bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Hepcidin and Hemoglobin After Anti‐TNF‐alpha Therapy in Children and Adolescents With Crohn Disease
Authors: Atkinson Meredith A. , Leonard Mary B. , Herskovitz Rita , Baldassano Robert N. , Denburg Michelle R.
Published: June 2017

Objectives:

Anemia is the most common systemic complication of inflammatory bowel disease, is more common in affected children than in adults, and is mediated in large part by chronic inflammation. Inflammation increases levels of the iron‐regulatory protein hepcidin, which have been elevated in adults with Crohn disease.

Methods:

We measured serum hepcidin‐25 and hemoglobin (Hgb) in 40 children and adolescents with Crohn disease at baseline and 10 weeks after initiation of anti‐tumor necrosis factor (TNF)‐α therapy. Measures of disease activity, inflammatory markers, and cytokines were obtained in all subjects. Anemia was defined by World Health Organization criteria.

Results:

At baseline hepcidin and C‐reactive protein levels were correlated, and 95% of subjects were anemic. After anti‐TNF‐α therapy, median (interquartile range) hepcidin concentrations decreased significantly and the distribution narrowed (27.9 [16.2, 52.9] vs 23.2 [11.1, 37.7] ng/mL, P = 0.01). Mean (standard deviation) Hgb also increased significantly (10.6 ± 1.2 to 10.9 ± 1.1 g/dL, P = 0.02), and the increase was sustained at 12 months, although 90% of participants continued to meet anemia criteria at 10 weeks. Disease activity and markers of inflammation also decreased and albumin levels increased. In generalized estimating equation analyses, higher TNF‐α, interleukin 6, erythrocyte sedimentation rate, and C‐reactive protein were associated with higher hepcidin concentrations (P = 0.04, P = 0.03, P = 0.003, and P < 0.001, respectively), and increased levels of disease activity were associated with higher hepcidin.

Conclusions:

In children with Crohn disease, anti‐TNF‐α therapy is associated with decreased levels of hepcidin and increased Hgb 10 weeks after induction. Improvement in anemia may be a secondary benefit for children who receive this therapy.
Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure
Authors: Mangus Richard S. , Bush Weston J. , Miller Christina , Kubal Chandrashekhar A.
Published: June 2017

Objectives:

Malnutrition and wasting predict clinical outcomes in children with severe chronic illness. Objectively calculated malnutrition in children with end‐stage organ failure has not been well studied. This analysis compares children with kidney, liver or intestine failure to healthy controls to quantitate the disparity in muscle and fat stores.

Methods:

Children younger than 19 years with end‐stage liver, kidney, or intestine failure and with pretransplant computed tomography (CT) imaging were selected from the transplant database. Age‐ and sex‐matched healthy controls were selected from the trauma database. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores. Analysis was conducted using the pooled and individually matched subject‐control differences.

Results:

There were 81 subjects included in the final analysis (liver [n = 35], kidney [n = 20], and intestine [n = 26]). Children with end‐stage liver disease had a 23% reduction in muscle mass, a 69% increase in visceral fat, and a 29% increase in subcutaneous fat. End‐stage renal disease patients had a 19% reduction in muscle mass and a 258% increase in subcutaneous fat. Intestine failure patients had a 24% reduction in muscle mass, a 30% increase in visceral fat, and a 46% increase in subcutaneous fat.

Conclusions:

These results demonstrate significant sarcopenia and increased fat stores in end‐stage organ failure patients, which supports the idea of an active physiologic mechanism to store fat while losing muscle mass. Sarcopenia may be related to total protein loss from a catabolic state, or from decreased synthesis (liver), wasting (kidney), or malabsorption (intestine).
Mineral Intake and Status of Cow's Milk Allergic Infants Consuming an Amino Acid‐based Formula
Authors: Harvey Bryan M. , Eussen Simone R.B.M. , Harthoorn Lucien F. , Burks A. Wesley
Published: June 2017

Data on the mineral status of infants with cow's milk allergy (CMA) consuming an amino acid‐based formula (AAF) have not been published. The present study aims to assess mineral status of term infants age 0 to 8 months diagnosed with CMA receiving an AAF for 16 weeks. Serum concentrations of calcium, phosphorus, chloride, sodium, potassium, magnesium, and ferritin were determined in 82 subjects at baseline and in 66 subjects after 16 weeks on AAF using standard methods and evaluated against age‐specific reference ranges. In addition to this, individual estimated energy and mineral intakes were compared to Adequate Intakes defined by the European Food Safety Authority and the US Institute of Medicine. The results of this study show that the AAF was effective in providing an adequate mineral status in infants with CMA. The vast majority of infants aged 0 to 6 months (formula only) and aged 6 to 12 months (formula and complementary foods) had adequate mineral intakes.
Moral Distress in PICU and Neonatal ICU Practitioners: A Cross-Sectional Evaluation*
Authors: Larson Charles Philip , Dryden-Palmer Karen D. , Gibbons Cathy , Parshuram Christopher S.
Published: June 2017

Objectives:

To measure the level of moral distress in PICU and neonatal ICU health practitioners, and to describe the relationship of moral distress with demographic factors, burnout, and uncertainty.

Design:

Cross-sectional survey.

Setting:

A large pediatric tertiary care center.

Subjects:

Neonatal ICU and PICU health practitioners with at least 3 months of ICU experience.

Interventions:

A 41-item questionnaire examining moral distress, burnout, and uncertainty.

Measurements and Main Results:

The main outcome was moral distress measured with the Revised Moral Distress Scale. Secondary outcomes were frequency and intensity Revised Moral Distress Scale subscores, burnout measured with the Maslach Burnout Inventory depersonalization subscale, and uncertainty measured with questions adapted from Mishel’s Parent Perception of Uncertainty Scale. Linear regression models were used to examine associations between participant characteristics and the measures of moral distress, burnout, and uncertainty. Two-hundred six analyzable surveys were returned. The median Revised Moral Distress Scale score was 96.5 (interquartile range, 69–133), and 58% of respondents reported significant work-related moral distress. Revised Moral Distress Scale items involving end-of-life care and communication scored highest. Moral distress was positively associated with burnout (r
2 = 0.27; p < 0.001) and uncertainty (r
2 = 0.04; p = 0.008) and inversely associated with perceived hospital supportiveness (r
2 = 0.18; p < 0.001). Nurses reported higher moral distress intensity than physicians (Revised Moral Distress Scale intensity subscores: 57.3 vs 44.7; p = 0.002). In nurses only, moral distress was positively associated with increasing years of ICU experience (p = 0.02) and uncertainty about whether their care was of benefit (r
2 = 0.11; p < 0.001) and inversely associated with uncertainty about a child’s prognosis (r
2 = 0.03; p = 0.03).

Conclusions:

In this single-center, cross-sectional study, we found that moral distress is present in PICU and neonatal ICU health practitioners and is correlated with burnout, uncertainty, and feeling unsupported.
Adverse Events Detection Through Global Trigger Tool Methodology: Results From a 5-Year Study in an Italian Hospital and Opportunities to Improve Interrater Reliability
Authors: Mortaro Alberto , Moretti Francesca , Pascu Diana , Tessari Lorella , Tardivo Stefano , Pancheri Serena , Marta Garon , Romano Gabriele , Mazzi Mariangela , Montresor Paolo , Naessens James M.
Published: June 2017

Objective

Global Trigger Tool (GTT) has been proposed as a low-cost method to detect adverse events (AEs). The validity of the methodology has been questioned because of moderate interrater agreement. Continuous training has been suggested as a means to improve consistency over time. We present the main findings of the implementation of the Italian version of the GTT and evaluate efforts to improve the interrater reliability over time.

Methods

The Italian version of the GTT was developed and implemented at the San Bonifacio Hospital, a 270-bed secondary care acute hospital in Verona, Italy. Ten clinical records randomly selected every 2 weeks were reviewed from 2009 to 2014. Two-stage interrater reliability assessment between team members was conducted on 2 subsamples of 50 clinical records before and after the implementation of specific review rules and staff training.

Results

Among 1320 medical records reviewed, a total of 366 AEs were found with at least 1 AE on 20.2% of all discharges, 27.7 AEs/100 admissions, and 30.6 AEs/1000 patient-days. Adverse events with harm score E and F were respectively 58.2% (n = 213) and 38.8% (n = 142). First round interrater reliability was comparable with other international studies. The interrater agreement improved significantly after intervention (κ interrater I = 0.52, κ interrater II = 0.80, P < 0.001).

Conclusions

Despite the improvements in the interrater consistency, overall results did not show any significant trend in AEs over time. Future studies may be directed to apply and adapt the GTT methodology to more specific settings to explore how to improve its sensitivity.
Characteristics and Risk Behaviors of Men Who Have Sex With Men and Women Compared With Men Who Have Sex With Men—20 US Cities, 2011 and 2014
Authors: Shadaker Shaun , Magee Matthew , Paz-Bailey Gabriela , Hoots Brooke E. ,   for the NHBS Study Group
Published: June 2017

Background:

Men who have sex with men (MSM) are heterogeneous with respect to sexual behavior. We examined differences in sex behaviors between men who have sex with men and women (MSMW) and men who have sex with men only (MSMO).

Methods:

Data for this analysis were from MSM who participated in National HIV Behavioral Surveillance in 2011 and 2014. We used the combined years to evaluate demographic and behavioral differences between MSMW and MSMO. Using log-linked Poisson regression models, adjusted prevalence ratios (aPR) were calculated for behavioral outcomes.

Results:

Overall, 2042 (11.9%) participants were classified as MSMW. MSMW were less likely than MSMO to have condomless sex with male partners [aPR 0.77; 95% confidence interval (CI): 0.74 to 0.81] and to have been diagnosed with another sexually transmitted disease (aPR 0.83; 95% CI: 0.72 to 0.95). MSMW were more likely than MSMO to have given money or drugs for sex (aPR 2.85; 95% CI: 2.52 to 3.24) or received money or drugs for sex (aPR 2.64; 95% CI: 2.37 to 2.93) and to ever have injected drugs (aPR 2.05; 95% CI: 1.80 to 2.34). MSMW had more total sex partners (median 6, interquartile range: 4–11 vs. 3, 2–8), casual sex partners (5, 2–10 vs. 3, 1–7), and condomless sex partners (2, 1–4 vs. 1, 0–2) in the last 12 months (P < 0.01 for all comparisons).

Conclusions:

MSMW have distinct sexual risk behaviors from MSMO and may contribute to HIV transmission among women. MSMW could benefit from tailored interventions to reduce HIV risk behaviors.
Trends in Internet Use Among Men Who Have Sex With Men in the United States
Authors: Paz-Bailey Gabriela , Hoots Brooke E. , Xia Mingjing , Finlayson Teresa , Prejean Joseph , Purcell David W. ,   for the NHBS Study Group
Published: June 2017

Background:

Internet-based platforms are increasingly prominent interfaces for social and sexual networking among men who have sex with men (MSM).

Methods:

MSM were recruited through venue-based sampling in 2008, 2011, and 2014 in 20 US cities. We examined changes in internet use (IU) to meet men and in meeting the last partner online among MSM from 2008 to 2014 using Poisson regression with generalized estimating equations to calculate adjusted prevalence ratios (APRs). We also examined factors associated with increased frequency of IU using data from 2014. IU was categorized as never, infrequent use (<once a week), and frequent use (≥once a week).

Results:

Frequent IU increased from 21% in 2008 to 44% in 2014 (APR = 1.39, 95% confidence interval: 1.36 to 1.42), and having met the last partner online increased from 19% in 2008 to 32% in 2014 (APR = 1.30, 95% confidence interval: 1.26 to 1.34). Those who never used the internet had fewer partners (median of 2 in the past 12 months, interquartile range: 1–4) compared with infrequent (4, 2–7) and frequent users (5, 3–12). HIV testing in the past 12 months also increased with increasing IU (58%, 68%, and 71%, respectively, P < 0.0001). Among HIV-positive participants, the percent HIV-positive awareness increased as IU increased (71%, 75%, and 79%, P < 0.005).

Conclusions:

Both IU to meet men and meeting the last partner online increased since 2008. Although men who used the internet more frequently reported more partners in the past 12 months, they were also more likely to report testing in the past 12 months and were more likely to be HIV-positive aware.
A Decline in HIV Testing Among Persons Who Inject Drugs in the Seattle Area, 2004–2015
Authors: Burt Richard D. , Tinsley Joe , Glick Sara Nelson
Published: June 2017

Background:

Promoting HIV testing is a key component of the public health response to HIV. Assessing HIV testing frequency among persons who inject drugs (PWID) monitors the status of these efforts and can identify unmet needs and opportunities to more effectively promote testing.

Methods:

Data were combined from 4 Seattle-area surveys of PWID from the National HIV Behavioral Surveillance (NHBS) program (2005–2015) and 6 surveys of Needle Exchange clients (2004–2015).

Results:

The proportion of PWID reporting an HIV test in the previous 12 months declined from 64% in 2005% to 47% in 2015 in the NHBS surveys and from 72% to 58% in the Needle Exchange surveys. These declines persisted in multivariate analyses controlling for differences in the study populations in age, race, sex, area of residence, education, current homelessness, drug most frequently injected, daily injection frequency, and combined male-to-male sex and amphetamine injection status. The proportion of NHBS participants reporting not knowing the HIV status of their last injection partner increased from 38% to 45%. The proportion not knowing the HIV status of their last sex partner increased from 27% to 38%.

Conclusions:

A decrease in HIV testing was found in 2 independent Seattle-area study populations. This was complemented by increases in the proportions not knowing the HIV status of their last sex and last injection partners. Research is needed to ascertain if such declines are observed elsewhere, the reasons for the decline, and appropriate means to effectively attain optimal HIV testing frequency among PWID.
Self-Reported Decline in Everyday Function, Cognitive Symptoms, and Cognitive Function in People With HIV
Authors: Laverick Rosanna , Haddow Lewis , Daskalopoulou Marina , Lampe Fiona , Gilson Richard , Speakman Andrew , Antinori Andrea , Bruun Tina , Vassilenko Anna , Collins Simon , Rodger Alison ,   for the Cognitive Impairment in People with HIV in the European Region (CIPHER) Study Group
Published: June 2017

Background:

We determined factors associated with self-reported decline in activities of daily living (ADLs) and symptoms of cognitive impairment in HIV positive adults in 5 European clinics.

Methods:

HIV+ adults underwent computerized and pen-and-paper neuropsychological tests and questionnaires of cognitive symptoms and ADLs. We considered cognitive function in 5 domains, psychosocial factors, and clinical parameters as potentially associated with symptoms. Separate regression analyses were used to determine factors associated with a decline in ADL (defined as self-reported decline affecting ≥2 ADLs and attributed to cognitive difficulties) and self-reported frequency of symptoms of cognitive impairment. We also estimated the diagnostic accuracy of both questionnaires as tests for cognitive impairment.

Results:

Four hundred forty-eight patients completed the assessments [mean age 45.8 years, 84% male, 87% white, median CD4 count 550 cells/mm3, median time since HIV diagnosis 9.9 years, 81% virologically suppressed (HIV-1 plasma RNA <50 copies/mL)]. Ninety-six (21.4%) reported decline in ADLs and attributed this to cognitive difficulties. Self-reported decline in ADLs and increased symptoms of cognitive impairment were both associated with worse performance on some cognitive tests. There were also strong associations with financial difficulties, depressive and anxiety symptoms, unemployment, and longer time since HIV diagnosis. Both questionnaires performed poorly as diagnostic tests for cognitive impairment.

Conclusions:

Patients' own assessments of everyday function and symptoms were associated with objectively measured cognitive function. However, there were strong associations with other psychosocial issues including mood and anxiety disorders and socioeconomic hardship. This should be considered when assessing HIV-associated cognitive impairment in clinical care or research studies.
Treating pain on skin graft donor sites: Review and clinical recommendations
Authors: Sinha Sarthak , Schreiner Amanda J. , Biernaskie Jeff , Nickerson Duncan , Gabriel Vincent A.
Published: June 2017

Split-thickness skin grafting is the most common reconstructive procedure in managing burn injuries. Harvesting split-thickness skin creates a new partial thickness wound referred to as the donor site. Pain at the donor site is reported to be one of the most distressing symptoms during the early postoperative period. Here, we (a) identify strategies for managing donor site pain, (b) assess the quality of individual studies, and (c) formulate evidence-based recommendations based on the amount and consistency of evidence. Our analysis revealed five distinct approaches to minimize donor site pain. These include: continuous subcutaneous local anesthetic infusion (three studies), subcutaneous anesthetic injection (five studies), topical agents (six studies), nonpharmacological interventions (three studies), and wound dressings (18 studies). Available randomized control trials typically evaluated pain on standardized scales (i.e. Visual Analog Scale, Numerical Rating Scale), and compared the experimental group with standard care. Recommended treatments include: (a) subcutaneous anesthetic injection of adrenaline-lidocaine; (b) ice application; (c) topical agents, such as lidocaine and bupivacaine; and (d) hydrocolloid- and polyurethane-based wound dressings accompanied with fibrin sealant. Methodologically sound randomized control trials examining the efficacy of modified tumescent solution, ropivacaine, plasma therapy, noncontact ultrasound, and morphine gels are lacking and should be a priority for future research.
Amplitude-Integrated EEG and Brain Sparing in Preterm Small-for-Gestational-Age Infants
Authors: Benavente-Fernández Isabel , Lubián-López Simón P. , Zafra-Rodríguez Pamela , Alonso-Ojembarrena Almudena , Segado-Arenas Antonio , Lechuga-Sancho Alfonso M.
Published: June 2017

Purpose:

Preterm small-for-gestational-age (SGA) infants are at risk for a high mortality rate and impaired cognitive development. Only a few studies have focused on amplitude-integrated EEG (aEEG) in preterm SGA infants. They have been shown to have a slower rate of brain maturation, but these findings have not consistently been related to neurodevelopmental outcomes. The aim of our study was to evaluate early aEEG monitoring in SGA compared with adequate-for-gestational-age preterms.

Methods:

This prospective cohort study enrolled infants with very low birth weight who were admitted to the neonatal intensive care unit at Hospital Puerta del Mar, Cádiz, Spain, from June 2009 to September 2012. This study was a subanalysis of SGA from the global cohort previously described by our group. Adverse outcome included severe intraventricular hemorrhage and/or death. Cerebral function was monitored using aEEG recordings during the first 72 hours of life.

Results:

Preterm SGA infants (18 SGA in the global cohort of 92 patients) had lower 1- and 5-minute Apgar scores, higher score for neonatal acute physiology perinatal extension II scores, and higher proportion of adverse outcomes. When comparing preterm adequate-for-gestational-age infants with SGA infants with good prognosis, those with SGA had more mature and continuous aEEG patterns. Low margin amplitude depression was not as severe in these patients, and a higher proportion of these patients developed sleep–wake cycles.

Conclusions:

The results of our study suggest that SGA infants with a good prognosis have a more mature aEEG pattern than preterm adequate-for-gestational-age patients with the same outcome. These findings support the brain sparing theory in SGA infants.
Resolving plasmid structures in Enterobacteriaceae using the MinION nanopore sequencer: assessment of MinION and MinION/Illumina hybrid data assembly approaches
Authors: George Sophie , Pankhurst Louise , Hubbard Alasdair , Votintseva Antonia , Stoesser Nicole , Sheppard Anna E. , Mathers Amy , Norris Rachel , Navickaite Indre , Eaton Chloe , Iqbal Zamin , Crook Derrick W. , Phan Hang T. T.
Published: June 2017

This study aimed to assess the feasibility of using the Oxford Nanopore Technologies (ONT) MinION long-read sequencer in reconstructing fully closed plasmid sequences from eight Enterobacteriaceae isolates of six different species with plasmid populations of varying complexity. Species represented were Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens and Klebsiella oxytoca, with plasmid populations ranging from 1–11 plasmids with sizes of 2–330 kb. Isolates were sequenced using Illumina (short-read) and ONT’s MinION (long-read) platforms, and compared with fully resolved PacBio (long-read) sequence assemblies for the same isolates. We compared the performance of different assembly approaches including SPAdes, plasmidSPAdes, hybridSPAdes, Canu, Canu+Pilon (canuPilon) and npScarf in recovering the plasmid structures of these isolates by comparing with the gold-standard PacBio reference sequences. Overall, canuPilon provided consistently good quality assemblies both in terms of assembly statistics (N50, number of contigs) and assembly accuracy [presence of single nucleotide polymorphisms (SNPs)/indels with respect to the reference sequence]. For plasmid reconstruction, Canu recovered 70 % of the plasmids in complete contigs, and combining three assembly approaches (Canu or canuPilon, hybridSPAdes and plasmidSPAdes) resulted in a total 78 % recovery rate for all the plasmids. The analysis demonstrated the potential of using MinION sequencing technology to resolve important plasmid structures in Enterobacteriaceae species independent of and in conjunction with Illumina sequencing data. A consensus assembly derived from several assembly approaches could present significant benefit in accurately resolving the greatest number of plasmid structures.
Pre-vaccine serotype composition within a lineage signposts its serotype replacement – a carriage study over 7 years following pneumococcal conjugate vaccine use in the UK
Authors: Gladstone Rebecca A. , Devine Vanessa , Jones Jessica , Cleary David , Jefferies Johanna M. , Bentley Stephen D. , Faust Saul N. , Clarke Stuart C.
Published: June 2017

Serotype replacement has been reported in carriage and disease after pneumococcal conjugate vaccine (PCV) introductions in the UK and globally. We previously described concurrent expansion and decline of sequence types associated with serotype replacement over 5 years following PCV introductions in the UK. Here we use whole-genome sequencing to fully characterise the population structure of pneumococcal isolates collected over seven winters encompassing PCV7 and PCV13 introductions in the UK, investigating the importance of lineages in serotype replacement. We analysed 672 pneumococcal genomes from colonised children of 4 years old or less. The temporal prevalence of 20 lineages, defined by hierarchical Bayesian analysis of population structure (BAPS), was assessed in the context of serotype replacement. Multiple serotypes were detected in the primary winter of sampling within three vaccine-type (VT) lineages BAPS4, BAPS10 and BAPS11, in which serotype replacement were observed. In contrast, serotype replacement was not seen in the remaining three VT lineages (BAPS1, BAPS13 and BAPS14), that expressed a single serotype (6B, 6A and 3, respectively) in the primary winter. One lineage, BAPS1 serotype 6B was undetectable in the population towards the end of the study period. The dynamics of serotype replacement, in this UK population, was preceded by the presence or absence of multiple serotypes within VT lineages, in the pre-PCV population. This observation could help predict which non-vaccine types (NVTs) may be involved in replacement in future PCV introductions here and elsewhere. It could further indicate whether any antibiotic resistance associated with the lineages is likely to be affected by replacement.
Women’s estimated HIV infections from sex in trials of pre-exposure prophylaxis in Africa: Implications for HIV prevention strategies
Authors: Gisselquist David
Published: June 2017

Introduction

During 2004-15, nine randomized controlled trials (RCT) for HIV prevention tested pre-exposure prophylaxis (PrEP) with oral drugs, vaginal gels, or vaginal rings among more than 17,000 women in Africa.

Methods

This study uses information from the nine RCTs to estimate the proportions of HIV from sexual and bloodborne risks, to consider reasons for success or failure with oral PrEP, and to consider risks with vaginal PrEP.

Results

Estimating from women’s reported frequencies of unprotected coital acts in six RCTs, only a minority of women’s infections came from sex. Oral PrEP may have succeeded in at least one trial by reducing infections from both bloodborne and sexual risks. Oral PrEP may have failed in several trials, at least in part, because some women used oral PrEP when they had sexual risks rather than daily as advised. Relatively high incidence with PrEP vaginal gels and rings vs. oral placebo suggests vaginal PrEP had little impact at best and may have been harmful.

Discussion

Evidence from this and other studies challenges the common belief most HIV in Africa comes from sex. This challenge has implications for HIV prevention strategies, including: warning about bloodborne risks; and reconsidering PrEP for young women.
Ecological characterization and infection of Anophelines (Diptera: Culicidae) of the Atlantic Forest in the southeast of Brazil over a 10 year period: Has the behaviour of the autochthonous malaria vector changed?
Authors: Buery Julyana Cerqueira , Rezende Helder Ricas , Natal Licia , Santana da Silva Leonardo , Maria Tironi de Menezes Regiane , Fux Blima , dos Santos Malafronte Rosely , Falqueto Aloisio , Cerutti Crispim
Published: June 2017

In the south and southeast of Brazil, autochthonous malaria cases can be found near Atlantic Forest fragments. The transmission is not totally clarified; thus, the behaviour of the possible vectors in those regions must be observed. An entomological and natural infection study was performed on anophelines (Diptera: Culicidae) captured in the municipalities of the mountainous region of Espírito Santo state in 2004-2005. Similarly, between the years 2014 and 2015, 12 monthly collections were performed at the permanent trapping station of the study mentioned above (Valsugana Velha, Santa Teresa, ES). Light traps with CO2(CO2-baited Center for Disease Control [CDC] traps) were set in open areas, at the edge of the forest (canopy and ground) and inside the forest (canopy and ground), whereas Shannon traps were set on the edge of the forest. A total of 1,414 anophelines were collected from 13 species.Anopheles (Kerteszia) cruziiDyar and Knab remained the most captured species in the CO2-baited CDC traps set in the forest canopy and was also the vector with the highest prevalence ofPlasmodium vivaxinfection according to molecular PCR techniques. Regarding mosquitoes of the subgenusNyssorhynchus,P. vivaxwas found only in abdomens, weakening the hypothesis that this subgenus also plays a role in malaria transmission in this specific region.

Sponsorship

Espírito Santo Research Foundation (Fundação de Amparo à Pesquisa e Inovação do Espírito Santo – FAPES).
Neural dynamics of real-world object vision that guide behaviour
Authors: Cichy Radoslaw M. , Kriegeskorte Nikolaus , Jozwik Kamila M. , van den Bosch Jasper J.F. , Charest Ian
Published: June 2017

1

Vision involves complex neuronal dynamics that link the sensory stream to behaviour. To capture the richness and complexity of the visual world and the behaviour it entails, we used an ecologically valid task with a rich set of real-world object images. We investigated how human brain activity, resolved in space with functional MRI and in time with magnetoencephalography, links the sensory stream to behavioural responses. We found that behaviour-related brain activity emerged rapidly in the ventral visual pathway within 200ms of stimulus onset. The link between stimuli, brain activity, and behaviour could not be accounted for by either category membership or visual features (as provided by an artificial deep neural network model). Our results identify behaviourally-relevant brain activity during object vision, and suggest that object representations guiding behaviour are complex and can neither be explained by visual features or semantic categories alone. Our findings support the view that visual representations in the ventral visual stream need to be understood in terms of their relevance to behaviour, and highlight the importance of complex behavioural assessment for human brain mapping.
Differential Community Detection in Paired Biological Networks
Authors: Mall Raghvendra , Ullah Ehsan , Kunjia Khalid , Bensmail Halima
Published: June 2017

Motivation

Biological networks unravel the inherent structure of molecular interactions which can lead to discovery of driver genes and meaningful pathways especially in cancer context. Often due to gene mutations, the gene expression undergoes changes and the corresponding gene regulatory network sustains some amount of localized re-wiring. The ability to identify significant changes in the interaction patterns caused by the progression of the disease can lead to the revelation of novel relevant signatures.

Methods

The task of identifying differential sub-networks in paired biological networks (A:control,B:case) can be re-phrased as one of finding dense communities in a single noisy differential topological (DT) graph constructed by taking absolute difference between the topological graphs of A and B. In this paper, we propose a fast two-stage approach, namely Differential Community Detection (DCD), to identify differential sub-networks as differential communities in a de-noised version of the DT graph. In the first stage, we iteratively re-order the nodes of the DT graph to determine approximate block diagonals present in the DT adjacency matrix using neighbourhood information of the nodes and Jaccard similarity. In the second stage, the ordered DT adjacency matrix is traversed along the diagonal to remove all the edges associated with a node, if that node has no immediate edges within a window. We then apply community detection methods on this de-noised DT graph to discover differential sub-networks as communities.

Results

Our proposed DCD approach can effectively locate differential sub-networks in several simulated paired random-geometric networks and various paired scale-free graphs with different power-law exponents. The DCD approach easily outperforms community detection methods applied on the original noisy DT graph and recent statistical techniques in simulation studies. We applied DCD method on two real datasets: a) Ovarian cancer dataset to discover differential DNA co-methylation sub-networks in patients and controls; b) Glioma cancer dataset to discover the difference between the regulatory networks of IDH-mutant and IDH-wild-type. We demonstrate the potential benefits of DCD for finding network-inferred bio-markers/pathways associated with a trait of interest.

Conclusion

The proposed DCD approach overcomes the limitations of previous statistical techniques and the issues associated with identifying differential sub-networks by use of community detection methods on the noisy DT graph. This is reflected in the superior performance of the DCD method with respect to various metrics like Precision, Accuracy, Kappa and Specificity. The code implementing proposed DCD method is available athttps://sites.google.com/site/raghvendramallmlresearcher/codes.
Three-dimensional plant architecture and sunlit-shaded patterns: a stochastic model of light dynamics in canopies
Authors: Retkute Renata , Townsend Alexandra J. , Murchie Erik H. , Jensen Oliver E. , Preston Simon P.
Published: June 2017

Background and Aims

Diurnal changes in solar position and intensity combined with the structural complexity of plant architecture result in highly variable and dynamic light patterns within the plant canopy. This affects productivity through the complex ways that photosynthesis responds to changes in light intensity. Current methods to characterise light dynamics, such as ray-tracing, are able to produce data with excellent spatio-temporal resolution but are computationally intensive and the resultant data are complex and high dimensional. This necessitates development of more economical models for summarising the data and for simulating realistic light patterns over the course of a day.

Methods

High-resolution reconstructions of field-grown plants are assembled in various configurations to form canopies, and a forward ray-tracing algorithm is applied to the canopies to compute light dynamics at high (1 minute) temporal resolution. From the ray-tracer output, the sunlit or shaded state for each patch on the plants is determined, and these data are used to develop a novel stochastic model for the sunlit-shaded patterns. The model is designed to be straightforward to fit to data using maximum likelihood estimation, and fast to simulate from.

Key Results

For a wide range of contrasting 3D canopies, the stochastic model is able to summarise, and replicate in simulations, key features of the light dynamics. When light patterns simulated from the stochastic model are used as input to a model of photoinhibition, the predicted reduction in carbon gain is similar to that from calculations based on the (extremely costly) ray-tracer data.

Conclusions

The model provides a way to summarise highly complex data in a small number of parameters, and a cost-effective way to simulate realistic light patterns. Simulations from the model will be particularly useful for feeding into larger-scale photosynthesis models for calculating how light dynamics affects the photosynthetic productivity of canopies.
Network Connectivity Determines Cortical Thinning In Early Parkinson’s Disease Progression
Authors: Yau Y. , Zeighami Y. , Baker T. , Larcher K. , Vainik U. , Dadar M. , Fonov V. , Hagmann P. , Griffa A. , Mišić B. , Collins D.L. , Dagher A.
Published: June 2017

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by motor and cognitive deficits. The neurodegenerative process is thought to move stereotypically from the brainstem up to the cerebral cortex, possibly reflecting the spread of toxic alpha-synuclein molecules. Using a large, longitudinal, multi-center database ofde novoPD patients, we tested whether focal reductions in cortical thickness could be explained by disease spread from a subcortical “disease reservoir” along the brain’s connectome. PD patients (n=105) and matched controls (n=57) underwent T1-MRI at entry and one year later. Over this period, PD patients demonstrated significantly greater loss of cortical thickness than healthy controls in parts of the left occipital and bilateral frontal lobes and right somatomotor-sensory cortex. Cortical regions with greater connectivity (measured functionally or structurally) to a “disease reservoir” evaluated via MRI at baseline demonstrated greater atrophy one year later. The atrophy pattern in the ventral frontal lobes resembled one described in certain cases of Alzheimer’s disease. Moreover, a multiple linear regression model suggested that cortical thinning was associated with impaired cognitive function at follow-up. Our findings suggest that disease propagation to the cortex in PD follows neural connectivity, and that disease spread to the cortex may herald the onset of cognitive impairment.
PathCORE-T: identifying and visualizing globally co-occurring pathways in large transcriptomic compendia
Authors: Chen Kathleen M. , Tan Jie , Way Gregory P. , Doing Georgia , Hogan Deborah A. , Greene Casey S.
Published: June 2017

Background

Investigators often interpret genome-wide data by analyzing the expression levels of genes within pathways. While this within-pathway analysis is routine, the products of any one pathway can affect the activity of other pathways. Past efforts to identify relationships between biological processes have evaluated overlap in knowledge bases or evaluated changes that occur after specific treatments. Individual experiments can highlight condition-specific pathway-pathway relationships; however, constructing a complete network of such relationships across many conditions requires analyzing results from many studies.

Results

We developed PathCORE-T framework by implementing existing methods to identify pathway-pathway transcriptional relationships evident across a broad data compendium. PathCORE-T is applied to the output of feature construction algorithms; it identifies pairs of pathways observed in features more than expected by chance asfunctionally co-occurring. We demonstrate PathCORE-T by analyzing an existing eADAGE model of a microbial compendium and building and analyzing NMF features from the TCGA dataset of 33 cancer types. The PathCORE-T framework includes a demonstration web interface, with source code, that users can launch to (1) visualize the network and (2) review the expression levels of associated genes in the original data. PathCORE-T creates and displays the network of globally co-occurring pathways based on features observed in a machine learning analysis of gene expression data.

Conclusions

The PathCORE-T framework identifies transcriptionally co-occurring pathways from the results of unsupervised analysis of gene expression data and visualizes the relationships between pathways as a network. PathCORE-T recapitulated previously described pathway-pathway relationships and suggested experimentally testable additional hypotheses that remain to be explored.
ComM is a hexameric helicase that promotes branch migration during natural transformation in diverse Gram-negative species
Authors: Nero Thomas M. , Dalia Triana N. , Wang Joseph Che-Yen , Kysela David T. , Bochman Matthew L. , Dalia Ankur B.
Published: June 2017

Acquisition of foreign DNA by natural transformation is an important mechanism of adaptation and evolution in diverse microbial species. Here, we characterize the mechanism of ComM, a broadly conserved AAA+ protein previously implicated in homologous recombination of transforming DNA (tDNA) in naturally competent Gram-negative bacterial species.In vivo, we found that ComM was required for efficient comigration of linked genetic markers inVibrio choleraeandAcinetobacter baylyi, which is consistent with a role in branch migration. Also, ComM was particularly important for integration of tDNA with increased sequence heterology, suggesting that its activity promotes the acquisition of novel DNA sequences.In vitro, we showed that purified ComM binds ssDNA, oligomerizes into a hexameric ring, and has bidirectional helicase and branch migration activity. Based on these data, we propose a model for tDNA integration during natural transformation. This study provides mechanistic insight into the enigmatic steps involved in tDNA integration and uncovers the function of a protein required for this conserved mechanism of horizontal gene transfer.
A Bayesian computational approach to explore the optimal duration of a cell proliferation assay
Authors: Browning Alexander P , McCue Scott W , Simpson Matthew J
Published: June 2017

Cell proliferation assays are routinely used to explore how a low density monolayer of cells grows with time. For a typical cell line with a doubling time of 12 hours (or longer), a standard cell proliferation assay conducted over 24 hours provides excellent information about the low-density exponential growth rate, but limited information about crowding effects that occur at higher densities. To explore how we can best detect and quantify crowding effects, we present a suite of in silico proliferation assays where cells proliferate according to a generalised logistic growth model. Using approximate Bayesian computation we show that data from a standard cell proliferation assay cannot reliably distinguish between classical logistic growth and more general non-logistic growth models. We then explore, and quantify, the trade-off between increasing the duration of the experiment and the associated decrease in uncertainty in the crowding mechanism.
The cavity method for community ecology
Authors: Barbier Matthieu , Arnoldi Jean-François
Published: June 2017

This article is addressed to researchers and students in theoretical ecology, as an introduction to “disordered systems” approaches from statistical physics, and how they can help understand large ecological communities. We discuss the relevance of these approaches, and how they fit within the broader landscape of models in community ecology. We focus on a remarkably simple technique, the cavity method, which allows to derive the equilibrium properties of Lotka-Volterra systems. We present its predictions, the new intuitions it suggests, and its technical underpinnings. We also discuss a number of new results concerning possible extensions, including different functional responses and community structures.
HiCcompare: a method for joint normalization of Hi-C datasets and differential chromatin interaction detection
Authors: Stansfield John C. , Dozmorov Mikhail G.
Published: June 2017

Changes in spatial chromatin interactions are now emerging as a unifying mechanism or-chestrating regulation of gene expression. Evolution of chromatin conformation capture methods into Hi-C sequencing technology now allows an insight into chromatin interactions on a genome-wide scale. However, Hi-C data contains many DNA sequence- and technology-driven biases. These biases prevent effective comparison of chromatin interactions aimed at identifying genomic regions differentially interacting between, disease-normal states or different cell types. Several methods have been developed for normalizing individual Hi-C datasets. However, they fail to account for biasesbetween two or more Hi-C datasets, hindering comparative analysis of chromatin interactions. We developed a simple and effective methodHiCcomparefor the joint normalization and differential analysis of multiple Hi-C datasets. The method avoids constraining Hi-C data within a rigid statistical model, allowing a data-driven normalization of biases using locally weighted linear regression (loess). The method identifies region-specific chromatin interaction changes complementary to changes due to large-scale genomic rearrangements, such as copy number variants (CNVs).HiCcompareoutperforms methods for normalizing individual Hi-C datasets in detectinga prioriknown chromatin interaction differences in simulated and real-life settings while detecting biologically relevant changes.HiCcompareis freely available as a Bioconductor R packagehttps://bioconductor.org/packages/HiCcompare/.

Author Summary

Advances in chromosome conformation capture sequencing technologies (Hi-C) have sparked interest in studying the 3-dimensional (3D) chromatin interaction structure of the human genome. The 3D structure of the genome is now considered as a primary regulator of gene expression. Changes to the 3D chromatin interactions are now emerging as a hallmark of cancer and other complex diseases. With the growing availability of Hi-C data generated under different conditions (e.g. tumor-normal, cell-type-specific), methods are needed to compare them. However, biases in Hi-C data hinder their comparative analysis. To account for biases, several normalization techniques have been developed for removing biases in individual Hi-C datasets, but very few were designed to account for between-datasets biases. We developed a new method and R packageHiCcomparefor the joint normalization of multiple Hi-C datasets and differential chromatin interaction detection. Our results show the superiority of our joint normalization methods compared to methods for normalizing individual datasets in detecting true chromatin interaction changes.HiCcompareenables further research into discovering the dynamics of 3D genomic changes.
An integrative method to unravel the host-parasite interactome: an orthology-based approach
Authors: Cuesta-Astroz Yesid , Santos Alberto , Oliveira Guilherme , Jensen Lars J.
Published: June 2017

The study of molecular host–parasite interactions is essential to understand parasitic infection and adaptation within the host system. As well, prevention and treatment of infectious diseases require clear understanding of the molecular crosstalk between parasites and their hosts. As yet, experimental large–scale identification of host–parasite molecular interactions remains challenging and the use of in silico predictions becomes then necessary. Here, we propose a computational integrative approach to predict host–parasite protein–protein interaction (PPI) networks resulting from the infection of human by 12 different parasites. We used an orthology-based method to transfer high–confidence intra–species interactions obtained from the STRING database to the corresponding inter–species protein pairs in the host–parasite system. To reduce the number of spurious predictions, our approach uses either the parasites predicted secretome and membrane proteins or only the secretome depending on whether they are uni- or multicellular respectively. Besides, the host proteome is filtered for proteins expressed in selected cellular localizations and tissues supporting the parasites growth. We evaluated the inferred interactions by analyzing the enriched biological processes and pathways in the predicted networks and their association to known parasitic invasion and evasion mechanisms. The resulting PPI networks were compared across parasites to identify common mechanisms that may define a global pathogenic hallmark. The predicted PPI networks can be visualized and downloaded at http://orthohpi.jensenlab.org.

Author Summary

A protein-protein interaction (PPI) network is a collection of interactions between proteins from one or more organisms. Host–parasite PPIs are key to understanding the biology of different parasitic diseases, since predicting PPIs enable to know more about the parasite invasion, infection and persist. Our understanding of PPIs between host and parasites is still very limited, as no many systematic experimental studies have so far been performed. Efficacy of treatments for parasitic diseases is limited and in many cases parasites evolve resistance. Thus, there is an urgent need to develop novel drugs or vaccines for these neglected diseases, and thus interest in the functions and interactions of proteins associated with parasitism processes. Here we developed an in silico method to shed light on the interactome in twelve human parasites by combining an orthology based strategy and integrating, domain–domain interaction data, sub-cellular localization and to give a spatial context, we only took in to account those human tissues that support the parasite’s tropism. Here we show that is possible to identify relevant interactions across different parasites and their human host and that these interactions are well supported based on the biology of the parasites.