bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site-specific genome editing for correction of induced pluripotent stem cells derived from dominant dystrophic epidermolysis bullosa
Authors: Shinkuma Satoru , Guo Zongyou , Christiano Angela M. 
Published: May 2016

Significance
Some inherited autosomal dominant disorders are caused by dominant negative mutations whose gene product adversely affects the normal gene product expressed from the other allele. Gene editing with engineered site-specific endonucleases leads to a double-strand break, which promotes nonhomologous end-joining (NHEJ). NHEJ is error-prone and conducive to the generation of frameshift mutations, leading to intentional knockout of a gene. Therefore, gene editing with engineered site-specific endonucleases is applicable to dominant negative disorders, to target only the mutant allele and leave the normal allele intact. This technique could provide a significant benefit for patients with dominant negative disorders in combination with induced pluripotent stem cell technology that acquires multipotential differentiation and unlimited self-renewal capacity.
Increased androgenic sensitivity in the hind limb muscular system marks the evolution of a derived gestural display
Authors: Mangiamele Lisa A. , Fuxjager Matthew J. , Schuppe Eric R. , Taylor Rebecca S. , Hödl Walter , Preininger Doris 
Published: May 2016

Significance
Diverse species signal using limb gestures, but little is known about how selection incorporates such movements into display routines. We study this issue in a tropical frog that produces complex waving displays with its hind limbs. We find not only that androgenic hormones activate such signaling behavior, but also that the signal’s recent evolution is marked by a dramatic increase in androgenic sensitivity of the thigh muscles that control hind limb maneuvering. Moreover, we demonstrate that this muscular phenotype mirrors that which is found in the larynx of other frogs that primarily produce androgen-dependent vocalizations as social signals. We therefore uncover strong coevolution between the emergence of complex sexual gestural signals and enhanced androgenic signaling mechanisms in the muscular system.
DyNet: visualization and analysis of dynamic molecular interaction networks
Authors: Goenawan Ivan H. , Bryan Kenneth , Lynn David J. 
Published: May 2016

Abstract
Summary : The ability to experimentally determine molecular interactions on an almost proteome-wide scale under different conditions is enabling researchers to move from static to dynamic network analysis, uncovering new insights into how interaction networks are physically rewired in response to different stimuli and in disease. Dynamic interaction data presents a special challenge in network biology. Here, we present DyNet, a Cytoscape application that provides a range of functionalities for the visualization, real-time synchronization and analysis of large multi-state dynamic molecular interaction networks enabling users to quickly identify and analyze the most ‘rewired’ nodes across many network states.
Availability and Implementation : DyNet is available at the Cytoscape (3.2+) App Store ( http://apps.cytoscape.org/apps/dynet ).
Contact : david.lynn@sahmri.com .
Supplementary Information : Supplementary data are available at Bioinformatics online.
WeSME: uncovering mutual exclusivity of cancer drivers and beyond
Authors: Kim Yoo-Ah , Madan Sanna , Przytycka Teresa M 
Published: May 2016

Abstract

Motivation
Mutual exclusivity is a widely recognized property of many cancer drivers. Knowledge about these relationships can provide important insights into cancer drivers, cancer-driving pathways and cancer subtypes. It can also be used to predict new functional interactions between cancer driving genes and uncover novel cancer drivers. Currently, most of mutual exclusivity analyses are preformed focusing on a limited set of genes in part due to the computational cost required to rigorously compute P-values.

Results
To reduce the computing cost and perform less restricted mutual exclusivity analysis, we developed an efficient method to estimate P-values while controlling the mutation rates of individual patients and genes similar to the permutation test. A comprehensive mutual exclusivity analysis allowed us to uncover mutually exclusive pairs, some of which may have relatively low mutation rates. These pairs often included likely cancer drivers that have been missed in previous analyses. More importantly, our results demonstrated that mutual exclusivity can also provide information that goes beyond the interactions between cancer drivers and can, for example, elucidate different mutagenic processes in different cancer groups. In particular, including frequently mutated, long genes such as TTN in our analysis allowed us to observe interesting patterns of APOBEC activity in breast cancer and identify a set of related driver genes that are highly predictive of patient survival. In addition, we utilized our mutual exclusivity analysis in support of a previously proposed model where APOBEC activity is the underlying process that causes TP53 mutations in a subset of breast cancer cases.

Availability and Implementation
http://www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/index.cgi#wesme

Supplementary information
Supplementary data are available at Bioinformatics online.
Kissing for Virtuosi: William Stukeley’s Philosophy of Pleasure (1757)
Authors: Klein Lawrence 
Published: May 2016

Abstract
The intellectual career of William Stukeley (1687–1765) has received much attention. However, one manuscript by Stukeley has never been discussed. In 1757 he composed a short treatise, ‘On the Philosophy of Pleasure’, in which he argued an unusual case, namely, that a man and woman ought to feel entitled to consummate their philosophic friendship with kissing. The manuscript illuminates an interesting episode in Stukeley’s private life, but it also has a broader significance. Firstly, it incorporates many of the themes developed elsewhere by Stukeley, showing how contemporary historical and scientific understanding could be synthesised with a mystical account, of ancient derivation, of the physical and social universe. Secondly, the manuscript sheds light on the changing relations of men and women. Social and cultural developments among the literate in eighteenth-century Britain were facilitating heterosocial interaction, outside the framework of courtship and marriage, in ways that enhanced both the possibilities for heterosocial friendship and the risks attached to it. In his manuscript, Stukeley sought to expand the physical expression of amicable affection between a woman and man: he was looking for ways to move beyond the constraints of Platonic love without falling into libertinism. His position accords with the idea that the pursuit of happiness in the eighteenth century had a sexual dimension. However, while Stukeley sought greater latitude in erotic expression, his effort illustrates the challenge of doing so without undermining the contemporary norms of social order.
Adpositions
Authors: Libert Alan 
Published: May 2016

Adposition is the name of a part of speech or word class. Although it may not be a familiar term to those outside of linguistics, the name of one of its subsets is: preposition. The latter type of word gets its name from the fact that it (generally) occurs before its complement; that is, the noun (or more correctly noun phrase) which it governs. Examples of these words in English are to, from, of, and under. In some languages, such as Turkish, the equivalent words are found after their complement, and they are called postpositions. The term adpositions is a general term that includes both prepositions and postpositions, as well as some more exotic items of the same sort: circumpositions (part of which occur before the complement, and part after it), inpositions (which occur within their complement) and what have been called ambipositions (which can occur either before or after their complement). Adpositions have been studied from various points of view, including syntax, semantics, and neurolinguistics, and this bibliography contains sections devoted to each of these. The number of works that has been written on them is very extensive (probably several thousand, leaving aside those works in which adpositions are not the main topic), and, because many of these works are descriptive, it is difficult to state that certain of them are seminal or of particular significance (unlike in more theoretical fields, such as generative syntax or grammaticalization). For these reasons, the list of works chosen for this article must necessarily be somewhat random—some have been more influential than others, but this may be in part because of their accessibility and/or the language(s) they treat. Nevertheless, this bibliography will give an idea of the type of research that has been done on adpositions, and it will include some of the best-known works on them. On the other hand, some lesser-known papers that deal with interesting or neglected aspects of prepositions are also listed. The works listed come from a variety of theoretical frameworks and a long span of time.
Oliver Goldsmith
Authors: Griffin Michael 
Published: May 2016

The life and work of the Irish poet, playwright, essayist, historian, and novelist Oliver Goldsmith (b. 1728–d. 1774) had not received a tremendous amount of attention since the 1960s, a decade that saw a substantial burst of editorial and critical work, and, in particular, the publication of Arthur Friedman’s five-volume edition of the Collected Works (Goldsmith 1966, cited under Editions) and Roger Lonsdale’s edition of The Poems of Goldsmith, Gray and Collins (Goldsmith, et al. 1969, cited under Editions). A good deal of the critical scholarship that has emerged since then has been in dialogue with, or in response to, those editions and to two-book length works of criticism by Ricardo Quintana (Quintana 1967, cited under General Collections and Studies) and Robert H. Hopkins (Hopkins 1969, cited under General Collections and Studies), which argued for a greater appreciation of the ironic registers of Goldsmith’s work. Indeed, much Goldsmith criticism has focused on the question of whether he should be understood as a sentimentalist or as a satirist, since the oeuvre as a whole exists along a seam between the satirical tenor of his Augustan predecessors and the emerging sensibility of his literary milieu and an expanding middle-class audience. As such, Goldsmith’s writings are in many ways highly representative of his mid-18th-century contexts. The relative lack of sustained scholarly and critical work on Goldsmith since the 1960s is also partly attributable to his work being in some senses too various to accommodate in single thematic or generic studies: he moved across the modes of 18th-century writing with considerable ease and success. The eclectic nature of his oeuvre, and the variety of tones and registers he used in writing across the genres, has resulted in his being characterized in various, often-inconsistent ways. That said, clusters of essays and articles have appeared since the late 20th century that have illustrated the richness and instructive ambiguities of his writing and thinking. Also, his Irishness has been intermittently, and with varying degrees of insight or success, studied throughout the critical heritage as a contributing factor in his social and political worldview. In this article, items that Friedman acknowledged and incorporated into the editorial apparatus of his 1966 edition—including earlier scholarship on the history and sources of Goldsmith’s Greek, Roman, and English histories, the prefaces to which feature in Friedman’s work—are largely omitted. The emphasis here is primarily on the biographical tradition, on criticism and scholarship published after 1966, and within that period on the substantial bodies of criticism surrounding the major poetry and Goldsmith’s one novel.
Field of Study, Earnings, and Self-Selection*
Authors: Kirkeboen Lars J. , Leuven Edwin , Mogstad Magne 
Published: May 2016

Abstract
This article examines the labor market payoffs to different types of postsecondary education, including field and institution of study. Instrumental variables (IV) estimation of the payoff to choosing one type of education compared to another is made particularly challenging by individuals choosing between several types of education. Not only does identification require one instrument per alternative, but it is also necessary to deal with the issue that individuals who choose the same education may have different next-best alternatives. We address these difficulties using rich administrative data for Norway’s postsecondary education system. A centralized admission process creates credible instruments from discontinuities that effectively randomize applicants near unpredictable admission cutoffs into different institutions and fields of study. The admission process also provides information on preferred and next-best alternatives from strategy-proof measures of individuals’ ranking of institutions and fields. The results from our IV approach may be summarized with three broad conclusions. First, different fields of study have substantially different labor market payoffs, even after accounting for institution and peer quality. Second, the effect on earnings from attending a more selective institution tends to be relatively small compared to payoffs to field of study. Third, the estimated payoffs to field of study are consistent with individuals choosing fields in which they have a comparative advantage. Comparing our estimates to those obtained from other approaches highlights the importance of using instruments to correct for selection bias and information on individuals’ ranking of institutions and fields to measure their preferred and next-best alternatives.
The Effect of Transiliac–Transsacral Screw Fixation for Pelvic Ring Injuries on the Uninjured Sacroiliac Joint
Authors: Mardam-Bey Sami W. , Beebe Michael J. , Black James C. , Chang Ellen Y. , Kubiak Erik N. , Bishop Julius A. , McAndrew Christopher M. , Ricci William M. , Gardner Michael J. 
Published: May 2016

Objective:
To evaluate the functional outcomes and pain in patients with unilateral posterior pelvic ring injuries treated with transiliac–transsacral screw fixation compared with unilateral iliosacral screw fixation.

Design:
Retrospective comparative study.

Setting:
Three academic level 1 trauma centers.

Patients/Participants:
From a group of 866 patients with pelvic ring injuries treated surgically, 86 patients with unilateral pelvic ring injuries treated with transiliac–transsacral screws and 97 patients treated with unilateral iliosacral screws were identified. Thirty-six patients treated with transiliac–transsacral fixation and 26 patients treated with unilateral iliosacral screws met the inclusion criteria and participated.

Intervention:
Patients were treated surgically for unstable pelvic ring injuries with either unilateral iliosacral screws or transiliac–transsacral screws at the discretion of the treating surgeon.

Main Outcome Measurement:
Majeed Pelvic Score.

Results:
There was no significant difference in Majeed Pelvic Scores between patients treated with transiliac–transsacral screws and those treated with unilateral iliosacral screws (72.8 ± 23.7 vs. 70.4 ± 19.0, P = 0.66). There was no difference in side-specific Numeric Rating Scale pain scores between patients treated with transiliac–transsacral screws and those treated with unilateral iliosacral screws on the injured side (2.5 ± 3.1 vs. 2.0 ± 2.4, P = 0.46) or the uninjured side (1.7 ± 2.8 vs. 0.8 ± 1.7, P = 0.12). Mean follow-up was greater than 3 years with no difference between the groups (mean 1270 vs. 1242 days, P = 0.84).

Conclusions:
Treatment of unilateral pelvic ring injuries with transiliac–transsacral screws does not adversely affect or improve patient outcomes or subjective pain scores when compared with those treated with unilateral iliosacral screws.

Level of Evidence:
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Compartment Syndrome of the Leg Associated With Fracture: An Algorithm to Avoid Releasing the Posterior Compartments
Authors: Tornetta Paul , Puskas Brian L. , Wang Kevin 
Published: May 2016

Objective:
The purpose of this study is to report on a prospective series of patients in whom an algorithm was used to attempt to avoid releasing the posterior compartments in patients with lower leg compartment syndrome (CS) and the safety of such a practice.

Design:
Prospective cohort study.

Setting:
Level 1 trauma center.

Patients:
A consecutive series of 39 patients was managed by one surgeon for CS using the reported protocol.

Intervention:
Patients diagnosed with a CS of the leg were managed with a single operative protocol. After a standard anterior and lateral compartment release through a full-length lateral incision was performed, the superficial and deep posterior compartments were measured with the heel resting on a bolster. Using the preoperative diastolic blood pressure, a ΔP < 30 was considered to be a positive finding warranting a separate medial incision for release of the posterior compartments. If the ΔP was ≥30, the posterior compartments were not released.

Main Outcome Measurements:
Need for medial release or development of posterior CS or sequelae.

Results:
A consecutive series of 39 patients were managed by 1 surgeon for CS using the described protocol. Two patients with an isolated posterior CS were excluded. The other 37 had clinical symptoms or compartment pressures consistent with anterior compartment involvement. Of 37 patients, 21 had (57%) symptoms suggesting posterior compartment involvement. The preoperative pressure measurements averaged 41 mm Hg with an average ΔP of 38. After full-length release of the anterior and lateral compartments, only 3/37 (8%) required a posterior release for a ΔP of <30 mm Hg. The lowest ΔP in the posterior compartments of the remaining 34 patients averaged 59 (32–86). The compartment pressures in the superficial and deep posterior compartments decreased by 22 mm Hg and 24 mm Hg, respectively, after the anterolateral release. None of the patients who had only an anterolateral release developed sequelae of a missed posterior CS.

Conclusions:
The use of the reported algorithm is effective in avoiding posterior compartment release.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Clinical Significance of Metastatic Lymph Nodes in the Gut of Patients with Pure and Mixed Primary Appendiceal Carcinoids
Authors: Ciarrocchi Andrea , Pietroletti Renato , Carlei Francesco , Amicucci Gianfranco 
Published: May 2016

BACKGROUND:
Right hemicolectomy is indicated for primary appendiceal carcinoids with diameters greater than 2 cm because of an increased risk of metastasis to the lymph nodes of the gut. However, the natural history of positive nodes remains unknown.

OBJECTIVE:
The aim of this study was to investigate the impact of metastatic lymph nodes on survival among patients with pure or mixed primary appendiceal carcinoids, while controlling for potential confounders such as age, sex, tumor size, surgical intervention, and lymph node rate (number of positive lymph nodes/lymph node yield).

DESIGN:
This is a retrospective comparative study..

SETTINGS:
Data were retrieved from the Surveillance, Epidemiology and End Results database.

PATIENTS:
Patients undergoing colectomy for appendiceal carcinoids between 1998 and 2009 were selected.

MAIN OUTCOME MEASURES:
The survival curves for the 2 groups were compared to evaluate differences in prognosis. Univariate and multivariate analyses were performed.

RESULTS:
Lymph node rates did not significantly differ between the pure and mixed carcinoid groups (p = 0.768), although overall survival was poorer among patients with mixed carcinoids (p = 0.004; HR, 0.498; 95% CI, 0.310–0.800). For pure carcinoids, surgical intervention (p = 0.029; HR, 0.241; 95% CI, 0.067–0.867), age (p < 0.001; HR, 1.083; 95% CI, 1.051–1.116), and lymph node rate (p = 0.039; HR, 5.295; 95% CI, 1.089–25.754) were independent predictors of overall survival. For mixed carcinoids, surgical intervention (p = 0.019; HR, 1.675; 95% CI, 1.088–2.578), tumor size (p < 0.001; HR, 0.442; 95% CI, 0.286–0.683), age (p < 0.001; HR, 1.041; 95% CI, 1.026–1.056), and lymph node rate (p < 0.001; HR, 17.471; 95% CI, 10.047–0.382) were significant prognostic factors.

LIMITATIONS:
The study is limited by its retrospective nature and by the shortcomings of the Surveillance, Epidemiology and End Results database related to the availability and quality of data.

CONCLUSION:
Based on the data retrieved from the Surveillance, Epidemiology and End Results database and adjusted for potential confounding factors, the lymph node rate of metastasis strongly impacts overall survival among patients with pure or mixed carcinoids. Nodal metastasis thus appears to be a reliable clinical hallmark of tumor aggressiveness.
Prevalence of Active Long-term Problems in Patients With Anorectal Malformations: A Systematic Review
Authors: Rigueros Springford Laurie , Connor Martin J. , Jones Katie , Kapetanakis Venediktos V. , Giuliani Stefano 
Published: May 2016

BACKGROUND:
Anorectal malformations are a spectrum of congenital anomalies of the rectum with high infantile survival rates and variable outcomes. Long-term (>10 years old) active problems associated with this condition have been poorly investigated.

OBJECTIVE:
The purpose of this review was to systematically define the prevalence of the most common active long-term problems in patients with a history of anorectal malformation repair.

DATA SOURCES:
MEDLINE, EMBASE, and the Cochrane Library were searched electronically using the OVID search platform.

STUDY SELECTION:
Original articles from August 1, 1994, to October 20, 2015, that included outcome data for patients aged ≥10 years with anorectal malformation. Cloaca was excluded from the study.

INTERVENTIONS:
Prevalence estimates of anorectal malformations were obtained from published articles. CIs were ascertained in the logit scale after transforming prevalence into log odds and were then transformed into the original scale. The same method was used for subgroup analysis investigating high and low anorectal malformations.

MAIN OUTCOME MEASURES:
The overall prevalences of fecal, urinary, and sexual dysfunction were analyzed.

RESULTS:
Twelve studies including 455 patients with a history of anorectal malformation repair were included for analysis. The range of reported prevalence of long-term active problems was as follows: fecal incontinence, 16.7% to 76.7%; chronic constipation, 22.2% to 86.7%; urinary incontinence, 1.7% to 30.5%; ejaculatory dysfunction, 15.6% to 41.2%; and erectile dysfunction, 5.6% to 11.8%.

LIMITATIONS:
The study was limited by its retrospective, small size; multiple complex associated anomalies often not reported; and heterogeneous composition of patients with limited stratification analysis.

CONCLUSIONS:
There is an overall high prevalence of active long-term issues in adolescents and young adults with anorectal malformations. Additional multicenter research is needed to define characteristics and predictors of long-term outcome, to implement effective follow-up, and to transition to adult health care.