bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Use Problems, Posttraumatic Stress Disorder, and Suicide Risk Among Trauma-Exposed Firefighters
Authors: Bing-Canar Hanaan , Ranney Rachel M. , McNett Sage , Tran Jana K. , Berenz Erin C. , Vujanovic Anka A.
Published: February 2019

Alcohol use problems are associated with suicidal desire and may provide an avenue to suicidal ideation and behavior. However, the influence of posttraumatic stress disorder (PTSD) on the nature of the relationship between alcohol use problems and suicide risk is not well understood. In particular, the potential for PTSD to moderate the association between alcohol use problems and suicide risk remains unexplored. The present study investigated the main and interactive effects of alcohol use problems (Alcohol Use Disorders Identification Test) and PTSD symptoms (PTSD Checklist for DSM-5) on suicide risk (Suicide Behaviors Questionnaire-Revised) in a sample of 632 trauma-exposed firefighters (93.5% men; M
age = 38.44 years, SD = 8.59). Hierarchical logistic regression analyses evaluated whether the main and interactive effects of PTSD symptom severity and alcohol use disorders were significantly related to suicide risk, above and beyond age and cumulative trauma. The main effects of PTSD symptom severity (odds ratio, 1.76; p < 0.001) and alcohol use problems (odds ratio, 1.37; p = 0.391) significantly positively predicted suicide risk; however, PTSD symptoms did not moderate an association between alcohol use problems and suicide risk after accounting for these main effects (p > 0.05). A secondary, exploratory aim demonstrated that all PTSD symptom clusters significantly positively predicted suicide risk (p's < 0.001), although none of these clusters interacted with alcohol use problems to predict suicide risk (p's > 0.05). Theoretical and clinical implications are discussed as they relate to the importance of screening for PTSD and alcohol use disorder among firefighter populations.
Validating the Alternative DSM-5 Criteria for Personality Disorders
Authors: Ozamiz-Etxebarria Naiara , Ortiz-Jauregi Miren Agurtzane , Escobar Javier I.
Published: February 2019

In 2010, the Working Group of Personality and Personality Disorders of the DSM-5 task force proposed a thorough diagnostic reformulation of the category of personality disorders. After debates and negotiations, these alternative criteria ended in Section III of the DSM-5 manual (diagnoses in need of further testing). We tested these alternative criteria in a sample of Basque-speaking patients from the Basque region of Spain who had clinical diagnoses of personality disorder, using instruments that had been developed and used as part of the DSM-5 field trials in the United States for assessing the proposed new diagnostic category. All study instruments were translated and adapted for use in the Basque language. Interviews were done twice (time 1 and time 2) and were scheduled at least 1 month apart to assess test-retest reliability. The results demonstrated that the DSM-5 alternative criteria worked well in this clinical sample, with highly satisfactory levels of reliability being attained and a good level of clinician's satisfaction related to the use of the new criteria. The alternative criteria in personality disorders seemed to work well in this European sample with unique linguistic features.
Influenza virus polymerase inhibitors in clinical development
Authors: Hayden Frederick G. , Shindo Nahoko
Published: February 2019

Purpose of review

We review antivirals inhibiting subunits of the influenza polymerase complex that are advancing in clinical development.

Recent findings

Favipiravir, pimodivir, and baloxavir are inhibitory in preclinical models for influenza A viruses, including pandemic threat viruses and those resistant to currently approved antivirals, and two (favipiravir and baloxavir) also inhibit influenza B viruses. All are orally administered, although the dosing regimens vary. The polymerase basic protein 1 transcriptase inhibitor favipiravir has shown inconsistent clinical effects in uncomplicated influenza, and is teratogenic effects in multiple species, contraindicating its use in pregnancy. The polymerase basic protein 2 cap-binding inhibitor pimodivir displays antiviral effects alone and in combination with oseltamivir in uncomplicated influenza, although variants with reduced susceptibility emerge frequently during monotherapy. Single doses of the polymerase acidic protein cap-dependent endonuclease inhibitor baloxavir are effective in alleviating symptoms and rapidly inhibiting viral replication in otherwise healthy and higher risk patients with acute influenza, although variants with reduced susceptibility emerge frequently during monotherapy. Combinations of newer polymerase inhibitors with neuraminidase inhibitors show synergy in preclinical models and are currently undergoing clinical testing in hospitalized patients.

These new polymerase inhibitors promise to add to the clinical management options and overall control strategies for influenza virus infections.
Body Composition Is Associated With Physical Performance in Individuals With Knee Osteoarthritis
Authors: Davis Hope C. , Blue Malia N. M. , Hirsch Katie R. , Luc-Harkey Brittney A. , Anderson Kara C. , Smith-Ryan Abbie E. , Pietrosimone Brian
Published: February 2019

Background/Objective

The purpose of this cross-sectional study was to determine associations between body composition, self-reported function, and physical performance after accounting for body mass index (BMI) in individuals with knee osteoarthritis.

Methods

Percent fat and lean mass were evaluated using dual energy x-ray absorptiometry. Self-reported function (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] function subscale) and physical performance (20-m walk, chair stand, and stair climb) were collected on 46 adults (30% male; BMI, 29.6 ± 3.8 kg/m2) with radiographically defined knee osteoarthritis (Kellgren-Lawrence grades 2–4). Linear regressions determined the unique association between WOMAC and physical performance explained individually by percent fat and lean mass (∆R
1) after accounting for BMI.

Results

Lower percent fat mass significantly associated with better physical performance after accounting for BMI (20-m walk: ∆R
2 = 0.10, p = 0.03; chair stand: ∆R
2 = 0.16, p = 0.01; stair climb: ∆R
2 = 0.11, p = 0.03). Higher percent lean mass significantly associated with better chair stand (∆R
2 = 0.09, p = 0.04) but not 20-m walk or stair climb (∆R
2 range, 0.04–0.07, p > 0.05). After accounting for BMI, neither percent fat nor lean mass associated with WOMAC. Body mass index did not significantly associate with WOMAC or physical performance.

Conclusions

Lower percent fat and higher percent lean mass associated with better physical performance after accounting for BMI. Body composition and BMI may be used together in the future to more comprehensively understand the association between obesity and disability.
The Impact of Echo Time Shifts and Temporal Signal Fluctuations on BOLD Sensitivity in Presurgical Planning at 7 T
Authors: Dymerska Barbara , De Lima Cardoso Pedro , Bachrata Beata , Fischmeister Florian , Matt Eva , Beisteiner Roland , Trattnig Siegfried , Robinson Simon Daniel
Published: February 2019

Objectives

Gradients in the static magnetic field caused by tissues with differing magnetic susceptibilities lead to regional variations in the effective echo time, which modifies both image signal and BOLD sensitivity. Local echo time changes are not considered in the most commonly used metric for BOLD sensitivity, temporal signal-to-noise ratio (tSNR), but may be significant, particularly at ultrahigh field close to air cavities (such as the sinuses and ear canals) and near gross brain pathologies and postoperative sites.

Materials and Methods

We have studied the effect of local variations in echo time and tSNR on BOLD sensitivity in 3 healthy volunteers and 11 patients with tumors, postoperative cavities, and venous malformations at 7 T. Temporal signal-to-noise ratio was estimated from a 5-minute run of resting state echo planar imaging with a nominal echo time of 22 milliseconds. Maps of local echo time were derived from the phase of a multiecho GE scan. One healthy volunteer performed 10 runs of a breath-hold task. The t-map from this experiment served as a criterion standard BOLD sensitivity measure. Two runs of a less demanding breath-hold paradigm were used for patients.

Results

In all subjects, a strong reduction in the echo time (from 22 milliseconds to around 11 milliseconds) was found close to the ear canals and sinuses. These regions were characterized by high tSNR but low t-values in breath-hold t-maps. In some patients, regions of particular interest in presurgical planning were affected by reductions in the echo time to approximately 13–15 milliseconds. These included the primary motor cortex, Broca's area, and auditory cortex. These regions were characterized by high tSNR values (70 and above). Breath-hold results were corrupted by strong motion artifacts in all patients.

Conclusions

Criterion standard BOLD sensitivity estimation using hypercapnic experiments is challenging, especially in patient populations. Taking into consideration the tSNR, commonly used for BOLD sensitivity estimation, but ignoring local reductions in the echo time (eg, from 22 to 11 milliseconds), would erroneously suggest functional sensitivity sufficient to map BOLD signal changes. It is therefore important to consider both local variations in the echo time and temporal variations in signal, using the product metric of these two indices for instance. This should ensure a reliable estimation of BOLD sensitivity and to facilitate the identification of potential false-negative results. This is particularly true at high fields, such as 7 T and in patients with large pathologies and postoperative cavities.
Prediabetes Is Associated With Increased Liver Stiffness Identified by Noninvasive Liver Fibrosis Assessment
Authors: Koc Ayse Selcan , Sumbul Hilmi Erdem
Published: February 2019

Patients with type 2 diabetes mellitus (DM) have been shown to have increased liver fibrosis (LF) as determined by liver elastography. However, the data on LF incidence in patients with prediabetes are scarce. This study was undertaken to determine the incidence of LF and associated parameters in prediabetic patients. Three study groups with equal number of participants defined on the basis of glucose metabolism status were included the following: normal glucose metabolism (NGM), prediabetes, and newly diagnosed type 2 DM (55 patients in each group). Liver stiffness measurements were carried out using liver elastography point quantification, and 7 kPa or greater was considered to denote the presence of LF. Patients were subdivided into 2 groups as those with or without LF. Of the NGM, prediabetes, and type 2 DM subjects involved in the study 3.6%, 27%, and 38% were found to have LF (P < 0.001), respectively. Glycated hemoglobin (HbA1c), triglycerides, and alkaline phosphatase levels independently correlated with liver stiffness measurements (P < 0.05, for each). In addition, presence of mild or moderate-severe liver steatosis, hypertension, waist circumference, and HbA1c were independent predictors of the LF status. Presence of mild or moderate-severe liver steatosis, hypertension, waist circumference (each 1-cm increment), and HbA1c (each 1% increment) were associated with a 2.78-fold, 7.16-fold, 68%, and 36.7% increased likelihood of LF, respectively. As compared with subjects with NGM, patients with impaired glucose metabolism were more likely to have LF. As in patients with type 2 DM, a significant proportion of patients with prediabetes (27%) have LF, which is closely or independently associated with markers of metabolic syndrome.
Quantitative Assessment of Thyroid Glands in Healthy Children With Shear Wave Elastography
Authors: Uysal Emine , Öztürk Mehmet
Published: February 2019

The local shear wave speed (in meters per second) and Young modulus (in kilopascals) of normal thyroid glands were defined in healthy children to determine reference values.

This prospective study assessed 107 pediatric cases (age interval, 3–17 years; mean, 9.37 ± 3.68 years), including 52 boys and 55 girls. The study group included children without thyroid gland disease (autoimmune, infectious, or neoplastic). Data about the sex, age, weight, height, and body mass index (BMI) of the subjects were recorded for all subjects. Elasticity values were measured from 3 different sites in both thyroid lobes and averaged.

Median values for elasticity and shear wave velocity measured in bilateral thyroid lobes were 6.38 ± 1.97 kPa (range, 3.00–12.5 kPa) and 1.45 ± 0.21 m/s (range, 1.03–2.04 m/s) on the right and 8.81 ± 3.00 kPa (range, 3.80–22.6 kPa) and 1.69 ± 0.26 m/s (range, 1.13–2.68 m/s) on the left. There was no significant difference between the elasticity values for the right and left thyroid lobes between boys and girls. There was a positive correlation between right thyroid lobe mean elasticity (in kilopascals) and shear wave velocity (in meters per second) values with age, BMI, and right thyroid lobe volume in the whole group. No significant correlation was found between left thyroid lobe mean elasticity (in kilopascals) and shear wave velocity (in meters per second) values with age, BMI, and left thyroid lobe volume in the study population.

This study determined mean elasticity and shear wave velocity values for thyroid gland in healthy children. This information can be used as a baseline for the investigation of thyroid diseases.
The Presence of Scarring and Associated Morbidity in the Burn Model System National Database
Authors: Goverman Jeremy , He Waverley , Martello Geoffrey , Whalen Ann , Bittner Edward , Schulz John , Gibran Nicole , Herndon David , Suman Oscar , Kowalske Karen , Meyer Walter J. , Ryan Colleen , Schneider Jeffrey
Published: February 2019

Introduction

Postburn scarring is common, but the risk factors, natural history, and consequences of such scars are still poorly understood. This study aims to describe the frequency of scar-related morbidity for up to 2 years after injury and to analyze the impact of burn scars on long-term functional, psychosocial, and reintegration outcomes.

Methods

Analysis was conducted on data collected between January 2006 and May 2014 from 960 patients (2440 anatomic burn sites) using the Burn Model System (BMS) database. Study population demographics were analyzed and odds ratios for the development of raised or thick scarring were determined. Regression analyses were used to evaluate the impact of hypertrophic scarring (HTS) on psychosocial outcomes, including the Community Integration Questionnaire, Satisfaction with Life Scale, Distress, and the Short Form 12. Symptoms associated with scarring were analyzed at discharge and 6, 12, and 24 months after burn using a set of questions on scarring developed by the BMS. Mixed-effect modeling was used to determine linear change over time and the significance of symptoms.

Results

The study population was primarily white (65.0%) and male (71.8%), with a mean (SD) age of 44.0 (15.2) years and mean total body surface area burned of 19.6% (17.9%). The incidence of raised or thick scars increased from 65% to 80% (P < 0.0001) for the 2-year follow-up period. The presence of scarring was not associated with Community Integration Questionnaire, Satisfaction with Life Scale, or Short Form 12 scores. Most patients reported symptoms associated with scarring at 2 years after burn, including dry or fragile skin, scars that restrict range of motion at a joint, issues with hand function, and scar pain and itch.

Conclusions

In this large, longitudinal, multicenter cohort of burn survivors, nearly all patients noted the presence of scarring, and a majority noted additional symptoms and morbidity related to their scars even at 2 years after injury. This study demonstrates a need for the continued support of burn survivors to address scar-related morbidity. Furthermore, future studies examining the impact of novel treatments for scarring should use similar scar problem questionnaires and distress scores.
The effects of cell type and culture condition on the procoagulant activity of human mesenchymal stromal cell-derived extracellular vesicles
Authors: Chance Tiffani C. , Rathbone Christopher R. , Kamucheka Robin M. , Peltier Grantham C. , Cap Andrew P. , Bynum James A.
Published: February 2019

BACKGROUND

Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have great potential as a cell-free therapy in wound healing applications. Because EV populations are not equivalent, rigorous characterization is needed before clinical use. Although there has been much focus on their RNA composition and regenerative capabilities, relatively less is known regarding the effects of MSC cell type (adipose tissue [Ad-MSCs] or bone marrow [BM-MSCs]) and culture condition (monolayer or spheroid) on MSC-EV performance, including characteristics related to their ability to promote coagulation, which could determine EV safety if administered intravenously.

METHODS

The successful isolation of EVs derived from Ad-MSCs or BM-MSCs cultured in either monolayer or spheroid cultures was confirmed by NanoSight (particle size distribution) and Western blot (surface marker expression). Extracellular vesicle surface expression of procoagulant molecules (tissue factor and phosphatidylserine) was evaluated by flow cytometry. Extracellular vesicle thrombogenicity was tested using calibrated thrombogram, and clotting parameters were assessed using thromboelastography and a flow-based adhesion model simulating blood flow over a collagen-expressing surface.

RESULTS

The MSC cell type and culture condition did not impact EV size distribution. Extracellular vesicles from all groups expressed phosphatidylserine and tissue factor on their surfaces were functionally thrombogenic and tended to increase clotting rates compared to the negative control of serum-free media without EVs. On average, EVs did not form significantly larger or stronger clots than the negative control, regardless of cell source or culture condition. Additionally, EVs interfered with platelet adhesion in an in vitro flow-based assay.

CONCLUSION

Adipose-derived EVs were more thrombogenic and expressed higher amounts of phosphatidylserine. Our findings suggest that, like intact MSCs, source variability among EVs is an important factor when considering EVs for potential therapeutic purposes.

LEVEL OF EVIDENCE

Therapeutic care management, level II.
Interaction between cardiovascular autonomic control and sex hormones in perimenopausal women under menopausal hormone therapy
Authors: Kiselev Anton R. , Neufeld Irina W. , Bobyleva Irina V. , Prokhorov Mikhail D. , Karavaev Anatoly S.
Published: February 2019

Objective

The aim of this study was to assess the dynamical interaction between the cardiovascular autonomic control and sex hormones in perimenopausal women under menopausal hormone therapy (MHT).

Patients and methods

Seventy women (age: 51.6±2.1 years) were treated with MHT. Standard time and frequency domain measures of heart rate variability (HRV) and index S of synchronization between the slow oscillations in HRV and photoplethysmographic waveform variability were studied during a 6-week treatment with MHT. We assessed also the dynamics of the following sex hormones: estradiol, follicle-stimulating hormone, dehydroepiandrosterone sulfate, and testosterone.

Results

MHT increased estradiol and decreased follicle-stimulating hormone. Hot flashes and index S were significantly decreased under MHT (P<0.05). Other autonomic indices were not significantly changed (P>0.05). Changes of index S did not correlate with changes of sex hormones and hot flushes (P>0.05).

Conclusion

The obtained results may indicate the independence of heart autonomic control (assessed by HRV measures) from women’s hormonal status. However, any changes in sex hormones contribute to changes in the systemic control of circulation, which is assessed by index S.
Association between thyroid abnormalities and hypertension among hospitalized US patients: data from the National Inpatient Sample
Authors: Basnet Sijan , Dhital Rashmi , Tharu Biswaraj , Ghimire Sushil , Poudel Dilli R.
Published: February 2019

Abnormalities of thyroid, namely hyperthyroidism and hypothyroidism, are both associated with increased risk of hypertension. We utilized the National Inpatient Sample from the years 2012–2014 to explore the risk of thyroid disorders in relation to those without a thyroid diagnosis. We found that hypertension was more commonly associated with hyperthyroidism (odds ratio: 1.18; 95% confidence interval: 1.16–1.21, P<0.0001) than with hypothyroidism (odds ratio: 1.06; 95% confidence interval: 1.06–1.07, P<0.0001) when both were compared with hypertension without a thyroid diagnosis.
Vitamin D status in acute myocardial infarction: a case–control study
Authors: Mohammad Ameen M. , Shammo Nazar A. , Jasem Jagar A.
Published: February 2019

Background

The association of vitamin D deficiency with coronary artery disease (CAD) is controversial. This study seeks the association between vitamin D deficiency and acute myocardial infarction (MI) in Iraq.

Patients and methods

A total of 104 patients with acute MI and 104 healthy controls were studied throughout 2015. Their demographic, cardiovascular risk factors, and clinical characteristics were recorded. Serum vitamin D measurement was carried out for all patients.

Results

Vitamin D was more deficient in cases than controls; the number of cases was 60 (57.7%) and 53 (51%), respectively. However, a statistically significant difference (P=0.6) was not obtained. In the patient group, type 2 diabetes mellitus showed a strong association with vitamin D deficiency; there were 31 (81.6%) diabetic patients and 29 (43.9%) nondiabetic patients (P<0.001).

Conclusion

No statistical association between vitamin D deficiency and acute MI was found. Nevertheless, a strong association between vitamin D deficiency and acute MI with type 2 diabetes mellitus was seen.
Bayesian and parsimony approaches reconstruct informative trees from simulated morphological datasets
Authors: Smith Martin R.
Published: February 2019

Phylogenetic analysis aims to establish the true relationships between taxa. Different analytical methods, however, can reach different conclusions. In order to establish which approach best reconstructs true relationships, previous studies have simulated datasets from known tree topologies, and identified the method that reconstructs the generative tree most accurately. On this basis, researchers have argued that morphological datasets should be analysed by Bayesian approaches, which employ an explicit probabilistic model of evolution, rather than parsimony methods—with implied weights parsimony sometimes identified as particularly inaccurate. Accuracy alone, however, is an inadequate measure of a tree's utility: a fully unresolved tree is perfectly accurate, yet contains no phylogenetic information. The highly resolved trees recovered by implied weights parsimony in fact contain as much useful information as the more accurate, but less resolved, trees recovered by Bayesian methods. By collapsing poorly supported groups, this superior resolution can be traded for accuracy, resulting in trees as accurate as those obtained by a Bayesian approach. By contrast, equally weighted parsimony analysis produces trees that are less resolved and less accurate, leading to less reliable evolutionary conclusions.
Diel CO
2
cycles and parental effects have similar benefits to growth of a coral reef fish under ocean acidification
Authors: Jarrold Michael D. , Munday Philip L.
Published: February 2019

Parental effects have been shown to buffer the negative effects of within-generation exposure to ocean acidification (OA) conditions on the offspring of shallow water marine organisms. However, it remains unknown if parental effects will be impacted by the presence of diel CO
2
cycles that are prevalent in many shallow water marine habitats. Here, we examined the effects that parental exposure to stable elevated (1000 µatm) and diel-cycling elevated (1000 ± 300 µatm) CO
2
had on the survival and growth of juvenile coral reef anemonefish,
Amphiprion melanopus
. Juvenile survival was unaffected by within-generation exposure to either elevated CO
2
treatment but was significantly increased (8%) by parental exposure to diel-cycling elevated CO
2
. Within-generation exposure to stable elevated CO
2
caused a significant reduction in juvenile growth (10.7–18.5%); however, there was no effect of elevated CO
2
on growth when diel CO
2
cycles were present. Parental exposure to stable elevated CO
2
also ameliorated the negative effects of elevated CO
2
on juvenile growth, and parental exposure to diel CO
2
cycles did not alter the effects of diel CO
2
cycles on juveniles. Our results demonstrate that within-generation exposure to diel-cycling elevated CO
2
and parental exposure to stable elevated CO
2
had similar outcomes on juvenile condition. This study illustrates the importance of considering natural CO
2
cycles when predicting the long-term impacts of OA on marine ecosystems.
Raw-material selectivity in hook-tool-crafting New Caledonian crows
Authors: Klump Barbara C. , Cantat Mathieu , Rutz Christian
Published: February 2019

Animals that manufacture foraging tools face the challenge of identifying suitable raw materials among a multitude of options. New Caledonian crows exhibit strong population-specific material preferences for the manufacture of hooked stick tools, but it is unknown how they identify their favourite plants. We investigated experimentally whether crows pay attention to the stems of plants (from which the tools are made) and/or their leaves (which are usually discarded during manufacture but may enable rapid and reliable species identification at a distance). Subjects were highly selective in choice trials with multiple plant species. Two additional treatments with experimental leaf–stem combinations revealed that birds can identify their preferred plant species by its stems alone, and possibly also its leaves. These findings encourage future experiments that investigate whether New Caledonian crows attend to features of the stem that are required for the production of efficient hooked stick tools. Our study provides one of the most detailed assessments to date of how non-human animals identify raw materials for tool manufacture.
Investigation of strontium transport and strontium quantification in cortical rat bone by time-of-flight secondary ion mass spectrometry
Authors: Kern Christine , Quade Mandy , Ray Seemun , Thomas Jürgen , Schumacher Matthias , Gemming Thomas , Gelinsky Michael , Alt Volker , Rohnke Marcus
Published: February 2019

Next-generation bone implants will be functionalized with drugs for stimulating bone growth. Modelling of drug release by such functionalized biomaterials and drug dispersion into bone can be used as predicting tool for biomaterials testing in future. Therefore, the determination of experimental parameters to describe and simulate drug release in bone is essential. Here, we focus on Sr2+transport and quantification in cortical rat bone. Sr2+dose-dependently stimulates bone-building osteoblasts and inhibits bone-resorbing osteoclasts. It should be preferentially applied in the case of bone fracture in the context of osteoporotic bone status. Transport properties of cortical rat bone were investigated by dipping experiments of bone sections in aqueous Sr2+solution followed by time-of-flight secondary ion mass spectrometry (ToF-SIMS) depth profiling. Data evaluation was carried out by fitting a suitable mathematical diffusion equation to the experimental data. An average diffusion coefficient ofD= (1.68 ± 0.57) · 10−13cm2s−1for healthy cortical bone was obtained. This value differed only slightly from the value ofD= (4.30 ± 1.43) · 10−13cm2s−1for osteoporotic cortical bone. Transmission electron microscopy investigations revealed a comparable nano- and ultrastructure for both types of bone status. Additionally, Sr2+-enriched mineralized collagen standards were prepared for ToF-SIMS quantification of Sr2+content. The obtained calibration curve was used for Sr2+quantification in cortical and trabecular bone in real bone sections. The results allow important insights regarding the Sr2+transport properties in healthy and osteoporotic bone and can ultimately be used to perform a simulation of drug release and mobility in bone.
Tensor clustering with algebraic constraints gives interpretable groups of crosstalk mechanisms in breast cancer
Authors: Seigal Anna , Beguerisse-Díaz Mariano , Schoeberl Birgit , Niepel Mario , Harrington Heather A.
Published: February 2019

We introduce a tensor-based clustering method to extract sparse, low-dimensional structure from high-dimensional, multi-indexed datasets. This framework is designed to enable detection of clusters of data in the presence of structural requirements which we encode as algebraic constraints in a linear program. Our clustering method is general and can be tailored to a variety of applications in science and industry. We illustrate our method on a collection of experiments measuring the response of genetically diverse breast cancer cell lines to an array of ligands. Each experiment consists of a cell line–ligand combination, and contains time-course measurements of the early signalling kinases MAPK and AKT at two different ligand dose levels. By imposing appropriate structural constraints and respecting the multi-indexed structure of the data, the analysis of clusters can be optimized for biological interpretation and therapeutic understanding. We then perform a systematic, large-scale exploration of mechanistic models of MAPK–AKT crosstalk for each cluster. This analysis allows us to quantify the heterogeneity of breast cancer cell subtypes, and leads to hypotheses about the signalling mechanisms that mediate the response of the cell lines to ligands.
Knee implant kinematics are task-dependent
Authors: Schütz Pascal , Postolka Barbara , Gerber Hans , Ferguson Stephen J. , Taylor William R. , List Renate
Published: February 2019

Although total knee arthroplasty (TKA) has become a standard surgical procedure for relieving pain, knowledge of the
in vivo
knee joint kinematics throughout common functional activities of daily living is still missing. The goal of this study was to analyse knee joint motion throughout complete cycles of daily activities in TKA subjects to establish whether a significant difference in joint kinematics occurs between different activities. Using dynamic videofluoroscopy, we assessed tibio-femoral kinematics in six subjects throughout complete cycles of walking, stair descent, sit-to-stand and stand-to-sit. The mean range of condylar anterior–posterior translation exhibited clear task dependency across all subjects. A significantly larger anterior–posterior translation was observed during stair descent compared to level walking and stand-to-sit. Local minima were observed at approximately 30° flexion for different tasks, which were more prominent during loaded task phases. This characteristic is likely to correspond to the specific design of the implant. From the data presented in this study, it is clear that the flexion angle alone cannot fully explain tibio-femoral implant kinematics. As a result, it seems that the assessment of complete cycles of the most frequent functional activities is imperative when evaluating the behaviour of a TKA design
in vivo
.
Fashion and art cycles are driven by counter-dominance signals of elite competition: quantitative evidence from music styles
Authors: Klimek Peter , Kreuzbauer Robert , Thurner Stefan
Published: February 2019

Human symbol systems such as art and fashion styles emerge from complex social processes that govern the continuous re-organization of modern societies. They provide a signalling scheme that allows members of an elite to distinguish themselves from the rest of society. Efforts to understand the dynamics of art and fashion cycles have been placed on ‘bottom-up’ and ‘top-down’ theories. According to ‘top-down’ theories, elite members signal their superior status by introducing new symbols (e.g. fashion styles), which are adopted by low-status groups. In response to this adoption, elite members would need to introduce new symbols to signal their status. According to many ‘bottom-up’ theories, style cycles evolve from lower classes and follow an essentially random pattern. We propose an alternative explanation based on counter-dominance signalling (CDS). In CDS, elite members want others to imitate their symbols; changes only occur when outsider groups successfully challenge the elite by introducing signals that contrast those endorsed by the elite. We investigate these mechanisms using a dynamic network approach on data containing almost 8 million music albums released between 1956 and 2015. The network systematically quantifies artistic similarities of competing musical styles and their changes over time. We formulate empirical tests for whether new symbols are introduced by current elite members (top-down), randomness (bottom-up) or by peripheral groups through counter-dominance signals. We find clear evidence that CDS drives changes in musical styles. This provides a quantitative, completely data-driven answer to a century-old debate about the nature of the underlying social dynamics of fashion cycles.
Analysis of microscopic bone properties in an osteoporotic sheep model: a combined biomechanics, FE and ToF-SIMS study
Authors: Müller R. , Henss A. , Kampschulte M. , Rohnke M. , Langheinrich A. C. , Heiss C. , Janek J. , Voigt A. , Wilke H. J. , Ignatius A. , Herfurth J. , El Khassawna T. , Deutsch A.
Published: February 2019

The present study deals with the characterization of bone quality in a sheep model of postmenopausal osteoporosis. Sheep were sham operated (
n
= 7), ovariectomized (
n
= 6), ovariectomized and treated with deficient diet (
n
= 8) or ovariectomized, treated with deficient diet and glucocorticoid injections (
n
= 7). The focus of the study is on the microscopic properties at tissue level. Microscopic mechanical properties of osteoporotic bone were evaluated by a combination of biomechanical testing and mathematical modelling. Sample stiffness and strength were determined by compression tests and finite-element analysis of stress states was conducted. From this, an averaged microscopic Young’s modulus at tissue level was determined. Trabecular structure as well as mineral and collagen distribution in samples of sheep vertebrae were analysed by micro-computed tomography and time-of-flight secondary ion mass spectrometry. In the osteoporotic sheep model, a disturbed fibril structure in the triple treated group was observed, but bone loss only occurred in form of reduced trabecular number and thickness and cortical decline, while quality of the residual bone was preserved. The preserved bone tissue properties in the osteoporotic sheep model allowed for an estimation of bone strength which behaves similar to the human case.
Autocatalytic networks in biology: structural theory and algorithms
Authors: Steel Mike , Hordijk Wim , Xavier Joana C.
Published: February 2019

Self-sustaining autocatalytic networks play a central role in living systems, from metabolism at the origin of life, simple RNA networks and the modern cell, to ecology and cognition. A collectively autocatalytic network that can be sustained from an ambient food set is also referred to more formally as a ‘reflexively autocatalytic food-generated’ (RAF) set. In this paper, we first investigate a simplified setting for studying RAFs, which is nevertheless relevant to real biochemistry and which allows an exact mathematical analysis based on graph-theoretic concepts. This, in turn, allows for the development of efficient (polynomial-time) algorithms for questions that are computationally intractable (NP-hard) in the general RAF setting. We then show how this simplified setting for RAF systems leads naturally to a more general notion of RAFs that are ‘generative’ (they can be built up from simpler RAFs) and for which efficient algorithms carry over to this more general setting. Finally, we show how classical RAF theory can be extended to deal with ensembles of catalysts as well as the assignment of rates to reactions according to which catalysts (or combinations of catalysts) are available.
Electromechanical vibration of microtubules and its application in biosensors
Authors: Li Si , Wang Chengyuan , Nithiarasu Perumal
Published: February 2019

An electric field (EF) has the potential to excite the vibration of polarized microtubules (MTs) and thus enable their use as a biosensor for the biophysical properties of MTs or cells. To facilitate the development, this paper aims to capture the EF-induced vibration modes and the associated frequency for MTs. The analyses were carried out based on a molecular structural mechanics model accounting for the structural details of MTs. Transverse vibration, radial breathing vibration and axial vibration were achieved for MTs subject to a transverse or an axial EF. The frequency shift and stiffness alteration of MTs were also examined due to the possible changes of the tubulin interactions in physiological or pathological processes. The strong correlation achieved between the tubulin interaction and MT vibration excited by EF provides a new avenue to a non-contacting technique for the structural or property changes in MTs, where frequency shift is used as a biomarker. This technique can be used for individual MTs and is possible for those in cells when the cytosol damping on MT vibrations is largely reduced by the unique features of MT–cytosol interface.
Innate ability of goats to sense and avoid ingestion of noxious insects while feeding
Authors: Berman Tali S. , Messeri Noa , Glasser Tzach A. , Inbar Moshe
Published: February 2019

Large mammalian herbivores regularly encounter noxious insects on their food plants. Recent evidence revealed that goats efficiently avoid insect ingestion while feeding, yet it is unknown whether this ability is innate. We experimentally examined the behavioural responses of naive goat kids to a common insect, the spring-webworm (
Ocnogyna loewii
). We filmed and analysed the kids' behaviour while feeding and compared it to the behaviour described in adults. Naive kids sorted the webworms apart from the food without ingesting them (all webworms survived). They exhibited behaviours similar to those displayed by adults, demonstrating an innate ability to avoid insect ingestion. The kids detected webworms using tactile stimulation, obtained by repeatedly touching the leaves with their muzzles. This enabled them to pick webworm-free leaves (leaving 93% of webworms behind). While adults frequently shook or discarded leaves with webworms or spat out webworms, these behaviours were rare in kids. The kids’ mean feeding rates doubled over the trials, indicating that their feeding efficiency on plants with and without insects improved with experience. As ingesting noxious insects could be fatal, innate avoidance is critical. These findings highlight the importance of direct interactions between mammalian and insect herbivores.
Unconditionally secure quantum bit commitment based on the uncertainty principle
Authors: Ping He Guang
Published: February 2019

Unconditionally secure quantum bit commitment (QBC) was considered impossible. But the no-go proofs are based on the Hughston–Jozsa–Wootters (HJW) theorem (a.k.a. the Uhlmann theorem). Recently, it was found that in high-dimensional systems, there exist some states which can display a chaos effect in quantum steering, so that the attack strategy based on the HJW theorem has to require the capability of discriminating quantum states with very subtle difference, to the extent that is not allowed by the uncertainty principle. With the help of this finding, here we propose a simple QBC protocol which manages to evade the no-go proofs.
The general coupled Hirota equations: modulational instability and higher-order vector rogue wave and multi-dark soliton structures
Authors: Zhang Guoqiang , Yan Zhenya , Wang Li
Published: February 2019

The general coupled Hirota equations are investigated, which describe the wave propagations of two ultrashort optical fields in a fibre. Firstly, we study the modulational instability for the focusing, defocusing and mixed cases. Secondly, we present a unified formula of high-order rational rogue waves (RWs) for the focusing, defocusing and mixed cases, and find that the distribution patterns for novel vector rational RWs of focusing case are more abundant than ones in the scalar model. Thirdly, theNth-order vector semirational RWs can demonstrate the coexistence ofNth-order vector rational RWs andNbreathers. Fourthly, we derive the multi-dark-dark solitons for the defocsuing and mixed cases. Finally, we derive a formula for the coexistence of dark solitons and RWs. These results further enrich and deepen the understanding of localized wave excitations and applications in vector nonlinear wave systems.
Thermal selection as a driver of marine ecological speciation
Authors: Teske Peter R. , Sandoval-Castillo Jonathan , Golla Tirupathi Rao , Emami-Khoyi Arsalan , Tine Mbaye , von der Heyden Sophie , Beheregaray Luciano B.
Published: February 2019

Intraspecific genetic structure in widely distributed marine species often mirrors the boundaries between temperature-defined bioregions. This suggests that the same thermal gradients that maintain distinct species assemblages also drive the evolution of new biodiversity. Ecological speciation scenarios are often invoked to explain such patterns, but the fact that adaptation is usually only identified when phylogenetic splits are already evident makes it impossible to rule out the alternative scenario of allopatric speciation with subsequent adaptation. We integrated large-scale genomic and environmental datasets along one of the world's best-defined marine thermal gradients (the South African coastline) to test the hypothesis that incipient ecological speciation is a result of divergence linked to the thermal environment. We identified temperature-associated gene regions in a coastal fish species that is spatially homogeneous throughout several temperature-defined biogeographic regions based on selectively neutral markers. Based on these gene regions, the species is divided into geographically distinct regional populations. Importantly, the ranges of these populations are delimited by the same ecological boundaries that define distinct infraspecific genetic lineages in co-distributed marine species, and biogeographic disjunctions in species assemblages. Our results indicate that temperature-mediated selection represents an early stage of marine ecological speciation in coastal regions that lack physical dispersal barriers.
Resolving the relationships of clams and cockles: dense transcriptome sampling drastically improves the bivalve tree of life
Authors: Lemer Sarah , Bieler Rüdiger , Giribet Gonzalo
Published: February 2019

Bivalvia has been the subject of extensive recent phylogenetic work to attempt resolving either the backbone of the bivalve tree using transcriptomic data, or the tips using morpho-anatomical data and up to five genetic markers. Yet the first approach lacked decisive taxon sampling and the second failed to resolve many interfamilial relationships, especially within the diverse clade Imparidentia. Here we combine dense taxon sampling with 108 deep-sequenced Illumina-based transcriptomes to provide resolution in nodes that required additional study. We designed specific data matrices to address the poorly resolved relationships within Imparidentia. Our results support the overall backbone of the bivalve tree, the monophyly of Bivalvia and all its main nodes, although the monophyly of Protobranchia remains less clear. Likewise, the inter-relationships of the six main bivalve clades were fully supported. Within Imparidentia, resolution increases when analysing Imparidentia-specific matrices. Lucinidae, Thyasiridae and Gastrochaenida represent three early branches. Gastrochaenida is sister group to all remaining imparidentians, which divide into six orders. Neoheterodontei is always fully supported, and consists of Sphaeriida, Myida and Venerida, with the latter now also containing Mactroidea, Ungulinoidea and Chamidae, a family particularly difficult to place in earlier work. Overall, our study, by using densely sampled transcriptomes, provides the best-resolved bivalve phylogeny to date.
Distributed plasticity in ant visual pathways following colour learning
Authors: Yilmaz Ayse , Grübel Kornelia , Spaethe Johannes , Rössler Wolfgang
Published: February 2019

Colour processing at early stages of visual pathways is a topic of intensive study both in vertebrate and invertebrate species. However, it is still unclear how colour learning and memory formation affects an insect brain in the peripheral processing stages and high-order integration centres, and whether associative colour experiences are reflected in plasticity of underlying neuronal circuits. To address this issue, we usedCamponotus blandusants as their proven colour learning and memory capabilities, precisely controllable age and experience, and already known central visual pathways offer unique access to analyse plasticity in neuronal circuits for colour vision in a miniature brain. The potential involvement of distinct neuropils—optic lobes (OLs), mushroom body (MB) input (collar) and output (vertical lobe), anterior optic tubercle (AOTU) and central complex (CX)—in associative colour experiences was assessed by quantification of volumetric and synaptic changes (MB collar) directly after colour conditioning and, 3 days later, after the establishment of long-term memory (LTM). To account for potential effects of non-associative light exposure, we compared neuronal changes in the brain of colour-naive foragers with those of foragers that had been exposed to light in a non-associative way. The results clearly show that the OLs, AOTU, and CX respond with plastic changes after colour learning and LTM formation. This suggests a complex neuronal network for colour learning and memory formation involving multiple brain levels. Such a colour-processing network probably represents an efficient design promoting fast and accurate behavioural decisions during orientation and navigation.
A systems-based map of human brain cell-type enriched genes and malignancy-associated endothelial changes
Authors: Dusart Philip , Hallström Björn M , Renne Thomas , Odeberg Jacob , Uhlén Mathias , Butler Lynn M
Published: February 2019

Changes in the endothelium of the cerebral vasculature can contribute to inflammatory, thrombotic and malignant disorders. The importance of defining cell type-specific genes and how they are modified in disease is increasingly recognised. Here, we developed a bioinformatics-based approach to identify normal brain cell-enriched genes, using bulk RNAseq data from 238 normal human cortex samples from 2 independent cohorts. We compared endothelial cell-enriched gene profiles with astrocyte, oligodendrocyte and neuron profiles. Global modifications to the endothelium in malignant disease were characterised, using RNAseq data from 516 human lower grade gliomas and 401 human glioblastoma multiforme samples. Lower grade glioma appeared to be an ‘endothelial intermediate’ between normal brain and glioblastoma multiforme. We identify the most highly glioblastoma multiforme-specific endothelial cell biomarkers, providing potential diagnostic or therapeutic targets. In summary, we provide a roadmap of endothelial cell identity in normal and malignant brain tissue, using a bioinformatics-based method developed to resolve bulk RNAseq datasets into constituent cell type-enriched profiles.