bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of allocentric spatial recall from new viewpoints in virtual reality
Authors: Negen James , Heywood‐Everett Edward , Roome Hannah E. , Nardini Marko
Published: March 2017

Using landmarks and other scene features to recall locations from new viewpoints is a critical skill in spatial cognition. In an immersive virtual reality task, we asked children 3.5–4.5 years old to remember the location of a target using various cues. On some trials they could use information from their own self‐motion. On some trials they could use a view match. In the very hardest kind of trial, they were ‘teleported’ to a new viewpoint and could only use an allocentric spatial representation. This approach provides a strict test for allocentric coding (without either a matching viewpoint or self‐motion information) while avoiding additional task demands in previous studies (it does not require them to deal with a small table‐top environment or to manage stronger cue conflicts). Both the younger and older groups were able to point back at the target location better than chance when they could use view matching and/or self‐motion, but allocentric recall was only seen in the older group (4.0–4.5). In addition, we only obtained evidence for a specific kind of allocentric recall in the older group: they tracked one major axis of the space significantly above chance, r(158) = .28, but not the other, r(158) = −.01. We conclude that there is a major qualitative change in coding for spatial recall around the fourth birthday, potentially followed by further development towards fully flexible recall from new viewpoints.
Auditory‐motor adaptation is reduced in adults who stutter but not in children who stutter
Authors: Daliri Ayoub , Wieland Elizabeth A. , Cai Shanqing , Guenther Frank H. , Chang Soo‐Eun
Published: March 2017

Previous studies have shown that adults who stutter produce smaller corrective motor responses to compensate for unexpected auditory perturbations in comparison to adults who do not stutter, suggesting that stuttering may be associated with deficits in integration of auditory feedback for online speech monitoring. In this study, we examined whether stuttering is also associated with deficiencies in integrating and using discrepancies between expected and received auditory feedback to adaptively update motor programs for accurate speech production. Using a sensorimotor adaptation paradigm, we measured adaptive speech responses to auditory formant frequency perturbations in adults and children who stutter and their matched nonstuttering controls. We found that the magnitude of the speech adaptive response for children who stutter did not differ from that of fluent children. However, the adaptation magnitude of adults who stutter in response to auditory perturbation was significantly smaller than the adaptation magnitude of adults who do not stutter. Together these results indicate that stuttering is associated with deficits in integrating discrepancies between predicted and received auditory feedback to calibrate the speech production system in adults but not children. This auditory‐motor integration deficit thus appears to be a compensatory effect that develops over years of stuttering.
Prioritizing risks for plant health in the Netherlands: a method to rank pests according to their probability of introduction
Authors: van der Gaag D. J. , van Leeuwen G. C. M. , Loomans A. J. M. , Potting R. P. J. , Verhoeven J. Th. J.
Published: March 2017

Countries take phytosanitary measures to reduce the probability of introduction (entry and establishment) of new pests. To deploy resources efficiently it is important to assess which pests pose a relatively high risk. This paper describes a methodology that was developed to assess, in a relatively short time, the probability of introduction of a large number of pests. Four risk criteria were defined: the probability of arrival despite current phytosanitary measures (P1), the probability of transfer (P2), the probability of establishment (P3) and the probability of eradication by official measures (P4). Four to five rating levels were distinguished for each criterion and rating guidance was developed. Rating levels for P1 were mainly based on the number of interceptions during import inspections, the number of findings of the pest in the country that could be linked to the pathway and current regulations on the pathway. Rating levels for P2 to P4 include descriptions of various situations that may occur and which are ranked according to the opinion of the authors. The combination P1 to P3 was a relative measure for the probability of introduction in the absence of official eradication measures and the combination P1 to P4 was a measure for the probability of introduction despite official eradication measures.
The Outcomes and Impact Scale – Revised: the psychometric properties of a scale assessing the impact of service provision
Authors: Koritsas S. , Hagiliassis N. , Cuzzillo C.
Published: March 2017

Background

The Outcomes and Impact Scale – Revised (O&IS‐R) was developed to measure the impact of service provision on adults with disability. The aim of this research was to explore the psychometric properties of the scale following a recent revision.

Method

Adults with disability and/or their carers or support workers participated in the research. Participants were recruited across Australia using a range of strategies and completed the scale in relation to a service or support that they nominated. Two forms of the scale were developed (easy and standard English), which could be completed in hardcopy or via a bespoke website.

Results

The O&IS‐R demonstrated good internal consistency and alternate form reliability. Factor analysis of the scale revealed one factor that clearly corresponded to the whole of life construct that the scale was designed to measure and, in general, participants with disability and staff understood the intent or purpose of the survey. All domains except the spiritual and political domain were considered to be relevant service outcomes. Some changes to wording were suggested to improve clarity.

Conclusions

The O&IS‐R is a psychometrically sound scale that can be used in service and research settings to measure the impact of services and supports.
Effect of serine protease inhibitor from squid ovary on gel properties of surimi from Indian mackerel
Authors: Singh Avtar , Benjakul Soottawat
Published: March 2017

Effects of serine protease inhibitor from squid ovary (SOSPI) and egg white powder (EWP) on gel properties of surimi from Indian mackerel (Rastrelliger kanagurta) were investigated. Breaking force of gel increased when SOSPI levels increased up to 2%. However, EWP showed higher efficiency in increasing breaking force of resulting surimi gel. Nevertheless, SOSPI (0.5–3%) had no effect on deformation. Trichloroacetic acid‐soluble peptide content in surimi gel decreased when the levels of SOSPI and EWP increased (p < .05). This was coincidental with more retained myosin heavy chain. Water holding capacity was increased with the addition of these protein additives, but resulted in lower whiteness. Microstructure study revealed that surimi gel added with 2% EWP was denser and had higher connectivity as compared to that containing 2% SOSPI. The SOSPI had no negative effect on sensory attributes and could serve as the alternative protein additive to improve gel strength of surimi.

Practical applications

Surimi from dark‐fleshed fish is prone to degradation of myofibrillar proteins caused by the endogenous proteases, thereby lowering textural property. To tackle the problem, protease inhibitors (egg white, porcine plasma protein, and bovine plasma protein) have been used by the surimi industries. Due to drawbacks of some particular inhibitors (religious constraints, off‐white color, off odor, etc.), the novel additives are still in demand. Ovary from squid processing industry, commonly discarded as the waste, can be an alternative natural protease inhibitor, which can improve the gel properties of surimi, especially produced from dark‐fleshed fish.
Supreme Court Elections: How Much They Have Changed, Why They Changed, and What Difference It Makes
Authors: Baum Lawrence
Published: March 2017

This essay draws on four recent studies of elections to state supreme courts in the United States to probe widely perceived changes in the scale and content of electoral campaigns for seats on state supreme courts.
1
Evidence from these studies and other sources indicates that changes have indeed occurred, though they are more limited than most commentaries suggest. These changes stem most directly from trends in state supreme court policy that have attracted interest-group activity, especially from the business community. Like their extent, the effects of change in supreme court campaigns have been meaningful although exaggerated by many observers. What we have learned about changes in supreme court elections has implications for choices among selection systems, but those implications are mixed and complex.
Identity and social solidarity: an ignored connection. A historical perspective on the state of Europe and its nations
Authors: Stråth Bo
Published: March 2017

The article comments on the ongoing de‐Europeanisation and re‐nationalisation of Europe from a historical perspective. The article argues that the building of national community from the 1870s onwards focused on the problem of social integration where the development of emotional feelings of belonging and solidarity was linked to the building of institutions for social politics in mutually reinforcing dynamics. The social question emerged in the wake of the spread of industrial capitalism. Its role is underexplored in the study of the building of national and European communities. The social question draws attention to the institutional capacity of nationstatesrather than nations based on emotions. Nationalism did not only mean the building of friend‐ enemy distinctions through ethnicity but also national socialism as a conservative reform strategy against class struggle socialism. This contention between two approaches to the problem of social integration moulded together national communities through emotions and institutions without deploying the concept of identity. The article outlines this development, culminating in the (West) European welfare states as nation– states in the strong sense of the merger of these two terms, and how it came to an end in the 1970s when a reverse development began towards social disintegration at the end accompanied by accelerating nationalism and xenophobia. The identity concept was mobilised in 1973 as a tool in the European integration project to compensate for the erosion of social institutions by means of emotions. It was taken over and politicised from having been a technical term in mathematics and psychoanalysis. The politicisation of the identity concept was an indication of a deep identity crisis in Europe and its nations. The identity therapy failed, and the identity crisis remains, accompanied by an ever louder nationalistic and xenophobic vocabulary. Emotions replace institutions. The methodological focus of the article is on the semantics around key concepts such as social politics, solidarity and identity in their historical context as forward‐looking and action‐oriented concepts in the construction of community. This approach with a focus onpast futuresis an alternative to the application of the retrospective analytical concepts of ethnic and civic nationalism outliningpresent pasts.
Multiple functional gastrointestinal disorders linked to gastroesophageal reflux and somatization: A population‐based study
Authors: Choung R. S. , Richard Locke G. , Schleck C. D. , Zinsmeister A. R. , Talley N. J.
Published: March 2017

Background

It is unknown why functional gastrointestinal disorders (FGIDs) overlap and limited information exists on risk factors for those with overlap. Our aim was to estimate the prevalence of combinations of FGIDs including reflux (FGIDs‐gastroesophageal reflux [GER]), and evaluate potential risk factors for people with multiple disorders in a representative US community.

Methods

A population‐based study was conducted by mailing a valid GI symptom questionnaire to an age‐ and gender‐stratified random sample of residents of Olmsted County, MN. Rome III definitions were used to identify people with FGIDs, and GER was defined by weekly or more frequent heartburn or acid regurgitation. The prevalence of people meeting multiple symptom complexes was estimated. Moreover, potential risk factors for people with multiple disorders were evaluated.

Key Results

A total of 3548 people provided data for each of the necessary symptom questions (mean age: 61±16 years, 54% female). Among these 3548 subjects, 2009 (57%) had no FGIDs‐GER, 906 (26%) had a pure FGID‐GER, 372 (10%) had 2 FGIDs‐GER, and 261 (7%) had 3 or more FGIDs‐GER. Somatization as assessed by a higher Somatic Symptom Checklist score (OR=3.3, 95% CI [2.7,4.1]) was associated with an increased odds for those with 3 or more FGIDs‐GER compared to subjects with a pure FGID‐GER adjusting for age and gender.

Conclusions and Inferences

Symptom complex overlap is common rather than rare in the community. GER is an integral symptom complex associated with both upper and lower FGIDs. Somatization is a strong risk factor for multiple FGIDs.
Thyroid Ultrasound: State of the Art. Part 2 – Focal Thyroid Lesions
Authors: Dighe Manjiri , Barr Richard , Bojunga Jörg , Cantisani Vito , Chammas Maria Cristina , Cosgrove David , Cui Xin Wu , Dong Yi , Fenner Franziska , Radzina Maija , Vinayak Sudhir , Xu Jun Mei , Dietrich Christoph F
Published: March 2017

Accurate differentiation of focal thyroid nodules (FTL) and thyroid abnormalities is pivotal for proper diagnostic and therapeutic work-up. In these two part articles, the role of ultrasound techniques in the characterization of FTL and evaluation of diffuse thyroid diseases is described to expand on the recently published World Federation in Ultrasound and Medicine (WFUMB) thyroid elastography guidelines and review how this guideline fits into a complete thyroid ultrasound exam.
Transcriptome Sequence of the Bloodstream Form of
Trypanoplasma borreli
, a Hematozoic Parasite of Fish Transmitted by Leeches
Authors: Carrington Mark , Dóró Eva , Forlenza Maria , Wiegertjes Geert F. , Kelly Steven
Published: March 2017

Here, we report a transcriptome sequence of
Trypanoplasma borreli
isolated from its natural host, the common carp,
Cyprinus carpio
. The transcriptome allows an analysis of abundant cell surface proteins and acts as a comparator for understanding the evolution and pathogenicity of other
Kinetoplastida
, including several that infect humans.
Genome Sequence of
Euphorbia mosaic virus
from Passionfruit and
Euphorbia heterophylla
in Florida
Authors: Polston J. E. , Londoño M. A. , Cohen A. L. , Padilla-Rodriguez M. , Rosario K. , Breitbart M.
Published: March 2017

Euphorbia mosaic virus
(EuMV) was found in a symptomatic passionfruit (
Passiflora edulis
) plant from Homestead, Florida, USA, as well as in the symptomatic weed
Euphorbia heterophylla
. This is the first identification of EuMV in Florida and the United States and the first report of a natural infection of passionfruit by EuMV.
Depressive symptoms in high-performance athletes and non-athletes: a comparative meta-analysis
Authors: Gorczynski Paul Filip , Coyle Melissa , Gibson Kass
Published: March 2017

Objective

To assess whether a difference exists in the prevalence of mild or more severe depressive symptoms between high-performance athletes and non-athletes.

Design

Comparative OR meta-analysis.

Data sources

We searched PsycINFO, PubMed, MEDLINE, CINAHL, SPORTDiscus and Google Scholar, as well as the reference lists of reviews of mental health issues in high-performance athletes.

Eligibility

We included studies that compared high-performance athletes and non-athletes, included a validated measure of depressive symptoms and included the prevalence of individuals who indicated at least mild depressive symptoms.

Results

Five articles reporting data from 1545 high-performance athletes and 1811 non-athletes were examined. A comparative OR meta-analysis found high-performance athletes were no more likely than non-athletes to report mild or more severe depressive symptoms (OR=1.15, 95% CI=0.954 to 1.383, p=0.145). Male high-performance athletes (n=940) were no more likely than male non-athletes (n=605) to report mild or more severe depressive symptoms (OR=1.17, 95% CI=0.839 to 1.616, p=0.362). For females, high-performance athletes (n=948) were no more likely than non-athletes (n=605) to report mild or more severe depressive symptoms (OR=1.11, 95% CI=0.846 to 1.442, p=0.464). Overall, male high-performance athletes (n=874) were 52% less likely to report mild or more severe depressive symptoms than female high-performance athletes (n=705) (OR=0.48, 95% CI=0.369 to 0.621, p<0.001).

Summary/conclusions

High-performance athletes were just as likely as non-athletes to report depressive symptoms. Researchers need to move beyond self-report measures of depressive symptoms and examine the prevalence of clinically diagnosed depressive disorders in athletes.
Review of criterion-referenced standards for cardiorespiratory fitness: what percentage of 1 142 026 international children and youth are apparently healthy?
Authors: Lang Justin J , Tremblay Mark S , Ortega Francisco B , Ruiz Jonatan R , Tomkinson Grant R
Published: March 2017

Purpose

To identify criterion-referenced standards for cardiorespiratory fitness (CRF); to estimate the percentage of children and youth that met each standard; and to discuss strategies to help improve the utility of criterion-referenced standards for population health research.

Methods

A search of four databases was undertaken to identify papers that reported criterion-referenced CRF standards for children and youth generated using the receiver operating characteristic curve technique. A pseudo-dataset representing the 20-m shuttle run test performance of 1 142 026 children and youth aged 9–17 years from 50 countries was generated using Monte Carlo simulation. Pseudo-data were used to estimate the international percentage of children and youth that met published criterion-referenced standards for CRF.

Results

Ten studies reported criterion-referenced standards for healthy CRF in children and youth. The mean percentage (±95% CI) of children and youth that met the standards varied substantially across age groups from 36%±13% to 95%±4% among girls, and from 51%±7% to 96%±16% among boys. There was an age gradient across all criterion-referenced standards where younger children were more likely to meet the standards compared with older children, regardless of sex. Within age groups, mean percentages were more precise (smaller CI) for younger girls and older boys.

Conclusion

There are several CRF criterion-referenced standards for children and youth producing widely varying results. This study encourages using the interim international criterion-referenced standards of 35 and 42 mL/kg/min for girls and boys, respectively, to identify children and youth at risk of poor health—raising a clinical red flag.
Patient and provider perspectives on the design and implementation of an electronic consultation system for kidney care delivery in Canada: a focus group study
Authors: Bello Aminu K , Molzahn Anita E , Girard Louis P , Osman Mohamed A , Okpechi Ikechi G , Glassford Jodi , Thompson Stephanie , Keely Erin , Liddy Clare , Manns Braden , Jinda Kailash , Klarenbach Scott , Hemmelgarn Brenda , Tonelli Marcello
Published: March 2017

Objectives

We assessed stakeholder perceptions on the use of an electronic consultation system (e-Consult) to improve the delivery of kidney care in Alberta. We aim to identify acceptability, barriers and facilitators to the use of an e-Consult system for ambulatory kidney care delivery.

Methods

This was a qualitative focus group study using a thematic analysis design. Eight focus groups were held in four locations in the province of Alberta, Canada. In total, there were 72 participants in two broad stakeholder categories: patients (including patients' relatives) and providers (including primary care physicians, nephrologists, other care providers and policymakers).

Findings

The e-Consult system was generally acceptable across all stakeholder groups. The key barriers identified were length of time required for referring physicians to complete the e-Consult due to lack of integration with current electronic medical records, and concerns that increased numbers of requests might overwhelm nephrologists and lead to a delayed response or an unsustainable system. The key facilitators identified were potential improvement of care coordination, dissemination of best practice through an educational platform, comprehensive data to make decisions without the need for face-to-face consultation, timely feedback to primary care providers, timeliness/reduced delays for patients' rapid triage and identification of cases needing urgent care and improved access to information to facilitate decision-making in patient care.

Conclusions

Stakeholder perceptions regarding the e-Consult system were favourable, and the key barriers and facilitators identified will be considered in design and implementation of an acceptable and sustainable electronic consultation system for kidney care delivery.
Association of centre volume and in-hospital mortality in heart failure hospitalisations
Authors: Madan Shivank , Sims Daniel , Saeed Omar , Patel Snehal R , Shin Jooyoung J , Jorde Ulrich P
Published: March 2017

Background

Centre volume is an important determinant of outcomes in patients requiring complex medical treatments or surgical procedures. Heart failure hospitalisation (HFH) has become an increasingly complex and resource intensive clinical event. We evaluated the effect of centre volume on mortality and costs in patients with HFH.

Methods

This was a retrospective registry-based analysis of adult patients discharged with a primary diagnosis of HF from hospitals across New York (NY) State over a 5-year period, between January 2009 and December 2013, using the Statewide Planning and Research Cooperative System inpatient discharge files. The primary outcome of interest was in-hospital mortality. All patients were followed from the day of admission to either in-hospital death or discharge alive.

Results

300 972 HFHs from 198 facilities across NY State were included. Five-year centre volume was associated with a decrease in in-hospital mortality in unadjusted (HR=0.872, 95% CI 0.863 to 0.881, p<0.001) and adjusted Cox models (HR=0.869, 95% CI 0.859 to 0.879, p<0.001). After dividing the overall cohort into three groups based on 5-year centre volume, groups with medium and high volume centres had lower in-hospital mortality when compared with the group with low volume centres. The results were consistent in various subgroup analyses. Furthermore, hospitals in the higher centre volume groups had increased HFH costs across different severity of illness categories and involved increased use of cardiac procedures.

Conclusions

Higher centre volume was associated with lower HFH mortality but increased HFH costs and increased cardiac procedures in a cohort of Medicare and non-Medicare beneficiaries.
Revisiting phylogenetic relationships in Phoradendreae (Viscaceae): utility of thetrnL-Fregion of chloroplast DNA and presence of a homoplasious inversion in the intergenic spacer
Authors: Ashworth Vanessa E.T.M.
Published: March 2017

The utility of the trnL-F region of the chloroplast DNA for inferring relationships in 26 taxa in the mistletoe tribe Phoradendreae (Viscaceae) was compared with that of sequences from three regions of the nuclear ribosomal DNA (nrDNA). Chloroplast- and nuclear-inferred phylogenies generally were congruent based on maximum parsimony analysis of nucleotide substitution data. Results suggested that the intron and intergenic spacer of the chloroplast partition were not sufficiently variable to resolve phylogenetic relationships among either close relatives or more distantly related species. The distribution of insertions and deletions generally supported the phylogeny inferred from nucleotide substitution data. However, presence or absence of a 59-nucleotide inversion in the trnL-F intergenic spacer of eight Phoradendron species showed no agreement with the topology inferred from molecular and morphological data. Combined analyses of the nuclear partitions and the chloroplast region (with the homoplasious inversion inserted in reverse orientation) provided strong support for P. californicum as sister to a clade uniting North American species and not as sister to a clade comprising more tropical species. Consistent with results from previous studies using nrDNA, a lineage in the Phoradendron leucarpum complex (comprising subsp. leucarpum and macrophyllum) was strongly supported, but subspecies tomentosum was not confidently placed.
Microprocessor Testing: Functional Meets Structural Test
Authors: Touati A. , Bosio A. , Girard P. , Virazel A. , Bernardi P. , Sonza Reorda M.
Published: March 2017

Structural test is widely adopted to ensure high quality for a given product. The availability of many commercial tools and the use of fault models make it very easy to generate and to evaluate. Despite its efficiency, structural test is also known for the risk of over-testing that may lead to yield loss. This problem is mainly due to the fact that structural test does not take into account the functionality of the circuit under test. On the other hand, functional test guarantees that the circuit is tested under normal conditions, thus avoiding any over- as well as under-testing issues. More in particular, for microprocessor testing, functional test is usually applied by exploiting the Software-Based-Self-Test (SBST) technique. SBST applies a set of functional test programs that are executed by the processor to achieve a given fault coverage. SBST fits particularly well for online testing of processor-based systems. In this work, we describe a technique able to execute functional test programs as if they were structural tests. In this way, they can be applied during the end-of-production test in order to achieve good fault coverage and, at the same time, avoiding any over-test problems. We will show that it is possible to map functional test programs into the classical structural test schemes, so that their application simply requires the presence of a scan chain. Finally, we present a compaction algorithm able to significantly reduce the test length. Results carried out on two different microprocessors show the advantages of such approach.
High Dynamic Range Low Distortion PWM Readout Method with Self-Adjusted Reference for Digital Pixel Sensors
Authors: Gao Zhiyuan , Zhou Yiming , Xu Jiangtao , Liu Huiying , Gao Jing
Published: March 2017

This paper presents a modified pulse width modulation (PWM) readout method for DPS with block-based self-adjusted reference voltage to extend dynamic range (DR). In this scheme, pixel arrays are divided into blocks with the same size, and the exposure process consists of two periods. During the first exposure, block-based reference voltage is generated based on the average photocurrent within the block. In the second exposure, the generated voltage is used as the reference voltage for PWM readout. Then the quantization results are combined together to represent the luminance information. DR and peak signal-to-noise ratio (PSNR) were discussed with different images and integration time. Simulation results show that this scheme can achieve a DR of over 96[Formula: see text]dB with 8-bit memory and 8-bit ADC and 145[Formula: see text]dB with 12-bit memory and 12-bit ADC. It also has 28.98[Formula: see text]dB PSNR on average, better than 20.11[Formula: see text]dB in fixed reference voltage method and 17.25[Formula: see text]dB in ramp reference voltage method. Combining the feature of active pixel sensor (APS) and PWM readout, this scheme allows better DR but also obtains less distortion of the image reconstruction.
Effect of α7 nicotinic acetylcholine receptor activation on cardiac fibroblasts: a mechanism underlying RV fibrosis associated with cigarette smoke exposure
Authors: Vang Alexander , Clements Richard T. , Chichger Havovi , Kue Nouaying , Allawzi Ayed , O’Connell Kelly , Jeong Euy-Myoung , Dudley Samuel C. , Sakhatskyy Pavlo , Lu Qing , Zhang Peng , Rounds Sharon , Choudhary Gaurav
Published: March 2017

Right ventricular (RV) dysfunction is associated with numerous smoking-related illnesses, including chronic obstructive pulmonary disease (COPD), in which it is present even in the absence of pulmonary hypertension. It is unknown whether exposure to cigarette smoke (CS) has direct effects on RV function and cardiac fibroblast (CF) proliferation or collagen synthesis. In this study, we evaluated cardiac function and fibrosis in mice exposed to CS and determined mechanisms of smoke-induced changes in CF signaling and fibrosis. AKR mice were exposed to CS for 6 wk followed by echocardiography and evaluation of cardiac hypertrophy, collagen content, and pulmonary muscularization. Proliferation and collagen content were evaluated in primary isolated rat CFs exposed to CS extract (CSE) or nicotine. Markers of cell proliferation, fibrosis, and proliferative signaling were determined by immunoblot or Sircol collagen assay. Mice exposed to CS had significantly decreased RV function, as determined by tricuspid annular plane systolic excursion. There were no changes in left ventricular parameters. RV collagen content was significantly elevated, but there was no change in RV hypertrophy or pulmonary vascular muscularization. CSE directly increased CF proliferation and collagen content in CF. Nicotine alone reproduced these effects. CSE and nicotine-induced fibroblast proliferation and collagen content were mediated through α7 nicotinic acetylcholine receptors and were dependent on PKC-α, PKC-δ, and reduced p38-MAPK phosphorylation. CS and nicotine have direct effects on CFs to induce proliferation and fibrosis, which may negatively affect right heart function.
Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases
Authors: Hodge Sandra , Tran Hai B. , Hamon Rhys , Roscioli Eugene , Hodge Greg , Jersmann Hubertus , Ween Miranda , Reynolds Paul N. , Yeung Arthur , Treiberg Jennifer , Wilbert Sibylle
Published: March 2017

We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides—2′-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2′-desoxy molecule (GS-560660)—with significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and H. influenzae. We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5–1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll-like receptor 2/4; or CD36. Particulate cytoplasmic immunofluorescence of NLRP3 inflammasome was also reduced significantly. We conclude that GS-459755 and GS-560660 may be useful for reducing airway inflammation in chronic lung diseases without inducing bacterial resistance.
Akt Activation Mediates Acquired Resistance to Fibroblast Growth Factor Receptor Inhibitor BGJ398
Authors: Datta Jharna , Damodaran Senthilkumar , Parks Hannah , Ocrainiciuc Cristina , Miya Jharna , Yu Lianbo , Gardner Elijah P. , Samorodnitsky Eric , Wing Michele R. , Bhatt Darshna , Hays John , Reeser Julie W. , Roychowdhury Sameek
Published: March 2017

Activation of FGFR signaling through mutations, amplifications, or fusions involving FGFR1, 2, 3, or 4 is seen in multiple tumors, including lung, bladder, and cholangiocarcinoma. Currently, several clinical trials are evaluating the role of novel FGFR inhibitors in solid tumors. As we move forward with FGFR inhibitors clinically, we anticipate the emergence of resistance with treatment. Consequently, we sought to study the mechanism(s) of acquired resistance to FGFR inhibitors using annotated cancer cell lines. We identified cancer cell lines that have activating mutations in FGFR1, 2, or 3 and treated them chronically with the selective FGFR inhibitor, BGJ398. We observed resistance to chronic BGJ398 exposure in DMS114 (small-cell lung cancer, FGFR1 amplification) and RT112 (urothelial carcinoma, FGFR3 fusion/amplification) cell lines based on viability assays. Reverse-phase protein array (RPPA) analysis showed increased phosphorylation of Akt (T308 and S473) and its downstream target GSK3 (S9 and S21) in both the resistant cell lines when compared with matching controls. Results of RPPA were confirmed using immunoblots. Consequently, the addition of an Akt inhibitor (GSK2141795) or siRNA was able to restore sensitivity to BGJ398 in resistant cell lines. These data suggest a role for Akt pathway in mediating acquired resistance to FGFR inhibition. Mol Cancer Ther; 16(4); 614–24. ©2017 AACR.
Serine Proteases Enhance Immunogenic Antigen Presentation on Lung Cancer Cells
Authors: Peters Haley L. , Tripathi Satyendra C. , Kerros Celine , Katayama Hiroyuki , Garber Haven R. , St. John Lisa S. , Federico Lorenzo , Meraz Ismail M. , Roth Jack A. , Sepesi Boris , Majidi Mourad , Ruisaard Kathryn , Clise-Dwyer Karen , Roszik Jason , Gibbons Don L. , Heymach John V. , Swisher Stephen G. , Bernatchez Chantale , Alatrash Gheath , Hanash Samir , Molldrem Jeffrey J.
Published: March 2017

Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer in patients; however, the antigenic targets of these reinvigorated T cells remain poorly defined. Lung cancer tumors contain tumor-associated macrophages (TAM) and neutrophils, which release the serine proteases neutrophil elastase (NE) and proteinase 3 (P3) into the tumor microenvironment. NE and P3 shape the antitumor adaptive immune response in breast cancer and melanoma. In this report, we demonstrate that lung cancer cells cross-presented the tumor-associated antigen PR1, derived from NE and P3. Additionally, NE and P3 enhanced the expression of human leukocyte antigen (HLA) class I molecules on lung cancer cells and induced unique, endogenous peptides in the immunopeptidome, as detected with mass spectrometry sequencing. Lung cancer patient tissues with high intratumoral TAMs were enriched for MHC class I genes and T-cell markers, and patients with high TAM and cytotoxic T lymphocyte (CTL) infiltration had improved overall survival. We confirmed the immunogenicity of unique, endogenous peptides with cytotoxicity assays against lung cancer cell lines, using CTLs from healthy donors that had been expanded against select peptides. Finally, CTLs specific for serine proteases–induced endogenous peptides were detected in lung cancer patients using peptide/HLA-A2 tetramers and were elevated in tumor-infiltrating lymphocytes. Thus, serine proteases in the tumor microenvironment of lung cancers promote the presentation of HLA class I immunogenic peptides that are expressed by lung cancer cells, thereby increasing the antigen repertoire that can be targeted in lung cancer. Cancer Immunol Res; 5(4); 319–29. ©2017 AACR.
Retrospective Analysis of Laparoscopic Partial Nephrectomies Using the Zero Ischemia Technique
Authors: Boyarsky Leonid , Stein Avi , Konstantinovsky Alex , Goldin Dmitry , Klein Ilan , May Tal , Freifeld Yuval , Moaad Yahya , Dekel Yoram
Published: March 2017

Purpose: To report a series of 89 off-clamp laparoscopic partial nephrectomies (LPN) performed without using any additional “nephron sparing” manipulations. Methods: Retrospective analysis of surgical characteristics, complications, postoperative results, and renal function changes. Results: Between March 2008 and May 2014, 89 LPN using zero ischemia technique were performed. Most of the patients (61.8%) were male. The median age was 62 years (23-88). The mean BMI was 27.5 kg/m2 (20.8-54.2). The median tumor size was 3.0 cm (1.0-8.0). Tumor location was upper, middle, and lower part of the kidney in 33 (37.0%), 42 (47.2%), and 14 (15.7%) of patients, respectively. The median operative time was 154 min (58-289). The median hemoglobin change was -1.6 g/dL (0.5-5.5). The transfusion rate was 7.9%. The mean preoperative glomerular filtration rate was 96.6 mL/min (21.5-180.0) with a mean postoperative decline of 6.52 mL/min. The mean creatinine elevation after LPN was 0.09 mg/dL. The median hospital stay was 6 days (2-24). The intraoperative complications rate was 2.3%. Early postoperative complication rate was 33.7%. Late complications occurred in 6.7%. In 7 cases (7.9%), the surgical margins were microscopically involved by tumor cells. Conversion rate was 3.4%. Conclusion: Data obtained in the current series show that laparoscopic partial nephrectomy can be successfully performed without hilar clamping. Our results are comparable with contemporary data. Larger prospective studies would be helpful in assessing the evidence-based advantages of the “zero ischemia” technique.
Shock due to Splenic Injury after Colonoscopy
Authors: Nallayici Erol G. , de Groot Reinier , van Zanten René A.A. , Lutke Holzik Martijn F.
Published: March 2017

Colonoscopy is a common and increasingly performed procedure. It is used both as a diagnostic and therapeutic modality. Splenic injury after colonoscopy is a rare, yet life-threatening complication, most often caused by traction on the splenocolic ligament or excessive manipulation during the procedure. Although non-operative treatment is preferred upon splenic injury, early surgical or radiological intervention may be necessary in specific cases, for example in case of haemodynamic instability. A 71-year-old Caucasian man was referred to our emergency room due to shock after colonoscopy 2 days earlier. A computed tomography scan showed splenic rupture with active intra-abdominal, venous blood loss, and microperforation of the colon. An immediate splenectomy and colon repair were performed through laparotomy. After 6 days, the patient was discharged from hospital in good health. Although splenic rupture is a rare complication of colonoscopy, patients with abdominal pain and/or shock should be checked for complications such as splenic injury and colon perforation.
Endoscopic Full-Thickness Resection of Synchronous Adenocarcinomas of the Distal Rectum
Authors: Andrisani Gianluca , Pizzicannella Margherita , Di Matteo Francesco Maria
Published: March 2017

Endoscopic full-thickness resection (EFTR) with an innovative full-thickness resection device (FTRD; Ovesco Endoscopy, Tübingen, Germany) allows a safe and complete full-thickness resection of early colorectal cancer. We present the first case of two EFTR performed at the same time to treat synchronous rectal adenocarcinomas.
The Role of Couples' Attachment Styles in Patients' Adjustment to Cancer
Authors: De Luca Rossella , Dorangricchia Patrizia , Salerno Laura , Lo Coco Gianluca , Cicero Giuseppe
Published: March 2017

Objective: This study aimed to understand how psychological variables and attachment styles can contribute to improve effective and functional adjustment to the disease and promote better psychological well-being. Methods: A total of 176 participants (88 couples) took part in this research. One member of each couple attended surgery centers at the Oncology Department of the University Hospital of Palermo. Each participant had filled in 5 questionnaires assessing the variables couple relationships, quality of life, anxiety, depression, and psychosocial adjustment to illness. Results: Significant correlations were found among the observed variables. Levels of anxiety and the attachment styles of couples influence adjustment to tumor disease and negatively affect the quality of conjugal relationships. Moreover, the results highlighted the correlation between levels of anxiety and depression in patients and in their respective partners. Finally, we found a correlation between the level of psychological distress of the patient and the level of marital satisfaction perceived by the partner: the latter is lower in couples where the oncological patient has high levels of distress. Conclusions: The results suggest that psychological variables and attachment styles of cancer patients and their partners may be important factors affecting adjustment in multiple domains.
HIV-Associated Kaposi's Sarcoma
Authors: Hoffmann Christian , Sabranski Michael , Esser Stefan
Published: March 2017

Kaposi's sarcoma (KS) is still one of the most common malignancies in patients with human immunodeficiency virus (HIV) infection. Large randomized clinical trials have shown a protective effect of combination antiretroviral therapy (cART) against the development of KS, even in patients with a relatively preserved immune system. In patients with sufficient cART, KS has become a rarity. In most patients with HIV-associated KS who initiate cART, the KS lesions stabilize with decreasing HIV plasma viremia and immune reconstitution, or even resolve completely without any specific treatment. In patients with advanced or rapidly progressive disease, especially in the setting of an immune reconstitution syndrome, cART should be combined with cytotoxic chemotherapies. With regard to the KS pathogenesis, several new therapies have been suggested, such as antiviral agents, cytokines, and inhibitors of angiogenesis.
Two SPINK1 Mutations Induce Early-Onset Severe Chronic Pancreatitis
Authors: Frossard Jean Louis , Morris Michael A.
Published: March 2017

The SPINK1 protein is a potent antiprotease that can inactivate any intrapancreatic trypsin activity that would otherwise induce autodigestion of the pancreas. SPINK1 mutations have been recognized to be associated with chronic pancreatitis in patients without a family history of pancreatitis. We here describe the case of a 24-year-old woman referred to our service for recurrent abdominal pain and search for the cause of chronic calcifying pancreatitis, who was found to carry 2 SPINK1 mutations.
Disseminated Coccidioidomycosis Presenting as Carcinomatosis Peritonei and Intestinal Coccidioidomycosis in a Patient with HIV
Authors: Malik Umer , Cheema Hira , Kandikatla Ramcharitha , Ahmed Yasir , Chakrala Kalyan
Published: March 2017

Coccidioidomycosis (CM) is a fungal infection endemic in southwestern regions of the United States, northwestern regions of Mexico, and some areas of Brazil and Argentina. Clinical presentation varies depending on the extent of the infection and the immune status of the host. The most common presentation ranges from flu-like symptoms to self-limiting pneumonia. Extrapulmonary presentations are uncommon and may involve the meninges, skin, and bone. Gastrointestinal and peritoneal involvement is extremely rare. Here we report a case of disseminated CM presenting as carcinomatosis peritonei as an AIDS-defining illness in a young male.
The Dicentric Chromosome dic(20;22) Is a Recurrent Abnormality in Myelodysplastic Syndromes and Is a Product of Telomere Fusion
Authors: MacKinnon Ruth N. , Duivenvoorden Hendrika M. , Campbell Lynda J. , Wall Meaghan
Published: March 2017

We describe a recurrent dicentric chromosome formed by telomere fusion between chromosome 20 and chromosome 22 in 4 cases of myelodysplastic syndromes (MDS) or acute myeloid leukaemia (AML). In particular, the presence of residual telomere sequences at the site of translocation in 3 of the 4 cases makes a compelling case for telomere fusion. This is the first description of a recurrent telomere fusion event in any malignant condition. The 20q subtelomeric region was retained in all 4 examples despite deletion of the 20q12 region closer to the centromere. The original dicentric chromosome in all 4 cases contained nucleolus organiser region material from the short arm of chromosome 22 and had also undergone secondary rearrangements that produced amplification of the common gained region on 20q. We propose that the sequence of events producing this chromosome abnormality is: degradation of the telomeres, formation of an unstable dicentric chromosome by 20q and 22p telomere fusion, breakage-fusion-bridge cycles causing copy number aberration between the centromeres, selection of cells with 20q12 deletion, and further selection of cells with 20q11.2 gain. The last 2 steps are driver events responsible for the abnormal chromosomes found in the malignant cells. Finding recurrent patterns in the complex genome reorganisation events that characterise poor-prognosis, complex-karyotype AML and MDS will help us understand the mechanisms and oncogenic driver mutations in these poorly understood malignancies.
A Rare Cause of Right-Sided Air Bubble on Chest Radiograph: Intrathoracic Gastric Volvulus Related to Morgagni Hernia
Authors: Sahin Abdurrahman , Artas Hakan , Yalniz Mehmet
Published: March 2017

Morgagni hernia is a rare disorder in adulthood, and most of the cases are asymptomatic. Symptomatic cases are extremely rare and present with life-threatening complications. Early diagnosis and surgery are lifesaving. We hereby present an adult case of symptomatic Morgagni hernia. Diaphragmatic herniation of the stomach and mesenteroaxial rotation led to intrathoracic gastric volvulus in this case. A right-sided air bubble on a chest radiogram was the only finding leading to the suspicion of diaphragmatic hernia. Computed tomography in the diagnosis of diaphragmatic hernias is of great importance.
Infiltrative Intraocular Conjunctival Squamous Cell Carcinoma after Local Resection and Brachytherapy: Clinical and Pathological Findings
Authors: Cano-Suárez Magnolia Trinidad , Saornil-Álvarez María Antonia , García-Álvarez Ciro , López-Lara Francisco , Frutos-Baraja Jesús María , García-Lagarto Elena
Published: March 2017

A pseudophakic 70-year-old man presented to the clinic with a slow-growing conjunctival mass in the left eye. He was diagnosed with a conjunctival exophytic lesion suspicious of invasive conjunctival squamous cell carcinoma (CSCC). Excisional biopsy showed a well-differentiated CSCC with positive margins and the patient underwent adjuvant brachytherapy. Six weeks later, examination of the anterior segment revealed cells in the anterior chamber and a neurotrophic corneal ulcer with corneal perforation. Considering the high suspicion of intraocular invasion of CSCC, the left eye was enucleated. Histopathologic findings showed scarring of the ciliary body with fibrosis temporally. Nasally, the sclera showed a lobular infiltration of well-differentiated squamous carcinoma. The central cornea exhibited a large ulcer with perforation and infiltrating squamous cells adhering to the posterior surface. To our knowledge, this is the first documented case of an intraocular diffuse recurrence of CSCC after resection and adjuvant brachytherapy, with clinicopathologic correlation of radiation effects on the ocular tissues.