bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of Herpes Simplex Virus Type 2 Seroprevalence From a National Probability Survey In Mexico, 2012
Authors: Sanchez-Aleman Miguel Angel , Del Villar-Tapia Yamira Georgina , Gutierrez Juan Pablo , Garcia-Cisneros Santa , Olamendi-Portugal Ma. Leonidez , Herrera-Ortiz Antonia , Velazquez-Meza Manuel , Conde-Glez Carlos J.
Published: August 2017

Background

Herpes simplex virus type 2 (HSV-2) seroprevalence and associated infection risk factors show differences by regions and countries. The aims of the study were to determine the HSV-2 seroprevalence and to evaluate the risk factors for HSV-2 in a national representative survey among adolescents and adults in Mexico.

Methods

A cross-sectional study was carried out in Mexico on the basis of the National Health and Nutrition Survey 2012, a national representative survey. Demographic, sexual behavior, reproductive health, and lifestyles indicators were considered in the current study. Participants provided biological samples—dried blood spots—to test for HSV-2 antibodies using enzyme-linked immunosorbent assay and Western blot. Bivariate and multivariate analyses were performed to identify variables associated with HSV-2 infections analyzed by sex.

Results

National HSV-2 seroprevalence was 9.9%, 2.4% among adolescents and 11.7% among adults with HSV-2 seroprevalence heterogeneous across the country. Women had 12.2% of antibodies against HSV-2 and men had 7.5%. The factors associated with HSV-2 infection among women were age (45–49 years; odds ratio [OR], 19.8), region (southwest; OR, 3.0), urbanization (urban; OR, 1.9), age at sexual debut (≤14 years; OR, 3.4), education level (any; OR, 3.0), and previous abortion (≥2 abortion; OR, 2.1). Among men, age (45–49 years; OR, 11.7), region (southwest; OR, 3.0), urbanization (urban, odds ratio [OR], 1.7), and HIV care (OR, 7.1) were associated with the infection.

Conclusions

Approximately 10% of Mexicans aged 15 to 49 years had HSV-2 antibodies, with differences by sex, region, education level, urbanization, HIV care, and childbirth, highlighting the relevance of health inequalities in the country: social inequalities seem to matter in terms of the probability of HSV-2 infections.
Histologic Grade 1 Is Associated With Increased Nonrelapsed Mortality in Lower Gastrointestinal Graft Versus Host Disease
Authors: Im Jin S. , Abraham Susan C. , Saliba Rima M. , Rondon Gabriela , Ross William A. , Rashid Asif , Shpall Elizabeth J. , Popat Uday , Qazilbash Muzaffar H. , Hosing Chitra , Oran Betul , Shah Nina , Tewari Priti , Nieto Yago , Kebriaei Partow , Champlin Richard E. , Alousi Amin M.
Published: August 2017

Histologic confirmation is considered a standard practice to diagnose gastrointestinal graft versus host disease (GI GVHD) and is often used in making treatment decisions. A histologic grade is often determined in cases that are diagnosed with GI GVHD. Although extensive crypt loss (histologic grade 4) is associated with high nonrelapse mortality (NRM), the prognostic value for the more common grade 1 is poorly understood. As clinical decisions are made on the degree of histologic evidence, it is important to establish its prognostic significance. Therefore, we evaluated 309 patients who underwent endoscopic biopsy for suspected GI GVHD within 6 months posttransplant between 2009 and 2012. The presence of histologic grade 1 was associated with increased NRM (hazard ratio=2.7,P=0.02) when compared with one of negative biopsy in patients with lower but not isolated upper GI GVHD. Multivariate competing-risk regression analysis confirmed the independent impact of histologic grade 1 in patients with early clinical stages of lower GI GVHD (stage 0 to 2) (hazard ratio=2.7,P=0.044). When compared with advanced histologic grades, histologic grade 1 did not lessen the adverse outcome for patients with advanced lower GI GVHD (stage 3 to 4) (cumulative incidence NRM of 84%). In conclusion, the presence of histologic grade 1 is associated with increased NRM in patients presenting with lower GI GVHD (stages 0 to 2) and is sufficient evidence for decision to initiate therapy. At the same time, histologic grade 1 does not lessen the markedly adverse impact of advanced lower GI GVHD (stage 3 to 4) and is not synonymous with “mild” GVHD.
Compassion Fatigue in Pediatric Emergency Department Staff
Authors: Nilan Laura M. , Patel Lina , Moffatt Mary E. , Linebarger Jennifer S. , Sherman Ashley K. , Randell Kimberly A.
Published: August 2017

Introduction

Compassion fatigue, a product of burnout (BO), secondary traumatic stress (STS), and compassion satisfaction (CS), is reduced capacity and interest in being empathetic for suffering individuals. Our objective was to determine prevalence of compassion fatigue in the pediatric emergency department.

Methods

We administered the Professional Quality of Life instrument, including BO, STS, and CS scales, to a convenience sample of pediatric emergency department staff (physicians, nurses, technicians, social workers, child life specialists). We categorized participants as having BO (high BO, low CS, moderate-low STS scores), STS (high STS, moderate-low BO, low CS), compassion fatigue (high STS and BO, low CS), and high-risk fatigue (high STS, moderate-low BO, low CS) and low risk (moderate-high CS, moderate-low BO, low STS) of compassion fatigue.

Results

One hundred seventy-seven staff (50% response rate) participated. The majority were white (90%) and female (88%), with participation highest among physicians (97%). Twenty-six percent had low CS scores, 26% had high BO scores, and 20% had high STS scores. Five percent met criteria for categorization as compassion fatigue, 24% for BO, and 24% for low risk of compassion fatigue. Current personal stress was associated with higher BO scores (P = 0.008) and secondary categorization as BO (P = 0.05). Recent work stress was associated with high STS scores (P = 0.03).

Discussion

Five percent of participants met criteria for compassion fatigue; a significant proportion had BO, STS, or CS scores, placing them at risk of compassion fatigue. Future studies should explore factors contributing to and interventions to minimize compassion fatigue.
Procalcitonin Levels in Critically Ill Children With Status Asthmaticus
Authors: Samraj Ravi S. , Crotty Eric J. , Wheeler Derek S.
Published: August 2017

Background

Children with status asthmaticus (SA) often present with fever and are evaluated with chest radiographs (CXRs). In the absence of a confirmatory test for bacterial infection, antibiotics are started whenever there are radiological infiltrates or if there is a suspicion of pneumonia. We undertook this study to determine if serum procalcitonin (PCT) levels at admission are altered in critically ill children with SA. We also sought to determine if serum PCT levels are elevated in children with radiological infiltrates or in children who were treated with antibiotics.

Methods

This is a prospective single-center observational study evaluating serum PCT levels in critically ill children with SA. Study subjects included children 1 to 21 years old, admitted to a pediatric intensive care unit (PICU) with SA between March 2012 and April 2013. For the purposes of this study, patients whose CXRs were read by the radiologist as probable bacterial pneumonia was defined as having “radiological bacterial pneumonia,” whereas patients who received antibiotics by the treating physician were defined as having “clinician-diagnosed pneumonia.”

Results

Sixty-one patients with a median age of 7.3 years (interquartile range, 4–10 years) were included in the study. Fifty-one percent were male. Average Pediatric Risk of Mortality III score was 2.7 (SD, 2.9). Three patients (5%) were determined to have radiological bacterial pneumonia, whereas 52 (85%) did not. Six patients (10%) were indeterminate. The mean PCT level for all patients was 0.65 (SD, 1.54) ng/mL, whereas the median PCT level was 0.3 ng/mL. There was no significant difference in the mean PCT levels between the patients with and without clinician-diagnosed pneumonia (0.33 [SD, 0.36] vs 0.69 [SD, 1.67], P = 0.44). Using a PCT cutoff level of 0.5 ng/mL, a significant association was found with the presence of fever (P = 0.004), but no significant association was found with the presence of CXR infiltrates, radiological bacterial pneumonia, hospital length of stay, PICU length of stay, Pediatric Risk of Mortality III scores, or receipt of antibiotics.

Conclusions

Serum PCT level was not elevated to greater than 0.5 ng/mL in 75% of this cohort of critically ill children with SA admitted to PICU. Presence of CXR infiltrates was not associated with higher PCT levels. Large clinical trials are needed to study the diagnostic and predictive role of PCT in this patient population.
A Content Analysis of Nonprofit Hospital Community Health Needs Assessments and Community Benefit Implementation Strategies in Philadelphia
Authors: Powell Rhea E. , Doty Amanda M. B. , Rising Kristin L. , Karp David N. , Baehr Avi , Carr Brendan G.
Published: August 2017

Context:

Nonprofit hospitals are mandated to perform a community health needs assessment, develop an implementation strategy to address community needs, and invest in improving community health through community benefit investments in order to maintain the tax exemptions afforded nonprofit hospitals.

Objective:

We sought to describe the regional health needs identified across community health needs assessments and the portfolio of implementation strategies reported to address those needs.

Design:

The study provides a content analysis of community health needs assessments and implementation strategies for nonprofit hospitals in one urban region.

Setting:

The study focused on nonprofit hospitals in Philadelphia, Pennsylvania.

Main Outcome Measures:

Community benefit documents were coded to characterize health needs and intervention activities using the 4 health factor categories of the County Health Rankings framework: clinical care, health behaviors, social and economic factors, and physical environment.

Results:

Hospitals predominantly identified health needs related to access to care, especially mental health and dental care, and insurance coverage and costs of care. In many instances, there is little alignment between needs identified through the community health needs assessments and the reported implementation strategies. Specifically, dental care, behavioral health, substance abuse, social factors, and health care and prescription drug costs were all cited as important community needs but were infrequently targeted by implementation strategies.

Conclusions:

Nonprofit hospital community health needs assessments in Philadelphia predominantly identify needs related to access to care and to some extent health behaviors. There is incomplete alignment between the needs identified in hospital assessments and the needs targeted in implementation strategies, underscoring a need for regional coordination in community benefit investments. Improved regional coordination between hospitals serving the region may offer the opportunity to eliminate duplicative efforts and increase the amount of funds available to address unmet needs.
Elevating Oral Health Interprofessional Practice Among Pediatricians Through a Statewide Quality Improvement Learning Collaborative
Authors: Nelson Joni D. , Spencer Sharon M. , Blake Christine E. , Moore Justin B. , Martin Amy B.
Published: August 2017

Context:

Because of persistent effects of early childhood caries and impacts of dental health professional shortages areas, the integration of oral health in primary care settings is a public health priority. In this study, we explored oral health interprofessional practice (OHIP) as an integrative pathway to reduce oral health disparities. OHIP can include performing oral health risk assessments, describing the importance of fluoride in the drinking water, implementing fluoride varnish application, and referring patients to a dental home.

Objective:

To conduct a formative evaluation of how 15 pediatric primary care practices implemented the adoption of OHIP in their clinical settings.

Design:

Using an ecological framework, we conducted a qualitative process evaluation to measure the factors that inhibited and facilitated OHIP adoption into pediatric settings. Document review analysis and qualitative interviews were conducted with pediatric practices to contextualize challenges and facilitators to OHIP adoption.

Setting and Participants:

A total of 15 Children's Health Insurance Program Reauthorization Act pediatric practices located in 13 South Carolina counties participated in this study.

Main Outcome Measures:

Outcomes of interest were the facilitators and challenges of OHIP adoption into pediatric primary care practices.

Results:

Thematic analysis revealed challenges for OHIP adoption including limited resources and capacity, role delineation for clinical and administrative staff, communication, and family receptiveness. OHIP training for clinical practitioners and staff and responsiveness from clinical staff and local dentists were facilitators of OHIP adoption. Twelve key recommendations emerged on the basis of participant experiences within OHIP, with developing an active dental referral network and encouraging buy-in from clinical staff for OHIP adoption as primary recommendations.

Conclusion:

We demonstrated the effectiveness of a learning collaborative meeting among pediatric primary care providers to adopt OHIPs. This work reveals an actionable pathway to support oral health equity advancement for children through an additional access point of preventive oral care, reinforcement of positive oral health behaviors, and interaction between parent and child for overall health and wellness of the family.
Safety and Effectiveness of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy After Regional Hepatic Embolization in Patients With Somatostatin-Expressing Neuroendocrine Tumors
Authors: Hamiditabar Mohammadali , Ali Muzammil , Bolek Luke , Vahdati Gelareh , Tworowska Izabela , Delpassand Ebrahim S.
Published: August 2017

Purpose

Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE is shown to be an effective therapeutic option for somatostatin-expressing neuroendocrine neoplasms. Some concerns are raised over safety of this modality in patients with a history of regional chemoembolization and radionuclide hepatic embolization (CRHE) and is cause of reluctance among some physicians for suggesting 177Lu-DOTATATE in this patient population.

Methods

We retrospectively reviewed 143 patients with somatostatin-expressing neuroendocrine tumors who underwent 177Lu-DOTATATE PRRT. Statistical analysis was performed on effect of 177Lu-DOTATATE in patients with and without prior CRHE using resampling procedures and correlation coefficient (r).

Results

Proportion of toxicity in patients with and without CRHE was comparable (P = 0.246). No statistically significant correlation (r) found between any toxicity and prior CRHE (r = −0.3 to −0.03) or time elapsed between embolization and the first cycle of PRRT (r = −0.59 to 0.17). Following PRRT, 76.5% of patients with CRHE experienced benefit (partial response + stable disease), whereas 23.4% experienced progressive disease. Patients with CRHE showed more stable disease (P = 0.048) and less progressive disease (P = 0.046) following PRRT compared with no CRHE. The CRHE and no-CRHE status shared same probability for developing partial response/complete response following PRRT (P = 0.50).

Conclusions

Treatment with 177Lu-DOTATATE did not show clinically or statistically significant toxicity in CRHE patients regardless of frequency of embolization or time interval between embolization and first PRRT. Results suggested a statistically significant higher response rate in patients with a history of CRHE. A prior history of CRHE is not a contraindication to subsequent PRRT.
Ospreys do not teach offspring how to kill prey at the nest
Authors: Howard Megan , Hoppitt Will
Published: August 2017

There is strong evidence for teaching in only a handful of species, most of which are cooperative breeders, leading some researchers to suggest that teaching may be more likely to evolve in such species. Alternatively, this initial distribution could be an artefact of the popularity and tractability of cooperative breeders as behavioural study systems. Therefore, establishing or refuting this potential evolutionary link requires researchers to assess potential cases of teaching in more non-cooperatively breeding species. We tested for teaching in the osprey (
Pandion haliaetus
), a non-cooperatively-breeding bird anecdotally reported to teach hunting skills to their offspring. We tested whether parents brought back more live prey to the nest as their offspring got older, allowing the latter to practice killing prey in a manner analogous to the progressive teaching seen in meerkats. We found the opposite trend to that predicted by the teaching hypothesis, indicating that ospreys do not teach their young at the nest.
Size and dielectric properties of skeletal stem cells change critically after enrichment and expansion from human bone marrow: consequences for microfluidic cell sorting
Authors: Xavier Miguel , de Andrés María C. , Spencer Daniel , Oreffo Richard O. C. , Morgan Hywel
Published: August 2017

The capacity of bone and cartilage to regenerate can be attributed to skeletal stem cells (SSCs) that reside within the bone marrow (BM). Given SSCs are rare and lack specific surface markers, antibody-based sorting has failed to deliver the cell purity required for clinical translation. Microfluidics offers new methods of isolating cells based on biophysical features including, but not limited to, size, electrical properties and stiffness. Here we report the characterization of the dielectric properties of unexpanded SSCs using single-cell microfluidic impedance cytometry (MIC). Unexpanded SSCs had a mean size of 9.0 µm; larger than the majority of BM cells. During expansion, often used to purify and increase the number of SSCs, cell size and membrane capacitance increased significantly, highlighting the importance of characterizing unaltered SSCs. In addition, MIC was used to track the osteogenic differentiation of SSCs and showed an increased membrane capacitance with differentiation. The electrical properties of primary SSCs were indistinct from other BM cells precluding its use as an isolation method. However, the current studies indicate that cell size in combination with another biophysical parameter, such as stiffness, could be used to design label-free devices for sorting SSCs with significant clinical impact.
Zonation of hepatic fat accumulation: insights from mathematical modelling of nutrient gradients and fatty acid uptake
Authors: Schleicher Jana , Dahmen Uta , Guthke Reinhard , Schuster Stefan
Published: August 2017

Intrinsic of non-alcoholic fatty liver diseases is an aberrant accumulation of triglycerides (steatosis), which occurs inhomogeneously within lobules. To improve our understanding of the mechanisms involved in this zonation patterning, we developed a mathematical multicompartment model of hepatic fatty acid metabolism accompanied by blood flow simulations. A model analysis determines the influence of the uptake process of fatty acids, the porto-central gradient of plasma fatty acid concentration, and the oxygen supply via blood on the zonation of triglyceride accumulation. From this theoretical perspective, the plasma oxygen gradient, but not the fatty acid gradient, leads the way to a zonated triglyceride accumulation by its decisive role in oxidative processes. In addition, the uptake mechanism of fatty acids seems to be fundamental for a pericentral dominance of steatosis. However, the mechanism of cellular fatty acid uptake from the blood is still under debate. Our theoretical approach supports the transporter-mediated uptake mechanism and reveals that the maximal velocity of fatty acid uptake affects the switching between a periportal and a pericentral triglyceride accumulation. Further research on hepatic fatty acid uptake is needed to push forward our understanding of aberrant triglyceride accumulation in diet-induced steatosis.
An ancient FMRFamide-related peptide–receptor pair induces defence behaviour in a brachiopod larva
Authors: Thiel Daniel , Bauknecht Philipp , Jékely Gáspár , Hejnol Andreas
Published: August 2017

Animal behaviour often comprises spatially separated sub-reactions and even ciliated larvae are able to coordinate sub-reactions of complex behaviours (metamorphosis, feeding). How these sub-reactions are coordinated is currently not well understood. Neuropeptides are potential candidates for triggering larval behaviour. However, although their immunoreactivity has been widely analysed, their function in trochozoan larvae has only been studied for a few cases. Here, we investigate the role of neuropeptides in the defence behaviour of brachiopod larvae. When mechanically disturbed, the planktonic larvae ofTerebratalia transversaprotrude their stiff chaetae and sink down slowly. We identified endogenous FLRFamide-type neuropeptides (AFLRFamide and DFLRFamide) inT. transversalarvae and show that the protrusion of the chaetae as well as the sinking reaction can both be induced by each of these peptides. This also correlates with the presence of FLRFamidergic neurons in the apical lobe and adjacent to the trunk musculature. We deorphanized the AFLRFamide/DFLRFamide receptor and detected its expression in the same tissues. Furthermore, the ability of native and modified FLRFamide-type peptides to activate this receptor was found to correspond with their ability to trigger behavioural responses. Our results show how FLRFamide-type neuropeptides can induce two coherent sub-reactions in a larva with a simple nervous system.
A variation on the Donsker–Varadhan inequality for the principal eigenvalue
Authors: Lu Jianfeng , Steinerberger Stefan
Published: August 2017

The purpose of this short paper is to give a variation on the classical Donsker–Varadhan inequality, which bounds the first eigenvalue of a second-order elliptic operator on a bounded domain
Ω
by the largest mean first exit time of the associated drift–diffusion process via

λ
1

≥

1

sup

x
∈
Ω

E

x

τ

Ω
c

.

Instead of looking at the mean of the first exit time, we study quantiles: let

d

p
,
∂
Ω

:
Ω
→

R

≥
0

be the smallest time
t
such that the likelihood of exiting within that time is
p
, then

λ
1

≥

log

(
1

/

p
)

sup

x
∈
Ω

d

p
,
∂
Ω

(
x
)

.

Moreover, as

p
→
0

, this lower bound converges to λ
1
.
Patterns of predator neophobia: a meta-analytic review
Authors: Crane Adam L. , Ferrari Maud C. O.
Published: August 2017

Neophobia, the fear of novel stimuli, plays a major role in animal ecology. Here, we review studies on predator neophobia and explore its underlying patterns within an ecological framework. Predator neophobia is typically assessed by observing behaviours in novel areas that bring potential risk from unknown predators, or by observing behaviours towards certain kinds of objects and odours that are novel. We conducted a literature review across taxa, surveying research on baseline and induced neophobia versus controls. We calculated effect sizes for the intensity of neophobic responses, and categorized data according to six factors (taxa, age class, background type, trophic position, test cue type and experimental treatment type). While accounting for each of the other factors, we found that baseline neophobia was stronger among birds and mammals, and towards novel areas, relative to other taxa and cue types. Baseline neophobia was lower for wild-caught animals and for those that were higher in trophic position, compared with those reared in captivity and from lower trophic levels. By contrast, induced neophobia was similar in intensity across taxa, background types and testing cue types, while again being lower among upper trophic-level members and among juvenile animals. Although induced neophobia occurred across all treatment types, brain lesions induced stronger neophobia than predation risk or social isolation. We discuss potential mechanisms underlying these results and highlight gaps in the literature.
Does red eye fluorescence in marine fish stand out?In situandin vivomeasurements at two depths
Authors: Harant U. K. , Wehrberger F. , Griessler T. , Meadows M. G. , Champ C. M. , Michiels N. K.
Published: August 2017

Since the discovery of red fluorescence in fish, much effort has been made to elucidate its potential contribution to vision. However, whatever that function might be, it always implies that the combination of red fluorescence and reflectance of the red iris is sufficient to generate a visual contrast. Here, we presentin vivoiris radiance measurements ofT. delaisiunder natural light fields at 5 and 20 m depth. We also took substrate radiance measurements of shaded and exposed foraging sites at those depths. To assess the visual contrast that can be generated by the red iris, we then calculated iris brightness in the 600-650 nm “red” waveband relative to substrate radiance. At 20 m depth,T. delaisiiris radiance substantially exceeded substrate radiance in the red waveband, regardless of exposure, and despite substrate fluorescence. Given that downwelling light in the 600-650 nm range is negligible at this depth, we can attribute this effect to iris fluorescence. As expected, contrasts were much weaker in 5 m – despite the added contribution of iris reflectance, but we identified specific substrates and conditions under which the pooled radiance caused by red reflectance and fluorescence still exceeded substrate radiance in the same waveband. Due to the negative effect of anesthesia on iris fluorescence these estimates are conservative. We conclude that the requirements to create visual brightness contrasts are fulfilled for a wide range of conditions in the natural environment ofT. delaisi.
Measuring Biotherapeutic Viscosity and Degradation On-Chip with Particle Diffusometry
Authors: Clayton K.N. , Lee D. , Wereley S.T. , Kinzer-Ursem T. L.
Published: August 2017

In absence of efficient ways to test drug stability and efficacy, pharmaceuticals that have been stored outside of set temperature conditions are destroyed, often at great cost. This is especially problematic for biotherapeutics, which are highly sensitive to temperature fluctuations. Current platforms for assessing the stability of protein-based biotherapeutics in high throughput and in low volumes are unavailable outside of research and development laboratories and are not efficient for use in production, quality control, distribution, or clinical settings. In these alternative environments, microanalysis platforms could provide significant advantages for the characterization of biotherapeutic degradation. Here we present particle diffusometry (PD), a new technique to study degradation of biotherapeutic solutions. PD uses a simple microfluidic chip and microscope setup to calculate the Brownian motion of particles in a quiescent solution using a variation of particle image velocimetry (PIV) fundamentals. We show that PD can be used to measure the viscosity of protein solutions to discriminate intact protein from degraded samples as well as to determine the change in viscosity as a function of therapeutic concentration. PD viscosity analysis is applied to two particularly important biotherapeutic preparations: insulin, a commonly used protein for diabetic patients, and monoclonal antibodies which are an emerging class of biotherapeutics used to treat a variety of diseases such as autoimmune disorders and cancer. PD-based characterization of solution viscosity is a new tool for biotherapeutic analysis, and owing to its easy setup could readily be implemented at key points of the pharmaceutical delivery chain and in clinical settings.
Issues in the statistical detection of data fabrication and data errors in the scientific literature: simulation study and reanalysis of Carlisle, 2017
Authors: Piraino Scott W.
Published: August 2017

Background

The detection of fabrication or error within the scientific literature is an important and underappreciated problem. Retraction of scientific articles is rare, but retraction may also be conservative, leaving open the possiblity that many fabricated or erroneous findings remain in the literature as a result of lack of scrutiny. A recently statistical analysis of randomized controlled trials [1] has suggested that the reported statistics form these trials deviate substantially from expectation under truely random assignment, raising the possiblity of fraud or error. It has also been proposed that the method used could be implemented to prospectively screen research, for example by applying the method prior to publication.

Methods and Findings

To assess the properties of the method proposed in [1], I carry out both theoretical and empirical evaluations of the method. Simulations suggest that the method is sensitive to assumptions that could reasonably be violated in real randomized controlled trials. This suggests that deviation for expectation under this method can not be used to measure the extent of fraud or error within the literature, and raises questions about the utlity of the method for propsective screening. Empirically analysis of the results of the method on a large set of randomized trials suggests that important assumptions may plausibly be violated within this sample. Using retraction as a proxy for fraud or serious error, I show that the method faces serious challenges in terms of precision and sensitivity for the purposes of screening, and that the performance of the method as a screening tool may vary across journals and classes of retractions.

Conclusions

The results in [1] should not be interpreted as indicating large amount of fraud or error within the literature. The use of this method for screening of the literature should be undertaken with great caution, and should recognize critical challenges in interpreting the results of this method.
Spatial Genome Organization as a Framework for Somatic Alterations in Human Cancer
Authors: Akdemir Kadir C. , Li Yilong , Verhaak Roel G. , Beroukhim Rameen , Cambell Peter , Chin Lynda , Futreal P. Andrew ,   on behalf of the PCAWG-Structural Variation Working Group
Published: August 2017

Genomic material within the nucleus is folded into successive layers in order to package and organize the long string of linear DNA. This hierarchical level of folding is closely associated with transcriptional regulation and DNA replication. Microscopic studies concluded that genome organization inside the nucleus is not random and chromosomes within the nucleus create territories1. More recent chromosome conformation studies have revealed that mammalian chromosomes are structured into tissue-invariant topologically associating domains (TADs) where the DNA within a given domain interacts more frequently together than with regions in other domains2,3. Genes within the same TADs represent similar expression and histone-modification profiles4. In addition, enhancer-promoter pairs within the same TAD respond similarly to hormone induction5or differentiation cues6. Therefore, regions separating different TADs (boundaries) have important roles in reinforcing the stability of these domain-wide features. Indeed, TAD boundary disruptions in human genetic disorders7,8or human cancers lead to misregulation of certain genes9,10, due tode novoenhancer exposure to promoters. Here, to understand effects and distributions of somatic structural variations across TADs, we utilized single nucleotide variations, deletions, inversions, tandem-duplications and complex rearrangements from 2658 high-coverage whole genome sequencing data across various cancer types with paired normal samples. We comprehensively profiled structural variations with respect to their effect on TAD boundaries, on the regulation of genes in human cancers.
Genome-wide association study of habitual physical activity in over 277,000 UK Biobank participants identifies multiple variants includingCADM2andAPOE
Authors: Klimentidis Yann C. , Raichlen David A. , Bea Jennifer , Garcia David O. , Mandarino Lawrence J. , Alexander Gene E. , Chen Zhao , Going Scott B.
Published: August 2017

Background/Objectives

Physical activity (PA) protects against a wide range of diseases. Engagement in habitual PA has been shown to be heritable, motivating the search for specific genetic variants that may ultimately inform efforts to promote PA and target the best type of PA for each individual.

Subjects/Methods

We used data from the UK Biobank to perform the largest genome-wide association study of PA to date, using three measures based on self-report (n=277,656) and two measures based on wrist-worn accelerometry data (n=67,808). We examined genetic correlations of PA with other traits and diseases, as well as tissue-specific gene expression patterns. With data from the Atherosclerosis Risk in Communities (ARIC; n=8,556) study, we performed a meta-analysis of our top hits for moderate-to-vigorous PA (MVPA).

Results

We identified 26 genome-wide loci across the five PA measures examined. Upon meta-analysis of the top hits for MVPA with results from the ARIC study, 8 of 10 remained significant at p<5×10−8. Interestingly, among these, the rs429358 variant in theAPOEgene was the most strongly associated with MVPA. Variants inCADM2, a gene recently implicated in risk-taking behavior and other personality and cognitive traits, were found to be associated with regular engagement in strenuous sports or other exercises. We also identified thirteen loci consistently associated (p<0.005) with each of the five PA measures. We find genetic correlations of PA with educational attainment traits, chronotype, psychiatric traits, and obesity-related traits. Tissue enrichment analyses implicate the brain and pituitary gland as locations where PA-associated loci may exert their actions.

Conclusions

These results provide new insight into the genetic basis of habitual PA, and the genetic links connecting PA with other traits and diseases.
Microscopic Dissipative Structuring at the Origin of Life
Authors: Michaelian Karo
Published: August 2017

Fundamental molecules of life are suggested to be formed, proliferated, and evolved through microscopic dissipative structuring and autocatalytic replication under the UV-C solar spectrum prevalent at Earth’s surface throughout the Archean. Evidence is given in the numerous salient characteristics of these, including their strong absorption in this spectral region, their rapid non-radiative decay through an inherent conical intersection, UV-C activation (phos-phorylation) of nucleotides, and UV-C induced denaturing of double helix RNA and DNA. The examples of the dissipative structuring and dissipative proliferation of the purines and of single strand DNA are given. This provides a physical-chemical foundation for understanding the origin and evolution of life.
Development of honeybee waggle dance and its differences between recruits and scouts
Authors: Ai Hiroyuki , Kobayashi Yuuki , Matake Toshiyuki , Takahashi Shinya , Hashimoto Koji , Maeda Sakashi , Tsuruta Naoyuki
Published: August 2017

The lifetime development of the waggle dance of 14 honeybees was automatically recorded just after the imaginal molt using high-definition camera modules connected with a Raspberry Pi computer and numbered radio-frequency identification tags fitted to the back of each bee. For most honeybees, waggle dance follow preceded the appearance of the first waggle dance from 1 week after the imaginal molt. The duration per trip increased just after waggle dance follow. Before the appearance of the first waggle dance, the honeybee repeatedly follows waggle dances that indicate a limited number (2–6) of food source locations. We discriminated between two types of foragers with different roles, recruits and novice scouts, by comparing the vectors indicated by the bees’ first waggle dance (sending vectors) with dances they had previously followed (received vectors). Of 14 tagged honeybees, 11 were categorized as recruits and 2 as novice scouts. For recruits (but not for novice scouts), the duration per trip increased significantly after waggle dances follow and substantially increased just before the appearance of the first waggle dance. Moreover, recruits increased the number of times they followed waggle dances indicating the same location, and their first waggle dance indicated this location. These results suggest that the differentiation of these two types of foragers is partly related to behavioral differences after waggle dance follows: whether trip is activated or not by follows a waggle dance.

Summary statement

Because of technological difficulties, there are no studies comparing the development of recruit and scout waggle dances. Using miniature radio frequency identification tags, we observed and clarified these developmental processes.

List of Abbreviations

AN

antenna

RFID

radio frequency identification.
MODULARITY FACILITATES FLEXIBLE TUNING OF PLASTIC AND EVOLUTIONARY GENE EXPRESSION RESPONSES DURING EARLY DIVERGENCE
Authors: Mäkinen Hannu , Sävilammi Tiina , Papakostas Spiros , Leder Erica , Vøllestad Leif Asbjørn , Primmer Craig
Published: August 2017

Gene expression changes have been recognized as important drivers of adaptation to changing environmental conditions. Little is known about the relative roles of plastic and evolutionary responses in complex gene expression networks during the early stages of divergence. Large gene expression data sets coupled within silicomethods for identifying co-expressed modules now enable systems genetics approaches also in non-model species for better understanding of gene expression responses during early divergence. Here, we combined gene co-expression analyses with population genetics to separate plastic and population (evolutionary) effects in expression networks using small salmonid populations as a model system. We show that plastic and population effects were highly variable among the six identified modules and that the plastic effects explained larger proportion of the total eigengene expression than population effects. A more detailed analysis of the population effects using aQST-FSTcomparison across 16622 annotated transcripts revealed that gene expression followed neutral expectations within modules and at the global level. Furthermore, two modules showed enrichment for genes coding for early developmental traits that have been previously identified as important phenotypic traits in thermal responses in the same model system indicating that co-expression analysis can capture expression patterns underlying ecologically important traits. We suggest that module-specific responses may facilitate the flexible tuning of expression levels to local thermal conditions. Overall, our study indicates that plasticity and neutral evolution are the main drivers of gene expression variance in the early stages of thermal adaptation in this system.
IVIM parameters have good scan-rescan reproducibility when evidential motion contaminated and poorly fitted image data are removed
Authors: Chevallier Olivier , Zhou Nan , He Jian , Loffroy Romaric , Wang Yi-Xiáng J.
Published: August 2017

Background

Intravoxel Incoherent Motion (IVIM) diffusion MRI is a promising technique for liver pathology evaluation, but this technique’s scan-rescan reproducibility has been reported to be unsatisfactory.

Objective

To understand whether IVIM MRI parameters for liver parenchyma can be good after removal of motion contaminated and/or poorly fitted image data.

Material and Methods

Eighteen healthy volunteers had liver scanned twice at the same session to assess scan-rescan repeatability, and again in another session after an average interval of 13 days to assess reproducibility. Diffusion weighted image were acquired with a 3T scanner using respiratory-triggered echo-planar sequence and 16b-values (0 to 800 s/mm2). Measurement was performed on the right liver with segmented-unconstrained least square fitting. Image series with evidential anatomical mismatch, apparent artifacts, and poorly fitted signal intensity vs.b-value curve were excluded. A minimum of three slices was deemed necessary for IVIM parameter estimation of a liver.

Results

With total 54 examinations, 6 scans did not satisfy inclusion criteria, leading to a success rate of 89%; and 14 volunteers were finally included. With each scan a mean of 5.3 slices (range: 3-10 slices) were utilized for analysis. Using thresholdb-value=80s/mm2, the coefficient of variation and within-subject coefficient of variation for repeatability and reproducibility were: 2.86% and 4.24% for Dslow, 3.81% and 4.24%, for PF, 18.16% and 24.88% for Dfast; and those for reproducibility were 2.48% and 3.24% for Dslow; 4.91% and 5.38% for PF; 21.18% and 30.89% for Dfast.

Conclusion

IVIM parameter scan-rescan reproducibility can be potentially good.
Genomic and structural features of the Yellow Fever virus from the 2016-2017 Brazilian outbreak
Authors: Gómez Mariela Martínez , de Abreu Filipe Vieira Santos , dos Santos Alexandre Araujo Cunha , de Mello Iasmim Silva , Santos Marta Pereira , Ribeiro Ieda Pereira , Ferreira-de-Brito Anielly , de Miranda Rafaella Moraes , de Castro Marcia Gonçalves , Ribeiro Mario Sergio , Laterrière Roberto da Costa , Aguiar Shirlei Ferreira , Meira Guilherme Louzada Silva , Antunes Deborah , Torres Pedro Henrique Monteiro , Vicente Ana Carolina Paulo , Guimarães Ana Carolina Ramos , Caffarena Ernesto Raul , Bello Gonzalo , Lourenço-de-Oliveira Ricardo , Bonaldo Myrna Cristina
Published: August 2017

Brazil has been suffering a severe sylvatic epidemic of yellow fever virus (YFV) since late 2016. Analysis of full-length YFV genomes from all hosts involved in the Brazilian 2017 outbreak reveals that they belong to sub-lineage 1E within modern-lineage, but display several unique amino acid substitutions in highly conserved positions at NS3 and NS5 viral proteins. Evolutionary analyses indicate that YFV carrying that set of amino acid substitution circulates in the Southern Brazilian region for several months before being detected in December 2016. Structural and selection analyses support that some of these substitutions were under positive selection and could impact enzyme structure and function. Altogether, this evidence demonstrated that the current Brazilian YFV carries unique amino acid signatures in the non-structural proteins and support the hypothesis that those substitutions may be affecting the viral fitness and transmissibility.
Piggy: A Rapid, Large-Scale Pan-Genome Analysis Tool for Intergenic Regions in Bacteria
Authors: Thorpe Harry A. , Bayliss Sion C. , Sheppard Samuel K. , Feil Edward J.
Published: August 2017

Despite overwhelming evidence that variation in intergenic regions (IGRs) in bacteria impacts on phenotypes, most current approaches for analysing pan-genomes focus exclusively on protein-coding sequences. To address this we present Piggy, a novel pipeline that emulates Roary except that it is based only on IGRs. We demonstrate the use of Piggy for pan-genome analyses ofStaphylococcus aureusandEscherichia coliusing large genome datasets. ForS. aureus,we show that highly divergent (“switched”) IGRs are associated with differences in gene expression, and we establish a multi-locus reference database of IGR alleles (igMLST; implemented in BIGSdb). Piggy is available athttps://github.com/harry-thorpe/piggy.
Modeling of Epigenetic Modification-Induced Changes in CRX-dependent Genescis-Regulatory Elements
Authors: Hossain Reafa A. , Dunham Nicholas R. , Harris Megan E. , Hutchinson Taylor L. , Kidd Justin M. , Kohler Lindsay R. , Salamon Gregory J. , Schmidt Alexander L. , Thomas Madison D. , Enke Raymond A. , Berndsen Christopher E.
Published: August 2017

Purpose

DNA methylation is a well characterized epigenetic repressor of mRNA transcription in many plant and vertebrate systems. However, the mechanism of this repression is not fully understood. The process of synthesizing a strand of RNA from DNA, or transcription, is controlled by proteins that regulate RNA polymerase activity by binding to specific gene regulatory sequences. Cone-rod homeobox (CRX) is a well-characterized mammalian transcription factor that controls photoreceptor cell specific gene expression. While much is known about the functions and DNA binding specificity of CRX, less is known about how DNA methylation modulates CRX binding affinity to genomic cis-regulatory elements.

Methods

We used bisulfite pyrosequencing of human ocular tissues to measure DNA methylation levels of the regulatory regions ofRHO,PDE6B, PAX6, andLINE. To describe the molecular mechanism of repression, we used molecular modeling to illustrate the effect of DNA methylation on humanRHOregulatory sequences.

Results

In this study, we demonstrate an inverse correlation between DNA methylation in regulatory regions adjacent to the humanRHOandPDE6Bgenes and their subsequent transcription in human ocular tissues. Docking of CRX to our DNA models shows that CRX interacts with the grooves of these sequences, suggesting changes in groove structure could regulate binding. Molecular dynamics simulations of theRHOpromoter and enhancer regions show changes in the flexibility and groove width upon epigenetic modification. Models also demonstrate that changes to the local dynamics of CRX binding sites withinRHOregulatory sequences which may account for the repression of CRX dependent transcription.

Conclusion

Collectively, these data demonstrate epigenetic regulation of CRX binding sites in human retinal tissue and provide insight into the mechanism of this mode of epigenetic regulation to be tested in future experiments.
Zinc detoxification: a functional genomics and transcriptomics analysis inDrosophila melanogastercultured cells
Authors: Mohr Stephanie E. , Rudd Kirstin , Hu Yanhui , Song Wei Roc , Gilly Quentin , Buckner Michael , Housden Benjamin E. , Kelley Colleen , Zirin Jonathan , Tao Rong , Amador Gabriel , Sierzputowska Katarzyna , Comjean Aram , Perrimon Norbert
Published: August 2017

Cells require some metals, such as zinc and manganese, but excess levels of these metals can be toxic. As a result, cells have evolved complex mechanisms for maintaining metal homeostasis and surviving metal intoxication. Here, we present the results of a large-scale functional genomic screen inDrosophilacultured cells for modifiers of zinc chloride toxicity, together with transcriptomics data for wildtype or genetically zinc-sensitized cells challenged with mild zinc chloride supplementation. Altogether, we identified 47 genes for which knockdown conferred sensitivity or resistance to toxic zinc or manganese chloride treatment, and more than 1800 putative zinc-responsive genes. Analysis of the ‘omics data points to the relevance of ion transporters, glutathione-related factors, and conserved disease-associated genes in zinc detoxification. Specific genes identified in the zinc screen include orthologs of human disease-associated genes CTNS, PTPRN (also known as IA-2), and ATP13A2 (also known as PARK9). We show that knockdown ofred dog mine (rdog; CG11897), a candidate zinc detoxification gene encoding an ABCC-type transporter family protein related to yeast cadmium factor (YCF1), confers sensitivity to zinc intoxication in cultured cells and thatrdogis transcriptionally up-regulated in response to zinc stress. As there are many links between the biology of zinc and other metals and human health, the ‘omics datasets presented here provide a resource that will allow researchers to explore metal biology in the context of diverse health-relevant processes.