bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolerability and Long-term Outcomes of Dose-Painted Neoadjuvant Chemoradiation to Regions of Vessel Involvement in Borderline or Locally Advanced Pancreatic Cancer
Authors: Wo Jennifer Y. , Niemierko Andrzej , Ryan David P. , Blaszkowsky Lawrence S. , Clark Jeffrey W. , Kwak Eunice L. , Lillemoe Keith D. , Drapek Lorraine N. , Zhu Andrew X. , Allen Jill N. , Faris Jason E. , Murphy Janet E. , Nipp Ryan , Fernandez-del Castillo Carlos , Ferrone Cristina R. , Hong Theodore S.
Published: February 2017

Purpose:

We reviewed our experience involving patients with borderline resectable or locally advanced pancreatic cancer, treated with the dose-painted (DP) boost technique to regions of vessel involvement which preclude upfront surgical resection. We evaluated patient outcomes with respect to tolerability and treatment outcomes.

Materials and Methods:

We retrospectively reviewed 99 patients with borderline resectable (n=25) or locally advanced pancreatic cancer (n=74) treated with DP-neoadjuvant chemoradiation from 2010 to 2015. Tumor and regional lymph nodes were prescribed 50.4 Gy and the region around the involved blood vessel was boosted to 58.8 Gy in 28 fractions. The primary outcome was acute toxicity and late duodenal toxicity. Secondary outcomes included conversion to surgical resectability, local failure, disease-free survival, and overall survival (OS). Cox proportional hazards models were performed to evaluate for predictors of survival.

Results:

All but 1 patient completed chemoradiation. The rates of grade 2+ and 3+ nausea were 40% and 12%, respectively. With regards to late toxicity, 5 patients developed potential RT-related grade 3+ duodenal complications including duodenal ulceration/bleeding (n=3) and duodenal stricture (n=2). With a median follow-up of 15 months, the median OS was 18.1 months. Among 99 patients in our study, 37 patients underwent surgical resection. For patients who underwent surgical resection (n=37), the median OS was 30.9 months. On multivariate analysis, only normalization of CA 19-9 post-RT was associated with improved OS.

Conclusions:

We found that DP-neoadjuvant chemoradiation to regions of vessel involvement is both feasible and well tolerated. In addition, we demonstrated that over one third of patients with initially deemed unresectable disease were able to undergo surgical resection after receiving neoadjuvant therapy including DP-chemoradiation.
Study on Mucin in Normal-Appearing Leg Skin
Authors: Fernandez-Flores Angel
Published: February 2017

Dermal deposits of mucin in the legs have been described associated with venous insufficiency. However, some degree of stasis dermatitis is generally common in aged individuals. Therefore, some amount of mucin is expected a priori in the reticular dermis of aged patients, even in the absence of clinical lesions. To test this hypothesis, the authors investigated the mucin in the legs of aged individuals without any dermatologic disease. Cutaneous samples were taken from the legs of 15 autopsy cases. A sample of the skin of the legs (either from the left or the right leg without any distinction being made) was randomly taken (without selecting any specific area or attending to macroscopical features). The skin samples were fixed in formaldehyde, and sections obtained from all samples were stained with hematoxylin and eosin, iron, and Alcian blue. Iron deposits were graded as 0/4 in 7 cases, as 1/4 in 4 cases, as 2/4 in 2 cases, and as 4/4 in 2 cases. Cases with greater deposits of iron also had other signs of stasis, such as neovascularization. All the samples scored 0 for dermal mucin deposits in the reticular dermis. The authors conclude that mucin deposits in the legs are not inherent to aging. Therefore, any mucin deposit in the reticular dermis, as well as expansion of the periadnexal dermis by mucin deposits, should be considered abnormal.
Cutaneous Emboli of Invasive Basidiomycosis in a Child With Aplastic Anemia
Authors: Lim Desmond Shi-Wei , Tan Poh-Lin , Jureen Roland , Tan Kong-Bing
Published: February 2017

Invasive fungal diseases are a significant cause of mortality among the immunocompromised. This report documents an unusual case of disseminated fungal infection in a child with severe aplastic anemia. The offending fungus, a Basidiomycete, is rarely known to cause human infections. The patient presented acutely with multiple purpuric skin lesions in various parts of the body. The skin biopsy revealed septated fungal hyphae embolized within small dermal blood vessels. Molecular sequencing indicated Earliella scabrosa as the likely organism. The clinical course of the infection was inexorable despite systemic antifungal treatment, resulting in mortality. The literature of human infections due to Basidiomycetes, the usefulness of histopathology in the early diagnosis of the infection, and possible treatment options are discussed.
Information Needs and Preferences of Parents Considering Treatment of Child Anxiety
Authors: Mak Leanne , Walker John R. , Hiebert-Murphy Diane , Altman Gary
Published: February 2017

Objective:

To assess the information needs and preferences of parents who were making decisions concerning treatment for their child's anxiety.

Methods:

Ninety-three parents were recruited from hospital-based clinics, a parent group, and a public information meeting. They completed a survey about preference for decision-making involvement, information needs, and preferences concerning source and amount of information.

Results:

Most (69%) parents indicated that they prefer a collaborative decision-making role. They rated very highly the need for general information related to treatment and information related to psychosocial interventions and medication treatment. Fewer parents rated information about logistics of treatment (e.g., scheduling, cost) as highly important although this information was considered important by many parents. Direct discussions with a provider, written information, and information accessed through the internet were the most preferred sources of information. Many parents indicated a preference for substantial amounts of information about psychosocial and medication treatments.

Conclusion:

Much of the information that parents want concerning treatment is not widely available. It would be helpful to develop evidence-based brochures and web information resources that focus on answering parents' questions concerning treatment of children's anxiety.
Stretching Exercises Improve Vascular Endothelial Dysfunction Through Attenuation of Oxidative Stress in Chronic Heart Failure Patients With an Implantable Cardioverter Defibrillator
Authors: Kato Michitaka , Masuda Takashi , Ogano Michio , Hotta Kazuki , Takagi Hisato , Tanaka Shinya , Kamada Yumi , Akiyama Ayako , Kamekawa Daisuke , Shimizu Ryosuke , Tabata Minoru , Tanabe Jun , Umemoto Takuya
Published: February 2017

PURPOSE:

Endurance training improves oxidative stress and vascular endothelial dysfunction in patients with chronic heart failure (CHF). However, patients with CHF and an implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) often avoid endurance training for fear of ICD shock. Recent studies have reported that stretching exercises enhance antioxidant activity and improve vascular responses. Therefore, we aimed to assess the effects of 4 weeks of stretching exercises on oxidative stress and vascular endothelial function in patients with CHF with an ICD or CRT-D.

METHODS:

Fifty sedentary patients with CHF (78% males; mean age = 70 ± 9 years; left ventricular ejection fraction = 26% ± 8%) with an ICD or CRT-D were randomly divided into a group that performed 4 weeks of stretching exercises (stretching group) and a group that continued a sedentary lifestyle (control group). We compared the reactive hyperemia peripheral arterial tonometry (RH-PAT) index and blood parameters, such as von Willebrand factor (vWF), malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL), reactive oxygen species (ROS), high-sensitivity C-reactive protein, pentraxin 3, and fibrinogen between the 2 groups before and after the 4-week study period.

RESULTS:

In the stretching group, a significant increase in the RH-PAT index and significant decreases in vWF, MDA-LDL, ROS, and fibrinogen concentrations were observed after the study compared with before (all P < .05). No significant changes were observed in the control group.

CONCLUSION:

Four weeks of stretching exercises improved vascular endothelial dysfunction through attenuation of oxidative stress in sedentary patients with CHF with an ICD or CRT-D.
Comparative Postural Control in COPD Patients and Healthy Individuals During Dynamic and Static Activities
Authors: Porto Elias F. , Pradella Cristiane O. , Rocco Carolina M. , Chueiro Mario , Maia Rafaella Q. , Ganança Fernando F. , Castro Antonio A. M. , Nascimento Oliver A. , Jardim José R.
Published: February 2017

PURPOSE:

Patients with chronic obstructive pulmonary disease (COPD) have body balance deficits, with consequent fall risk. It is possible that body sway in patients with COPD affects their ability to perform daily activities. The purpose of this study was to determine whether body balance is similar in patients with COPD and healthy persons when performing static and dynamic activities. In addition, we wanted to assess whether impairment of balance is related to the presence of falls in patients with COPD.

METHODS:

This is a cross-sectional study, in which every spirometric classification in patients with COPD (mild, moderate, severe, and very severe degrees) and age-matched healthy subjects was assessed. Subjects who were current smokers and patients who underwent physical training in the last 6 months prior to the start of the study were excluded. Static balance was assessed by computerized posturography and dynamic body balance using the Berg Balance Scale.

RESULTS:

Ninety-three patients with COPD and 39 healthy persons were evaluated. Mean age was 67.3 (10.8) and 65.1 (9.7) years and mean forced expiratory volume in 1 second (FEV1) was 50.4 (19.0) and 89.2 (23.6) for patients with COPD and healthy individuals, respectively. The impairment of body balance was higher for the group of patients with COPD (P = .0005). Patients with greater impairment in body balance had greater incidence of falls, and body balance was more affected with age in patients with COPD than in healthy persons.

CONCLUSION:

Impairment of body balance is more frequent in patients with COPD than in healthy persons while performing dynamic activities, and a greater incidence of falls activities was also found for this group.
Environmental market factors associated with electronic health record adoption among cancer hospitals
Authors: Tarver Will L. , Menachemi Nir
Published: February 2017

Background:

Although recent literature has explored the relationship between various environmental market characteristics and the adoption of electronic health records (EHRs) among general, acute care hospitals, no such research currently exists for specialty hospitals, including those providing cancer care.

Purpose:

The aim of the study was to examine the relationship between market characteristics and the adoption of EHRs among Commission on Cancer (CoC)-accredited hospitals.

Methods/Approach:

Secondary data on EHR adoption combined with hospital and environmental market characteristics were analyzed using logistic regression. Using the resource dependence theory, we examined how measures of munificence, complexity, and dynamism are related to the adoption of EHRs among CoC-accredited hospitals and, separately, hospitals not CoC-accredited.

Findings:

In a sample of 2,670 hospitals, 141 (0.05%) were academic-based CoC-accredited hospitals and 562 (21%) were community-based CoC-accredited hospitals. Measures of munificence such as cancer incidence rates (OR = 0.99, CI [0.99, 1.00], p = .020) and percentage population aged 65+ (OR = 0.99, CI [0.99, 1.00], p = .001) were negatively associated with basic EHR adoption, whereas urban location was positively associated with comprehensive EHR adoption (OR = 3.07, CI [0.89, 10.61], p = .076) for community-based CoC-accredited hospitals. Measures of complexity such as hospitals in areas with less competition were less likely to adopt a basic EHR (OR = 0.33, CI [0.19, 0.96], p = .005), whereas Medicare Managed Care penetration was positively associated with comprehensive EHR adoption (OR = 1.02, CI [1.00, 1.05], p = .070) among community-based CoC-accredited hospitals. Lastly, dynamism, measured as population change, was negatively associated with the adoption of comprehensive EHRs (OR = 0.99, CI [0.99, 1.00], p = .070) among academic-based CoC-accredited hospitals.

Practice implications:

A greater understanding of the environment’s relationship to health information technology adoption in cancer hospitals will help stakeholders in these institutions make informed strategic decisions about information technology investments guided by their facilities’ respective environmental factors. The results of this study may also be useful to hospital chief information officers and chief executive officers seeking to either improve their quality of care or achieve and maintain accreditation in providing cancer care.
Novel TBX3 mutation in a family of Cypriot ancestry with ulnar-mammary syndrome
Authors: Tanteles George A. , Nicolaou Nayia , Syrimis Andreas , Metaxa Rafaella , Nicolaou Michael , Christophidou-Anastasiadou Violetta , Skordis Nicos
Published: February 2017

Ulnar-mammary syndrome (UMS) is an autosomal dominant disorder resulting from TBX3 haploinsufficiency. It typically affects limb, apocrine gland, hair, tooth and genital development and shows marked intrafamilial and interfamilial variability in phenotypic expression. We report a family (twin brothers and their father) affected with UMS because of a novel TBX3 mutation. The twin brothers showed classical features of UMS, whereas their father was mildly affected. The c.1423C>T (p.Q475*) nonsense mutation in exon 6 of the TBX3 gene identified in the patients by targeted Sanger sequencing is predicted to lead to premature termination of translation. This is the first report of a Cypriot family with UMS resulting from a novel TBX3 mutation. This report provides additional evidence in support of the rich variability in phenotypic expression, the mutational heterogeneity and ethnic diversity associated with this rare condition.
Reliability and cross-cultural adaptation of the Turkish version of the Spinal Cord Injury Spasticity Evaluation Tool
Authors: Akpinar Pinar , Atici Arzu , Kurt Kubra N. , Ozkan Feyza U. , Aktas Ilknur , Kulcu Duygu G.
Published: February 2017

The Spinal Cord Injury Spasticity Evaluation Tool is a 7-day recall self-reported questionnaire that assesses the problematic and useful effects of spasticity on daily life in patients with spinal cord injury (SCI). We aimed to determine the reliability and cross-cultural validation of the Turkish translation of the Spinal Cord Injury Spasticity Evaluation Tool (SCI-SETT). After translation and back translation of the Spinal Cord Injury Spasticity Evaluation Tool, 66 patients between the ages of 18 and 88 years with SCI, American Spinal Injury Association impairment scale grades from A to D with spasticity, and at least 6 months after injury were assessed. Participants rated the SCI-SETT at the same time period of the day, 1 week apart, and test–retest agreement was investigated. Also, the Penn Spasm Frequency Scale, self-assessment of spasticity severity, self-assessment of spasticity impact, Functional Independence Measure motor subscale, and 36-Item Short Form Health Survey were assessed for the evaluation of the convergent validity. There were 45 participants with tetraplegia and 21 patients with paraplegia. The test–retest reliability for the SCI-SETT was good. The intraclass correlation coefficient was 0.80 at 95% confidence interval. There were no significant correlations between the SCI-SETT scores and Functional Independence Measure motor subscale and Penn Spasm Frequency Scale scores. There was a significant correlation between the SCI-SETT scores and vitality scores of the 36-Item Short Form Health Survey. The SCI-SETT showed statistically significant correlations with other measures including self-assessed spasticity severity and self-assessed spasticity impact (P<0.05). The SCI-SETT is a reliable self-rating tool for assessing spasticity in patients with SCI in the Turkish population.
Psychometric Properties of the Reconstructed Hamilton Depression and Anxiety Scales
Authors: Porter Eliora , Chambless Dianne L. , McCarthy Kevin S. , DeRubeis Robert J. , Sharpless Brian A. , Barrett Marna S. , Milrod Barbara , Hollon Steven D. , Barber Jacques P.
Published: February 2017

Although widely used, the Hamilton Rating Scale for Depression (HRSD) and Hamilton Anxiety Rating Scale (HARS) discriminate poorly between depression and anxiety. To address this problem, Riskind, Beck, Brown, and Steer (J Nerv Ment Dis. 175:474–479, 1987) created the Reconstructed Hamilton Scales by reconfiguring HRSD and HARS items into modified scales. To further analyze the reconstructed scales, we examined their factor structure and criterion-related validity in a sample of patients with major depressive disorder and no comorbid anxiety disorders (n = 215) or with panic disorder and no comorbid mood disorders (n = 149). Factor analysis results were largely consistent with those of Riskind et al. The correlation between the new reconstructed scales was small. Compared with the original scales, the new reconstructed scales correlated more strongly with diagnosis in the expected direction. The findings recommend the use of the reconstructed HRSD over the original HRSD but highlight problems with the criterion-related validity of the original and reconstructed HARS.
Measurement of Perceived Stress in Age-Related Macular Degeneration
Authors: Dougherty Bradley E. , Cooley San-San L. , Davidorf Frederick H.
Published: February 2017

Purpose

To validate the Perceived Stress Scale (PSS) in patients with age-related macular degeneration (AMD) using Rasch analysis.

Methods

Study participants with AMD were recruited from the retina service of the Department of Ophthalmology at the Ohio State University during clinical visits for treatment or observation. Visual acuity with habitual distance correction was assessed. A 10-item version of the PSS was administered in large print or by reading the items to the patient. Rasch analysis was used to investigate the measurement properties of the PSS, including fit to the model, ability to separate between people with different levels of perceived stress, category response structure performance, and unidimensionality.

Results

A total of 137 patients with a diagnosis of AMD were enrolled. The mean (±SD) age of participants was 82 ± 9 years. Fifty-four percent were female. Median Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity of the better eye was 65 letters (Snellen 20/50), with a range of approximately 20/800 to 20/15. Forty-seven percent of participants were receiving an anti-VEGF injection on the day of the study visit. The response category structure was appropriate. One item, “How often have you felt confident in your ability to handle your personal problems?” was removed due to poor fit statistics. The remaining nine items showed good fit to the model, acceptable measurement precision as assessed by the Rasch person separation statistic, and unidimensionality. There was some evidence of differential item functioning by age and visual acuity.

Conclusions

The Perceived Stress Scale demonstrated acceptable measurement properties and may be useful for the measurement of perceived stress in patients with AMD.
Effective Use of Calcineurin Inhibitor in Combination Therapy for Interstitial Lung Disease in Patients With Dermatomyositis and Polymyositis
Authors: Shimojima Yasuhiro , Ishii Wataru , Matsuda Masayuki , Kishida Dai , Ikeda Shu-ichi
Published: February 2017

Objective

The current study demonstrated the potential use of calcineurin inhibitor (CNI) in combination therapy for interstitial lung disease (ILD) complicated with dermatomyositis (DM) and polymyositis (PM).

Methods

Thirty DM/PM patients with ILD were enrolled in this study. Continuous intravenous administration of cyclosporine A (IV-CsA) was simultaneously started with corticosteroid in patients presenting more than two respiratory distress factors as follows: <70 mmHg of PaO2, percentage of vital capacity <70%, and/or exertional dyspnea. Other patients took CNI orally with corticosteroid. When a patient presented exacerbation of ILD, intravenous cyclophosphamide pulse therapy (IVCY) was additionally administrated. Clinical outcomes were compared with those of 21 patients who had been previously treated in our hospital before starting this study, as the historical comparison group.

Results

Seven patients underwent IV-CsA, maintaining the drug concentration in blood between 300 and 350 ng/mL, and six of them had favorable outcomes without any adverse events. Eight out of the 30 patients additionally required IVCY. Meanwhile, the frequency of death ascribable to respiratory failure was 6.7%, which was significantly lower than that of the historical comparison group (P = 0.043). Furthermore, longer survival free from exacerbation and severe adverse event was significantly shown (P = 0.029).

Conclusions

For repressing the activity of ILD in DM/PM patients, stabilizing the blood concentration of CNI immediately is a reasonable treatment as well as initiating immunosuppressive therapy in the early phase of the illness. IV-CsA may be a useful option for achieving this purpose in patients with severe ILD.
Treatment Satisfaction in Systemic Lupus Erythematosus
Authors: Mathias Susan D. , Berry Pamela , Pascoe Katie , de Vries Jane , Askanase Anca D. , Colwell Hilary H. , Chang David J.
Published: February 2017

Objective

The aim of this study was to develop a patient-reported outcome measure specific for systemic lupus erythematosus (SLE) to assess patient satisfaction with treatment, treatment options, and medical care.

Methods

Patients with SLE were recruited from four US rheumatology practices. Concept elicitation interviews identified aspects that patients considered important and relevant regarding satisfaction with treatment and medical care. Concept elicitation interviews and clinical input were used to draft the Lupus Satisfaction Questionnaire (LSQ). A second cohort of patients with SLE participated in combined concept elicitation/cognitive debriefing interviews, after which the LSQ was revised.

Results

Fourteen patients completed concept elicitation interviews: 93% were female, 57% were white, and 85% had moderate/severe SLE. Current treatments included hydroxychloroquine (93%), steroids (79%), and belimumab (57%), and 43% were biologic naive. Patients were generally satisfied with their treatment and medical care; however, they were dissatisfied with treatment adverse effects and the number of available treatment options. Cognitive debriefing interviews (n = 8) demonstrated that the LSQ was comprehensive, clear, and relevant; therefore, only minor revisions were made to the questionnaire. The LSQ assesses satisfaction with current SLE treatments (25 items), medical care (11 items), and insurance coverage (3 items). The draft LSQ was evaluated in 195 adults with SLE. Fifty-eight percent of patients reported that they were “somewhat satisfied” with their SLE treatment.

Conclusions

The LSQ has been developed to assess treatment satisfaction among patients with SLE. Following further testing to support its validity and reliability, it will provide a useful tool to facilitate assessment of satisfaction with treatments for SLE and help inform treatment decisions.
Time, Sex, Gender, History, and Dementia
Authors: Rocca Walter A.
Published: February 2017

A growing body of epidemiologic evidence indicates a decline in the incidence or prevalence of dementia in high income countries in the past 25 years. In this commentary, I first suggest that the decline in the incidence or prevalence of dementia is not explained completely by the factors considered so far, and that a broader historical perspective may be needed. Second, I suggest that the overall declining trend may conceal trends in opposite directions for the two major subtypes of dementia, the neurovascular and the neurodegenerative type. Third, I suggest some areas of future research to further elucidate the trends. The future of dementia remains somewhat unclear. Even if the incidence continues to decline, the prevalence may remain the same or increase if survival of persons affected by dementia increases. In addition, even if the prevalence declines, the total number of persons affected by dementia may remain the same or increase if the size of the elderly population expands. Finally, we cannot be sure that the decline in incidence will continue in the coming decades. With cautious optimism, we may conclude that the burden of dementia may be modified over time by human practices, including public health and medicine.
Sir Sam Edwards. 1 February 1928 — 7 July 2015
Authors: Warner Mark
Published: February 2017

Sam Edwards was one of the leading physicists of the second half of the twentieth century. He was Cavendish Professor at the University of Cambridge, a Vice President of the Royal Society, a member of the Académie des Sciences and of the US National Academy, and a senior figure in the university and his college. He played a major role in public life, most notably as chairman of the Science Research Council (SRC), responsible for research funding in the UK. He was chairman of the British Association, chief government scientist to the Department of Energy, and chairman of the Defence Scientific Advisory Council. He was equally in demand to lead or to help set up bodies abroad, particularly the Max Planck Institute for Polymers in Mainz, Germany. Remarkably, Sam made some of his most celebrated scientific discoveries, for instance the theory of spin glasses and the rheology of high polymer melts, while serving as the full-time head of the SRC. Conversely, his scientific insights informed his leadership in advising the government. His later science was in highly applicable areas: he was an active advisor to Unilever, Dow, Lucas and many other companies that rely on research.
Route choice in pedestrians: determinants for initial choices and revising decisions
Authors: Liao Weichen , Kemloh Wagoum Armel U. , Bode Nikolai W. F.
Published: February 2017

In moving pedestrian crowds, the distribution of individuals over different available routes emerges from the decisions of individuals that may be influenced by the actions of others. Understanding this phenomenon not only is important for research into collective behaviour, but also has practical applications for building safety and event management. Here, we study the mechanisms underlying pedestrian route choice, focusing on how time-independent information, such as path lengths, and time-dependent information, such as queue lengths, affect both initial decisions and subsequent changes in route choices. We address these questions using experiments with nearly 140 volunteers and an individual-based model for route choice. Crucially, we consider a wide range of route choice scenarios. We find that initial route choices of pedestrians achieve a balanced usage of available routes. Our model suggests that pedestrians performing trade-offs between exit widths and predicted exit crowdedness can explain this emergent distribution in many contexts. Few pedestrians adjust their route choice in our experiments. Simulations suggest that these decisions could be explained by pedestrians comparing estimates of the time it would take them to reach their target using different routes. Route choice is complex, but our findings suggest that conceptually simple behaviours may explain many movement decisions.
Three-dimensional printing spiders: back-and-forth glue application yields silk anchorages with high pull-off resistance under varying loading situations
Authors: Wolff Jonas O. , Herberstein Marie E.
Published: February 2017

The anchorage of structures is a crucial element of construction, both for humans and animals. Spiders use adhesive plaques to attach silk threads to substrates. Both biological and artificial adhesive structures usually have an optimal loading angle, and are prone to varying loading situations. Silk anchorages, however, must cope with loading in highly variable directions. Here we show that the detachment forces of thread anchorages of orb-web spiders are highly robust against pulling in different directions. This is gained by a two-step back-and-forth spinning pattern during the rapid production of the adhesive plaque, which shifts the thread insertion point towards the plaque centre and forms a flexible tree root-like network of branching fibres around the loading point. Using a morphometric approach and a tape-and-thread model we show that neither area, nor width of the plaque, but the shift of the loading point towards the plaque centre has the highest effect on pull-off resistance. This is explained by a circular propagation of the delamination crack with a low peeling angle. We further show that silken attachment discs are highly directional and adjusted to provide maximal performance in the upstream dragline. These results show that the way the glue is applied, crucially enhances the toughness of the anchorage without the need of additional material intake. This work is a starting point to study the evolution of tough and universal thread anchorages among spiders, and to develop bioinspired ‘instant’ anchorages of thread- and cable-like structures to a broad bandwidth of substrates.
Cell dynamics in tumour environment after treatments
Authors: Shahriyari Leili
Published: February 2017

Most cancer treatments cause necrotic cell deaths in the tumour microenvironment. Necrotic cells send signals to immune cells to start the wound healing process in the tissue. Therefore, we assume after stopping treatments there is a wound that needs to be healed. We develop a simple computational model to investigate cell dynamics during the wound healing process after treatments. The model predicts that the involvement of high-fitness cancer cells in the wound healing leads to fast relapse, and cancer cells outside of the wound can cause a slow recurrence of the tumour. Therefore, the absence of relapse after treatments may imply a slow-developing tumour that might not reach an observable size in the patients' lifetime. Additionally, the model indicates that the location of remaining cancer cells after treatments is an important factor in the recurrence time. The fastest recurrence happens when high-fitness cancer cells remain inside of the wound. However, the longest time to recurrence corresponds to cancer cells located outside of the wound. Note that this model is the first attempt to study cell dynamics in the wound healing process after cancer treatments, and it has some limitations that might influence the results. Experiments are needed to validate the results.
Effective equations governing an active poroelastic medium
Authors: Collis J. , Brown D. L. , Hubbard M. E. , O’Dea R. D.
Published: February 2017

In this work, we consider the spatial homogenization of a coupled transport and fluid–structure interaction model, to the end of deriving a system of effective equations describing the flow, elastic deformation and transport in an active poroelastic medium. The ‘active’ nature of the material results from a morphoelastic response to a chemical stimulant, in which the growth time scale is strongly separated from other elastic time scales. The resulting effective model is broadly relevant to the study of biological tissue growth, geophysical flows (e.g. swelling in coals and clays) and a wide range of industrial applications (e.g. absorbant hygiene products). The key contribution of this work is the derivation of a system of homogenized partial differential equations describing macroscale growth, coupled to transport of solute, that explicitly incorporates details of the structure and dynamics of the microscopic system, and, moreover, admits finite growth and deformation at the pore scale. The resulting macroscale model comprises a Biot-type system, augmented with additional terms pertaining to growth, coupled to an advection–reaction–diffusion equation. The resultant system of effective equations is then compared with other recent models under a selection of appropriate simplifying asymptotic limits.
Repressing Integrase attachment site operation with CRISPR-Cas9 inE. coli
Authors: Shur Andrey , Murray Richard M.
Published: February 2017

Serine integrases are bacteriophage proteins responsible for integrating the phage genome into that of the host. Synthetic biologists have co-opted these proteins into useful tools for permanent DNA logic, utilizing their specific DNA recombination abilities to build synthetic cell differentiation and genetic memory systems. Each integrase has a specific pair of DNA sequences (attP/attB sites) that it recombines, but multiple identical sites can result in unpredictable recombination. We have developed a way to control integrase activity on identical attP/attB sites by using catalytically dead Cas9 (dCas9) as a programmable binding protein that can compete with integrase for binding to specific attachment sites. Utilizing a plasmid that contains two identical Bxb1 attP sites, integration can be repressed up to 8 fold at either one of the two attP sites when guide RNA and dCas9 are present. Guide RNA sequences that bind specifically to attB, or either of two attP sites, have been developed. Future goals are to utilize this technology to construct larger and more complex integrase logic circuits.
Activity in the Fronto-Parietal Multiple-Demand Network is Robustly Associated with Individual Differences in Working Memory and Fluid Intelligence
Authors: Assem Moataz , Blank Idan Asher , Mineroff Zachary , Ademoglu Ahmet , Fedorenko Evelina
Published: February 2017

Numerous brain lesion and fMRI studies have linked individual differences in executive abilities and fluid intelligence to brain regions of the fronto-parietal “multiple-demand” (MD) network. Yet, fMRI studies have yielded conflicting evidence as to whether better executive abilities are associated with stronger or weaker MD activations and whether this relationship is restricted to the MD network. Here, in a large-sample (n=216) fMRI investigation, we found that stronger activity in MD regions – functionally defined in individual participants – was robustly associated with more accurate and faster responses on a spatial working memory task performed in the scanner, as well as fluid intelligence measured independently (n=114). In line with some prior claims about a relationship between language and fluid intelligence, we also found a weak association between activity in the brain regions of the left fronto-temporal language network during an independent passive reading task, and performance on the working memory task. However, controlling for the level of MD activity abolished this relationship, whereas the MD activity-behavior association remained highly reliable after controlling for the level of activity in the language network. Finally, we demonstrate how unreliable MD activity measures, coupled with small sample sizes, could falsely lead to the opposite, negative, association that has been reported in some prior studies. Taken together, these results demonstrate that a core component of individual differences variance in executive abilities and fluid intelligence is selectively and robustly positively associated with the level of activity in the MD network, a result that aligns well with lesion studies.
MiR-126 impairs the intestinal barrier function via inhibiting S1PR2 mediated activation of PI3K/AKT signaling pathway
Authors: Chen Tanzhou , Xue Haibo , Lin Ruoyang , Huang Zhiming
Published: February 2017

Background

Aberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD.

Methods

In this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2. The transendothelial electrical resistance assay was used to measured the value of TEER.

Results

The expressions of miR-126, S1PR2 and S1P in the pathological tissues of IBD patients were significantly higher than that of the control group. Moreover, miR-126 overexpression contributed to intestinal mucosal barrier dysfunctionin vitro.S1PR2 was a direct target of miR-126, and S1PR2 expression was negatively regulated by miR-126 in Caco-2 cells. However, S1PR2 activated by S1P had the protection effect for the integrity and permeability of intestinal mucosal barrier via a PI3K/Akt dependent mechanism. MiR-126 silencing possessed obvious protective effects on the intestinal barrier function, but these effects could be reversed by JTE-013 or LY294002.

Conclusion

MiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.
ChromVAR: Inferring transcription factor variation from single-cell epigenomic data
Authors: Schep Alicia N. , Wu Beijing , Buenrostro Jason D. , Greenleaf William J.
Published: February 2017

Single cell ATAC-seq (scATAC) yields sparse data that makes application of conventional computational approaches for data analysis challenging or impossible. We developed chromVAR, an R package for analyzing sparse chromatin accessibility data by estimating the gain or loss of accessibility within sets of peaks sharing the same motif or annotation while controlling for known technical biases. chromVAR enables accurate clustering of scATAC-seq profiles and enables characterization of known, or thede novoidentification of novel, sequence motifs associated with variation in chromatin accessibility across single cells or other sparse epigenomic data sets.
Sweep Dynamics (SD) plots: Computational identification of selective sweeps to monitor the adaptation of influenza A viruses
Authors: Klingen Thorsten R. , Reimering Susanne , Loers Jens , Mooren Kyra , Klawonn Frank , Krey Thomas , Gabriel Gülsah , McHardy Alice C.
Published: February 2017

Monitoring changes in influenza A virus genomes is crucial to understand its rapid evolution and adaptation to changing conditions e.g. establishment within novel host species. Selective sweeps represent a rapid mode of adaptation and are typically observed in human influenza A viruses. We describe Sweep Dynamics (SD) plots, a computational method combining phylogenetic algorithms with statistical techniques to characterize the molecular adaptation of rapidly evolving viruses from longitudinal sequence data. To our knowledge, it is the first method that identifies selective sweeps, the time periods in which these occurred and associated changes providing a selective advantage to the virus. We studied the past genome-wide adaptation of the 2009 pandemic H1N1 influenza A (pH1N1) and seasonal H3N2 influenza A (sH3N2) viruses. The pH1N1 influenza virus showed simultaneous amino acid changes in various proteins, particularly in seasons of high pH1N1 activity. Partially, these changes resulted in functional alterations facilitating sustained human-to-human transmission. In the evolution of sH3N2 influenza viruses, we detected changes characterizing vaccine strains, which were occasionally revealed in selective sweeps one season prior to the WHO recommendation. Taken together, SD plots allow monitoring and characterizing the adaptive evolution of influenza A viruses by identifying selective sweeps and their associated signatures.
Reversed graph embedding resolves complex single-cell developmental trajectories
Authors: Qiu Xiaojie , Mao Qi , Tang Ying , Wang Li , Chawla Raghav , Pliner Hannah , Trapnell Cole
Published: February 2017

Organizing single cells along a developmental trajectory has emerged as a powerful tool for understanding how gene regulation governs cell fate decisions. However, learning the structure of complex single-cell trajectories with two or more branches remains a challenging computational problem. We present Monocle 2, which uses reversed graph embedding to reconstruct single-cell trajectories in a fully unsupervised manner. Monocle 2 learns an explicit principal graph to describe the data, greatly improving the robustness and accuracy of its trajectories compared to other algorithms. Monocle 2 uncovered a new, alternative cell fate in what we previously reported to be a linear trajectory for differentiating myoblasts. We also reconstruct branched trajectories for two studies of blood development, and show that loss of function mutations in key lineage transcription factors diverts cells to alternative branches on the a trajectory. Monocle 2 is thus a powerful tool for analyzing cell fate decisions with single-cell genomics.
COPII-coated membranes function as transport carriers of intracellular procollagen-1
Authors: Gorur Amita , Yuan Lin , Kenny Samuel J , Baba Satoshi , Xu Ke , Schekman Randy
Published: February 2017

The coat protein complex II (COPII) is essential for the secretion of large cargo, such as the 300 nm precursor fibrils of procollagen I (PC1). Previous work has shown that the CUL3-KLHL12 complex increases the size of COPII vesicles to over 300 nm in diameter and accelerates the secretion of PC1; however, the role of large COPII vesicles as PC1 transport carriers was not unambiguously demonstrated. In this study, using stochastic optical reconstruction microscopy (STORM), correlated light electron microscopy (CLEM), and live cell imaging we report the existence of mobile COPII-coated vesicles that completely encapsulate the cargo PC1 and are physically separated from ER. We have also developed a cell-free COPII vesicle budding reaction that reconstitutes the capture of PC1 into large COPII vesicles. This process requires COPII proteins and the GTPase activity of the COPII subunit SAR1. We conclude fromin vivoandin vitroevidence that large COPII vesicles arebona fidecarriers of PC1.

COPII may play a direct or indirect role in the traffic of large protein complexes such as procollagen. Using high resolution imaging techniques in intact cells and in vitro reconstituted vesicles, Gorur et al. show that COPII coated vesicles carry procollagen1.
Soil classification predicts differences in prokaryotic communities across a range of geographically distant soils once pH is accounted for
Authors: Kaminsky Rachel , Trouche Blandine , Morales Sergio E.
Published: February 2017

Agricultural land is typically managed based on visible plant life at the expense of the belowground majority. However, microorganisms mediate processes sustaining plant life and the soil environment. To understand the role of microbes we first must understand what controls soil microbial community assembly. We assessed the distribution and composition of prokaryotic communities from soils representing four geographic regions on the South Island of New Zealand. These soils are under three different uses (dairy, sheep and beef, and high country farming) and are representative of major soil classification groups (brown, pallic, gley and recent). We hypothesized that pH would account for major community patterns based on 16S profiles, but that land use and location would be secondary modifiers. Community diversity and structure was linked to pH, coinciding with land use. Soil classification correlated with microbial community structure and evenness, but not richness in high country and sheep and beef communities. The impact of land use and pH remained significant at the regional scale, but soil classification provided support for community variability not explained by either of those factors. These results suggest that several edaphic properties must be examined at multiple spatial scales to robustly examine soil prokaryotic communities.
The role of audit quality and culture influence on earnings management in companies with excessive free cash flow
Authors: Astami Emita W. , Rusmin Rusmin , Hartadi Bambang , Evans John
Published: February 2017

Purpose

The purpose of this paper is to examine the effect of culture and audit quality on managers’ decisions regarding accounting accruals. It focuses on companies experiencing excessive free cash flow, as these companies have been associated with an agency problem.

Design/methodology/approach

This study measures the magnitude of discretionary accruals as a proxy for earnings management using the cross-sectional modified Jones model. Excessive free cash flow is scrutinized by the method used by Chung et al. (2005). Listed companies in nine countries in the Asia-Pacific region are represented in this study. The statistical analyses are used to examine the influence of cultural aspect, the role of external monitoring by high-quality auditors and the earnings management practice in the companies with excessive free-cash-flow.

Findings

The empirical results presented in this paper provide support for the proposition that managers of companies with excessive free-cash-flow will make investment decisions that are not always in the best interest of the shareholders and use accounting discretion to increase reported earnings. This study provides empirical evidence that these companies have been associated with an agency problem and the role of external auditor persists in a setting, where cultural differences prevail in across countries.

Practical implications

In cross-border trade and investment, the findings provide the opportunity to exploit a setting, where cultural differences prevail, whereas other potentially influential variables, including the role of external monitoring by high-quality auditors, are relatively constant across countries.

Originality/value

Previous studies (Leuz et al., 2003; and Enomoto et al., 2015) examine factors influencing earnings management internationally have concentrated on legal institutions and investor protection. Han et al. (2010) completed a cross-country study on the effects of national culture on earnings management. This study focuses on companies across countries experiencing with excessive free cash flow and examines the cultural aspect and the effectiveness of external monitoring by high-quality auditors operating in different countries in mitigating managerial opportunism.