bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventing painful age-related bone fractures
Authors: Thompson Michelle L , Chartier Stephane R , Mitchell Stefanie A , Mantyh Patrick W
Published: November 2016

Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient’s functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures.
Does modifying competition affect the frequency of technical skills in junior rugby league?
Authors: Morley David , Ogilvie Paul , Till Kevin , Rothwell Martyn , Cotton Wayne , O’Connor Donna , McKenna Jim
Published: November 2016

The technical demands of games can be affected by changing the number of players, pitch size and rules. This controlled trial compared the frequency of technical skills between a ‘traditional’ and newly introduced systematically ‘modified’ game of primary rugby league. A total of 475 primary rugby league players (Under 7s to 9s) were filmed playing traditional ( n = 49) and modified ( n = 249) formats. Notational analysis examined the frequency of technical skills (e.g. number of passes) within ‘traditional’ and ‘modified’ games. At each age category, multivariate analysis of variance indicated the clear superiority of the ‘modified’ game for the frequency of technical skills (e.g. Under 7s total skill opportunities – ‘traditional’ = 342.9 ± 47.0; ‘modified’ = 449.4 ± 93.3, d = 1.44, p < 0.001). Systematically modifying the competitive game is an effective way to increase skill opportunities for children within rugby league. Future research should examine the outcomes of modifying games in optimizing skill development in youth sport.
Validity and reliability of a 3-axis accelerometer for measuring weightlifting movements
Authors: Flores Francisco J , Sedano Silvia , de Benito Ana M , Redondo Juan C
Published: November 2016

The purpose of the current study was to assess the validity and reliability of measures obtained by a 3-axis commercial accelerometer during weightlifting movements in comparison with kinematic data derived from the 3D videography. Kinematic data from 3D videography were obtained from 11 track & field throwers performing 3 trials each one at different loads in power snatch, power clean and jerk from the rack. The results showed that the accelerometer measures were highly correlated with derived acceleration data from 3D videography data in the vertical plane (Z axis) taking up to the pull phase (including first pull, transition and second pull) for power snatch and power clean and up to the highest point of the bar path before the catch position (including dip, drive and split phases) for jerk from the rack. On the basis of these results, this device was proven to be valid and reliable on Z axis on the weightlifting movements studied. Thus, this system may be a useful and easy to handle tool to measure acceleration during real-time training sessions.
Social Media News Use and Political Discussion
Authors: Ji Qihao
Published: November 2016

Social media has been evidenced as a meaningful platform in terms of informing citizens and promoting democracy. The present research adds to the existing literature by examining various predictors of social media political discussion. Special attention was paid to social media news use, social media network, trust, as well as various control variables in a nondemocratic state, China. Results indicated a unique role of social media news dissemination in predicting social media political discussion. Moreover, news friending, the number of followers and followees, along with political interest predicted news dissemination. In addition, only the number of followees predicted news reception. Theoretical implications are discussed in detail.
Design of Hack-Resistant Diabetes Devices and Disclosure of Their Cyber Safety
Authors: Sackner-Bernstein Jonathan
Published: November 2016

Background:

The focus of the medical device industry and regulatory bodies on cyber security parallels that in other industries, primarily on risk assessment and user education as well as the recognition and response to infiltration. However, transparency of the safety of marketed devices is lacking and developers are not embracing optimal design practices with new devices.

Achieving cyber safe diabetes devices:

To improve understanding of cyber safety by clinicians and patients, and inform decision making on use practices of medical devices requires disclosure by device manufacturers of the results of their cyber security testing. Furthermore, developers should immediately shift their design processes to deliver better cyber safety, exemplified by use of state of the art encryption, secure operating systems, and memory protections from malware.
Comparison of Locking Plate with Interfragmentary Screw Versus Plantarly Applied Anatomic Locking Plate for Lapidus Arthrodesis: A Biomechanical Cadaveric Study
Authors: Cottom James M. , Baker Joseph S.
Published: November 2016

Arthrodesis of the first metatarsal cuneiform joint, or Lapidus procedure, is a widely accepted treatment for hallux valgus. Recent studies have focused on comparing various constructs for this procedure both in the laboratory and clinical settings. The current study compared in a cadaveric model the strength of 2 constructs. The first construct utilized a medially applied low-profile locking plate and an interfragmentary screw directed from plantar-distal to dorsal-proximal. The second construct consisted of a plantarly applied plate with a compression screw placed through the plate from plantar-distal to dorsal-proximal. The ultimate load to failure for the 2 groups tested was 255.38 ± 155.38 N and 197.48 ± 108.61 N, respectively (P = .402). There was no significant difference found between the 2 groups with respect to ultimate load to failure, stiffness of the construct, or moment at time of failure. In conclusion, the medially applied plate with plantar interfragmentary screw appears to be stronger than the plantar Lapidus plate tested for first metatarsal cuneiform arthrodesis, though this difference did not reach statistical significance.

Levels of Evidence: Level V: Biomechanical Study
Foot and Ankle Fellowship Websites: An Assessment of Accessibility and Quality
Authors: Hinds Richard M. , Danna Natalie R. , Capo John T. , Mroczek Kenneth J.
Published: November 2016

Background. The Internet has been reported to be the first informational resource for many fellowship applicants. The objective of this study was to assess the accessibility of orthopaedic foot and ankle fellowship websites and to evaluate the quality of information provided via program websites. Methods. The American Orthopaedic Foot and Ankle Society (AOFAS) and the Fellowship and Residency Electronic Interactive Database (FREIDA) fellowship databases were accessed to generate a comprehensive list of orthopaedic foot and ankle fellowship programs. The databases were reviewed for links to fellowship program websites and compared with program websites accessed from a Google search. Accessible fellowship websites were then analyzed for the quality of recruitment and educational content pertinent to fellowship applicants. Results. Forty-seven orthopaedic foot and ankle fellowship programs were identified. The AOFAS database featured direct links to 7 (15%) fellowship websites with the independent Google search yielding direct links to 29 (62%) websites. No direct website links were provided in the FREIDA database. Thirty-six accessible websites were analyzed for content. Program websites featured a mean 44% (range = 5% to 75%) of the total assessed content. The most commonly presented recruitment and educational content was a program description (94%) and description of fellow operative experience (83%), respectively. Conclusions. There is substantial variability in the accessibility and quality of orthopaedic foot and ankle fellowship websites. Clinical Relevance. Recognition of deficits in accessibility and content quality may assist foot and ankle fellowships in improving program information online.

Levels of Evidence: Level IV
Quantitative estimation of a ratio of intracranial cerebrospinal fluid volume to brain volume based on segmentation of CT images in patients with extra-axial hematoma
Authors: Nguyen Ha Son , Patel Mohit , Li Luyuan , Kurpad Shekar , Mueller Wade
Published: November 2016

Background

Diminishing volume of intracranial cerebrospinal fluid (CSF) in patients with space-occupying masses have been attributed to unfavorable outcome associated with reduction of cerebral perfusion pressure and subsequent brain ischemia.

Objective

The objective of this article is to employ a ratio of CSF volume to brain volume for longitudinal assessment of space-volume relationships in patients with extra-axial hematoma and to determine variability of the ratio among patients with different types and stages of hematoma.

Patients and methods

In our retrospective study, we reviewed 113 patients with surgical extra-axial hematomas. We included 28 patients (age 61.7 +/− 17.7 years; 19 males, nine females) with an acute epidural hematoma (EDH) ( n = 5) and subacute/chronic subdural hematoma (SDH) ( n = 23). We excluded 85 patients, in order, due to acute SDH ( n = 76), concurrent intraparenchymal pathology ( n = 6), and bilateral pathology ( n = 3). Noncontrast CT images of the head were obtained using a CT scanner (2004 GE LightSpeed VCT CT system, tube voltage 140 kVp, tube current 310 mA, 5 mm section thickness) preoperatively, postoperatively (3.8 ± 5.8 hours from surgery), and at follow-up clinic visit (48.2 ± 27.7 days after surgery). Each CT scan was loaded into an OsiriX (Pixmeo, Switzerland) workstation to segment pixels based on radiodensity properties measured in Hounsfield units (HU). Based on HU values from −30 to 100, brain, CSF spaces, vascular structures, hematoma, and/or postsurgical fluid were segregated from bony structures, and subsequently hematoma and/or postsurgical fluid were manually selected and removed from the images. The remaining images represented overall brain volume—containing only CSF spaces, vascular structures, and brain parenchyma. Thereafter, the ratio between the total number of voxels representing CSF volume (based on values between 0 and 15 HU) to the total number of voxels representing overall brain volume was calculated.

Results

CSF/brain volume ratio varied significantly during the course of the disease, being the lowest preoperatively, 0.051 ± 0.032; higher after surgical evacuation of hematoma, 0.067 ± 0.040; and highest at follow-up visit, 0.083 ± 0.040 ( p < 0.01). Using a repeated regression analysis, we found a significant association ( p < 0.01) of the ratio with age (odds ratio, 1.019; 95% CI, 1.009–1.029) and type of hematoma (odds ratio, 0.405; 95% CI, 0.303–0.540).

Conclusion

CSF/brain volume ratio calculated from CT images has potential to reflect dynamics of intracranial volume changes in patients with space-occupying mass.
Critical religion and critical research on religion: A response to the April 2016 editorial
Authors: Fitzgerald Timothy
Published: November 2016

This response takes up some of the editorial comments for further clarification and critique. My point has been that ‘politics’ is as much a modern invention as ‘religion’. We cannot understand the rhetorical function of ‘religion’ if we treat it as a stand-alone category referring to some supposed object or objects in the world. I am especially concerned here to keep in view the oscillating binary categories of which ‘religion' forms one parasitic half, and ‘politics' or ‘science' the other. This critical problematization of the liberal categories of the understanding opposes and challenges their current institutionalization in the liberal academy, where they now serve the Neoliberal agenda and the reproduction of the dominant, globalising imperatives of private property.
Where are you organizationally situated? Views from here
Authors: Cadge Wendy , Barton Becky
Published: November 2016

We reflect personally and historically on some of the institutions that have nurtured and shaped conversations at the intersections of sociology and religious studies, particularly professional associations. Our argument is simple. The ways different scholars understand the relationship between the sociology of religion and religious studies have a lot to do with the institutions that nurtured us and through which we engage in the conversation. We push back on simple black and white distinctions that paint their approaches in oppositions: more historical vs. more contemporary, more qualitative vs. more quantitative, more concerned with normative concerns vs. more “objective”—in favor of a more nuanced view. We keep in mind the Christian origins of the main professional organizations at these intersections and call for deeper dialogue not just between sociologists and scholars in religious studies but with colleagues involved with a range of other groups.
In defense of dualism: Competing and complementary frameworks in religious studies and the sociology of religion
Authors: Wood Richard L
Published: November 2016

The term “dualism” is used in quite divergent connotations across religious studies, sociology, theology, anthropology, and other academic fields. This paper characterizes the differing usages of the term, and uses them to explore the sometimes-converging and sometimes-orthogonal relationship between academic fields, with a focus on religious studies and the sociology of religion. I argue that although the two fields have mutually benefited from insights originating on either side of their divide—and thus converged in important ways—substantive differences remain. Their differing understandings of “dualism” represents important theoretical and analytic divergence, and the justified critique of certain forms of dualism has been used to reject all versions of the concept, including some—here termed “embodied dualism” or “experiential dualism”—that remain analytically crucial to the study of social life generally and religion particularly.
Pro Bono and Clinical Work in Law Schools: Summary and Analysis
Authors: Dignan Frank , Grimes Richard , Parker Rebecca
Published: November 2016

This article describes the results and implications of a survey carried completed in 2014 and looking at the nature and extent of pro bono and clinical work in UK law schools. The survey is one of an ongoing series conducted every 2–3 years on behalf of the influential NGO, LawWorks (The Solicitors Pro Bono Group). The findings of this, the most recent survey, shows clearly that more law schools than ever are engaged in pro bono and clinical initiatives – a trend that has been increasingly evident over the past 15 years. To date over 70% of UK-based law schools have clinics. Not only is it the rule rather than the exception to do so but the numbers and scope of clinics in law schools that participate have grown considerably. These developments were reported to an international conference in 2015 (GAJE, Turkey) and delegates there concluded that such a survey would have global appeal and that work should now be carried out with a view to implementing such an initiative. This would have the potential to encourage the growth of pro bono work and might influence policy beyond law schools amongst government and the legal profession – leading to improved levels of legal education and increased access to justice.
Perception of Sung Speech in Bimodal Cochlear Implant Users
Authors: Crew Joseph D. , Galvin John J. , Fu Qian-Jie
Published: November 2016

Combined use of a hearing aid (HA) and cochlear implant (CI) has been shown to improve CI users’ speech and music performance. However, different hearing devices, test stimuli, and listening tasks may interact and obscure bimodal benefits. In this study, speech and music perception were measured in bimodal listeners for CI-only, HA-only, and CI + HA conditions, using the Sung Speech Corpus, a database of monosyllabic words produced at different fundamental frequencies. Sentence recognition was measured using sung speech in which pitch was held constant or varied across words, as well as for spoken speech. Melodic contour identification (MCI) was measured using sung speech in which the words were held constant or varied across notes. Results showed that sentence recognition was poorer with sung speech relative to spoken, with little difference between sung speech with a constant or variable pitch; mean performance was better with CI-only relative to HA-only, and best with CI + HA. MCI performance was better with constant words versus variable words; mean performance was better with HA-only than with CI-only and was best with CI + HA. Relative to CI-only, a strong bimodal benefit was observed for speech and music perception. Relative to the better ear, bimodal benefits remained strong for sentence recognition but were marginal for MCI. While variations in pitch and timbre may negatively affect CI users’ speech and music perception, bimodal listening may partially compensate for these deficits.
How Do Psychiatrists Apply the Minimum Clinically Important Difference to Assess Patient Responses to Treatment?
Authors: McMichael Alan J. , Rolison Jonathan J. , Boeri Marco , Kane Joseph P. M. , O’Neill Francis A. , Kee Frank
Published: November 2016

Symptom report scales are used in clinical practice to monitor patient outcomes. Using them permits the definition of a minimum clinically important difference (MCID) beyond which a patient may be judged as having responded to treatment. Despite recommendations that clinicians routinely use MCIDs in clinical practice, statisticians disagree about how MCIDs should be used to evaluate individual patient outcomes and responses to treatment. To address this issue, we asked how clinicians actually use MCIDs to evaluate patient outcomes in response to treatment. Sixty-eight psychiatrists made judgments about whether hypothetical patients had responded to treatment based on their pre- and posttreatment change scores on the widely used Positive and Negative Syndrome Scale. Psychiatrists were provided with the scale’s MCID on which to base their judgments. Our secondary objective was to assess whether knowledge of the patient’s genotype influenced psychiatrists’ responder judgments. Thus, psychiatrists were also informed of whether patients possessed a genotype indicating hyperresponsiveness to treatment. While many psychiatrists appropriately used the MCID, others accepted a far lower posttreatment change as indicative of a response to treatment. When psychiatrists accepted a lower posttreatment change than the MCID, they were less confident in such judgments compared to when a patient’s posttreatment change exceeded the scale’s MCID. Psychiatrists were also less likely to identify patients as responders to treatment if they possessed a hyperresponsiveness genotype. Clinicians should recognize that when judging patient responses to treatment, they often tolerate lower response thresholds than warranted. At least some conflate their judgments with information, such as the patient’s genotype, that is irrelevant to a post hoc response-to-treatment assessment. Consequently, clinicians may be at risk of persisting with treatments that have failed to demonstrate patient benefits.
Metabolomic biomarkers predictive of early structural lung disease in cystic fibrosis
Authors: Esther Charles R. , Turkovic Lidija , Rosenow Tim , Muhlebach Marianne S. , Boucher Richard C. , Ranganathan Sarath , Stick Stephen M.
Published: November 2016

Neutrophilic airway inflammation plays a role in early structural lung disease in cystic fibrosis, but the mechanisms underlying this pathway are incompletely understood.

Metabolites associated with neutrophilic inflammation were identified by discovery metabolomics on bronchoalveolar lavage fluid supernatant from 20 preschool children (2.9±1.3 years) with cystic fibrosis. Targeted mass-spectrometric detection of relevant metabolites was then applied to 34 children (3.5±1.5 years) enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) who underwent chest computed tomography and bronchoalveolar lavage from two separate lobes during 42 visits. Relationships between metabolites and localised structural lung disease were assessed using multivariate analyses.

Discovery metabolomics identified 93 metabolites associated with neutrophilic inflammation, including pathways involved in metabolism of adenyl purines, amino acids and small peptides, cellular energy and lipids. In targeted mass spectrometry, products of adenosine metabolism, protein catabolism and oxidative stress were associated with structural lung disease and predicted future bronchiectasis, and activities of enzymes associated with adenosine metabolism were elevated in the samples with early disease.

Metabolomics analyses revealed metabolites and pathways altered with neutrophilic inflammation and destructive lung disease. These pathways can serve as biomarkers and potential therapeutic targets for early cystic fibrosis lung disease.
IFN-α/IFN-λ responses to respiratory viruses in paediatric asthma
Authors: Bergauer Annika , Sopel Nina , Kroß Bettina , Vuorinen Tytti , Xepapadaki Paraskevi , Weiss Scott T. , Blau Ashley , Sharma Himanshu , Kraus Cornelia , Springel Rebekka , Rauh Manfred , Mittler Susanne , Graser Anna , Zimmermann Theodor , Melichar Volker O. , Kiefer Alexander , Kowalski Marek L. , Sobanska Anna , Jartti Tuomas , Lukkarinen Heikki , Papadopoulos Nikolaos G. , Finotto Susetta
Published: November 2016

We analysed the influence of rhinovirus (RV) in nasopharyngeal fluid (NPF) on type I and III interferon (IFN) responses (e.g.IFN-α and IFN-λ) and their signal transduction, at baseline and during disease exacerbation, in cohorts of pre-school children with and without asthma.

At the time of recruitment into the Europe-wide study PreDicta, and during symptoms, NPF was collected and the local RV colonisation was analysed. Peripheral blood mononuclear cells (PBMCs) were challengedin vitrowith RV or not. RNA was analysed by quantitative real-time PCR and gene arrays. Serum was analysed with ELISA for IFNs and C-reactive protein.

We found that PBMCs from asthmatic children infectedin vitrowith the RV1b serotype upregulatedMYD88,IRF1,STAT1andSTAT2mRNA, whereasMYD88,IRF1,STAT1andIRF9were predominantly induced in control children. Moreover, during symptomatic visits because of disease exacerbation associated with RV detection in NPF, IFN-α production was found increased, while IFN-λ secretion was already induced by RV in asthmatic children at baseline.

During asthma exacerbations associated with RV, asthmatic children can induce IFN-α secretion, indicating a hyperactive immune response to repeated respiratory virus infection.
Correlates of tuberculosis risk: predictive biomarkers for progression to active tuberculosis
Authors: Petruccioli Elisa , Scriba Thomas J. , Petrone Linda , Hatherill Mark , Cirillo Daniela M. , Joosten Simone A. , Ottenhoff Tom H. , Denkinger Claudia M. , Goletti Delia
Published: November 2016

New approaches to control the spread of tuberculosis (TB) are needed, including tools to predict development of active TB from latent TB infection (LTBI). Recent studies have described potential correlates of risk, in order to inform the development of prognostic tests for TB disease progression. These efforts have included unbiased approaches employing “omics” technologies, as well as more directed, hypothesis-driven approaches assessing a small set or even individual selected markers as candidate correlates of TB risk. Unbiased high-throughput screening of blood RNAseq profiles identified signatures of active TB risk in individuals with LTBI, ≥1 year before diagnosis. A recent infant vaccination study identified enhanced expression of T-cell activation markers as a correlate of risk prior to developing TB; conversely, high levels of Ag85A antibodies and high frequencies of interferon (IFN)-γ specific T-cells were associated with reduced risk of disease. Others have described CD27−IFN-γ+CD4+T-cells as possibly predictive markers of TB disease. T-cell responses to TB latency antigens, including heparin-binding haemagglutinin and DosR-regulon-encoded antigens have also been correlated with protection.

Further studies are needed to determine whether correlates of risk can be used to prevent active TB through targeted prophylactic treatment, or to allow targeted enrolment into efficacy trials of new TB vaccines and therapeutic drugs.
Prevalence and characteristics ofTERTandTERCmutations in suspected genetic pulmonary fibrosis
Authors: Borie Raphael , Tabèze Laure , Thabut Gabriel , Nunes Hilario , Cottin Vincent , Marchand-Adam Sylvain , Prevot Grégoire , Tazi Abdellatif , Cadranel Jacques , Mal Herve , Wemeau-Stervinou Lidwine , Bergeron Lafaurie Anne , Israel-Biet Dominique , Picard Clement , Reynaud Gaubert Martine , Jouneau Stephane , Naccache Jean-Marc , Mankikian Julie , Ménard Christelle , Cordier Jean-François , Valeyre Dominique , Reocreux Marion , Grandchamp Bernard , Revy Patrick , Kannengiesser Caroline , Crestani Bruno
Published: November 2016

Telomerase reverse transcriptase (TERT) or telomerase RNA (TERC) gene mutation is a major monogenic cause of pulmonary fibrosis. Sequencing ofTERT/TERCgenes is proposed to patients with familial pulmonary fibrosis. Little is known about the possible predictors of this mutation and its impact on prognosis.

We retrospectively analysed all the genetic diagnoses made between 2007–2014 in patients with pulmonary fibrosis. We evaluated the prevalence ofTERT/TERCdisease-associated variant (DAV), factors associated with a DAV, and the impact of the DAV on survival.

237 patients with pulmonary fibrosis (153 with familial pulmonary fibrosis, 84 with telomere syndrome features without familial pulmonary fibrosis) were tested forTERT/TERCDAV. DAV was diagnosed in 40 patients (16.8%), including five with non-idiopathic interstitial pneumonia. Prevalence ofTERT/TERCDAV did not significantly differ between patients with familial pulmonary fibrosis or with only telomere syndrome features (18.2%versus16.4%). Young age, red blood cell macrocytosis, and low platelet count were associated with the presence of DAV; the probability of DAV was increased for patients 40–60 years. Transplant-free survival was lower with than withoutTERT/TERCDAV (4.2versus7.2 years; p=0.046).

TERT/TERCDAV were associated with specific clinical and biological features and reduced transplant-free survival.
Feature-based classification of human transcription factors into hypothetical sub-classes related to regulatory function
Authors: Ehsani Rezvan , Bahrami Shahram , Drabløs Finn
Published: November 2016

Background

Transcription factors are key proteins in the regulation of gene transcription. An important step in this process is the opening of chromatin in order to make genomic regions available for transcription. Data on DNase I hypersensitivity has previously been used to label a subset of transcription factors as Pioneers, Settlers and Migrants to describe their potential role in this process. These labels represent an interesting hypothesis on gene regulation and possibly a useful approach for data analysis, and therefore we wanted to expand the set of labeled transcription factors to include as many known factors as possible. We have used a well-annotated dataset of 1175 transcription factors as input to supervised machine learning methods, using the subset with previously assigned labels as training set. We then used the final classifier to label the additional transcription factors according to their potential role as Pioneers, Settlers and Migrants. The full set of labeled transcription factors was used to investigate associated properties and functions of each class, including an analysis of interaction data for transcription factors based on DNA co-binding and protein-protein interactions. We also used the assigned labels to analyze a previously published set of gene lists associated with a time course experiment on cell differentiation.

Results

The analysis showed that the classification of transcription factors with respect to their potential role in chromatin opening largely was determined by how they bind to DNA. Each subclass of transcription factors was enriched for properties that seemed to characterize the subclass relative to its role in gene regulation, with very general functions for Pioneers, whereas Migrants to a larger extent were associated with specific processes. Further analysis showed that the expanded classification is a useful resource for analyzing other datasets on transcription factors with respect to their potential role in gene regulation. The analysis of transcription factor interaction data showed complementary differences between the subclasses, where transcription factors labeled as Pioneers often interact with other transcription factors through DNA co-binding, whereas Migrants to a larger extent use protein-protein interactions. The analysis of time course data on cell differentiation indicated a shift in the regulatory program associated with Pioneer-like transcription factors during differentiation.

Conclusions

The expanded classification is an interesting resource for analyzing data on gene regulation, as illustrated here on transcription factor interaction data and data from a time course experiment. The potential regulatory function of transcription factors seems largely to be determined by how they bind DNA, but is also influenced by how they interact with each other through cooperativity and protein-protein interactions.
Composite cell sheet for periodontal regeneration: crosstalk between different types of MSCs in cell sheet facilitates complex periodontal-like tissue regeneration
Authors: Zhang Hao , Liu Shiyu , Zhu Bin , Xu Qiu , Ding Yin , Jin Yan
Published: November 2016

Background

Tissue-engineering strategies based on mesenchymal stem cells (MSCs) and cell sheets have been widely used for periodontal tissue regeneration. However, given the complexity in periodontal structure, the regeneration methods using a single species of MSC could not fulfill the requirement for periodontal regeneration.

Methods

We researched the interaction between the periodontal ligament stem cells (PDLSCs) and jaw bone marrow-derived mesenchymal stem cells (JBMMSCs), and constructed a composite cell sheet comprising both of the above MSCs to regenerate complex periodontium-like structures in nude mice.

Results

Our results show that by co-culturing PDLSCs and JBMMSCs, the expressions of bone and extracellular matrix (ECM)-related genes and proteins were significantly improved in both MSCs. Further investigations showed that, compared to the cell sheet using PDLSCs or JBMMSCs, the composite stem cell sheet (CSCS), which comprises these two MSCs, expressed higher levels of bone- and ECM-related genes and proteins, and generated a composite structure more similar to the native periodontal tissue physiologically in vivo.

Conclusions

In conclusion, our results demonstrate that the crosstalk between PDLSCs and JBMMSCs in cell sheets facilitate regeneration of complex periodontium-like structures, providing a promising new strategy for physiological and functional regeneration of periodontal tissue.
Role of dendritic cell maturation factors produced by human invariant NKT cells in immune tolerance
Authors: Lee Hyeong-Woo , Jie Hyun Bae , Bollyky Paul L , Sarracino David , Kim Tong-Soo , Wilson Brian S
Published: November 2016

In this study, we used the culture supernatant of iNKT cells to identify human myeloid DC maturation factors produced by human CD4+ iNKT cells. S100A8 had a strong maturation effect. Notably, the recombinant S100A8 protein displayed properties of DC maturation functioning, and the induction of DC differentiation by both the purified and the recombinant protein were blocked by anti-S100A8 and anti-TLR-4 mAbs. DC differentiation induced by anti-major histocompatibility complex class II/CD1d Ab, S100A8, or both was qualitatively indistinguishable from that induced by the coculture of DCs and iNKT cells or via culture supplementation with supernatants from activated CD4+ iNKT cells. S100A8 also induced CD4+/CD25+/Foxp3+ Treg cells from naïve T cells. S100A8 may contribute to DC differentiation by elevating transcription factors or activating transcription factor-2, heat shock factor-1, or both, in mature DCs. S100A8 is a novel candidate iNKT cell-dependent DC maturation factor.
Chronic alcohol consumption inhibits peripheral NK cell development and maturation by decreasing the availability of IL-15
Authors: Zhang Faya , Little Alex , Zhang Hui
Published: November 2016

NK cells are innate immune cells and have important roles in antiviral and antitumor immunity. Based on the transcriptional regulation, organ distribution, and cell function, NK cells have recently been further divided into cytotoxic conventional NK cells (cNK) and noncytotoxic helper-like group 1 innate lymphoid cells (ILC1s). It is well known that chronic alcohol consumption decreases peripheral NK cell number and cytolytic activity; however, the underlying mechanism remains to be elucidated. How chronic alcohol consumption affects ILC1s is, to our knowledge, completely unexplored. Herein, we used a well-established mouse model of chronic alcohol consumption to study the effects of alcohol on transcription factor expression, maturation, and cytokine production of cNK cells and ILC1s in various organs. We found that alcohol consumption significantly decreased Eomes-expressing cNK cells in all the examined organs, except BM, but did not significantly affect ILC1s. Alcohol consumption compromised cNK cell development and maturation. Exogenous IL-15/IL-15Rα treatment caused full recovery of Eomes-expressing cNK cell number and maturation. Taken together, our data indicated that chronic alcohol consumption decreases cNK cell number and cytolytic activity by arresting cNK cell development at the CD27+CD11b+ stage. This developmental arrest of NK cells results from a lack of IL-15 availability in the microenvironment. IL-15/IL-15Rα treatment can recover alcohol consumption-induced developmental defect in NK cells.
Differing rates of antibody acquisition to merozoite antigens in malaria: implications for immunity and surveillance
Authors: McCallum Fiona J , Persson Kristina E M , Fowkes Freya J I , Reiling Linda , Mugyenyi Cleopatra K , Richards Jack S , Simpson Julie A , Williams Thomas N , Gilson Paul R , Hodder Anthony N , Sanders Paul R , Anders Robin F , Narum David L , Chitnis Chetan , Crabb Brendan S , Marsh Kevin , Beeson James G
Published: November 2016

Antibodies play a key role in acquired human immunity to Plasmodium falciparum (Pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity. We examined responses to a range of merozoite antigens in 2 different cohorts of children and adults with different age structures and levels of malaria exposure. Overall, antibodies were associated with age, exposure, and active infection, and the repertoire of responses increased with age and active infection. However, rates of antibody acquisition varied between antigens and different regions within an antigen following exposure to malaria, supporting our hypothesis. Antigen-specific responses could be broadly classified into early response types in which antibodies were acquired early in childhood exposure and late response types that appear to require substantially more exposure for the development of substantial levels. We identified antigen-specific responses that were effectively boosted after recent infection, whereas other responses were not. These findings advance our understanding of the acquisition of human immunity to malaria and are relevant to the development of malaria vaccines targeting merozoite antigens and the selection of antigens for use in malaria surveillance.
Misreading and the Marketplace: Dickens and Du Maurier in a Commercial Age
Authors: McIntosh Hugh
Published: November 2016

“Misreading and the Marketplace” explores how the culture of popular reading in nineteenth-century America played up a specific kind of critique: the refusal to share social anxieties at the heart of British novels. From excitement about the revolutionary mob that threatens Charles Dickens's A Tale of Two Cities to reconsiderations of Svengali, the villain of George Du Maurier's Trilby, American reactions and revisions treated British fears playfully. I argue that this form of misreading reflected more than the simple desire for national distinction. Tension between American audiences and English novelists presented an exaggerated version of a gap between readers and authors that an emerging consumerist culture was making apparent throughout the transatlantic world. Understanding this broader context helps explain why the late works of both Dickens and Du Maurier seem to echo their American misreaders, reimagining social nightmares as pleasant fantasies.
Henry James's Minimalist Novel
Authors: Zubernis Emily
Published: November 2016

What is a minimalist novel? This essay approaches the question through readings of Henry James, a writer notorious for the complexity of his prose style. James's writing is never simple and rarely brief, of course, but it is often remarkably unproductive. Indeed, the very complexity of style in late James erodes the accumulation of detail that would build toward historical, cultural, and psychological insight in a typical realist novel. The surface density of James's prose toggles between the profound and the “merely” stylistic: circuitous sentences approach their objects with extreme hesitation, and clauses accumulate without clarifying, massing instead into a thick linguistic fog. Thus James's writing delivers an image of the minimalist novel not as a thing of terse flatness or truncated form but as an extravagantly intricate withdrawal from the novel's meaning-making functions. In The Ambassadors, this withdrawal responds to the inherent maximalism of the novel's primary antagonist, advertising. The Ambassadors reveals advertising as a form of representation uninterested in the material object. Against advertising's abstraction, the novel uses opaque, empty style to keep its surface unbearably visible, thereby rendering interpretation unsatisfyingly tentative.
Phospholipid composition and a polybasic motif determine D6 PROTEIN KINASE polar association with the plasma membrane and tropic responses
Authors: Barbosa Inês C. R. , Shikata Hiromasa , Zourelidou Melina , Heilmann Mareike , Heilmann Ingo , Schwechheimer Claus
Published: November 2016

Polar transport of the phytohormone auxin through PIN-FORMED (PIN) auxin efflux carriers is essential for the spatiotemporal control of plant development. The Arabidopsis thaliana serine/threonine kinase D6 PROTEIN KINASE (D6PK) is polarly localized at the plasma membrane of many cells where it colocalizes with PINs and activates PIN-mediated auxin efflux. Here, we show that the association of D6PK with the basal plasma membrane and PINs is dependent on the phospholipid composition of the plasma membrane as well as on the phosphatidylinositol phosphate 5-kinases PIP5K1 and PIP5K2 in epidermis cells of the primary root. We further show that D6PK directly binds polyacidic phospholipids through a polybasic lysine-rich motif in the middle domain of the kinase. The lysine-rich motif is required for proper PIN3 phosphorylation and for auxin transport-dependent tropic growth. Polybasic motifs are also present at a conserved position in other D6PK-related kinases and required for membrane and phospholipid binding. Thus, phospholipid-dependent recruitment to membranes through polybasic motifs might not only be required for D6PK-mediated auxin transport but also other processes regulated by these, as yet, functionally uncharacterized kinases.
Delayed neurogenesis with respect to eye growth shapes the pigeon retina for high visual acuity
Authors: Rodrigues Tania , Krawczyk Michal , Skowronska-Krawczyk Dorota , Matter-Sadzinski Lidia , Matter Jean-Marc
Published: November 2016

The macula and fovea located at the optical centre of the retina make primate visual perception unique among mammals. Our current understanding of retina ontogenesis is primarily based on animal models having no macula and no fovea. However, the pigeon retina and the human macula share a number of structural and functional properties that justify introducing the former as a new model system for retina development. Comparative transcriptome analysis of pigeon and chicken retinas at different embryonic stages reveals that the genetic programmes underlying cell differentiation are postponed in the pigeon until the end of the period of cell proliferation. We show that the late onset of neurogenesis has a profound effect on the developmental patterning of the pigeon retina, which is at odds with the current models of retina development. The uncoupling of tissue growth and neurogenesis is shown to result from the fact that the pigeon retinal epithelium is inhibitory to cell differentiation. The sum of these developmental features allows the pigeon to build a retina that displays the structural and functional traits typical of primate macula and fovea.
Phosphorylated Groucho delays differentiation in the follicle stem cell lineage by providing a molecular memory of EGFR signaling in the niche
Authors: Johnston Michael J. , Bar-Cohen Shaked , Paroush Ze'ev , Nystul Todd G.
Published: November 2016

In the epithelial follicle stem cells (FSCs) of the Drosophila ovary, Epidermal Growth Factor Receptor (EGFR) signaling promotes self-renewal, whereas Notch signaling promotes differentiation of the prefollicle cell (pFC) daughters. We have identified two proteins, Six4 and Groucho (Gro), that link the activity of these two pathways to regulate the earliest cell fate decision in the FSC lineage. Our data indicate that Six4 and Gro promote differentiation towards the polar cell fate by promoting Notch pathway activity. This activity of Gro is antagonized by EGFR signaling, which inhibits Gro-dependent repression via p-ERK mediated phosphorylation. We have found that the phosphorylated form of Gro persists in newly formed pFCs, which may delay differentiation and provide these cells with a temporary memory of the EGFR signal. Collectively, these findings demonstrate that phosphorylated Gro labels a transition state in the FSC lineage and describe the interplay between Notch and EGFR signaling that governs the differentiation processes during this period.
Insights from imaging the implanting embryo and the uterine environment in three dimensions
Authors: Arora Ripla , Fries Adam , Oelerich Karina , Marchuk Kyle , Sabeur Khalida , Giudice Linda C. , Laird Diana J.
Published: November 2016

Although much is known about the embryo during implantation, the architecture of the uterine environment in which the early embryo develops is not well understood. We employed confocal imaging in combination with 3D analysis to identify and quantify dynamic changes to the luminal structure of murine uterus in preparation for implantation. When applied to mouse mutants with known implantation defects, this method detected striking peri-implantation abnormalities in uterine morphology that cannot be visualized by histology. We revealed 3D organization of uterine glands and found that they undergo a stereotypical reorientation concurrent with implantation. Furthermore, we extended this technique to generate a 3D rendering of the cycling human endometrium. Analyzing the uterine and embryo structure in 3D for different genetic mutants and pathological conditions will help uncover novel molecular pathways and global structural changes that contribute to successful implantation of an embryo.
Surgical Management of the Aging Athlete
Authors: DeFroda Steven F. , Feller Ross , Klinge Stephen A.
Published: November 2016

Epidemiologic data show that the number of middle aged (>40 yr) and elderly (>65 yr) individuals continues to increase steadily, creating an expanding need for sports medicine care. Management of injuries in this subset of patients is expanding well beyond sustaining a patient’s ability to perform activities of daily living. In fact, many older individuals increasingly expect to maintain reasonably high activity levels throughout their lifespan as well as after musculoskeletal injury. While a number of the emerging physiologic benefits of physical activity in older patients have been outlined, no recent review has outlined the current best surgical techniques, rehabilitation protocols, and return-to-sport recommendations for older athletes after soft-tissue repair or reconstruction as well as joint replacement. The goal of orthopaedic care in the elderly patient is shifting from simple pain relief toward return to athletic activity.
A Review of Injury Patterns in Athletes Competing in Combined Competitions: Heptathlon and Decathlon
Authors: Kim Brian Young , Vigil Daniel V.
Published: November 2016

Decathlon and heptathlon, the flagship events in the category of “combined events” within the sport of track and field, are contested by athletes possessing skill and talent in running, jumping, and throwing. The athleticism required to excel in decathlon and heptathlon has led to the unofficial recognition of the Olympic champions in these events, as “the greatest athletes in the world.” The diversity of training and the intense demands of competition place these athletes at risk for a variety of injuries. The team physician or event physician must be knowledgeable about this unique group of athletes to deliver appropriate medical care when needed. The purpose of this article is to review the common injuries and injury patterns affecting the combined event athlete.