bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging challenges in understanding trypanosome antigenic variation
Authors: McCulloch Richard , Cobbold Christina A. , Figueiredo Luisa , Jackson Andrew , Morrison Liam J. , Mugnier Monica R. , Papavasiliou Nina , Schnaufer Achim , Matthews Keith
Published: December 2017

Many pathogens evade host immunity by periodically changing the proteins they express on their surface — a phenomenon termed antigenic variation. An extreme form of antigenic variation, based around switching the composition of a variant surface glycoprotein (VSG) coat, is exhibited by the African trypanosome Trypanosoma brucei, which causes human disease. The molecular details of VSG switching in T. brucei have been extensively studied over the last three decades, revealing in increasing detail the machinery and mechanisms by which VSG expression is controlled and altered. However, several key components of the models of T. brucei antigenic variation that have emerged have been challenged through recent discoveries. These discoveries include new appreciation of the importance of gene mosaics in generating huge levels of new VSG variants, the contributions of parasite development and body compartmentation in the host to the infection dynamics and, finally, potential differences in the strategies of antigenic variation and host infection used by the crucial livestock trypanosomes T. congolense and T. vivax. This review will discuss all these observations, which raise questions regarding how secure the existing models of trypanosome antigenic variation are. In addition, we will discuss the importance of continued mathematical modelling to understand the purpose of this widespread immune survival process.
Chronic Chagas cardiomyopathy: a therapeutic challenge and future strategies
Authors: Maya Juan D. , Lapier Michel , Castillo Christian , Kemmerling Ulrike , Campos-Estrada Carolina , López-Muñoz Rodrigo
Published: December 2017

Infectious diseases are the main cause of acquired dilated cardiomyopathy. This group of disorders shares in common inflammatory cell infiltrate and myocardial remodeling. As part of its pathophysiology, there is coronary microvascular dysfunction, distinct from that observed in coronary artery disease. Chagas cardiomyopathy presents several vascular characteristics that are similar to those presented in other acquired cardiomyopathies. There is convincing evidence of the microvascular involvement and the inflammatory processes that lead to endothelial activation and ischemic damage. Current therapy for the Chagas disease is limited, and it is proposed to combine it with other pharmacological strategies that modify critical physiopathological aspects beneficial for the clinical course of the Chagas cardiomyopathy.
The immune response against Trypanosoma cruzi in the human placenta
Authors: Kemmerling Ulrike , Castillo Christian , Liempi Ana , Medina Lisvaneth , Carrillo Ileana , Droguett Daniel , Maya Juan D. , Galanti Norbel
Published: December 2017

Congenital Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is partially responsible for the increasing globalization of Chagas disease despite its low transmission. During congenital transmission, the parasite reaches the fetus by crossing the placental barrier. However, the success or impairment of congenital transmission of the parasite is the product of a complex interaction between the parasite, the maternal and fetus/newborn immune responses and placental factors. There is other evidence apart from the low congenital transmission rates, which suggests the presence of defense mechanisms against T. cruzi. Thus, the typical amastigote nests (intracellular parasites) cannot be observed in placentas from mothers with chronic Chagas disease nor in human placental chorionic villi explants infected in vitro with the parasite. In the latter, only a few parasite antigens and DNA are identified. Accordingly, other infections of the placenta are not commonly observed. All these evidences suggest that the placenta can mount defense mechanisms against T. cruzi.
Effect of core cooling on the radius of sub-Neptune planets
Authors: Vazan A. , Ormel C. W. , Dominik C.
Published: December 2017

Sub-Neptune planets are very common in our Galaxy and show a large diversity in their mass-radius relation. In sub-Neptunes most of the planet mass is in the rocky part (hereafter, core), which is surrounded by a modest hydrogen-helium envelope. As a result, the total initial heat content of such a planet is dominated by that of the core. Nonetheless, most studies contend that the core cooling only has a minor effect on the radius evolution of the gaseous envelope because the cooling of the core is in sync with the envelope; that is most of the initial heat is released early on timescales of ~10–100 Myr. In this Letter we examined the importance of the core cooling rate for the thermal evolution of the envelope. Thus, we relaxed the early core cooling assumption and present a model in which the core is characterized by two parameters: the initial temperature and the cooling time. We find that core cooling can significantly enhance the radius of the planet when it operates on a timescale similar to the observed age, i.e. ~Gyr. Consequently, the interpretation of the mass-radius observations of sub-Neptunes depends on the assumed core thermal properties and the uncertainty therein. The degeneracy of composition and core thermal properties can be reduced by obtaining better estimates of the planet ages (in addition to their radii and masses) as envisioned by future observations.
Branche in Zahlen
Authors: Mewis Dirk
Published: December 2017

Dieser Artikel ist nur als PDF-Dokument verfügbar.
Krankenhaushygiene - Antibiotic Stewardship
Authors: Walger Peter
Published: December 2017

Hygienemaßnahmen sind wichtig, richtig und unbedingt notwendig. Aber sie sind nur eine Seite der Medaille, um Infektionen zu verhindern. Die andere Seite ist die optimale Therapie von Infektionen. Unter dem Strategiebegriff „Antibiotic Stewardship“ (ABS) gibt es inzwischen zahlreiche Leitlinien und Empfehlungen für einen sinnvollen Antibiotikagebrauch. Eine Klinik ist gut beraten, in ABS zu investieren, denn die positiven Effekte auf das klinische und ökonomische Outcome sind nicht von der Hand zu weisen.
Gesundheitstelematik - Zu viel gewollt
Authors: Schmücker Paul
Published: December 2017

Der Weg zu einer Elektronischen Gesundheitskarte ist steinig und unerfreulich. Seit mittlerweile 14 Jahren wird in Deutschland darum gerungen – mit bislang überschaubarem Ergebnis. Warum gelingt hier nicht, was in Österreich längst funktioniert? Und wie soll es weitergehen? Eine Bestandsaufnahme.
Sleep Disorders in Pregnancy
Authors: Bazalakova Mihaela
Published: December 2017

Sleep and pregnancy are dynamic processes with unique and evolving physiological substrates. Given the “restorative hypothesis” of sleep as an anabolic process essential for cellular and tissue regeneration, the largely unexplored role of sleep in gestational physiology and pregnancy outcomes promises to be a fascinating topic. Emerging literature suggests that objectively measured or self-reported short sleep duration may be a risk for adverse pregnancy outcomes, including gestational diabetes mellitus (GDM), gestational hypertension, and cesarean delivery. In this review, we discuss obstructive sleep apnea (OSA) and restless legs syndrome (RLS), two sleep disorders prevalent in pregnancy. OSA is especially likely in high-risk pregnancy where it is associated with comorbid cardiovascular and metabolic disturbances. We review new data strongly suggesting that OSA is an independent risk factor for GDM and gestational hypertension. It remains to be seen if sleep disruption, whether or not in the context of gestational RLS and gestational OSA, is a modifiable factor for adverse pregnancy outcomes. Clinicians are encouraged to query sleep symptoms in pregnant women and to have a low threshold to pursue investigations for OSA, including the subjective symptoms of snoring, witnessed apneas, and daytime sleepiness, and also medical comorbidities, such as chronic hypertension.
Neuroimaging in Pregnant Women
Authors: Chansakul Thanissara , Young Geoffrey
Published: December 2017

Choosing the most appropriate diagnostic neuroimaging study for a pregnant woman involves assessing the pretest likelihood of serious treatable neurologic disease, the diagnostic utility of various available computed tomography (CT) and magnetic resonance (MR) modalities, and the risks of each. Of these three elements—pretest differential diagnosis, utility of MRI and CT, and risks of MR and CT—the risk component is perhaps the least well understood by most physicians. We provide a basic review of the intrinsic risks of MRI and CT, particularly radiation biology and radiation safety, as well as the risks pertaining to the use of contrast agents, to reduce provider confusion and anxiety and improve quality, safety, and efficiency of neuroimaging diagnosis in pregnant patients. We believe that a better understanding of the associated very low risks with mother and fetus will reassure the reader that CT remains the most appropriate tool for initial rapid diagnosis of acute neurological conditions in pregnancy and that in urgent situations CT should not be withheld or delayed due to exaggerated concern about radiation. Noncontrast MRI, while not without risk, is generally considered safe in pregnancy, as no evidence of fetal adverse effects has been demonstrated to date. Iodinated CT contrast agents are likely safer than gadolinium-based MRI contrast agents because of gadolinium accumulation in the amniotic fluid and fetal tissue, although no harmful effects of tissue gadolinium accumulation are known. In most but not all pregnant patients presenting with a new or worsening neurological abnormality, the risks intrinsic to the disease will outweigh the risks of imaging. In an individual patient, the pretest probability of serious treatable disease and acuity of presentation will usually suggest an optimal imaging strategy and choice of test. This optimal strategy will also depend on the immediate availability and level of sophistication of the scanners, software, technologists, and radiologists. As such, the standard of care for imaging in pregnancy requires direct consultation between the referring clinician and radiologist to determine the most appropriate strategy and brief documentation of the resulting consensus risk–benefit assessment.
Spinal Cord Injuries – When Is the Initial Tomography Insufficient?
Authors: Rodrigues Pedro Augusto Sousa , Ghizoni Enrico , Tedeschi Helder , Joaquim Andrei Fernandes
Published: December 2017

Introduction Spinal cord injury (SCI) is common in polytrauma patients. The standard exam for the initial evaluation is computed tomography (CT), due to its higher sensitivity and specificity when compared with plain radiographs. However, CT is insufficient for the management of some cases, especially to evaluate ligamentous and spinal cord injuries. The objective of the present study is to describe clinical scenarios in which the CT scan was insufficient to guide the treatment of SCIs.

Methods We present the cases of four polytrauma patients with normal CT scans at admission and with unstable or surgically-treated lesions.

Discussion The cases reported evidence the need for ongoing neurological surveillance with serial physical examination and magnetic resonance imaging (MRI) in cases of neurological injury not explained by CT or occult instability.

Conclusion Computed tomography is not always sufficient to determine the management of SCIs. A comprehensive evaluation of the clinical data, CT findings and, occasionally, MRI findings is crucial in order to choose the best conduct.
Liver Sinusoidal Endothelial Cell: An Update
Authors: Maretti-Mira Ana , DeLeve Laurie
Published: December 2017

This update focuses on two main topics. First, recent developments in our understanding of liver sinusoidal endothelial cell (LSEC) function will be reviewed, specifically elimination of blood-borne waste, immunological function of LSECs, interaction of LSECs with liver metastases, LSECs and liver regeneration, and LSECs and hepatic fibrosis. Second, given the current emphasis on rigor and transparency in biomedical research, the update discusses the need for standardization of methods to demonstrate identity and purity of isolated LSECs, pitfalls in methods that might lead to a selection bias in the types of LSECs isolated, and questions about long-term culture of LSECs. Various surface markers used for immunomagnetic selection are reviewed.
Konservative Therapiemöglichkeiten der weiblichen Inkontinenz
Authors: Kretschmer Alexander , Bauer Ricarda
Published: December 2017

In der vorliegenden Übersichtsarbeit werden aktuelle konservative Therapiemöglichkeiten der weiblichen Harninkontinenz analysiert. Hierbei wird zwischen Belastungsharninkontinenz, Dranginkontinenz und Mischformen unterschieden und der Wert einer rationalen Diagnostik zur besseren Unterscheidungsmöglichkeit zwischen den Unterformen dargelegt. Hinsichtlich der konservativen Therapie wird ein besonderer Fokus auf Lebensstiländerungen, Blasentraining, Beckenbodentherapie und medikamentöse Therapieformen gelegt und werden aktuelle Studienergebnisse diskutiert. Zusätzlich werden aktuelle Expertenempfehlungen zu den einzelnen Therapieoptionen dargestellt, um eine Inklusion der aktuellen Evidenz in den Klinikalltag zu erleichtern.
Klinische Klassifikation von Gesichtsschmerzen: Implementierung der Evidenz in die klinische Praxis
Authors: von Piekartz Harry , Janfrüchte Lukas
Published: December 2017

Orofaziale Schmerzen sind aufgrund ihrer Komplexität schwierig zu diagnostizieren. Die Autoren bieten einen Überblick über die
Pathophysiologie und die beitragenden Faktoren der orofazialen Schmerzen inklusiver einer Klassifikation, die Physio- und Manualtherapeuten
in der Praxis unterstützt – Handwerkszeug, um Patienten mit Gesichtsschmerzen adäquat zu untersuchen und zu therapieren.
Atropin zur Prävention der Myopieprogression – Datenlage, Nebenwirkungen, praktische Empfehlungen
Authors: Schittkowski Michael , Sturm Veit
Published: December 2017

Die Prävalenz der Myopie hat in den letzten Jahrzehnten weltweit zugenommen. In den südostasiatischen Metropolen werden Raten von ≥ 80% bei jungen Erwachsenen erreicht. Diese teilweise dramatische Zunahme ist vor allem den veränderten Lebensgewohnheiten geschuldet. Seit mehr als 100 Jahren weiß man um die hemmende Wirkung des Atropins auf die Myopieprogression. Obgleich der genaue Wirkungsmechanismus noch unbekannt ist, wurde in der letzten Dekade doch eine evidenzbasierte Behandlungsstrategie entwickelt. Atropintropfen können die Myopieprogression bei asiatischen Kindern im Mittel um − 0,54 Dioptrien (dpt)/Jahr und bei kaukasischen Kindern um − 0,35 dpt/Jahr mildern. Zu beachten ist jedoch eine Nichtansprechrate von ca. 10%. Die Behandlung sollte nur bei Schulkindern (Alter ≥ 6 Jahre) mit einer nachgewiesenen Progressionsrate von − 0,5 dpt im Vorjahr begonnen werden. Die zykloplegisch ermittelte Ausgangsrefraktion sollte zumindest − 2 dpt (sphärisches Äquivalent) betragen. Empfohlen wird die Applikation 0,01%iger Tropfen 1× am Abend vor dem Schlafengehen in den Bindehautsack. Die Therapie mit 0,01% gilt als gut verträglich und nebenwirkungsarm. Die Behandlung wird zunächst über 2 Jahre durchgeführt, da zum Teil im 2. Jahr eine bessere Effektivität erzielt wurde. Ein halbjährliches Kontrollintervall während der Behandlung mit jeweiliger Bestimmung der Refraktion in Zykloplegie und Messung der Achsenlänge wird empfohlen. Anschließend kann ein Auslassversuch erfolgen, wenn die Progression unter − 0,25 dpt/Jahr im 2. Jahr gefallen ist. Auch nach Therapieende sind weitere Kontrollen angezeigt, wobei eine erneute Behandlung bei einem neuerlichen Ansteigen der Progression über − 0,5 dpt/Jahr anzuraten ist. Ferner ist zu beachten, dass die Behandlung mit Atropinaugentropfen eine Off-Label-Anwendung darstellt.
Excitation of the three principal spin waves in yttrium iron garnet using a wavelength-specific multi-element antenna
Authors: Bang Wonbae , Jungfleisch Matthias B. , Lim Jinho , Trossman Jonathan , Tsai C. C. , Hoffmann Axel , Ketterson John B.
Published: December 2017

We report systematic measurements of the dispersion of long wavelength spin waves for the magnetic field along the three principal directions (supporting the forward volume, backward volume and Damon-Eshbach modes) of a 3.05 μm thick yttrium iron garnet film on a lattice-matched (111) gadolinium gallium garnet substrate obtained using a lithographically patterned, multi-element, 50 μm spatially-resonant, antenna.
Dislocations penetrating an Al/Si interface
Authors: Zhang Zhibo , Urbassek Herbert M.
Published: December 2017

We study indentation of a nanolayered material consisting of a Si top layer above an Al substrate, using molecular dynamics simulation. We focus on the activity of Si dislocations upon reaching the interface. We find that passage of the dislocations through the interface is possible, if the slip systems of the two crystals are aligned. Upon absorption at the interface, the Si dislocations generate slip which leads to 1-monolayer deep interface pits with well-defined steps; on the Al side dislocations and stacking fault planes are generated, which are pinned to the interface pit. For interfaces with not well aligned slip systems, the passage of dislocations is strongly suppressed. However, still interface pits, albeit with less well defined contours, and stacking fault planes aligned with the interface are created.
Color printing enabled by phase change materials on paper substrate
Authors: Ji Hong-Kai , Tong Hao , Qian Hang , Liu Nian , Xu Ming , Miao Xiang-Shui
Published: December 2017

We have coated phase change materials (PCMs) on rough and flexible substrates to achieve multicolor changeable devices. The principle of the device is based on an earlier discovery that lights have strong interference effect in PCM films, leading to various colors by reflection. In this work, paper substrates are laminated by parylene layers to protect the device from water before coated with functional PCM films. The PCM-based color printing (PCP) on paper is not affected by rough surfaces and shows a similar color appearance as that on smooth surfaces. In particular, the color-printed device can be patterned by UV lithography to display a clear and tunable optical image, and it exhibits a low sensitivity to the angle of view. Such PCP has potential applications for low-cost, disposable, and flexible displays.
Impact of hemlock woolly adelgid (Adelges tsugae) infestation on xylem structure and function and leaf physiology in eastern hemlock (Tsuga canadensis)
Authors: Huggett Brett A. , Savage Jessica A. , Hao Guang-You , Preisser Evan L. , Holbrook N. Michele
Published: December 2017

Hemlock woolly adelgid (Adelges tsugae Annand) (HWA) is an invasive insect that feeds upon the foliage of eastern hemlock (Tsuga canadensis (L.) Carrière) trees, leading to a decline in health and often mortality. The exact mechanism leading to the demise of eastern hemlocks remains uncertain because little is known about how HWA infestation directly alters the host’s physiology. To evaluate the physiological responses of eastern hemlock during early infestation of HWA, we measured needle loss, xylem hydraulic conductivity, vulnerability to cavitation, tracheid anatomy, leaf-level gas exchange, leaf water potential and foliar cation and nutrient levels on HWA-infested and noninfested even-aged trees in an experimental garden. HWA infestation resulted in higher xylem hydraulic conductivity correlated with an increase in average tracheid lumen area and no difference in vulnerability to cavitation, indicating that needle loss associated with HWA infestation could not be attributed to reduced xylem transport capacity. HWA-infested trees exhibited higher rates of net photosynthesis and significant changes in foliar nutrient partitioning, but showed no differences in branch increment growth rates compared with noninfested trees. This study suggests that HWA-induced decline in the health of eastern hemlock trees is not initially caused by compromised water relations or needle loss.
Instrument constituencies and epistemic community theory
Authors: Zito Anthony R
Published: December 2017

This contribution fleshes out the insights that the epistemic community (EC) approach can make to studying the public policy process and to how policy instruments are formulated and implemented. This contribution places the EC concept in the context of how policy instruments evolve and are supported by a separate network type, the instrument constituency (IC). It studies the conceptual differences between the EC and IC, analyses the conceptual progress and research output of the EC literature, and then reviews the EC literature to develop new analytical propositions about how epistemic communities, in relation to instrument constituencies, shape instrument change. This contribution then explores the value of these network concepts and propositions by examining four United States federal environmental policy instruments. It concludes that there is strong evidence for the role of ICs, and to a lesser extent, ECs, and that such public policy analysis would benefit from a greater network conceptualization.
DiffGraph: an R package for identifying gene network rewiring using differential graphical models
Authors: Zhang Xiao-Fei , Ou-Yang Le , Yang Shuo , Hu Xiaohua , Yan Hong
Published: December 2017

We develop DiffGraph, an R package that integrates four influential differential graphical models for identifying gene network rewiring under two different conditions from gene expression data. The input and output of different models are packaged in the same format, making it convenient for users to compare different models using a wide range of datasets and carry out follow-up analysis. Furthermore, the inferred differential networks can be visualized both non-interactively and interactively. The package is useful for identifying gene network rewiring from input datasets, comparing the predictions of different methods and visualizing the results.

Availability and implementation

The package is available at https://github.com/Zhangxf-ccnu/DiffGraph.

Supplementary information

Supplementary data are available at Bioinformatics online.
Quality Assurance and Program Development
Authors: Sanders Matthew R. , Kirby James N.
Published: December 2017

Interventions need to remain relevant, appropriate, and effective for the populations they aim to target. This chapter focuses on describing a quality assurance process that can be used by program developers to facilitate program innovation through a 10-stage research-and-development cycle. Using the Triple P system as the exemplar, we illustrate how the model can be applied continuously from initial program development, program adaptation, to global international dissemination to ensure the program is ready for dissemination and will benefit as many families as possible. The intervention development framework presented outlines important considerations and lessons learned in the development cycle of interventions. The framework aims to ensure that the quality assurance and quality control of interventions remains high so that interventions can be as successful as possible.
Sentence mood
Authors: Portner Paul
Published: December 2017

Sentence mood is the linguistic category which marks the fundamental conversational function, or “sentential force,” of a sentence. Exemplified by the universal types of declarative, interrogative, and imperative sentences (as well as by less-common types), sentence mood has been a major topic of research in both linguistics and philosophy. This chapter identifies the two main theories which address the topic, one based on speech act theory and the other on dynamic approaches to meaning. It explains and evaluates current research which uses the two theories, and identifies the most important insights which come out of each.
The Cultural Origins of the Anglican Church in Kenya
Authors: Karanja John
Published: December 2017

Adopting a grassroots approach, this chapter argues that in its response to, and appropriation of, missionary teachings, the early Anglican Church in Kenya was heavily indebted to indigenous models and experiences for its impetus, dynamism, and direction. The author’s findings are compared with related studies elsewhere in Africa, especially in Uganda, to ask why the Anglican Church in Kenya was different, and to point to what was distinctly its own. The study focuses on central Kenya because it is inhabited by a relatively homogeneous people. It discusses three elements of central Kenya’s culture that shaped its response to Christianity: its pragmatic nature, its conflict resolution mechanism, and its desire to master and exercise power. The period of study starts with the arrival of the first missionary in 1900 and ends in 1932 with the young Church having overcome its first major crisis.
The East African Revival
Authors: Peterson Derek R.
Published: December 2017

The East African Revival was a Christian conversion movement that began in northern Rwanda and southern Uganda in the mid-1930s and spread throughout eastern Africa during the 1940s and 1950s. Learning from Bunyan’s Pilgrim’s Progress—which was foundational literature in Anglican mission stations—converts engaged in radical acts of self-editing. They disavowed kin relationships, disposed of their possessions, and confessed their sins without regard to propriety. Other Christians thought them a menace to the whole social order. This chapter studies the contentious process by which the Revival was domesticated. Through the reconfiguration of legal codes, by the operation of church discipline, heedless converts were, over time, made members of civil society. There was a great amount of disciplinary work that had to occur before the Revival could safely become a source of inspiration in the field of World Christianity.
Anglican Liturgical Developments in New Contexts
Authors: Weil Louis
Published: December 2017

The deep roots of Anglican liturgical prayer in English history and culture raise the question of whether that liturgical tradition can achieve authentic expression in other cultural contexts. The planting of that tradition through missionary expansion in the Anglo-Americas did not initially raise that question because of the indebtedness of both Canada and the United States to their English origins. Even as the Anglican tradition was planted in non-Anglo environments, local liturgical practice long continued in the use of the 1662 Book of Common Prayer or of the substantially similar Book of Common Prayer of the Episcopal Church. Only in the latter part of the twentieth century was Anglican liturgical evolution seriously affected by cultural diversity.
Anglicanism in Southern Africa during the Twentieth Century
Authors: Heaney Robert S.
Published: December 2017

Theological and ecclesiological consolidation between 1900 and 1948 created the conditions for apartheid. This led to a period between 1948 and 1989 that witnessed some Anglican complicity with apartheid but saw a Church largely in resistance against it, not least through black theology. The year 1990 ushered in a decade where the Church had to move from a posture of resistance to one of critical solidarity by providing vision for nation-building. Reconciliation, Africanization, and combating poverty were priorities for a Church serving a nation reborn. Much can be learned here as Anglicans continue to struggle with consolidating identity, resisting injustice, and building practices for life-giving Communion.
Tailor-made exopolysaccharides—CRISPR-Cas9 mediated genome editing in Paenibacillus polymyxa
Authors: Rütering Marius , Cress Brady F , Schilling Martin , Rühmann Broder , Koffas Mattheos A G , Sieber Volker , Schmid Jochen
Published: December 2017

Application of state-of-the-art genome editing tools like CRISPR-Cas9 drastically increase the number of undomesticated micro-organisms amenable to highly efficient and rapid genetic engineering. Adaptation of these tools to new bacterial families can open up entirely new possibilities for these organisms to accelerate as biotechnologically relevant microbial factories, also making new products economically competitive. Here, we report the implementation of a CRISPR-Cas9 based vector system in Paenibacillus polymyxa, enabling fast and reliable genome editing in this host. Homology directed repair allows for highly efficient deletions of single genes and large regions as well as insertions. We used the system to investigate the yet undescribed biosynthesis machinery for exopolysaccharide (EPS) production in P. polymyxa DSM 365, enabling assignment of putative roles to several genes involved in EPS biosynthesis. Using this simple gene deletion strategy, we generated EPS variants that differ from the wild-type polymer not only in terms of monomer composition, but also in terms of their rheological behavior. The developed CRISPR-Cas9 mediated engineering approach will significantly contribute to the understanding and utilization of socially and economically relevant Paenibacillus species and extend the polymer portfolio.
Choroidal Microvasculature Dropout is Not Associated With Myopia, But is Associated With Glaucoma
Authors: Shin Joong Won , Kwon Junki , Lee Jiyun , Kook Michael S.
Published: December 2017

Purpose:

To investigate the frequency of choroidal microvasculature dropout (CMvD) in healthy myopic eyes in comparison with that of myopic open-angle glaucoma (OAG) eyes and determine whether myopia is independently associated with CMvD.

Patients and Methods:

Choroidal layer microvasculature images were obtained using optical coherence tomography angiography in 89 myopic OAG patients and 89 age-matched and refractive error-matched healthy myopic eyes. CMvD was defined as a complete loss of the microvasculature network on the choroidal layer vessel density (VD) map. The frequency of CMvD was compared between myopic OAG and healthy myopic eyes. Hemispheric comparisons of various parameters were performed between CMvD-affected and CMvD-unaffected hemiretina. The association of myopia with the presence and angular circumference of CMvD was evaluated using logistic and linear regression analyses.

Results:

CMvD was identified in 40 eyes (47.6%) with myopic OAG, whereas no CMvD was found in healthy myopic eyes. Mean hemispheric visual field sensitivity (294.9±321.1 vs. 610.5±387.5, P=0.006), retinal nerve fiber layer thickness (68.9±11.5 vs. 82.5±20.6 μm, P=0.001), and circumpapillary VD (50.5%±7.3% vs. 53.9%±8.8%, P=0.048) were significantly worse in the CMvD-affected hemiretina than in the CMvD-unaffected hemiretina. The presence and angular circumference of CMvD was significantly associated with parameters (visual field mean deviation, retinal nerve fiber layer thickness, and circumpapillary VD; P<0.05) representing glaucoma severity rather than parameters (refractive error and axial length; P>0.05) representing myopic change.

Conclusions:

CMvD was observed only in glaucomatous eyes and associated with severity of glaucomatous damage in myopic OAG subjects. The angular circumference of CMvD was significantly related to glaucoma severity.
Online Depressive Symptom Self-Management: Comparing Program Outcomes for Adults With Multiple Sclerosis Versus Those With Other Chronic Diseases
Authors: Tietjen Kiira , Wilson Marian , Amiri Solmaz , Dietz Jeremy
Published: December 2017

Aims: The goals of the study were to evaluate participant engagement and effects of an Internet-based, self-directed program for depressive symptoms. We compared outcomes of adults with multiple sclerosis (MS) with those of adults with other chronic diseases. Methods: This was a secondary analysis of a randomized controlled pilot study. Data were explored for differences between people diagnosed with MS and those with other chronic disease diagnoses. Data were obtained from 47 participants who participated in the original parent study (11 had MS). Participants with at least a moderate preexisting depressive symptom burden on the Patient Health Questionnaire (PHQ) were randomly divided into either a control group or the 8-week “Think Clearly About Depression” online depression self-management program. Study tools were administered at baseline, week 4, and week 8 to evaluate whether the online program improved depressive symptom self-management. Analysis examined differences between participants with and without an MS diagnosis in the treatment and control groups. Results: Average baseline depressive symptom burdens were severe for those with MS and those without MS as measured by the PHQ. Number needed to treat analysis indicated that 1 in every 2 treatment group participants with MS found clinically significant reductions in depressive symptoms by week 8. All participants with MS completed all online program modules. When compared with those with other chronic diseases, participants with MS showed a trend toward greater improvements in the PHQ and health distress scores in addition to self-efficacy in exercising regularly, social/recreational activities, and controlling/managing depression at the end of 8 weeks. Conclusions: An online depressive symptom self-management program is acceptable to people with MS and may be helpful to address undertreated depressive symptoms. The number of participants limits available statistics and ability to generalize results.
The Relationship Between Pain Interference and Psychosocial Well-Being Among Veterans With Spinal Cord Injuries/Disorders
Authors: Etingen Bella , Miskevics Scott , LaVela Sherri L.
Published: December 2017

Objectives: The study objectives were to compare psychosocial well-being in individuals with spinal cord injuries/disorders (SCI/D) and above-mean (“high”) versus below-mean (“low”) pain interference, and to determine whether psychosocial well-being was negatively associated with pain interference. Methods: Data were collected via a cross-sectional survey mailed in late 2014 to early 2015 to a national sample of veterans with SCI/D who received prior-year Veterans Affairs healthcare and assessed demographics, injury-related factors, select health conditions, pain interference, and psychosocial well-being. Bivariate comparisons and multivariate linear regressions identified factors related to higher pain interference. Results: Approximately 79% of the sample (n = 813) reported high pain interference. Veterans with high (vs. low) pain interference reported worse perceptions of all included psychosocial well-being measures. Regression results indicated that higher pain interference was associated with higher grief/loss (β = 0.38, P < .0001) and negative psychosocial illness impact (β = 0.39, P < .0001), and lower positive affect (β = −0.39, P < .0001), resilience (β = −0.31, P < .0001), and life satisfaction (β = −0.39, P < .0001). Conclusions: The pain experience is independently associated with poor psychosocial well-being among individuals with SCI/D. Efforts to decrease perceptions of pain interference and improve factors associated with psychosocial well-being may symbiotically improve outcomes in SCI/D cohorts. Such efforts may focus on effective pain management programs aligned with patients’ treatment preferences.
Return to Sport After Short-Stem Total Hip Arthroplasty
Authors: Ortmaier Reinhold , Pichler Hannes , Hitzl Wolfgang , Emmanuel Katja , Mattiassich Georg , Plachel Fabian , Hochreiter Josef
Published: December 2017

Objectives:

Information about sport activity after short-stem total hip arthroplasty (THA) is scarce in the literature. We therefore aimed to evaluate the rate of return to sport after short-stem THA.

Methods:

We evaluated the sport pattern, rate of return to sport, activity level, extent of sport activity, and subjective rating and sense of well-being in 137 patients (137 hips) after short-stem THA. The minimum follow-up time was 18 months. All results were analyzed according to gender (male and female) and age (≤60, >60-≤70, and >70 years).

Results:

Ninety-two percent of all patients practiced sport before surgery, and 91% of the patients returned to sport. Most patients returned to sport within the first 6 months after surgery. There was a decline in the number of sport disciplines from preoperatively to postoperatively, which was from 2.9 to 2.6 (P = 0.025). High-impact activities decreased postoperatively, but most low-impact activities did not change significantly. Eighty percent of all patients were involved in recreational sports.

Conclusion:

In this study, we observed an excellent rate of return to sport after short-stem THA. Most patients returned to the same level of sport activity that they had before the onset of restricting symptoms, with the majority of patients having a great sense of well-being during and after sports, and almost no pain in the affected hip.
Hematoxylin and Eosin Counterstaining Protocol for Immunohistochemistry Interpretation and Diagnosis
Authors: Grosset Andrée-Anne , Loayza-Vega Kevin , Adam-Granger Éloïse , Birlea Mirela , Gilks Blake , Nguyen Bich , Soucy Geneviève , Tran-Thanh Danh , Albadine Roula , Trudel Dominique
Published: December 2017

Hematoxylin and eosin (H&E) staining is a well-established technique in histopathology. However, immunohistochemistry (IHC) interpretation is done exclusively with hematoxylin counterstaining. Our goal was to investigate the potential of H&E as counterstaining (H&E-IHC) to allow for visualization of a marker while confirming the diagnosis on the same slide. The quality of immunostaining and the fast-technical performance were the main criteria to select the final protocol. We stained multiple diagnostic tissues with class I IHC tests with different subcellular localization markers (anti-CK7, CK20, synaptophysin, CD20, HMB45, and Ki-67) and with double-staining on prostate tissues with anti-high molecular weight keratins/p63 (DAB detection) and p504s (alkaline phosphatase detection). To validate the efficacy of the counterstaining, we stained tissue microarrays from the Canadian Immunohistochemistry Quality Control (cIQc) with class II IHC tests (ER, PR, HER2, and p53 markers). Interobserver and intraobserver concordance was assessed by κ statistics. Excellent agreement of H&E-IHC interpretation was observed in comparison with standard IHC from our laboratory (κ, 0.87 to 1.00), and with the cIQc reference values (κ, 0.81 to 1.00). Interobserver and intraobserver agreement was excellent (κ, 0.89 to 1.00 and 0.87 to 1.00, respectively). We therefore show for the first time the potential of using H&E counterstaining for IHC interpretation. We recommend the H&E-IHC protocol to enhance diagnostic precision for the clinical workflow and research studies.
On the decidability of population size histories from finite allele frequency spectra
Authors: Baharian Soheil , Gravel Simon
Published: December 2017

Understanding the historical events that shaped current genomic diversity has applications in historical, biological, and medical research. However, the amount of historical information that can be inferred from genetic data is finite, which leads to an identifiability problem. For example, different historical processes can lead to identical distribution of allele frequencies. This identifiability issue casts a shadow of uncertainty over the results of any study which uses the frequency spectrum to infer past demography. It has been argued that imposing mild ‘reasonableness’ constraints on demographic histories can enable unique reconstruction, at least in an idealized setting where the length of the genome is nearly infinite. Here, we discuss this problem for finite sample size and genome length. Using the diffusion approximation, we obtain bounds on likelihood differences between similar demographic histories, and use them to construct pairs of very different reasonable histories that produce almost-identical frequency distributions. The finite-genome problem therefore remains poorly determined even among reasonable histories. Where fits to few-parameter models produce narrow parameter confidence intervals, large uncertainties lurk hidden by model assumption.
Phylofactorization: a graph-partitioning algorithm to identify phylogenetic scales of ecological data
Authors: Washburne Alex D. , Silverman Justin D. , Morton James T. , Becker Daniel J. , Crowley Daniel , Mukherjee Sayan , David Lawrence A. , Plowright Raina K.
Published: December 2017

The problem of pattern and scale is a central challenge in ecology. The problem of scale is central to community ecology, where functional ecological groups are aggregated and treated as a unit underlying an ecological pattern, such as aggregation of “nitrogen fixing trees” into a total abundance of a trait underlying ecosystem physiology. With the emergence of massive community ecological datasets, from microbiomes to breeding bird surveys, there is a need to objectively identify the scales of organization pertaining to well-defined patterns in community ecological data.

The phylogeny is a scaffold for identifying key phylogenetic scales associated with macroscopic patterns. Phylofactorization was developed to objectively identify phylogenetic scales underlying patterns in relative abundance data. However, many ecological data, such as presence-absences and counts, are not relative abundances, yet it is still desireable and informative to identify phylogenetic scales underlying a pattern of interest. Here, we generalize phylofactorization beyond relative abundances to a graph-partitioning algorithm for any community ecological data.

Generalizing phylofactorization connects many tools from data analysis to phylogenetically-informe analysis of community ecological data. Two-sample tests identify three phylogenetic factors of mammalian body mass which arose during the K-Pg extinction event, consistent with other analyses of mammalian body mass evolution. Projection of data onto coordinates defined by the phylogeny yield a phylogenetic principal components analysis which refines our understanding of the major sources of variation in the human gut microbiome. These same coordinates allow generalized additive modeling of microbes in Central Park soils and confirm that a large clade of Acidobacteria thrive in neutral soils. Generalized linear and additive modeling of exponential family random variables can be performed by phylogenetically-constrained reduced-rank regression or stepwise factor contrasts. We finish with a discussion of how phylofac-torization produces an ecological species concept with a phylogenetic constraint. All of these tools can be implemented with a new R package available online.
Insights into DNA substrate selection by APOBEC3G from structural, biochemical, and functional studies
Authors: Ziegler Samantha J. , Liu Chang , Landau Mark , Buzovetsky Olga , Desimmie Belete A. , Zhao Qi , Sasaki Tomoaki , Burdick Ryan C. , Pathak Vinay K. , Anderson Karen S. , Xiong Yong
Published: December 2017

Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 (A3) proteins are a family of cytidine deaminases that catalyze the conversion of cytidine to uridine in single-stranded DNA (ssDNA). A3 proteins act in the innate immune response to viral infection by mutating the viral ssDNA. One of the most well-studied human A3 family members is A3G, which is a potent inhibitor of HIV-1. Each A3 protein prefers a specific substrate sequence for catalysis - for example, A3G deaminates the third cytidine in the CCCA sequence motif. However, the interaction between A3G and ssDNA is difficult to characterize due to poor solution behavior of the full-length protein and loss of DNA affinity of the truncated protein. Here, we present a novel DNA-anchoring fusion strategy, which we have used to capture an A3G-ssDNA interaction. We characterized an A3G-DNA binding pocket that is important for the enzyme to scan the DNA for its hotspot. The results provide insights into the mechanism by which A3G selects and deaminates its preferred substrates and help define how A3 proteins are tailored to recognize specific DNA sequences. This knowledge contributes to a better understanding of the mechanism of DNA substrate selection by A3G, as well as A3G antiviral activity against HIV-1.
Identification of methylation and hydroxymethylation haplotype blocks as distal regulatory elements aids in deconvolution of heterogeneous brain tissues
Authors: Ma Qin , Xu Zhengzheng , Lu Huan , Xu Ziying , Zhou Yuanyuan , Yuan Bifeng , Ci Weimin
Published: December 2017

5-Hydroxymethylcytosine (5hmC) is an oxidation product of 5-methylcytosine (5mC), and adjacent CpG sites in the mammalian genome can be co-methylated and co-hydroxymethylated due to the processivity of DNMT and TET enzymes. We applied TAB-seq and oxBS-seq to selectively detect 5hmC and 5mC, respectively, at base resolution in the mouse cortex, olfactory bulb and cerebellum tissues. We found that majority of the called 5hmC CpG sites frequently had 5mC modification simultaneously and enriched in gene body regions of neuron development related genes in brain tissues. These results supported a prominent role of oxidizing 5mC to 5hmC as new epigenetic mark. Strikingly, by a systematic search of regions that show highly coordinated methylation and hydroxymethylation (MHBs and hMHBs), we found that MHBs significantly overlapped with hMHBs in gene body regions which further supported that oxidized 5mC to 5hmC co-ordinately in a subset of cells within heterogeneous brain tissues. Consistently, using a metric called methylation haplotype load, we defined a subset of 1,361 tissue-specific MHBs and 3,818 shared MHBs which were predominantly regulatory elements, and aids in deconvolution of heterogeneous brain tissues. Our results provide new insights into the role of co-ordinately oxidized 5mC to 5hmC as distal regulatory elements may involve in regulating tissue identity.
Long-read sequencing technology indicates genome-wide effects of non-B DNA on polymerization speed and error rate
Authors: Guiblet Wilfried M. , Cremona Marzia A. , Cechova Monika , Harris Robert S. , Kejnovska Iva , Kejnovsky Eduard , Eckert Kristin , Chiaromonte Francesca , Makova Kateryna D.
Published: December 2017

DNA conformation may deviate from the classical B-form in ~13% of the human genome. Non-B DNA regulates many cellular processes; however, its effects on DNA polymerization speed and accuracy have not been investigated genome-wide. Such an inquiry is critical for understanding neurological diseases and cancer genome instability. Here we present the first simultaneous examination of DNA polymerization kinetics and errors in the human genome sequenced with Single-Molecule-Real-Time technology. We show that polymerization speed differs between non-B and B-DNA: it decelerates at G-quadruplexes and fluctuates periodically at disease-causing tandem repeats. Analyzing polymerization kinetics profiles, we predict and validate experimentally non-B DNA formation for a novel motif. We demonstrate that several non-B motifs affect sequencing errors (e.g., G-quadruplexes increase error rates) and that sequencing errors are positively associated with polymerase slowdown. Finally, we show that highly divergent G4 motifs have pronounced polymerization slowdown and high sequencing error rates, suggesting similar mechanisms for sequencing errors and germline mutations.