bluuebunny/crossref_metadata_2025 huggingface dataset:
TraR directly regulates transcription initiation by mimicking the combined effects of the global regulators DksA and ppGpp
Authors: Gopalkrishnan Saumya , Ross Wilma , Chen Albert Y. , Gourse Richard L.
Published: June 2017

Significance

TraR is a 73-amino acid protein encoded in the transfer region operon (
tra
) of the
Escherichia coli
conjugative F plasmid. Here we describe evidence for a model in which TraR mimics the combined regulatory activities of the transcription factor DksA and the second messenger ppGpp. By interacting with the residues in RNA polymerase that form a ppGpp binding pocket, we suggest that TraR provides a means for regulating transcription initiation by targeting the secondary channel even under conditions that do not result in induction of ppGpp. TraR-like proteins appear to be ubiquitous in bacteria even in phyla distant from the proteobacteriaceae, in support of the accumulating evidence that very small proteins can have a large impact on bacterial biology.
Disentangling the effects of selection and loss bias on gene dynamics
Authors: Iranzo Jaime , Cuesta José A. , Manrubia Susanna , Katsnelson Mikhail I. , Koonin Eugene V.
Published: June 2017

Significance

Evolution of microbes is dominated by horizontal gene transfer and the incessant host–parasite arms race that promotes the evolution of diverse antiparasite defense systems. The evolutionary factors governing these processes are complex and difficult to disentangle, but rapidly growing genome databases provide ample material for testing evolutionary models. Rigorous mathematical modeling of evolutionary processes, combined with computer simulation and comparative genomics, allowed us to elucidate the evolutionary regimes of different classes of microbial genes. Only genes involved in key informational and metabolic pathways are subject to strong selection, whereas most of the others are effectively neutral or even burdensome. Mobile genetic elements and defense systems are costly, supporting the understanding that their evolution is governed by the same factors.
Microfluidic guillotine for single-cell wound repair studies
Authors: Blauch Lucas R. , Gai Ya , Khor Jian Wei , Sood Pranidhi , Marshall Wallace F. , Tang Sindy K. Y.
Published: June 2017

Significance

Whereas tissues can repair wounds regularly, single cells—including muscle cells, neurons, and cancer cells—are increasingly recognized to have a wound response. Ability to understand and control single-cell repair holds the potential for new strategies to treat human diseases. Existing wounding methods and model organisms are insufficient for elucidating the biological mechanisms involved. This paper reports a microfluidic guillotine for the high-throughput bisection of hundreds of cells reproducibly. The fine time resolution achieved enables mechanistic studies critical for a molecular understanding of single-cell wound repair currently impossible with existing wounding methods. The work here will lay the foundation for understanding how single cells heal themselves, a fundamental feature distinguishing living from nonliving matter.
Diffusive dynamics during the high-to-low density transition in amorphous ice
Authors: Perakis Fivos , Amann-Winkel Katrin , Lehmkühler Felix , Sprung Michael , Mariedahl Daniel , Sellberg Jonas A. , Pathak Harshad , Späh Alexander , Cavalca Filippo , Schlesinger Daniel , Ricci Alessandro , Jain Avni , Massani Bernhard , Aubree Flora , Benmore Chris J. , Loerting Thomas , Grübel Gerhard , Pettersson Lars G. M. , Nilsson Anders
Published: June 2017

Significance

The importance of a molecular-level understanding of the properties, structure, and dynamics of liquid water is recognized in many scientific fields. It has been debated whether the observed high- and low-density amorphous ice forms are related to two distinct liquid forms. Here, we study experimentally the structure and dynamics of high-density amorphous ice as it relaxes into the low-density form. The unique aspect of this work is the combination of two X-ray methods, where wide-angle X-ray scattering provides the evidence for the structure at the atomic level and X-ray photon-correlation spectroscopy provides insight about the motion at the nanoscale, respectively. The observed motion appears diffusive, indicating liquid-like dynamics during the relaxation from the high-to low-density form.
Small mitochondrial Arf (smArf) protein corrects p53-independent developmental defects of
Arf
tumor suppressor-deficient mice
Authors: van Oosterwijk Jolieke G. , Li Chunliang , Yang Xue , Opferman Joseph T. , Sherr Charles J.
Published: June 2017

Significance

Although the potent antiproliferative effects of the Arf tumor suppressor depend on p53, Arf also exhibits less well understood p53-independent activities.
Arf
-null mice are blind and males exhibit defective spermatogenesis, two focal anomalies not observed in
Trp53
-null animals. An N-terminally truncated and unstable Arf protein (smArf), translated from a second internal AUG codon within the full-length Arf mRNA, lacks amino acid residues required for p53 activation and has been reported to localize to mitochondria and trigger mitophagy. Missing potent p53-dependent tumor suppressor activity, p15
smArf
can surprisingly act independently of p19
Arf
to correct the focal developmental defects of
Arf
-null mice. The unusual features of the
Ink4a-Arf
(
Cdkn2a
) locus, which include alternative reading frames and internal translational initiation, are unprecedented in mammals.
Lexical patterns of place in English and Norwegian
Authors: Hasselgård Hilde
Published: June 2017

This paper presents a contrastive analysis of the English noun place and the corresponding Norwegian nouns plass and sted. The study involves two stages. First the patterns of cross-linguistic correspondences of the nouns are established by means of translational data from the English–Norwegian Parallel Corpus. The correspondence patterns reveal both differences and commonalities between the words. Secondly, recurrent lexical bundles involving place, sted, and plass are investigated in order to discover their selectional preferences. The combined approach to the meanings and usage patterns of the words show the two Norwegian nouns to be almost in complementary distribution in many of their patterns. Place is broader in its meaning and shares senses and uses with both of the Norwegian nouns, although in certain contexts sted/plass correspond to different nouns (e.g. room or space), or to adverbs in -where. Certain idiomatic expressions are similar across the languages, but non-literal uses typically do not correspond to a spatial expression in the other language.
Citations in research writing
Authors: Šinkūnienė Jolanta
Published: June 2017

The paper investigates disciplinary, cultural and genre factors and their influence on citation in research writing. The study is based on literature and linguistics research articles written by Lithuanian and British researchers in their native languages as well as literature and linguistics BA papers written by Lithuanian students in English. The focus of the study is on frequency distribution, syntactic integration and types of citations. The results of the study of research articles confirm clear disciplinary variation in the way citations are employed in research writing. No obvious cultural differences were observed in the analysed expert texts, which points towards discipline as a decisive factor in citational trends in literature and linguistics. Citation trends in linguistic and literature BA papers were similar to a certain extent; however, students who wrote literature papers seem to cite more in the manner of professional writers and thus display more similarity with the conventional citational practices of their field.
Induced beliefs about a fictive energy drink influences 200‐m sprint performance†
Authors: de la Vega Ricardo , Alberti Sara , Ruíz‐Barquín Roberto , Soós István , Szabo Attila
Published: June 2017

Placebo and nocebo effects occur in response to subjective expectations and their subsequent neural actions. Research shows that information shapes expectations that, consequently, influence people's behaviour. In this study, we examined the effects of a fictive and inert green colour energy drink provided for three groups (n = 20/group) with different information. The first group was led to expect that the drink augments running performance (positive information), the second group was led to expect that the drink may or may not improve performance (partial‐positive information), while the third group was told that earlier research could not demonstrate that the drink improves performance (neutral/control). At baseline, the three groups did not differ in their 200‐m sprint performance (p > .05). One week later, 20‐min immediately after ingesting the drink, all participants again ran 200 m. The positive information group increased its performance by 2.41 s, which was statistically significant (p < .001) and also perceived its sprint‐time shorter (p < .05) than the other two groups. A better performance (0.97 s) that approached but did not reach statistical significance was also noted in the partial‐positive information group, and a lesser change (0.72 s) that was statistically not significant was noted in the neutral information control group. These results reveal that drinking an inert liquid, primed with positive information, changes both the actual and the self‐perceived time on a 200‐m sprint. The current findings also suggest that the level of certainty of the information might be linked to the magnitude of change in performance.
Bio-Docklets: virtualization containers for single-step execution of NGS pipelines
Authors: Kim Baekdoo , Ali Thahmina , Lijeron Carlos , Afgan Enis , Krampis Konstantinos
Published: June 2017

Processing of next-generation sequencing (NGS) data requires significant technical skills, involving installation, configuration, and execution of bioinformatics data pipelines, in addition to specialized postanalysis visualization and data mining software. In order to address some of these challenges, developers have leveraged virtualization containers toward seamless deployment of preconfigured bioinformatics software and pipelines on any computational platform. We present an approach for abstracting the complex data operations of multistep, bioinformatics pipelines for NGS data analysis. As examples, we have deployed 2 pipelines for RNA sequencing and chromatin immunoprecipitation sequencing, preconfigured within Docker virtualization containers we call Bio-Docklets. Each Bio-Docklet exposes a single data input and output endpoint and from a user perspective, running the pipelines as simply as running a single bioinformatics tool. This is achieved using a “meta-script” that automatically starts the Bio-Docklets and controls the pipeline execution through the BioBlend software library and the Galaxy Application Programming Interface. The pipeline output is postprocessed by integration with the Visual Omics Explorer framework, providing interactive data visualizations that users can access through a web browser. Our goal is to enable easy access to NGS data analysis pipelines for nonbioinformatics experts on any computing environment, whether a laboratory workstation, university computer cluster, or a cloud service provider. Beyond end users, the Bio-Docklets also enables developers to programmatically deploy and run a large number of pipeline instances for concurrent analysis of multiple datasets.
Advanced experimental approaches to marine water-column biogeochemical processes
Authors: Legendre Louis , Rivkin Richard B , Jiao Nianzhi
Published: June 2017

This “Food for Thought” article examines the potential uses of several novel scientific and technological developments, which are currently available or being developed, to significantly advance or supplement existing experimental approaches to study water-column biogeochemical processes (WCB-processes). After examining the complementary roles of observation, experiments and numerical models to study WCB-processes, we focus on the main experimental approaches of free-water in situ experiments, and at-sea and on-land meso- and macrocosms. We identify some of the incompletely resolved aspects of marine WCB-processes, and explore advanced experimental approaches that could be used to reduce their uncertainties. We examine three such approaches: free-water experiments of lengthened duration using bioArgo floats and gliders, at-sea mesocosms deployed several 100s m below the sea-surface using new biogeochemical sensors, and 50 m-tall on-land macrocosms. These approaches could lead to significant progress in concepts related to marine WCB-processes.
Opera and Film
Authors: Citron Marcia J.
Published: June 2017

Opera and film have enjoyed a close relationship since the beginning of cinema. In the silent era, operatic stories and stars graced the screen, and opera music was played live. Through the sound era and the advent of television, opera continued to appear in mediated form. In recent years, digital formats, the Internet, and streaming have affected how opera is viewed and consumed. Moreover, film in all its forms has exerted increasing influence on the staging of live opera. Opera and film is a relatively new area of study, emerging with Jeremy Tambling’s pioneering book Opera, Ideology, and Film (New York: St. Martin’s, 1987). Its practitioners come mostly from musicology but also other fields, including comparative literature, German studies, and Italian studies. At first, filmic opera was treated as a derivative of opera, but it has become an area in its own right, although adaptation still figures in some interpretations. The intersection of opera and film spans a wide range of types and behaviors. “Film” includes television as well as cinema, and streaming in addition to more conventional modes of presentation. Perhaps the main internal categorization is whether an opera constitutes the whole of a film, which is labeled an opera-film (although two early studies call it film-opera), or whether it occurs in a regular film, where the possibilities are legion. These can include a scene in the opera house, as in the Marx Brothers’ A Night at the Opera (1935); a story about an opera singer, as in Franco Zeffirelli’s Callas Forever (2002); opera music on the soundtrack, as in Mike Nichols’s Closer (2004); or an operatic tone to the film, as in Francis Ford Coppola’s The Godfather (1972) and The Godfather Part II (1974). With a few exceptions, research on opera and film has appeared in the form of essays in single-authored critical studies, in anthologies, and in journals, with each essay on a specific element or film. Given the hybrid nature of the topic, theory draws on many disciplines, especially film studies, film-music studies, opera studies, media studies, and performance studies. Most research avoids a focus on any single theory or ideology, and instead adopts an eclectic approach that is practical and tailored to the situation. Theories of spectatorship, ontology, and narrative have been beneficial from film studies. Film-music studies has provided key concepts with respect to function (diegesis and its various categories), sound, and voice, the last especially important in Michal Grover-Friedlander’s work. Opera studies offers many tools for the interpretation of the music, although they must be tempered by the conditions of a mechanically reproduced work. Media studies is often central, especially in recent scholarship, but at the very least it infuses most research at some fundamental level.
Game Theory and Psychology
Authors: Colman Andrew M. , Krockow Eva M.
Published: June 2017

Game theory is a branch of decision theory focusing on interactive decisions, applicable whenever the actions of two or more decision makers jointly determine an outcome that affects them all. Strategic reasoning amounts to deciding how to act to achieve a desired objective, taking into account how others will act and the fact that they will also reason strategically. The primitive concepts of the theory are players (decision makers), strategies (alternatives among which each player chooses), and payoffs (numerical representations of the players’ preferences among the possible outcomes of the game). The theory’s fundamental assumptions are (i) that all players have consistent preferences and are instrumentally rational in the sense of invariably choosing an alternative that maximizes their individual payoffs, relative to their knowledge and beliefs at the time; and (ii) that the specification of the game and the players’ preferences and rationality are common knowledge among the players (explained below under Common Knowledge). Game theory amounts to working out the implications of these assumptions in particular classes of games and thereby determining how rational players will act. Psychology is the study of the nature, functions, and phenomena of behavior and mental experience, and two branches of psychology provide bridges to and from game theory: cognitive psychology, concerned with all forms of cognition, including decision making, and social psychology, concerned with how individual behavior and mental experience are influenced by other people. Psychology uses empirical research methods, including controlled experiments, and its usefulness for studying games emerges from three considerations. First, many games turn out to lack determinate game-theoretic solutions, and psychological theories and empirical evidence are therefore required to discover and understand how people play them and how they behave in real-life social interactions with the corresponding strategic structures. Second, human decision makers have bounded rationality and are rarely blessed with full common knowledge; consequently, except in the simplest cases, they do not necessarily choose strategies that maximize their payoffs even when determinate game-theoretic solutions exist. Third, human decision makers have other-regarding preferences and sometimes do not even try to maximize their personal payoffs, without regard to the payoffs of others, and psychological theory and empirical research are therefore required to provide a realistic account of strategic interactions. Psychology has investigated strategic interaction since the 1950s; behavioral game theory, a branch of the emergent subdiscipline of behavioral economics, has used similar techniques since the late 1980s, although a small number of early examples of experimental economics can be traced back to the 1940s.
Decision Making in Surgery for Nonsaccular Posterior Inferior Cerebellar Artery Aneurysms With Special Reference to Intraoperative Assessment of Collateral Blood Flow and Neurophysiological Function
Authors: Narducci Alessandro , Xu Ran , Vajkoczy Peter
Published: June 2017

BACKGROUND

Posterior inferior cerebellar artery (PICA) aneurysms represent a challenging pathology. PICA sacrifice is often necessary, due to the high proportion of nonsaccular aneurysms that can be found in this location. Several treatments are available, but the infrequency of these aneurysms and the increasing number of endovascular techniques have limited the development of a standardized algorithm for cases in which open surgery is indicated.

OBJECTIVE

We present our series of nonsaccular PICA aneurysms, in the attempt to define an algorithm for their surgical management.

METHODS

We retrospectively reviewed the operation database, identifying patients harboring nonsaccular PICA aneurysms who were surgically treated at our institution from 2007 to 2016.

RESULTS

During a 9-yr period, 17 patients harboring 18 nonsaccular PICA aneurysms were surgically treated at our institution. Fourteen (7.7%) aneurysms were located within the proximal PICA (including those located at the vertebral artery–PICA junction), and 4 were located distally. We performed PICA revascularization in 8 (57.1%) cases of proximal aneurysms (n = 4, PICA–PICA bypass; n = 4, occipital artery–PICA bypass). We based our decision whether to perform bypass on intraoperative test occlusion with indocyanine green (ICG) videoangiography and neurophysiological monitoring. In no cases, bypass was necessary for distal aneurysms.

CONCLUSION

For nonsaccular PICA aneurysms, in which vessel occlusion is often necessary, it is possible to adopt a selective use of revascularization techniques. Intraoperative occlusion test with ICG videoangiography and neurophysiological monitoring provides reliable indications, allowing real-time assessment of collateral circulation.
Monitoring Anesthesia Care Delivery and Perioperative Mortality in Kenya Utilizing a Provider-driven Novel Data Collection Tool
Authors: Sileshi Bantayehu , Newton Mark W. , Kiptanui Joash , Shotwell Matthew S. , Wanderer Jonathan P. , Mungai Mary , Scherdin Jon , Harris Paul A. , Vermund Sten H. , Sandberg Warren S. , McEvoy Matthew D.
Published: June 2017

Background

Perioperative mortality rate is regarded as a credible quality and safety indicator of perioperative care, but its documentation in low- and middle-income countries is poor. We developed and tested an electronic, provider report–driven method in an East African country.

Methods

We deployed a data collection tool in a Kenyan tertiary referral hospital that collects case-specific perioperative data, with asynchronous automatic transmission to central servers. Cases not captured by the tool (nonobserved) were collected manually for the last two quarters of the data collection period. We created logistic regression models to analyze the impact of procedure type on mortality.

Results

Between January 2014 and September 2015, 8,419 cases out of 11,875 were captured. Quarterly data capture rates ranged from 423 (26%) to 1,663 (93%) in the last quarter. There were 93 deaths (1.53%) reported at 7 days. Compared with four deaths (0.53%) in cesarean delivery, general surgery (n = 42 [3.65%]; odds ratio = 15.80 [95% CI, 5.20 to 48.10]; P < 0.001), neurosurgery (n = 19 [2.41%]; odds ratio = 14.08 [95% CI, 4.12 to 48.10]; P < 0.001), and emergency surgery (n = 25 [3.63%]; odds ratio = 4.40 [95% CI, 2.46 to 7.86]; P < 0.001) carried higher risks of mortality. The nonobserved group did not differ from electronically captured cases in 7-day mortality (n = 1 [0.23%] vs. n = 16 [0.58%]; odds ratio =3.95 [95% CI, 0.41 to 38.20]; P = 0.24).

Conclusions

We created a simple solution for high-volume, prospective electronic collection of perioperative data in a lower- to middle-income setting. We successfully used the tool to collect a large repository of cases from a single center in Kenya and observed mortality rate differences between surgery types.
Comparison of 4 Methods for Dynamization of Locking Plates: Differences in the Amount and Type of Fracture Motion
Authors: Henschel Julia , Tsai Stanley , Fitzpatrick Daniel C. , Marsh John L. , Madey Steven M. , Bottlang Michael
Published: June 2017

Background:

Decreasing the stiffness of locked plating constructs can promote natural fracture healing by controlled dynamization of the fracture. This biomechanical study compared the effect of 4 different stiffness reduction methods on interfragmentary motion by measuring axial motion and shear motion at the fracture site.

Methods:

Distal femur locking plates were applied to bridge a metadiaphyseal fracture in femur surrogates. A locked construct with a short-bridge span served as the nondynamized control group (LOCKED). Four different methods for stiffness reduction were evaluated: replacing diaphyseal locking screws with nonlocked screws (NONLOCKED); bridge dynamization (BRIDGE) with 2 empty screw holes proximal to the fracture; screw dynamization with far cortical locking (FCL) screws; and plate dynamization with active locking plates (ACTIVE). Construct stiffness, axial motion, and shear motion at the fracture site were measured to characterize each dynamization methods.

Results:

Compared with LOCKED control constructs, NONLOCKED constructs had a similar stiffness (P = 0.08), axial motion (P = 0.07), and shear motion (P = 0.97). BRIDGE constructs reduced stiffness by 45% compared with LOCKED constructs (P < 0.001), but interfragmentary motion was dominated by shear. Compared with LOCKED constructs, FCL and ACTIVE constructs reduced stiffness by 62% (P < 0.001) and 75% (P < 0.001), respectively, and significantly increased axial motion, but not shear motion.

Conclusions:

In a surrogate model of a distal femur fracture, replacing locked with nonlocked diaphyseal screws does not significantly decrease construct stiffness and does not enhance interfragmentary motion. A longer bridge span primarily increases shear motion, not axial motion. The use of FCL screws or active plating delivers axial dynamization without introducing shear motion.
Transcranial Doppler Microemboli Monitoring for Stroke Risk Stratification in Blunt Cerebrovascular Injury
Authors: Bonow Robert H. , Witt Cordelie E. , Mosher Bryan P. , Mossa-Basha Mahmud , Vavilala Monica S. , Rivara Frederick P. , Cuschieri Joseph , Arbabi Saman , Chesnut Randall M.
Published: June 2017

Objectives:

To assess whether microemboli burden, assessed noninvasively by bedside transcranial Doppler ultrasonography, correlates with risk of subsequent stroke greater than 24 hours after hospital arrival among patients with blunt cerebrovascular injury. The greater than 24-hour time frame provides a window for transcranial Doppler examinations and therapeutic interventions to prevent stroke.

Design:

Retrospective cohort study.

Setting:

Level I trauma center.

Patients:

One thousand one hundred forty-six blunt cerebrovascular injury patients over 10 years.

Interventions:

None.

Measurements and Main Results:

We identified 1,146 blunt cerebrovascular injury patients; 54 (4.7%) experienced stroke detected greater than 24 hours after arrival. Among those with isolated internal carotid artery injuries, five of nine with delayed stroke had positive transcranial Dopplers (at least one microembolus detected with transcranial Dopplers) before stroke, compared with 46 of 248 without (risk ratio, 5.05; 95% CI, 1.41–18.13). Stroke risk increased with the number of microemboli (adjusted risk ratio, 1.03/microembolus/hr; 95% CI, 1.01–1.05) and with persistently positive transcranial Dopplers over multiple days (risk ratio, 16.0; 95% CI, 2.00–127.93). Among patients who sustained an internal carotid artery injury with or without additional vessel injuries, positive transcranial Dopplers predicted stroke after adjusting for ipsilateral and contralateral internal carotid artery injury grade (adjusted risk ratio, 2.91; 95% CI, 1.42–5.97). No patients with isolated vertebral artery injuries had positive transcranial Dopplers before stroke, and positive transcranial Dopplers were not associated with delayed stroke among patients who sustained a vertebral artery injury with or without additional vessel injuries (risk ratio, 0.90; 95% CI, 0.21–3.83).

Conclusions:

Microemboli burden is associated with higher risk of stroke due to internal carotid artery injuries, but monitoring was not useful for vertebral artery injuries.
Dendritic cell vaccination for metastatic melanoma: a 14-year monoinstitutional experience
Authors: de Rosa Francesco , Ridolfi Laura , Fiammenghi Laura , Petrini Massimiliano , Granato Anna M. , Ancarani Valentina , Pancisi Elena , Soldati Valentina , Cassan Serena , Bulgarelli Jenny , Framarini Massimo , Tauceri Francesca , Migliori Giuseppe , Brolli Claudia , Gentili Giorgia , Petracci Elisabetta , Nanni Oriana , Riccobon Angela , Ridolfi Ruggero , Guidoboni Massimo
Published: June 2017

Although immunomodulating antibodies are highly effective in metastatic melanoma, their toxicity, related to the activation of T lymphocytes, can be severe. Anticancer vaccines promote a fairly specific response and are very well tolerated, but their effectiveness has yet to be demonstrated. We have been treating patients with advanced melanoma with an autologous dendritic cell vaccine since 2001; to better characterize the safety and efficacy of our product, we designed a retrospective study on all of our patients treated with the vaccine to date. We retrospectively reviewed both case report forms of patients included in clinical trials and medical records of those treated within a compassionate use program. Response was assessed according to the Response Evaluation Criteria In Solid Tumors criteria and toxicity has been graded according to CTCAE 4.0. Although the response rate has been rather low, the median overall survival of 11.4 months and the 1-year survival rate of 46.9% are encouraging, especially considering the fact that data were obtained in a heavily pretreated population and only about one quarter of the patients had received ipilimumab and/or BRAF inhibitors. Multivariate analysis confirmed that the development of an immune response was significantly correlated with a better prognosis (hazard ratio 0.54; P=0.019). The adverse events observed were generally mild and self-limiting. Our analysis confirms the excellent tolerability of our vaccine, making it a potential candidate for combination therapies. As efficacy seems largely restricted to immunoresponsive patients, future strategies should aim to increase the number of these patients.
Bullous Pemphigoid: Use of C4d Immunofluorescent Staining in a Case With Repeated Negative Conventional Direct Immunofluorescence Studies
Authors: Kassaby Sarah S. , Hicks Alexander , Leicht Stuart , Youngberg George A.
Published: June 2017

Direct immunofluorescence (DIF) using frozen section material from a fresh/preserved perilesional biopsy is the gold standard for the immunopathologic diagnosis of bullous pemphigoid (BP). DIF in BP shows linear dermoepidermal junction (DEJ) staining for C3, with or without staining for IgG. In some situations, only a formalin-fixed lesional biopsy is obtained (with no fresh/preserved perilesional biopsy for DIF). In this setting, paraffin section C4d immunohistochemistry has proven to be diagnostically useful, demonstrating linear DEJ positivity for C4d. We present a novel use of C4d staining for the diagnosis of BP, specifically analyzing C4d perilesional frozen section DIF in a case where standard perilesional frozen section DIF for IgG/C3 was available, but was negative. An 80-year-old woman presented with a pruritic bullous lesion on her left upper extremity, clinically thought to represent BP. Lesional histologic findings were typical for BP, but perilesional frozen section DIF staining was negative for IgG and C3. A second set of biopsies processed at a different laboratory yielded the same result. A diagnosis of bullous scabies was considered. Subsequently, perilesional frozen section DIF for C4d was obtained, which showed strong linear DEJ positivity, confirming the diagnosis of BP. DIF for C4d is widely used in transplant pathology, since C4d is persistent in tissue, versus C3. Our case demonstrates that perilesional frozen section DIF staining for C4d may be positive and diagnostic in BP, even when conventional DIF staining for IgG and C3 is negative.
Detection of High-Risk Histologic Features and Tumor Upstaging of Nonmelanoma Skin Cancers on Debulk Analysis: A Quantitative Systematic Review
Authors: Singh Babu , Dorelles Adriana , Konnikov Nellie , Nguyen Bichchau M.
Published: June 2017

BACKGROUND

Histologic analysis of tumor debulks from Mohs micrographic surgery (MMS) or wide local excision may lead to the detection of adverse features missed on initial biopsy.

OBJECTIVE

Determine the incidence of (1) high-risk features on debulk analysis compared with initial biopsy and (2) upstaging of tumors on debulk analysis according to the American Joint Committee of Cancer-7th Edition (AJCC-7) and the Brigham and Women's Alternative (BWH) staging criteria.

MATERIALS AND METHODS

A comprehensive search strategy using PubMed/MEDLINE, Web of Science, and EMBASE was conducted to identify articles published from 1960 to present that detail histology of initial biopsy and debulked tumor.

RESULTS

Fourteen studies, encompassing 2,565 cases of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were included in the data extraction process. BCCs (30.9%) were reclassified from a low-risk histologic subtype to a high-risk subtype on debulk analysis (p < .001). Cases with perineural invasion (89.4%) were detected on debulk analysis. SCC tumors (9.1% and 11.1%) were upstaged according to the AJCC-7 and BWH Alternative criteria, respectively. Ninety percent of high-risk BWH T2b SCCs were inaccurately staged lower on initial biopsy.

CONCLUSION

Tumor debulk analysis in MMS may aid in the identification of additional high-risk features, thereby improving staging accuracy, treatment decisions and patient outcomes.
Early Cleft Lip Repair Revisited: A Safe and Effective Approach Utilizing a Multidisciplinary Protocol
Authors: Hammoudeh Jeff A. , Imahiyerobo Thomas A. , Liang Fan , Fahradyan Artur , Urbinelli Leo , Lau Jennifer , Matar Marla , Magee William , Urata Mark
Published: June 2017

Background:

The optimal timing for cleft lip repair has yet to be established. Advances in neonatal anesthesia, along with a growing body of literature, suggesting benefits of earlier cleft lip and nasal repair, have set the stage for a reexamination of current practices.

Methods:

In this prospective study, cleft lip and nasal repair occurred on average at 34.8 days (13–69 days). Nasal correction was achieved primarily through molding the nasal cartilage without the placement of nasal sutures at the time of repair. A standardized anesthetic protocol aimed at limiting neurotoxicity was utilized in all cases. Anesthetic and postoperative complications were assessed. A 3-dimensional nasal analysis compared pre- and postoperative nasal symmetry for unilateral clefts. Surveys assessed familial response to repair.

Results:

Thirty-two patients were included (27 unilateral and 5 bilateral clefts). In this study, the overall complication rate was 3.1%. Anthropometric measurements taken from 3-dimensional-image models showed statistically significant improvement in ratios of nostril height (preoperative mean, 0.59; postoperative mean, 0.80), nasal base width (preoperative mean, 1.96; postoperative mean, 1.12), columella length (preoperative mean, 0.62; postoperative mean, 0.89; and columella angle (preoperative mean, 30.73; postoperative mean, 9.1). Survey data indicated that families uniformly preferred earlier repair.

Conclusions:

We present evidence that early cleft lip and nasal repair can be performed safely and is effective at improving nasal symmetry without the placement of any nasal sutures. Utilization of this protocol has the potential to be a paradigm shift in the treatment of cleft lip and nasal deformity.
Unusual Cause of Thoracic Wall Pain in a Kayaker: A Case Report
Authors: Evans Guy Morgan , Bhogal Gurjit
Published: June 2017

Chest wall injuries are common in paddle-based sports such as kayaking. We present the case of a 46-year-old amateur kayaker who presented with signs and symptoms in keeping with a rib stress response or fracture. The patient failed to respond to conservative management and subsequent imaging revealed an obstructed left kidney with associated hydronephrosis. This case report highlights the importance of considering the wider differential diagnoses when managing athletes participating in paddle-based sports, especially when symptoms fail to settle with appropriate conservative management.
Differences in Athletic Performance Between Sportsmen With Symptomatic Femoroacetabular Impingement and Healthy Controls
Authors: Mullins Karen , Hanlon Michael , Carton Patrick
Published: June 2017

Objective:

Femoroacetabular impingement (FAI) is a commonly recognized condition in athletes characterized by activity-related hip pain and stiffness, which if left untreated can progress to hip osteoarthritis. The aim of the study was to determine the effect of symptomatic FAI on performance in young athletes based on the hypothesis that athletes with FAI would show deficits in performance compared with healthy controls.

Design:

The functional performance of a cohort of preoperative, competitive sportsmen with symptomatic FAI (FAI group, n = 54), was compared with that of a group of age, sex and activity-level matched controls (n = 66).

Outcome Measures:

Participants performed functional tests including a 10-m sprint, a modified agility T-test, a maximal deep squat test and a single-leg drop jump (reactive strength index). Hip range of motion was assessed by measuring maximal hip flexion, abduction, and internal rotation (at 90 degree hip flexion).

Results:

The FAI group was significantly slower during the 10-m sprint (3%, P = 0.002) and agility T-test (8%, P < 0.001); flexion, abduction, and internal rotation values for the FAI group were reduced compared with controls (P < 0.001). No significant differences between groups were identified for squat depth or reactive strength index. The FAI group also reported higher levels of anterior groin pain during the 10-m sprint, modified agility T-test, and while squatting.

Conclusions:

Many sportsmen with confirmed FAI continue sports participation up to and after diagnosis, despite issues with activity-related pain and stiffness. This study highlights the functional limitations in speed, agility, and flexibility that are likely to be present in this group of FAI patients.
Outcomes and Time to Emergence of Auditory Skills After Cochlear Implantation of Children With Charge Syndrome
Authors: Young Nancy M. , Tournis Elizabeth , Sandy Jenelle , Hoff Stephen R. , Ryan Maura
Published: June 2017

Objective:

Review perioperative complications, benefits, and the timeframe over which auditory skills develop in children with CHARGE syndrome who receive a cochlear implant (CI).

Study Design:

IRB-approved retrospective chart review of children with CHARGE syndrome who had at least 12 months of cochlear implant use.

Setting:

Tertiary care children's hospital.

Patients:

Twelve children, seven males and five females. Mean age implant = 3.5 years (1.7–8.2 yr); mean duration follow-up = 4.7 years (1.5–10.1 yr).

Intervention:

Cochlear implantation.

Main Outcome Measures:

Auditory skills categorized into four levels, temporal bone imaging findings, perioperative complications, time to emergence of speech perception, expressive communication mode.

Results:

All children imaged with magnetic resonance imaging had cochlear nerve deficiency in at least one ear. Speech awareness threshold improved with the CI compared with aided preoperative in 83% of children, with means of 51.7 dB SAT preoperative and 27.1 dB with the CI (p ≤ 0.002). Overall, four children improved to auditory Level 2 (improved detection), three obtained Level 3 (closed-set speech perception), and three had open-set speech perception with their CIs (Level 4) that was first evident at 3.5, 3.3, and 0.8 years postimplant testing. Two children had minimal or limited improvement. One child with hypoplasia of the cochlear nerve obtained open-set levels.

Conclusion:

Auditory skills may develop slowly in children with CHARGE syndrome who receive a CI but most can achieve at least improved detection. In our series, half acquired some speech perception ability. Cochlear nerve deficiency is frequent, but should not be a contraindication to implantation.
Baseline Hepatitis B Virus Titer Predicts Initial Postpartum Hepatic Flare
Authors: Liu Jinfeng , Wang Jing , Qi Caijing , Cao Furong , Tian Zhen , Guo Dandan , Yan Taotao , Li Qian , Yang Shujuan , Fu JianJun , Tang Xianmei , Kou Xiaoni , Liu Na , Jiang Zicheng , Zhao Yingren , Chen Tianyan
Published: June 2017

Background and Goals:

A series of changes in the immune system occur during pregnancy and puerperium. Currently, we aim to characterize both the natural changes in liver inflammation and its association with hepatitis B viremia during this special period.

Patients and Methods:

Chronic hepatitis B (CHB) gravidas were recruited and followed up to 52 weeks postpartum. Virological and biochemical parameters were assessed throughout the period.

Results:

A total of 1097 CHB mothers had finished the entire follow-up including 451 accepting telbivudine, 178 accepting tenofovir, and 468 without antiviral therapy. Among the mothers, 11.94% went through hepatic flare in the first trimester and the rate decreased to 2.1% at the time of delivery. Nevertheless, a much higher frequency (19.78%) was observed in the early postpartum. Interestingly, alanine aminotransferase level decreased along with the development of pregnancy and then suddenly increased in the first month of puerperium. In addition, a downward trend was observed on the titer of HBsAg and HBeAg after delivery. Of note, an obvious higher frequency of alanine aminotransferase flare was revealed in mothers with high viremia (>6 log10 IU/mL). With multivariate analysis, only hepatitis B virus titer at baseline was strongly associated with hepatic flare during early postpartum (95% confidence interval, 1.012-3.049, P=0.045). The predictive rates of hepatic flare at baseline viral load of 6, 7, and 8 log10 IU/mL were 16.67%, 28.30%, and 30.60%, respectively.

Conclusions:

CHB gravidas with high viremia should be monitored closely during entire pregnancy, and extended antiviral therapy is recommend to those mothers with baseline viremia >7 log10 IU/mL.
Highly Concentrated Preterm Formula as an Alternative to Powdered Human Milk Fortifier
Authors: Willeitner Andrea , Anderson Michael , Lewis Jami
Published: June 2017

Objective:

The aim of the study was to assess clinical feasibility and tolerance of concentrated preterm formula at 30 kcal/oz (CPF30) to fortify human milk to a caloric density of 24 kcal/oz, compared to conventional powdered human milk fortifier (PHMF).

Study Design:

Very low birth weight neonates were stratified by birth weight and randomized to receive human milk fortification using CPF30 or PHMF. Infants were monitored from first introduction of human milk fortification, until fortified feeds were well tolerated. Primary outcome was weight gain; secondary outcomes included other measures of feeding intolerance (residual gastric aspirates, feeds held, prokinetic therapy), sepsis, and death. The clinical and study personnel were blinded to the intervention.

Results:

No significant differences in weight gain or other measures of feeding tolerance were demonstrated between CPF30 and PHMF. Macronutrient intake was similar between both groups. Infants with a birth weight of ≥ 1000 g who received CPF30, experienced fewer days NPO (nil per os; nothing per mouth) and a trend toward lower incidence of NEC, compared with those who received PHMF.. The amount of human milk consumed was significantly lower in the CPF30 group.

Conclusions:

Both fortifiers were similarly well tolerated. Fortification of human milk with CPF30 is a safe and feasible alternative to conventional PHMF.
Multidrug-resistant tuberculosis in Brazil: a snapshot from the National Reference Laboratory for Tuberculosis and other Mycobacterioses
Authors: Redner Paulo , Alves da Silva Duanne , Fandinho Montes Fátima C.O. , Antunes Luis Caetano M.
Published: June 2017

Tuberculosis (TB) is a major public health concern worldwide. In 2015, there were approximately 10.4 million new cases of the disease, with 1.4 million deaths. Another major issue regarding TB is the worldwide emergence of drug-resistant strains. The National Reference Laboratory for Tuberculosis and other Mycobacterioses assists the entire network of the Tuberculosis Control Program in Brazil by performing complex diagnostic procedures for the entire country. Here we report the drug susceptibility testing activities of the laboratory between 2013 and 2015. Our numbers highlight the importance of vigilant control programmes to quickly detect, treat and eliminate drug-resistant TB cases, so as to avoid dissemination of drug-resistant forms of this important disease.
Fatigue and physical fitness of mildly disabled persons with multiple sclerosis: a cross-sectional study
Authors: Valet Maxime , Lejeune Thierry , Glibert Yumiko , Hakizimana Jean C. , Van Pesch Vincent , El Sankari Souraya , Detrembleur Christine , Stoquart Gaëtan
Published: June 2017

Fatigue is frequent and disabling in persons with multiple sclerosis (pwMS) with mild neurological disability. These patients also have impaired physical fitness. Whether mildly disabled pwMS are deconditioned, and this deconditioning is linked to fatigue, remains unknown. Our aim is to determine the physical fitness of mildly disabled patients with multiple sclerosis and study its relationship with perceived fatigue and to link perceived fatigue with other parameters. Twenty patients (14 women; mean age: 45.5 years) with mild disability (Expanded Disability Status Scale 0–4) underwent a 2-min walking test, Timed Up-and-Go test, aerobic capacity testing, and isometric knee extension testing to assess strength and neuromuscular fatigability. They completed questionnaires assessing perceived fatigue, psychological status, and physical activity. Correlation coefficients and multivariate regression were used to analyze the relationships among variables. Seventeen (85%) patients reported a high level of fatigue. Thirteen (65%) patients had subnormal aerobic capacity. Fatigue was weakly to moderately associated with aerobic capacity, mobility, walking capacity, depression, and neuromuscular fatigability. An association of disease duration, aerobic capacity, and the neuromuscular fatigability index explained 65.1% of fatigue. A high proportion of pwMS with mild neurological disability are fatigued and deconditioned. Perceived fatigue is linked to aerobic capacity, neuromuscular fatigability, depression, mobility, and walking capacity. Focusing on these parameters could help in the management of fatigue.
DICER1 Mutations Are Consistently Present in Moderately and Poorly Differentiated Sertoli-Leydig Cell Tumors
Authors: de Kock Leanne , Terzic Tatjana , McCluggage W. Glenn , Stewart Colin J.R. , Shaw Patricia , Foulkes William D. , Clarke Blaise A.
Published: June 2017

Ovarian Sertoli-Leydig cell tumors (SLCTs) are uncommon sex cord-stromal tumors associated with both germ-line and somatic DICER1 mutations, the frequency of which has varied widely in different studies (0% to 62.5%). The current World Health Organization Classification includes 3 histologic types of SLCTs (well-differentiated, moderately differentiated, and poorly differentiated); heterologous elements and/or retiform patterns may be present in moderately and poorly differentiated neoplasms. We investigated the frequency of DICER1 mutations in a series of 38 ovarian tumors initially diagnosed as SLCTs, and explored whether identified mutations were associated with specific morphologic features. Specialist pathology review performed blinded to molecular results confirmed 34 tumors to be SLCTs (22 moderately differentiated, 8 poorly differentiated; 4 well-differentiated), while the remaining 4 neoplasms were considered not to represent SLCTs. Of the 34 cases diagnosed as SLCTs, 30 (88%) harbored ≥1 DICER1 mutation. All 30 moderately differentiated/poorly differentiated SLCTs contained mutations, but we did not find deleterious DICER1 mutations in the 4 well-differentiated SLCTs. Our study reports the highest DICER1 mutation frequency to date in SLCTs, with 100% of moderately differentiated and poorly differentiated tumors being DICER1-mutated. This suggests that DICER1 mutation may be a defining feature of these neoplasms. Although the number of cases is limited, well-differentiated SLCTs appear to be DICER1-independent. Moderately differentiated and poorly differentiated SLCT components often coexist with each other and form part of a spectrum, while well-differentiated SLCTs usually occur in pure form, suggesting that fundamentally, these represent 2 separate and independent tumor types with a different pathogenesis. We suggest that all patients with ovarian SLCTs undergo germ-line DICER1 mutation testing.