to better outcomes for infants than methadone maintenance treatment (MMT).

Objectives:

The authors gathered recent evidence to answer the following PICO (population, intervention, comparison, and outcome) question: In opioid-dependent pregnant women, how does buprenorphine compared with methadone administration affect NAS?

Data sources:

A literature search was completed in PubMed, Scopus, Embase, and Web of Science databases and limited to the past 5 years. The following parameters were analyzed in the articles: NAS occurrence, length of hospital stay in days, NAS treatment length, and amount of pharmacotherapy administered to treat NAS.

Conclusions:

In comparison to methadone, buprenorphine exposure in utero is associated with significantly shorter hospital stays for the infant after delivery, shorter length of NAS treatment, and decreased frequency/duration of pharmacotherapy for NAS symptoms in the infant.

Implications for practice:

Based on the findings, a weak recommendation can be made for the use of BMT over MMT in opioid-dependent pregnant women. However, further research is necessary to definitively recommend buprenorphine over methadone use in this population, especially regarding the effect of maternal severity of addiction on adherence to BMT, and long-term effects of in utero buprenorphine exposure.
DNP Practice Improvement Initiative
Authors: Tharp-Barrie Kim , Williams Tracy E. , Howard Patricia B. , El-Mallakh Peggy , MacCallum Tricia
Published: December 2019

This article describes a practice improvement initiative (PII) demonstrating the impact of doctorate of nursing practice (DNP) skills beyond direct patient care. The Donna Wright Competency Assessment Model, AACN DNP Essentials, and National Organization of Nurse Practitioner Faculties nurse practitioner competencies framed the PII. The DNP graduates planned, implemented, and evaluated an assessment of 1,055 staff nurses on shift hand-off, physical assessment, and hand hygiene. Results indicated that 95% of the staff nurses scored 100% on competency assessment. The PII model was adopted for future competency evaluation.
Using a Nursing Salon to Identify and Develop an Initiative for Family Caregivers of Older Adults
Authors: Sullivan-Bolyai Susan , Pellegrini Linda , Boucher Jean , Gravlin Gayle , O'Neil William , Coco Angelina , Vitello Joan
Published: December 2019

The purpose of the Aging Well Nursing-Interprofessional Salon was to explore current local community healthcare issues for older adults and to develop innovative strategies that support and enhance their health. An initiative emerged from the salon that focuses on identifying caregivers to ensure their awareness of available support resources. We are in the process of developing a pilot plan that includes collaboration of PhD and doctorate of nursing practice students, nursing faculty, and community agencies that support older adults.
The Influence of Social Networks on Antiretroviral Therapy Initiation Among HIV-Infected Antiretroviral Therapy–Naive Youth in Rural Kenya and Uganda
Authors: Brown Lillian B. , Balzer Laura B. , Kabami Jane , Kwarisiima Dalsone , Sang Norton , Ayieko James , Chen Yiqun , Chamie Gabriel , Charlebois Edwin D. , Camlin Carol S. , Cohen Craig R. , Bukusi Elizabeth , Kamya Moses R. , Moody James , Havlir Diane V. , Petersen Maya L.
Published: December 2019

Background:

HIV-infected youth in sub-Saharan Africa are less likely to initiate antiretroviral therapy (ART) than older adults.

Setting and Methods:

Adult (≥15 years) residents enumerated during a census in 32 communities in rural Kenya and Uganda named social contacts in 5 domains: health, money, emotional support, food, and free time. Named contacts were matched to other enumerated residents to build social networks among 150,395 adults; 90% were tested for HIV at baseline. Among youth (15–24 years) who were ART naive at baseline (2013–2014), we evaluated whether having ≥1 network contact who was HIV infected predicted ART initiation within 3 years and modification of this association by age and strength of contact, using logistic regression with robust standard errors.

Results:

Among 1120 HIV-infected youth who were ART naive at baseline, 805 remained alive and community residents after 3 years. Of these, 270 (33.5%) named at least one baseline HIV-infected contact; 70% (569/805) subsequently initiated ART. Youth with ≥1 HIV-infected same-age baseline contact were more likely to initiate ART [adjusted odds ratio (aOR), 2.95; 95% confidence interval (CI): 1.49 to 5.86] than those with no HIV-infected contact, particularly if the contact was a strong tie (named in >1 domain; aOR, 5.33; 95% CI: 3.34 to 8.52). When nonhousehold contacts were excluded, having an HIV-infected same age contact who was a strong tie remained associated with ART initiation (aOR, 2.81; 95% CI: 1.76 to 4.49).

Conclusions:

Interventions that increase and strengthen existing social connections to other HIV-infected peers at the time of HIV diagnosis may increase ART initiation among HIV-infected youth.
Management of Osteoporosis in Patients Living With HIV—A Systematic Review and Meta-analysis
Authors: Starup-Linde Jakob , Rosendahl Simone Bruhn , Storgaard Merete , Langdahl Bente
Published: December 2019

Objective:

Osteoporosis is reported as a common comorbidity in patients living with HIV (PLHIV). The aim of this systematic review and meta-analysis is to assess the evidence on fracture risk in PLHIV, bone mineral density (BMD) in PLHIV compared with controls, longitudinal changes in BMD in PLHIV, and effect of antiosteoporosis treatment in PLHIV.

Methods:

A systematic literature search was conducted using the databases Medline at PubMed and EMBASE using the search terms: “HIV” and “fracture” or “bone turnover,” or “bone mineral density.” Eligibility criteria followed the aim of the study and include randomized controlled trials and observational studies. Two reviewers extracted the data independently. Meta-analysis was performed using random-effects model assessing fracture risk, BMD compared with controls, and changes in BMD.

Results:

One hundred forty-two of 2397 papers identified were included in the systematic review, and subsequently, 84 were included in the meta-analysis. The risks of a fragility fracture [1.51, 95% confidence interval (CI): 1.41 to 1.63] and hip fracture (4.05, 95% CI: 2.99 to 5.49) were increased. PLHIV have lower BMD at the hip (z-score −0.31, 95% CI: −0.46 to −0.27) and lumbar spine (z-score −0.36, 95% CI: −0.39 to −0.15) compared with controls. The reduced BMD did not fully explain the increased fracture risk in PLHIV.

Conclusions:

Current management of osteoporosis in PLHIV follows general osteoporosis guidelines; however, the increased fracture risk is not fully explained by lower BMD, and thus, antiosteoporosis intervention may be beneficial at a higher BMD in PLHIV.
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.
The Association Between Vitamin D Status and Pulmonary Function in Pediatric Patients With Cystic Fibrosis
Authors: Gomes Allison , Parker Anna , Zelig Rena
Published: December 2019

Sufficient vitamin D levels play an essential role in bone health and, more recently, in pulmonary function. Achieving sufficient vitamin D levels is challenging, especially among individuals with malabsorptive diseases, such as cystic fibrosis (CF). Cystic fibrosis is characterized by a progressive loss of pulmonary function and fat malabsorption, increasing the risk for vitamin D deficiency. After reviewing the literature for pediatric patients with CF, the association between vitamin D status and pulmonary function remains unclear. More studies are needed to evaluate whether adequate vitamin D status can assist in maintaining pulmonary function and slowing disease progression.
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.

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.

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

Introduction

A 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.

Methods

We 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.

Results

Genome- 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.

Conclusions

Our 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

Antibiotics 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

The 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

Cognitive 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

Emergence 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

Grape 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

Reverse 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.
Evolutionary Response to Resource Deprivation: Parallelism and Nonmonotonicity
Authors: Behringer Megan G. , Ho Wei-Chin , Miller Samuel F. , Meraz John C. , Boyer Gwyneth F. , Lynch Michael
Published: December 2019

Establishing reliable frameworks for predicting unknown outcomes from empirical observations is of great interest to ecologists and evolutionary biologists. Strong predictability in evolutionary responses has been previously demonstrated by the repeated observation of similar phenotypes or genotypes across multiple natural or experimental populations in analogous environments. However, the degree to which evolutionary outcomes can be predicted across environmental gradients, or in fluctuating environments, remains largely unexplored. Presumably, the phenotypic evolution in an intermediate environment could be interpolated from the evolved phenotypes observed in two extreme environments, but this assumption remains to be fully tested. Here, we report on the experimental evolution ofEscherichia coliunder three nutritional transfer periods: every day, every 10 days, and every 100 days, representing increasing severity in feast/famine cycles. After 900 days of experimental evolution, populations experiencing intermediate durations of starvation had evolved longer times to reach maximum growth rate, smaller colony sizes, higher biofilm formation, and higher mutation rates than populations evolving in the other environmental extremes. Because the intermediately starved populations exhibit significantly high molecular parallelism, these distinct phenotypes are likely due to non-monotonic deterministic forces instead of increased stochastic forces commonly associated with fluctuating environments. Our results demonstrate novel complexities associated with evolutionary predictability across environmental gradients and highlight the risk of using interpolation in evolutionary biology.
MrDNA: A multi-resolution model for predicting the structure and dynamics of nanoscale DNA objects
Authors: Maffeo Christopher , Aksimentiev Aleksei
Published: December 2019

Although the field of structural DNA nanotechnology has been advancing with an astonishing pace,de novodesign of complex 3D nanostructures remains a laborious and time-consuming process. One reason for that is the need for multiple cycles of experimental characterization to elucidate the effect of design choices on the actual shape and function of the self-assembled objects. Here, we demonstrate a multi-resolution simulation framework,mrdna, that, in 30 minutes or less, can produce an atomistic-resolution structure of an arbitrary DNA nanostructure with accuracy on par with that of a cryo-electron microscopy (cryo-EM) reconstruction. We demonstrate fidelity of ourmrdnaframework through direct comparison of the simulation results with the results of cryo-EM reconstruction of multiple 3D DNA origami objects. Furthermore, we show that our approach can characterize an ensemble of conformations adopted by dynamic DNA nanostructures, the equilibrium structure and dynamics of DNA objects constructed using a self-assembly principle other than origami, i.e., wireframe DNA objects, and to study the properties of DNA objects under a variety of environmental conditions, such as applied electric field. Implemented as an open source Python package, our framework can be extended by the community and integrated with DNA design and molecular graphics tools.
Standardized Effect Sizes and Image-Based Meta-Analytical Approaches for fMRI Data
Authors: Bossier Han , Nichols Thomas E. , Moerkerke Beatrijs
Published: December 2019

Scientific progress is based on the ability to compare opposing theories and thereby develop consensus among existing hypotheses or create new ones. We argue that data aggregation (i.e. combine data across studies or research groups) for neuroscience is an important tool in this process. An important prerequisite is the ability to directly compare fMRI results over studies. In this paper, we discuss how an observed effect size in an fMRI data-analysis can be transformed into a standardized effect size. We demonstrate how these enable direct comparison and data aggregation over studies. Furthermore, we also discuss the influence of key parameters in the design of an fMRI experiment (such as number of scans and the sample size) on (statistical) properties of standardized effect sizes. In the second part of the paper, we give an overview of two approaches to aggregate fMRI results over studies. The first corresponds to extending the two-level general linear model approach as is typically used in individual fMRI studies with a third level. This requires the parameter estimates corresponding to the group models from each study together with estimated variances and meta-data. Unfortunately, there is a risk of running into unit mismatches when the primary studies use different scales to measure the BOLD response. To circumvent, it is possible to aggregate (unitless) standardized effect sizes which can be derived from summary statistics. We discuss a general model to aggregate these and different approaches to deal with between-study heterogeneity. Furthermore, we hope to further promote the usage of standardized effect sizes in fMRI research.
Skill Acquisition is Enhanced by Reducing Trial-To-Trial Repetition
Authors: Vleugels Lore WE , Swinnen Stephan P , Hardwick Robert M
Published: December 2019

Developing approaches to improve motor skill learning is of considerable interest across multiple disciplines. Previous research has typically shown that repeating the same action on consecutive trials enhances short-term performance, but has detrimental effects on longer term skill acquisition. However, most prior research has contrasted the effects of repetition only at the block level; here we examined the effects of repeating individual trials embedded in a larger randomized block a feature that is often overlooked when generating random trial orders in learning tasks. With four days of practice, a “Minimal Repeats Group”, who rarely experienced repeating stimuli on consecutive trials during training improved to a greater extent than a “Frequent Repeats Group”, who were frequently presented with repeating stimuli on consecutive trials during training. Our results extend the previous finding of the beneficial effects of random as compared to blocked practice on performance, showing that reduced trial-to-trial repetition during training is favorable with regards to skill learning. This research highlights that limiting the number of repeats on consecutive trials is a simple behavioral manipulation that can enhance the process of skill learning. Data/analysis code and supplementary materials available at https://osf.io/p3278/

NEW & NOTEWORTHY

Numerous studies have shown that performing different sub-tasks across consecutive blocks of trials enhances learning. Here we examined whether the same effect would occur on a trial-to-trial level. Our Minimal Repeats Group, who primarily responded to different stimuli on consecutive trials, learned more than our Frequent Repeats Group, who frequently responded to the same stimulus on consecutive trials. This shows that minimizing trial-to-trial repetition is a simple and easily applicable manipulation that can enhance learning.
Estimation of Genetic Diversity in Genus Mentha Collected From Azad Jammu And Kashmir, Pakistan
Authors: Abasi Fozia , Ahmad Israr , khan Sami Ullah , Ahmad Khawaja Shafique , Ulfat Aneela , Khurshid Rubab
Published: December 2019

Mints are perennial aromatic herbs used both for medicinal and aromatic purposes. Flora of Pakistan has reported six species of genus Mentha. Taxonomy of genus Mentha is more complex and confusing due to inter specific hybridization. The present research is the first documented report from Pakistan for the purpose to dissect Mentha specimens using molecular tools. A total of 17 SCoT and SSR markers used to dissect genetic diversity among 41 Mentha specimens. The results revealed substantial variation among Mentha specimens. The molecular data analyzed through NTSYS and Power marker software’s. Dendrogram constructed on the base of similarity coefficients generated using weighted pair group method of arithmetic means (UPGMA) recorded high level of polymorphism. Polymorphic Information Content (PIC) for molecular markers recorded in the range of 5-8. Mean genetic distance (GD) was estimated in the range from 0.35% to 100%. The minimum and maximum GD recorded in one combination each as P2-P4 and M41-P10. The present study was explored the efficiency of SCoT and SSR markers for evaluating the genetic diversity of medicinal plants. The present research was concluded that both morphological and molecular dendrogram determined considerable level of diversity among Mentha species. Furthermore, specific primers and DNA chloroplast technology could be needed for further molecular analysis to refine the data more up to varietal level.
Oxytocin shapes spontaneous activity patterns in the developing visual cortex by activating somatostatin interneurons
Authors: Maldonado Paloma P , Nuno-Perez Alvaro , Kirchner Jan , Hammock Elizabeth , Gjorgjieva Julijana , Lohmann Christian
Published: December 2019

Spontaneous network activity shapes emerging neuronal circuits during early brain development, however how neuromodulation influences this activity is not fully understood. Here, we report that the neuromodulator oxytocin powerfully shapes spontaneous activity patterns.In vivo, oxytocin strongly decreased the frequency and pairwise correlations of spontaneous activity events in visual cortex (V1), but not in somatosensory cortex (S1). This differential effect was a consequence of oxytocin only increasing inhibition in V1 and increasing both inhibition and excitation in S1. The increase in inhibition was mediated by the depolarization and increase in excitability of somatostatin+(SST) interneurons specifically. Accordingly, silencing SST+neurons pharmacogenetically fully blocked oxytocin’s effect on inhibitionin vitroas well its effect on spontaneous activity patternsin vivo. Thus, oxytocin decreases the excitatory/inhibitory ratio and modulates specific features of V1 spontaneous activity patterns that are crucial for refining developing synaptic connections and sensory processing later in life.
Hotspot Dosages of Most Rapid Antibiotic Resistance Evolution
Authors: Reding Carlos , Catalán Pablo , Jansen Gunther , Bergmiller Tobias , Rosenstiel Phillip , Schulenburg Hinrich , Gudelj Ivana , Beardmore Robert
Published: December 2019

We treatedEscherichia coliwith the antibiotic erythromycin from zero to high dosages to determine how the evolutionary dynamics of antibiotic resistant phenotypes and genotypes depend on dose. The most rapid increase in resistance was observed just below erythromycin’s minimal inhibitory concentration (MIC) and genotype-phenotype correlations determined from whole genome sequencing revealed the molecular basis of this: simultaneous selection for copy number variation in 3 resistance mechanisms which shared an ‘inverted-U’ pattern of dose-dependent selection with several insertion sequences and an integron. Many genes did not conform to this pattern, however, because of changes in selection as dose increased: media adaptation at zero-to-low dosages gave way to drug target (ribosomal RNA operon) amplification at mid dosages whereas prophage-mediated drug efflux dominated at higher dosages where population densities were lowest. All dosages sawE. coliamplify the efflux operonsacrandemrEat rates that correlated strongly with changes in population density that exhibited an inverted-U geometry too. However, we show by example that inverted-U geometries are not a universal feature of dose-resistance relationships.
Comparing current noise in biological and solid-state nanopores
Authors: Fragasso A. , Schmid S. , Dekker C.
Published: December 2019

Nanopores bear great potential as single-molecule tools for bioanalytical sensing and sequencing, due to their exceptional sensing capabilities, high-throughput, and low cost. The detection principle relies on detecting small differences in the ionic current as biomolecules traverse the nanopore. A major bottleneck for the further progress of this technology is the noise that is present in the ionic current recordings, because it limits the signal-to-noise ratio and thereby the effective time resolution of the experiment. Here, we review the main types of noise at low and high frequencies and discuss the underlying physics. Moreover, we compare biological and solid-state nanopores in terms of the signal-to-noise ratio (SNR), the important figure of merit, by measuring free translocations of a short ssDNA through a selected set of nanopores under typical experimental conditions. We find that SiNx solid-state nanopores provide the highest SNR, due to the large currents at which they can be operated and the relatively low noise at high frequencies. However, the real game-changer for many applications is a controlled slowdown of the translocation speed, which for MspA was shown to increase the SNR >160-fold. Finally, we discuss practical approaches for lowering the noise for optimal experimental performance and further development of the nanopore technology.