bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating potential competitive interactions following stocking through trophic niche breadth
Authors: Taylor Matthew D. , Lowry Michael B. , Becker Alistair
Published: July 2018

Responsible fisheries enhancement should include comprehensive monitoring programs to detect ecological effects of fish releases and support adaptive management. Competition for food and shelter is one such impact, and density-dependent effects may occur if release numbers are above levels that the ecosystem can support. Herein we present a novel application of trophic niche breadth estimated from stable isotope data to examine potential competitive interactions arising from eastern king prawn (Melicertus plebejus) stocking. Eastern king prawn and potential competitors (Macrobrachium intermedium, Atherinosoma microstoma, Leptatherina presbyteroides, Ambassis jacksoniensis and Gobiopterus semivestitus) were sampled from two stocked and two reference estuaries, before and after stocking. Stable isotope ratios were measured and used to model trophic overlap and trophic niche breadth. A statistically significant increase in niche breadth was evident for two competing species in one stocked estuary, and one competing species in another. M. intermedium, the species that had the greatest trophic overlap with eastern king prawn, did not show any change in niche breadth. The potential for competition and the role of environmental variability (including rainfall and run-off, mouth opening regime and seasonal changes) in driving the patterns observed are discussed. This approach shows promise for monitoring competitive effects arising from aquaculture-based fisheries enhancements in the future.
Principles and practice of acquiring drone-based image data in marine environments
Authors: Joyce K. E. , Duce S. , Leahy S. M. , Leon J. , Maier S. W.
Published: July 2018

With almost limitless applications across marine and freshwater environments, the number of people using, and wanting to use, remotely piloted aircraft systems (or drones) is increasing exponentially. However, successfully using drones for data collection and mapping is often preceded by hours of researching drone capabilities and functionality followed by numerous limited-success flights as users tailor their approach to data collection through trial and error. Working over water can be particularly complex and the published research using drones rarely documents the methodology and practical information in sufficient detail to allow others, with little remote pilot experience, to replicate them or to learn from their mistakes. This can be frustrating and expensive, particularly when working in remote locations where the window of access is small. The aim of this paper is to provide a practical guide to drone-based data acquisition considerations. We hope to minimise the amount of trial and error required to obtain high-quality, map-ready data by outlining the principles and practice of data collection using drones, particularly in marine and freshwater environments. Importantly, our recommendations are grounded in remote sensing and photogrammetry theory so that the data collected are appropriate for making measurements and conducting quantitative data analysis.
How do students cope with machine translation output of multiword units? An exploratory study
Authors: Daems Joke , Carl Michael , Vandepitte Sonia , Hartsuiker Robert J. , Macken Lieve
Published: July 2018

In this chapter, we take a closer look at students’ post-editing of multiword units (MWUs) from English into Dutch. The
data consists of newspaper articles post-edited by translation students as collected by means of advanced keystroke
logging tools.

We discuss the quality of the machine translation (MT) output for various types of MWUs, and compare this with the
final post-edited quality. In addition, we examine the external resources consulted for each type of MWU. Results
indicate that contrastive MWUs are harder to translate for the MT system, and harder to correct by the student
post-editors than non-contrastive MWUs. We further find that consulting a variety of external resources helps student
post-editors solve MT problems.
Multiword expressions in multilingual information extraction
Authors: Thurmair Gregor
Published: July 2018

Multilingual Information Extraction requires significant Multiword Expressions (MWE) processing as many such items are
multiwords. The lexical representation of MWEs supports large bilingual lexicons (for Persian, Pashto, Turkish,
Arabic); multiwords are represented like single words, extended by two annotations: MWE head, and lemma plus part of
speech for the MWE parts. In text analysis, MWEs are recognised as part of the parsing process, mot as pre- or
post-processing components. The analysis design extends the X-bar scheme by a level for multiword rules. In transfer,
MWEs are translated as elementary nodes like single word lemmata, to present key concepts for relevance judgement in
Information Extraction. Evaluation shows that 90% of the MWE patterns in the lexicon can be analysed with about 150
MWE-specific rules, and that more than 90% of text document tokens are covered by the proposed integrated single and
multiword processing.
A native origin for Present-Day Englishthey, their, them
Authors: Cole Marcelle
Published: July 2018

It is commonly held that Present-Day Englishthey, their, themare not descended from Old English but derive from the Old Norse third-person plural pronounsþeir, þeira, þeim. This paper argues that the early northern English orthographic and distributional textual evidence agrees with an internal trajectory for the ‘þ-’ type personal pronouns in the North and indicates an origin in the Old English demonstrativesþā, þāra, þām. The Northern Middle English third-person plural pronominal system was the result of the reanalysis from demonstrative to personal pronoun that is common cross-linguistically in Germanic and non-Germanic languages alike.
‘Biolinguistics’
Authors: Levine Robert
Published: July 2018

The ‘Biolinguistics’ program seeks to establish specific neuroanatomical models corresponding to the representations and operations characterizing the species-specific language faculty in human beings. Yet after decades of research, no neural structures corresponding to specific linguistic structures, rules, constraints or principles have ever been identified. A key to biolinguistics’ failure is, I suggest, its long-term adherence to two dubious assumptions: (i) a kind of literalism in envisaging the relationship between neural anatomy and linguistic representations, reflecting a seriously misconstrual of Marr’s (1982) tripartite division of cognition, and (ii) a view of such representations as objects fundamentally different from other components of human cognitive capacity. (ii) rests on the premise that phrase markers are the optimal formal representation of natural language sentences, despite major empirical difficulties that syntactic accounts based hierarchical phrase structure face in handling a wide variety of grammatical patterns, including non-canonical coordinations and ellipsis constructions. In contrast, proof-theoretic approaches such as type-logical grammar do not face these difficulties, and their foundational assumptions link language to the higher-order cognitive functions supporting deductive reasoning. This conclusion suggests a promising alternative to the current, essentially result-free ‘Biolinguistic’ paradigm.
Describing linguistic objects in a realist way
Authors: Lieb Hans-Heinrich
Published: July 2018

The essay is divided into four Parts A to D: Part A (Sections 1 to 3), Topic and background; B. Grammatical description (Sections 4 to 6); C. Grammars and theories of language: motivating axiomatization (Sections 7 to 9); and D. Grammars as axiomatic theories (Sections 10 and 11). The essay characterizes grammatical description, both informal and formal, from a realist point of view as the description of abstract objects, not to be confused with the concrete data to which the description must be ultimately related. The importance of theories of natural human languages for grammars is emphasized, also in view of comparative grammar writing, and is demonstrated by the detailed analysis of a grammatical statement taken from an informal grammar. There is a discussion of adequacy problems that arise in current frameworks for formal grammars due to an absence of theories of language from such frameworks. A format for axiomatic grammars is outlined by which an axiomatic grammar ‘presupposes’ a theory of language, in a technical sense. The view of grammars is non-reductionist; concepts of theory integration are characterized that allow us to integrate grammars with linguistic and non-linguistic theories. The conception of linguistics itself is non-reductionist, too, through applying a concept of inter-discipline that relates linguistics to other disciplines.
Optimisation of the CZTSe thin film composition obtained by a sequential electrodeposition process
Authors: Katırcı Ramazan , Walls John Michael
Published: July 2018

The influence of the elemental composition of CuZnSn coatings deposited by electrodeposition on the formation of the Cu2ZnSnSe4 crystal structure following a selenisation process was investigated using X-ray diffraction, scanning electron microscopy and Raman spectroscopy. This study showed that the optimum alloy ratio to achieve the Cu2ZnSnSe4 crystal without impurity phases was in the range of 0.37–0.50 for Cu/(Zn+Sn) and 2.5–4 for Zn/Sn.
Ca2+tapulting HSCs into action
Authors: Guitart Amelie V. , Finch Andrew J. , Kranc Kamil R.
Published: July 2018

In this issue of JEM, Umemoto et al. (https://doi.org/10.1084/jem.20180421) demonstrate that calcium influx stimulates mitochondrial metabolism and initiates proliferation in hematopoietic stem cells (HSCs). Extracellular adenosine, sourced from surrounding hematopoietic progenitors, inhibits this calcium influx, thereby suppressing mitochondrial metabolism and promoting HSC quiescence. This is the first demonstration that a calcium–mitochondria pathway regulates HSC division.
Biaryl sulfonamide motifs up- or down-regulate ion channel activity by activating voltage sensors
Authors: Liin Sara I. , Lund Per-Eric , Larsson Johan E. , Brask Johan , Wallner Björn , Elinder Fredrik
Published: July 2018

Voltage-gated ion channels are key molecules for the generation of cellular electrical excitability. Many pharmaceutical drugs target these channels by blocking their ion-conducting pore, but in many cases, channel-opening compounds would be more beneficial. Here, to search for new channel-opening compounds, we screen 18,000 compounds with high-throughput patch-clamp technology and find several potassium-channel openers that share a distinct biaryl-sulfonamide motif. Our data suggest that the negatively charged variants of these compounds bind to the top of the voltage-sensor domain, between transmembrane segments 3 and 4, to open the channel. Although we show here that biaryl-sulfonamide compounds open a potassium channel, they have also been reported to block sodium and calcium channels. However, because they inactivate voltage-gated sodium channels by promoting activation of one voltage sensor, we suggest that, despite different effects on the channel gates, the biaryl-sulfonamide motif is a general ion-channel activator motif. Because these compounds block action potential–generating sodium and calcium channels and open an action potential–dampening potassium channel, they should have a high propensity to reduce excitability. This opens up the possibility to build new excitability-reducing pharmaceutical drugs from the biaryl-sulfonamide scaffold.
Emotional Expressions as Speech Act Analogs
Authors: Scarantino Andrea
Published: July 2018

In this article I articulate the Theory of Affective Pragmatics, which combines insights from the Basic Emotion View and the Behavioral Ecology View of emotional expressions. My core thesis is that emotional expressions are ways of manifesting one’s emotions but also of representing states of affairs, directing other people’s behaviors, and committing to future courses of actions. Since these are some of the main things we can do with language, my article’s take home message is that, from a communicative point of view, much of what we can do with language we can also do with nonverbal emotional expressions.
Natural Kinds, Mind Independence, and Defeasibility
Authors: Ereshefsky Marc
Published: July 2018

A standard requirement on natural kinds is that they be mind independent. However, many kinds in the human and social sciences, even the natural sciences, depend on human thought. This article suggests that the mind independence requirement on natural kinds be replaced with the requirement that natural kind classifications be defeasible. The defeasibility requirement does not require that natural kinds be mind independent, so it does not exclude mind dependent scientific kinds from being natural kinds. Furthermore, the defeasibility requirement captures the idea that natural kind classifications are tools for investigating the empirical world.
Self-controlled multilevel writing architecture for fast training in neuromorphic RRAM applications
Authors: García-Redondo Fernando , López-Vallejo Marisa
Published: July 2018

Memristor crossbar arrays naturally accelerate neural networks applications by carrying out parallel multiply-add operations. Due to the abrupt SET operation characterizing most RRAM devices, on-chip training usually requires either from iterative write/read stages, large and variation-sensitive circuitry, or both, to achieve multilevel capabilities. This paper presents a self-controlled architecture to program multilevel devices with a short and fixed operation duration. We rely on an ad hoc scheme to self-control the abrupt SET, choking the writing stimulus as the cell addresses the desired level. To achieve this goal, we make use of the voltage divider concept by placing a variable resistive load in series with the target cell. We validated the proposal against thorough simulations using RRAM cells fitting extremely fast physical devices and a commercial 40 nm CMOS technology, both exhibiting variability. For every case the proposed architecture allowed progressive and almost-linear resistive levels in each

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Wireless Sensor Network on LPG Gas Leak Detection and Automatic Gas Regulator System Using Arduino
Authors: Dewi L , Somantri Y
Published: July 2018

Most of LPG explosions are caused by undetected gas leakage in the pre-detection condition. So that, LPG detection system is needed. The purpose of this system is to detect gas leakage, neutralize it, and prevent the explosion. Gas leakage could happen due to improper regulator installation or the hose is broken. This detection should not work in just one location because gas can leak at the gas regulator and its hose. Therefore, Wireless Sensor Network (WSN) is one of the methods that suitable for detecting gas leakage in the wider area. This method uses two or more gas sensors to detect leakage in two or more locations around the gas tube and its distribution line. WSN system works based on gas sensor MQ-6 and wireless module Bluetooth HC-05. Explosion prevention system works based on alarm/buzzer, exhaust fan, and automatic gas regulator. If the gas leaks, the sensor will send its data wirelessly to Arduino. Then, explosion prevention system will be activated. The system will turn the alarm/buzzer on, automatically releases gas regulator, and neutralizes the air with the exhaust fan. Both systems will be fully controlled by Arduino platform.
Archaeal imaging: leading the hunt for new discoveries
Authors: Bisson-Filho Alexandre W. , Zheng Jenny , Garner Ethan
Published: July 2018

Since the identification of the archaeal domain in the mid-1970s, we have collected a great deal of metagenomic, biochemical, and structural information from archaeal species. However, there is still little known about how archaeal cells organize their internal cellular components in space and time. In contrast, live-cell imaging has allowed bacterial and eukaryotic cell biologists to learn a lot about biological processes by observing the motions of cells, the dynamics of their internal organelles, and even the motions of single molecules. The explosion of knowledge gained via live-cell imaging in prokaryotes and eukaryotes has motivated an ever-improving set of imaging technologies that could allow analogous explorations into archaeal biology. Furthermore, previous studies of essential biological processes in prokaryotic and eukaryotic organisms give methodological roadmaps for the investigation of similar processes in archaea. In this perspective, we highlight a few fundamental cellular processes in archaea, reviewing our current state of understanding about each, and compare how imaging approaches helped to advance the study of similar processes in bacteria and eukaryotes.
Can Cerebral Near-infrared Spectroscopy Predict Cerebral Ischemic Events in Neurosurgical Patients? A Narrative Review of the Literature
Authors: Khozhenko Andrey , Lamperti Massimo , Terracina Sergio , Bilotta Federico
Published: July 2018

Cerebral near-infrared spectroscopy (NIRS) is considered a valuable noninvasive modality for cerebral oxygenation monitoring during cardiovascular surgery and cardiac arrest. We assessed the capability of cerebral NIRS to predict cerebral desaturation and the related neurological outcomes in neurosurgical patients. A literature search in different electronic medical databases was performed from inception to January 2018. A total of 286 citations were found and finally 48 studies were retrieved, only 7 of these were eligible and included for review. A meta-analysis was not feasible because of high heterogeneity of patients’ groups, different NIRS techniques used in the studies and different outcome criteria selected. The qualitative assessment showed controversial data on the threshold value of cerebral near-infrared spectroscopy used for detecting cerebral ischemia in neurosurgical patients. The evidence on the selected studies is not strong enough, at the moment, to recommend cerebral NIRS as a mandatory monitor to detect cerebral deoxygenation able to predict the future neurological outcome in neurosurgical patients. Further studies are needed to validate a threshold value for cerebral ischemia and the relationship between NIRS-detected cerebral desaturation and clinical outcome in the neurosurgical population.
Advising the MSIII for audition rotations to maximize chances of matching with an orthopaedic residency program
Authors: Loeffelholz Zachary , Cannada Lisa K.
Published: July 2018

Every year there are several hundred applicants who do not match into their desired specialty. Orthopaedics is no exception. However, working with the 3rd year medical student in preparation for audition rotations can help in maximizing their success. It is important that the advisor know the students, their background, interests and qualifications. This article outlines a plan and provides tips in preparing the 3rd year medical student for the selection of and maximizing their performance on audition rotations. This can translate into a successful match experience.
Long-term comparative study between transforaminal and interlaminar epidural injection of steroids in lumbar radiculopathy due to single-level disc herniation
Authors: Soliman Amr Atteya , Fahmy Mahmoud
Published: July 2018

Background:

Epidural steroid injection is commonly used in treating radicular pain secondary to lumbar disc prolapse, which is a common clinical condition. Two main techniques were suggested to deliver the steroids: interlaminar and transforaminal injections.

Methods:

From June 2013 to March 2016 we performed a prospective study on 40 patients between the ages of 19 and 55 yr. All the patients had low back pain and lower limb radiculopathy secondary to a single-level lumbar disc prolapse. The pupose of this study was to compare interlaminar and tranforaminal injection techniques regarding the short-term and long-term improvement of back pain, leg pain, and functional outcomes. On admission the patients were evaluated using a visual analogue scale (VAS) for back and leg pain, and the Oswestry Disability Index (ODI) for functional capacity. They were followed for a period of 47 to 49 wk (mean 48 wk), and clinical and functional outcomes were assessed using the same tools for evaluation.

Results:

We found that VAS and ODI improved in both the transforaminal and interlaminar groups both short and long term, but the only statistically significant improvement was in VAS for leg pain and the ODI in the transforaminal group.

Conclusions:

Epidural steroid injection is generally a safe procedure, but the transforaminal approach gives better results than the interlaminar approach in relieving radicular pain and improving functional outcome.
Radiographic evaluation of intercristal line in North Cyprus population
Authors: Aydin Deniz , Ertugrul Mut Senem , Harman Ferhat
Published: July 2018

Background:

The intercristal line (ICL) is a beneficial guideline for lumbar procedures but it can differ according to the age, gender, and ethnicity of the patient. The aim of this study was to measure the lumbar vertebrae level crossed by the ICL in a North Cyprus population.

Methods:

In this study, anteroposterior lumbosacral radiographs of 350 patients were evaluated retrospectively. The ICL was drawn as it connects the most superior points of the iliac crests on anteroposterior lumbosacral radiographs. Patients were grouped by age (18 to 40 yr and 41-65 yr) and gender. Both L4 and L5 vertebrae were divided into three equal parts with horizontal lines. Each part and the L4-L5 disc space were numbered ascending from 1 to 7 from the upper border of L4 vertebrae to the lower border of L5 vertebrae. The range of lumbar vertebrae levels crossed by the ICL was recorded and compared between different age and gender groups.

Results:

A total of 296 anteroposterior lumbosacral radiographs were included in the study. One hundred and sixty-nine (57%) were men and 127 (43%) were women. The ICL level was found between the lower third of L4 and upper third of L5 in most spines (80%). The ICL level distribution was found between the upper third of L4 and middle third of L5 in all patients. It was observed that the ICL level was lower in younger people and in women.

Conclusions:

In 80% of a North Cyprus population, the ICL level was found to be between the lower third of L4 and upper third of L5, and depended on age and gender.
Biochemistry, Physiology, and Tissue Interactions of Contemporary Biodegradable Injectable Dermal Fillers
Authors: Herrmann Jennifer L. , Hoffmann Rachel K. , Ward Chloe E. , Schulman Joshua M. , Grekin Roy C.
Published: July 2018

BACKGROUND

Injectable dermal fillers are becoming increasingly popular for soft tissue augmentation and rejuvenation. Most contemporary biodegradable products are derived from hyaluronic acid, calcium hydroxylapatite, or poly-l-lactic acid. Achievement of desired cosmetic outcomes is largely dependent on selection of the optimal injectable product based on the chemical composition, the physiologic interactions with surrounding tissue, product longevity, and a thorough understanding of potential adverse reactions.

OBJECTIVE

To review and describe the biochemistry, physiology, and tissue interactions of the most commonly used contemporary biodegradable dermal fillers.

METHODS

A thorough review of the literature was performed with additional review of pertinent clinical cases and corresponding histopathology.

RESULTS

This article provides a comprehensive review of the biochemistry, physiology, and potential tissue interactions of the most commonly used biodegradable dermal fillers. The underlying biochemical properties of each product and how they contribute to specific physiologic and adverse tissue reactions is described.

CONCLUSION

Understanding of the innate differences in the physical properties, and physiologic responses to soft tissue fillers allows clinicians to achieve desired aesthetic outcomes with fewer adverse events.
Estimation of Prognosis in Invasive Cutaneous Melanoma: An Independent Study of the Accuracy of a Gene Expression Profile Test
Authors: Greenhaw Bradley N. , Zitelli John A. , Brodland David G.
Published: July 2018

BACKGROUND

Cutaneous melanomas (CMs) with similar clinical and histopathologic features can harbor differing capacities for metastasis. A validated gene expression profile (GEP) test offers prognostic information by classifying CMs as low risk (Class 1A/1B) or high risk (Class 2A/2B) for metastasis.

OBJECTIVE

The authors sought to perform an independent study of the predictive accuracy of the GEP test, to determine what clinical and histopathologic features predict high-risk classification, and to evaluate how intermediate classes (1B & 2A) performed clinically.

MATERIALS AND METHODS

Using our institution's prospectively collected melanoma registry, the authors identified patients who had been treated for CM within the last 5 years and undergone GEP testing. Clinical, histopathologic, and outcomes data were analyzed. A subcohort of patients with known metastatic disease were identified and tested.

RESULTS

The GEP test accurately identified 77% of metastatic CMs as high risk (Class 2). The GEP had a negative predictive value of 99% for Class 1 CMs. Class 2 CMs were 22 times more likely to metastasize.

CONCLUSION

The GEP test's performance in our independent cohort corresponded with previous industry-sponsored studies and proved to be a helpful clinical prognostic tool with the potential to direct patient care protocols.
Quantification of Changes in Visual Function During Disease Development in a Mouse Model of Pigmentary Glaucoma
Authors: Grillo Stephanie L. , Montgomery Christa L. , Johnson Heather M. , Koulen Peter
Published: July 2018

Purpose:

We investigated the relationship between visual parameters that are commonly affected during glaucomatous disease progression with functional measures of retina physiology using electroretinography and behavioral measures of visual function in a mouse model of glaucoma. Electroretinogram components measuring retinal ganglion cell (RGC) responses were determined using the non-invasive Ganzfeld flash electroretinography (fERG) to assess RGC loss in a mouse model of glaucoma.

Methods:

Intraocular pressure (IOP), behaviorally assessed measures of visual function, namely visual acuity and contrast sensitivity as well as fERG responses were recorded in 4- and 11-month-old male DBA/2 mice. Scotopic threshold response (STR) and photopic negative response components as well as oscillatory potentials (OPs) were isolated from fERG responses and correlated with IOP, optomotor reflex measurements, and RGC counts.

Results:

The 11-month-old DBA/2 mice had significantly elevated IOP, reduced visual performance, as assessed behaviorally, significant RGC loss, deficits in standardized fERG responses, reduced STRs, and differences in OP amplitudes and latencies, when compared with 4-month-old mice of the same strain. STRs and OPs correlated with some visual and physiological parameters. In addition, elevated IOP and RGC loss correlated positively with measures of visual function, specifically with surrogate measures of RGC function derived from fERG.

Conclusions:

Our data suggest that RGC function as well as interactions of RGCs with other retinal cell types is impaired during glaucoma. In addition, a later OP wavelet denoted as OP4 in this study was identified as a very reproducible indicator of loss of visual function in the glaucoma mouse model.
Outcomes of Patients With Cirrhosis Undergoing Orthopedic Procedures
Authors: Parikh Neehar D. , Chang Yu-Hui , Tapper Elliot B. , Mathur Amit K.
Published: July 2018

Introduction:

The population of patients with cirrhosis is growing and shifting toward a more elderly demographic and thus are at risk of developing orthopedic complications. There is lack of data on safety of orthopedic procedures in this population.

Methods:

We performed an analysis of the Nationwide Inpatient Sample from 2005 to 2011 for patients undergoing hip arthroplasty, knee arthroplasty, and spinal laminectomy/fusion, stratified by presence of cirrhosis. The primary endpoint was in-hospital mortality and secondary endpoints included length of stay (LOS) and costs.

Results:

There were 693,610 inpatient stays for orthopedic procedures conducted during the study period, with 3014 (0.43%) patients coded as having cirrhosis. Patients with cirrhosis had a lower median age (62 vs. 66 y; P<0.001) and were more likely to be male (52.3% vs. 41.1%; P<0.001). The inpatient mortality rate was significantly higher in patients with cirrhosis (2.4% vs. 0.4%; P<0.001) as was median LOS (4 vs. 3 d; P<0.001) and mean costs ($19,321 vs. $18,833; P<0.001). Patients with decompensated cirrhosis (vs. compensated cirrhosis) had significantly higher inpatient mortality rates (5.8% vs. 1.1%; P<0.001) with higher LOS and costs (P<0.001). On multivariable analysis, cirrhosis was associated with an increased risk of mortality (odds ratio, 4.22; 95% confidence interval, 2.92-6.10). Hospital cirrhosis volume was inversely associated with mortality, while hospital orthopedic procedure volumes had an inconsistent impact on outcomes.

Conclusions:

Inpatient orthopedic procedures in patients with cirrhosis result in high postoperative mortality, LOS, and costs. Careful patient selection is warranted to optimize cirrhosis patient postoperative outcomes.
Multiple protein disulfide isomerases support thrombosis
Authors: Essex David W. , Wu Yi
Published: July 2018

Purpose of review

The present review provides an overview of recent findings on new members of the protein disulfide isomerase (PDI) family required for thrombosis.

Recent findings

Twenty years ago PDI was shown to mediate platelet aggregation, and 10 years ago PDI was shown to support thrombosis in vivo. Subsequently, other members of this endoplasmic reticulum family of enzymes, ERp57 and ERp5, were demonstrated to support thrombosis. A fourth member, ERp72, was recently shown to be required for platelet accumulation and fibrin deposition in vivo. None of these enzymes can individually support these processes. Moreover, aggregation of platelets deficient in a specific PDI is only recovered by the PDI that is missing. This implies that each PDI has a distinct role in activation of the αIIbβ3 fibrinogen receptor and platelet aggregation. Free thiols can be labeled in both subunits of αIIbβ3, suggesting cysteine-based reactions are involved in relaying conformational changes from the cytoplasmic tails to the integrin headpiece of this integrin.

Multiple members of the PDI family support platelet function, and hemostasis and thrombosis with distinct roles in these processes. The individual cysteine targets of each enzyme and how these enzymes are integrated into a network that supports hemostasis and thrombosis remain to be elucidated.
Mixed Adenoma Well-differentiated Neuroendocrine Tumor (MANET) of the Digestive System
Authors: La Rosa Stefano , Uccella Silvia , Molinari Francesca , Savio Antonella , Mete Ozgur , Vanoli Alessandro , Maragliano Roberta , Frattini Milo , Mazzucchelli Luca , Sessa Fausto , Bongiovanni Massimo
Published: July 2018

Mixed neuroendocrine-nonneuroendocrine neoplasm (MiNEN) consisting of adenoma and well-differentiated neuroendocrine tumor (NET) has been recently defined as “MANET.” However, the clinico-pathologic and pathogenetic features of this entity are not thoroughly studied. We examined the clinico-pathologic features of 12 MANETs by expanding their p53 and β-catenin expression profiles as well as the presence of microsatellite instability and KRAS, BRAF, and PIK3CA mutations in the 2 tumor components. In all cases, the adenomatous component represented the larger part of the lesions and the NET was localized in the deep central portion of polyps. In 9 cases the latter was represented by NET G1, in 2 by NET G2, and in 1 by NET G3. In all cases, the glandular and NET components were intimately admixed, with zone of transition between the tumor components. The NET component was p53 negative in all cases and 3 of 8 cases showed variable nuclear positivity for β-catenin. All patients with follow-up data were alive and free of disease after a mean follow-up time of 9 years. No mutations in KRAS, BRAF, and PIK3CA genes and no microsatellite instability were found in both tumor components. Review of the literature also identified 59 previously reported MANETs and no tumor-related death has been found. Like mixed adenoneuroendocrine carcinomas, a high-grade malignant form of MiNENs with a poorly differentiated neuroendocrine carcinoma component, a common origin for both tumor constituents may be hypothesized. Moreover, the current series provides evidence that MANET is an indolent disease that needs to be distinguished from aggressive high-grade MiNENs.
Are Enterocolic Mucosal Mast Cell Aggregates Clinically Relevant in Patients Without Suspected or Established Systemic Mastocytosis?
Authors: Johncilla Melanie , Jessurun Jose , Brown Ian , Hornick Jason L. , Bellizzi Andrew M. , Shia Jinru , Yantiss Rhonda K.
Published: July 2018

The World Health Organization considers enterocolic mast cell aggregates with atypical morphologic and/or immunohistochemical features diagnostic of systemic mastocytosis mostly because published data are heavily influenced by inclusion of symptomatic patients with systemic disease. We occasionally encounter atypical mast cells in gastrointestinal biopsy samples from patients in whom systemic mastocytosis is not suspected. The aim of this study was to describe the clinicopathologic features and implications of atypical enterocolic mast cell aggregates in 16 patients without suspected or established systemic mastocytosis. Mast cell infiltrates were assessed for morphology, distribution, associated inflammatory cells, and CD117 and CD25 immunoexpression. Most (63%) patients were women; 15 underwent endoscopic examination for screening (n=7), abdominal pain (n=3), diarrhea (n=3), changing bowel habits (n=1), and dysphagia (n=1). Mast cell aggregates were detected in 1 colectomy specimen for cancer. Colonic involvement was most common (n=14) and resulted in polypoid (n=10), edematous (n=2), or normal (n=3) mucosae. All cases featured CD117/CD25+, ovoid mast cells concentrated beneath the epithelium, or diffusely involving the entire mucosal thickness. Eosinophils were numerous and obscured mast cells in 63% of cases. Spontaneous resolution of symptoms occurred in all patients (mean follow-up: 54 mo), and asymptomatic patients remained symptom-free (mean follow-up: 17 mo). Of 4 patients evaluated for systemic mastocytosis, 3 had negative bone marrow biopsies and one lacked a KIT mutation in peripheral blood. We conclude that, although careful clinical assessment of patients with incidental enterocolic mast cell aggregates is reasonable, labeling them with a systemic hematologic disorder may not be justified.
Facial Implants: Controversies and Criticism. A Comprehensive Review of the Current Literature
Authors: Rojas Yoel A. , Sinnott Catherine , Colasante Cesar , Samas John , Reish Richard G.
Published: July 2018

Background:

Polyethylene (Medpor) and silicone are two of the most popular materials used today for facial skeleton implantation. Previous studies have identified common complications with the use of these implants, but patient follow-up has been short. This review of the literature examines complications and patient follow-up in cases using Medpor and silicone implants for reconstructive and aesthetic operations of the mid and lower face over the past 20 years.

Methods:

A literature search was conducted through the PubMed database. Keywords used were as follows: (“mandible implants” or “malar implants” or “chin implants”) AND (“reconstruction” or “augmentation”) AND (“Medpor” or “silicone”).

Results:

There were nine studies with 626 patients in the Medpor group and five studies with 365 patients in the silicone group. The silicone group had a higher incidence of infections and displacements. The Medpor group showed a higher incidence of prominence problems. Exposure/extrusion rates were low for both implant types. Chin and mandibular implants were the safest, whereas malar implants had a high incidence of prominence problems. The average follow-up for Medpor was 36.6 months and 24 months for silicone. There were wide ranges of follow-up times, from 2 weeks up to 15 years. A limited number of articles included an averaged time within their ranges. Reported follow-up times were not linked to specific complications.

Conclusions:

Medpor implantation is more common than silicone. Complication rates are low with the use of both materials. Patient follow-up is deficient and has not improved in the past 20 years, raising questions on the reliability of complication rates.
Incidental Detection of Tracer Avidity in Liposarcoma on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT
Authors: Malik Dharmender , Mittal Bhagwant Rai , Kumar Rajender , Singh Harmandeep , Bhattacharya Anish , Singh Shrawan Kumar
Published: July 2018

68Ga-labeled prostate-specific membrane antigen (PSMA) PET/CT is emerging as new reference standard for imaging of prostate cancer because of superb diagnostic performance in disease staging and recurrence detection. However, a number of isolated reports have been published recently regarding the nonspecific uptake of 68Ga-PSMA in nonprostatic benign or malignant pathologies. We describe the case of a 76-year-old man who underwent 68Ga-labeled PSMA PET/CT for suspicion of prostate cancer. Whole-body PET/CT of whom revealed tracer avidity in lipomatous lesion involving the left sartorius muscle. Histopathologic examination of lesion revealed a well-differentiated liposarcoma.
Unsuspected Metastases to Muscles in Osteosarcoma Detected on 18F-Sodium Fluoride PET-CT
Authors: Usmani Sharjeel , Marafi Fahad , Rasheed Rashid , Bakiratharajan David , Al Maraghy Muneera , Al Kandari Fareeda
Published: July 2018

Metastasis of osteosarcoma to the muscles is extremely rare. 18F-sodium fluoride (NaF) is a bone-seeking agent that can also localize extraosseous calcifying lesions. We report the case of a 33-year-old woman with osteosarcoma of the right fibula treated with surgery and chemotherapy 2 years back who was referred for 18F-NaF PET-CT to evaluate possible metastatic lesions. 18F-NaF PET-CT unexpectedly detected 2 foci of soft tissue increased tracer uptake in the right lateral abdominal and left paraspinal muscles, which corresponded to the focal calcification in the muscles. The pathological examination revealed metastatic osteosarcoma to the muscles.
Risk Factors for Incomplete Bladder Emptying After Prolapse Repairs and Slings
Authors: Smithling Katelyn R. , Mwesigwa Patricia J. , Siddiquie Moiuri M. , Gutman Robert E.
Published: July 2018

Objective

The aim of this study was to determine the risk factors for catheter use and incomplete bladder emptying (IE) more than 1 week after prolapse repairs and slings.

Methods

This is a case-control study of women with prolapse repairs and/or sling from June 2011 to April 2016. All underwent standardized postoperative voiding trial before discharge. Controls and cases of IE were identified by codes and chart review; cases were defined as those needing any postoperative catheterization. We excluded patients with preoperative catheter use or postvoid residual (PVR) greater than 150 mL and those needing postoperative catheterization for reasons other than IE. Univariate and multivariate analyses were performed.

Results

A total of 475 (30.6%) cases and 478 controls were identified from 1552 eligible patients. Any catheter use was associated with higher uroflow PVR (71.2 vs 54.1 mL, P = 0.006), lower uroflow maximum flow (19.4 vs 25.4 mL/s, P < 0.001), and less detrusor overactivity (DO) (22.0% vs 28.7%, P = 0.03). Seventy-seven (5.0%) patients used catheters more than 1 week, and 15 patients (1.5%) required sling revision.

Factors on multivariate analysis associated with any catheter use include office PVR [odds ratio (OR), 1.004; 1.00–1.008], uroflow maximum flow (OR, 0.96; 0.94–0.98), sling (OR, 2.40; 1.51–3.81), and anterior repair (OR, 1.81; 1.15–2.85). Factors associated with IE more than 1 week include uroflow maximum flow (OR, 0.90; 0.84–0.95), DO (OR, 0.21; 0.05–0.83), sling (OR, 3.68; 1.32–10.20), and uterosacral suspensions (OR, 3.43; 1.23–9.54).

Conclusions

Overall, the incidence of short-term catheter use was 31%, prolonged IE more than 1 week was 5%, and 1.5% required sling revision. Sling placement, lower maximum flow, and higher preoperative PVR, anterior repair, and uterosacral ligament suspension are risk factors for IE, and presence of DO is protective.
The Impact of Microclimate on Skin Health With Absorbent Incontinence Product Use
Authors: Falloon Sabrina S. , Abbas Shabira , Stridfeldt Chatrine , Cottenden Alan
Published: July 2018

This integrative review considers the role of skin occlusion and microclimate in incontinence-associated dermatitis (IAD), with a particular focus on disposable, body-worn, absorbent incontinence products. Although the mechanisms are not fully understood, the primary causes of IAD are well-established: occluded skin, in prolonged contact with urine and/or feces and exposed to abrasive forces, is more likely to be affected, and each of these factors can be influenced by wearing absorbent incontinence products. Studies comparing the effect of various absorbent products on skin health have been hindered by the many differences between compared products, making it difficult to clearly attribute any differences in performance to particular materials or design features. Nevertheless, the large and significant differences that have sometimes been found invite further work. Breathable back sheets can significantly reduce the temperature of occluded skin and the humidity of the adjacent air, and several treatments for nonwoven top sheet materials (used next to the skin) have been shown to impart antimicrobial properties in the laboratory, but an impact on IAD incidence or severity has yet to be demonstrated directly. Recent work to introduce sensing technology into absorbent incontinence products to reduce the exposure of skin to urine and feces, by encouraging prompt product changing, seems likely to yield measurable benefits in terms of reducing incidents of IAD as the technology develops. Published work to date suggests that there is considerable potential for products to be engineered to play a significant role in the reduction of IAD among users.
Health Utility, Social Interactivity, and Peristomal Skin Status
Authors: Nichols Thomas
Published: July 2018

PURPOSE:

The objective of this study was to examine relationships among social interaction, health utility, and peristomal skin status in adults with ostomies.

DESIGN:

Cross-sectional, descriptive.

SUBJECTS AND SETTING:

15,591 persons residing in the United States were randomly selected from 3 multinational proprietary databases of individuals who had undergone surgery.

METHODS:

The study was a cross-sectional assessment utilizing the SF36v2 survey instrument. Potential subjects were sent an e-mail letter of invitation that included instructions for completing the questionnaire, an informed consent form, and nontransferable link to an electronic survey. Health utility was derived from the SF6D, and the Hawthorne Friendship Scale was used to measure social connectivity. Social functioning was derived from the SF36v2. A minimally important social value of health (MISVH) is reported as the minimum quality-adjusted life-days to be of benefit (influence) within indices of social connectivity and function. A self-reported determinant of peristomal skin health was included.

RESULTS:

Increased social interactivity, defined as social functioning and social connectivity, was associated with increased health utility. In addition, health utility decreased as peristomal skin integrity worsened. A MISVH can be demonstrated.

CONCLUSION:

Findings indicate that peristomal skin complications are more than dermatologic issues. They negatively affect the well-being of those who must cope and adapt to their impact and the community at large. Social interaction is also negatively influenced.
Cell-type specific visualization and biochemical isolation of endogenous synaptic proteins in mice
Authors: Zhu Fei , Collins Mark O. , Harmse Johan , Choudhary Jyoti S. , Grant Seth G. N. , Komiyama Noboru H.
Published: July 2018

In recent years, the remarkable molecular complexity of synapses has been revealed, with over 1000 proteins identified in the synapse proteome. Although it is known that different receptors and other synaptic proteins are present in different types of neurons and synapses, the extent of synapse diversity across the brain is largely unknown, mainly owing to technical limitations. Combining mouse genetics and proteomics we have previously reported highly efficient methods for purification of synaptic protein complexes under native conditions. In that approach, tandem affinity purification (TAP) tags were fused to the carboxyl terminus of PSD95 using gene targeting in mice. Here we report an approach that restricts tagging of endogenous PSD95 to cells expressing Cre recombinase. In addition, we developed a labelling strategy enabling visualization of endogenous PSD95 tagged by fluorescent proteins in Cre-expressing cells. We demonstrate the feasibility of proteomic characterisation of synapse proteomes and visualization of synapse proteins in specific cell types. We find that composition of PSD95 complexes purified from specific cell types differs from those extracted from tissues with diverse cellular composition. Therefore, these novel conditional PSD95 tagging lines will not only serve as powerful tools for precisely dissecting synapse diversity in specific subsets of regions/neuronal cells, but also provide an opportunity to better understand brain region-specific alterations associated with various psychiatric/neurological diseases. The newly developed conditional gene tagging methods can be applied to many different synaptic proteins and will thus facilitate research on the molecular complexity of synapses.
Model-based analysis of positive selection significantly expands the list of cancer driver genes, including RNA methyltransferases
Authors: Zhao Siming , Liu Jun , Nanga Pranav , Liu Yuwen , Cicek A. Ercument , Knoblauch Nicholas , He Chuan , Stephens Matthew , He Xin
Published: July 2018

Identifying driver genes is a central problem in cancer biology, and many methods have been developed to identify driver genes from somatic mutation data. However, existing methods either lack explicit statistical models, or rely on very simple models that do not capture complex features in somatic mutations of driver genes. Here, we present driverMAPS (Model-based Analysis of Positive Selection), a more comprehensive model-based approach to driver gene identification. This new method explicitly models, at the single-base level, the effects of positive selection in cancer driver genes as well as highly heterogeneous background mutational process. Its selection model captures elevated mutation rates in functionally important sites using multiple external annotations, as well as spatial clustering of mutations. Its background mutation model accounts for both known covariates and unexplained local variation. Simulations under realistic evolutionary models demonstrate that driverMAPS greatly improves the power of driver gene detection over state-of-the-art approaches. Applying driverMAPS to TCGA data across 20 tumor types identified 159 new potential driver genes. Cross-referencing this list with data from external sources strongly supports these findings. The novel genes include the mRNA methytransferases METTL3-METTL14, and we experimentally validated METTL3 as a potential tumor suppressor gene in bladder cancer. Our results thus provide strong support to the emerging hypothesis that mRNA modification is an important biological process underlying tumorigenesis.