bluuebunny/crossref_metadata_2025 huggingface dataset:
Taxonomy of 'Euconnus complex'. Part XV. Disentangling the Euconnus-Sciacharis knot (Coleoptera, Staphylinidae, Scydmaeninae)
Authors: JAŁOSZYŃSKI PAWEŁ , NEWTON ALFRED F.
Published: November 2017

Many species currently placed in Sciacharis Broun were once included in Euconnus Thomson, and their taxonomic history is complicated due to diffuse and overlapping diagnoses of both genera applied by previous authors, numerous virtually unjustified transfers of species between them, and hundreds of species not assigned to any subgenus. Based on comparative morphological studies of respective type species, we clarify the status of Allomaoria Franz, Austroconophron Franz, Magellanoconnus Franz, Neuraphoconnus Franz and Valdivioconnus Franz. All of them, except for Neuraphoconnus, were originally described as subgenera of Euconnus, later transferred to Sciacharis. Austroconophron is removed from synonymy with Sciacharis s. str. and resurrected as subgenus of Euconnus (resulting in Euconnus (Austroconophron Franz, status rest.); Allomaoria is retained as a junior synonym of Sciacharis s. str.; Magellanoconnus is removed from Sciacharis and restituted as genus (resulting in Magellanoconnus Franz, status rest.); Anthicimimus Franz, previously removed from subgenus of Sciacharis and elevated to genus rank, is reduced to subgenus of Magellanoconnus (resulting in Magellanoconnus (Anthicimimus stat. rev.); Neuraphoconnus is removed from synonymy with Magellanoconnus and resurrected as genus (resulting in Neuraphoconnus Franz, status rest.); and Valdivioconnus is transferred from subgenus of Sciacharis to subgenus of Microscydmus Saulcy & Croissandeau (resulting in Microscydmus (Valdivioconnus Franz, status rev.). The only Australian species of Magellanoconnus is transferred to Kangarooconnus Jałoszyński, gen. n. (resulting in Kangarooconnus carinifrons (Franz), comb. n.). A complete checklist of 302 species and subspecies previously or currently placed in Sciacharis (including 102 restituted and 50 new combinations) is given. Three replacement names are proposed for secondary homonyms resulted from new combinations: Euconnus (Austroconophron) caledonensides Newton, nom. n. (for Euconnus caledonensis Franz, 1986, not Euconnus caledonensis Franz, 1979); Magellanoconnus (s. str.) castrianus Jałoszyński & Newton, nom. n. (for Magellanoconnus castrii (Franz, 1967: 636), not Magellanoconnus castrii (Franz, 1967: 614)); and Sciacharis (Sciacharis) bryantides Newton, nom. n. (for Euconnus bryanti Franz, 1975, not Euconnus bryanti Lhoste, 1939). Lectotypes are designated (des. Jałoszyński) for Euconnus tindoui Franz, 1971, Phagonophana lanosa Broun, 1885, and Neuraphoconnus caledonicus Franz, 1971.
First description of the male of the type species Meotipa picturata Simon, 1895 and description of a new Meotipa species (Araneae, Theridiidae) from India
Authors: MURTHAPPA PRASHANTHAKUMARA S. , MALAMEL JOBI J. , PRAJAPATI DHRUV A. , SEBASTIAN POTHALIL A. , VENKATESHWARLU MIDIDODDI
Published: November 2017

The present paper reports the first description of the type species of the theridid genus Meotipa, Meotipa picturata Simon, 1895 and redescribe the female of the same species with one new species Meotipa multuma sp.nov. from India. The two species are described in detail and we provide digital images and illustrations. Chrysso makiling, Barrion-Dupo & Barrion is transferred to Meotipa Simon, 1895 based on the presence of the generic characters of the last genus.
Intrinsic and Atmospherically Forced Variability of the AMOC: Insights from a Large-Ensemble Ocean Hindcast
Authors: Leroux Stephanie , Penduff Thierry , Bessières Laurent , Molines Jean-Marc , Brankart Jean-Michel , Sérazin Guillaume , Barnier Bernard , Terray Laurent
Published: November 2017

This study investigates the origin and features of interannual–decadal Atlantic meridional overturning circulation (AMOC) variability from several ocean simulations, including a large (50 member) ensemble of global, eddy-permitting (1/4°) ocean–sea ice hindcasts. After an initial stochastic perturbation, each member is driven by the same realistic atmospheric forcing over 1960–2015. The magnitude, spatiotemporal scales, and patterns of both the atmospherically forced and intrinsic–chaotic interannual AMOC variability are then characterized from the ensemble mean and ensemble spread, respectively. The analysis of the ensemble-mean variability shows that the AMOC fluctuations north of 40°N are largely driven by the atmospheric variability, which forces meridionally coherent fluctuations reaching decadal time scales. The amplitude of the intrinsic interannual AMOC variability never exceeds the atmospherically forced contribution in the Atlantic basin, but it reaches up to 100% of the latter around 35°S and 60% in the Northern Hemisphere midlatitudes. The intrinsic AMOC variability exhibits a large-scale meridional coherence, especially south of 25°N. An EOF analysis over the basin shows two large-scale leading modes that together explain 60% of the interannual intrinsic variability. The first mode is likely excited by intrinsic oceanic processes at the southern end of the basin and affects latitudes up to 40°N; the second mode is mostly restricted to, and excited within, the Northern Hemisphere midlatitudes. These features of the intrinsic, chaotic variability (intensity, patterns, and random phase) are barely sensitive to the atmospheric evolution, and they strongly resemble the “pure intrinsic” interannual AMOC variability that emerges in climatological simulations under repeated seasonal-cycle forcing. These results raise questions about the attribution of observed and simulated AMOC signals and about the possible impact of intrinsic signals on the atmosphere.
Observations of Ash, Ice, and Lightning within Pyrocumulus Clouds Using Polarimetric NEXRAD Radars and the National Lightning Detection Network
Authors: LaRoche Kendell T. , Lang Timothy J.
Published: November 2017

A pyrocumulus is a convective cloud that can develop over a wildfire. Under certain conditions, pyrocumulus clouds become vertically developed enough to produce lightning. NEXRAD dual-polarization weather radar and upgraded National Lightning Detection Network (NLDN) data were used to analyze 10 case studies of ash plumes and pyrocumulus clouds from 2013 that either did or did not produce detected lightning. Past research has shown that pyrocumulus cases are most likely to produce lightning when there is a decrease in differential reflectivity (toward 0 dB) and an increase in the correlation coefficient (to >0.8), as measured by polarimetric radar, due to the transition from pure smoke/ash to frozen hydrometeors. All pyrocumulus cases that produced lightning in this study displayed the polarimetric characteristics of rimed ice within their respective clouds. Time series analysis of radar-inferred ash and rimed ice volumes within ash plumes and pyrocumulus clouds showed that NLDN-detected lightning occurred only after the cloud contained significant amounts of precipitation-sized rimed ice. The results suggest that the recently dual-pol-enabled NEXRADs and the more sensitive NLDN network can be used to explore ash plume and pyrocumulus microphysical structure and lightning production.
Criminal Justice Contact and Relapse Among Patients Seeking Treatment for Opioid Use Disorder
Authors: Kopak Albert M. , Lawson Steven W. , Hoffmann Norman G.
Published: November 2017

The rapid rise in opioid use has recently contributed to several pressing concerns, including an unprecedented number of fatal overdoses, a marked increase in treatment admissions, a spike in emergency department visits, and a significant proportion of adults who test positive for opioids at the time of arrest. The majority of arrestees who test positive for opioids after being booked into jail also report prior engagement with a substance use treatment program, highlighting the need to address posttreatment substance use and involvement in the criminal justice system. The current study was conducted to untangle the posttreatment substance use–arrest relationship and better understand how one may influence the other. Analyses conducted with 396 adults, drawn from a nationwide sample of patients seeking treatment for opioid use disorder, demonstrated that posttreatment arrest increased the likelihood of substance use, but the evidence suggested that this relationship was not reciprocal. These results have significant implications for criminal justice practices with regard to using alternatives to arrest as methods to minimize posttreatment substance use.
The road to TRAs is paved with good intentions: Dispossession through delivery in post-apartheid Cape Town
Authors: Levenson Zachary
Published: November 2017

Dispossession need not be the product of malicious intentions or a deliberate programme of accumulation. As I argue in this article, it may paradoxically be the consequence of social spending, or what I call dispossession through delivery. Using as a case study the proliferation of temporary relocation areas (TRAs) in post-apartheid Cape Town, I show how what appears as adequate housing from the municipal government’s perspective exacerbates social isolation, perpetuates squatting and aggravates unemployment, transport costs and interpersonal violence. I draw on 17 months of ethnographic fieldwork in TRAs and land occupations, NGO reports and interviews with housing officials to understand dispossession through delivery in these relocation sites. While TRAs began as emergency housing in cases of environmental catastrophes, they have become regularised as a form of state-provisioned housing even in non-emergency situations and, above all, in cases of land occupations. They are but one of a range of technologies of delivery that facilitate dispossession, and I conclude this article with a discussion of how formal housing distribution and informal settlement upgrading have similar effects. When these various technologies of delivery are understood as bound together in a single articulation, ‘dispossession through delivery’ challenges the standard opposition between neoliberalism and social spending that characterises much of the literature and begins to map novel socio-spatial effects of one trajectory of urbanisation in a Southern city.
Further Evaluation of Presentation Format of Competing Stimuli for Treatment of Automatically Maintained Challenging Behavior
Authors: Clay Casey J. , Clohisy Annie M. , Ball Alexandra M. , Haider Aqdas F. , Schmitz Brittany A. , Kahng SungWoo
Published: November 2017

Behavioral interventions have been effective in reducing automatically maintained skin picking for individuals with disabilities including autism spectrum disorder (ASD). A competing stimulus assessment (CSA) is typically utilized in behavioral intervention and assessment to identify potential stimuli which compete with the reinforcer for various forms of challenging behavior (CB). Treatment evaluations have validated the results of these assessments by demonstrating competing stimuli may reduce levels of CB. In Phase 1 of this study, we conducted a functional analysis (FA) to determine what variables were maintaining skin picking of an 11-year-old girl diagnosed with ASD. In Phase 2, we conducted a CSA to determine which stimulus competed the most with skin picking. In Phase 3, we utilized a multielement with reversal design to compare the effectiveness of three presentation formats: (a) single stimulus (single), (b) multiple stimuli (multiple), and (c) alternating stimuli (alternating) in reducing levels of automatically maintained CB. We found noncontingent access to a single item was the most effective intervention to decrease skin picking. This study adds to the literature on reducing CB in children with ASD by incorporating a CSA before the evaluation of different formats of delivering competing stimuli, across extended duration session times.
Priests and Midwives
Authors: Heady Patrick
Published: November 2017

Godparenthood is a distinctive form of ritual kinship associated with Christianity—most strongly developed in Catholic and Orthodox societies. There is general agreement among researchers that it is important both subjectively and practically. Nevertheless, the underlying logic of the system remains rather elusive—since the usual explanations, in terms of either patronage or religious belief, receive rather limited support from the data. Ethnographic evidence shows that the dyadic and triadic relationships of god(co)parenthood often involve neither practical patronage nor spiritual guidance. It is clear that a satisfactory explanation of godparenthood needs to go beyond these surface functions: the question is how? In this article, I argue that there are parallels between god(co)parenthood as it operates in Catholic Europe and the sacralization of kinship ties in segmentary lineage systems found in other parts of the world. In both cases, sacralized kinship ties link individuals to encompassing kinship categories which can also be localized in appropriate ways. I argue that this provides a cognitive framework in which kin-based and locally based cooperation can operate in a mutually sustaining fashion—and that the commitment to god(co)parenthood reflects the felt need for cooperation of this kind. To support this interpretation, I refer to fieldwork in northeast Italy. I also draw on historical and survey data to show that the interpretation is consistent with the history and geography of godparenthood within Europe.
Merely “Design Marketing”? Professional Perspectives on the Use and Misuse of Environmental Visualizations in Community Engagement
Authors: Groulx Mark , Lewis John L.
Published: November 2017

Environmental visualizations can improve the publics’ understanding of spatial information and enhance dialogue during community engagement. By interviewing and surveying planning and design professionals, this study examines motivations for using environmental visualizations in community engagement. Professionals recognize the communicative benefits of environmental visualizations, but also acknowledge that they are sometimes used to constrain public debate by enhancing project imagibility. This article contributes to a critical assessment of the ethical use of environmental visualization by exploring techniques and practices that can create misinformation within community engagement. Overall findings contribute to a clearer understanding of environmental visualizations as a form of design marketing.
Risk and Protective Factors for Difficulty Controlling Violent Behavior in National Guard and Reserve Service Members
Authors: Worthen Miranda , Rathod Sujit D. , Cohen Gregory , Sampson Laura , Ursano Robert , Gifford Robert , Fullerton Carol , Galea Sandro , Ahern Jennifer
Published: November 2017

Violent behavior is an important problem for military service members and veterans. A representative cohort of U.S. Reserve and National Guard personnel ( N = 1,293) were interviewed to assess self-reported problems controlling violent behavior, deployment traumas, posttraumatic stress disorder (PTSD), alcohol abuse, and social support. Poisson regression models were used to estimate the associations of violent behavior with risk and protective factors. Problems controlling violent behavior were uncommon among male (3.3%) and female (1.7%) service members. Adjusted prevalence ratios (aPR) showed associations between violent behavior and deployment traumas (aPR = 1.67, 95% confidence interval [CI] = [1.34, 2.08]), PTSD (aPR = 9.95, 95% CI = [5.09, 19.48]), and PTSD symptom severity (aPR for each additional PTSD symptom = 1.07, 95% CI = [1.06, 1.09]). Social support was associated with lower prevalence of violent behavior (aPR = 0.62, 95% CI = [0.52, 0.76]). The association between violent behavior and alcohol abuse was not statistically significant (aPR = 1.94, 95% CI = [0.92, 4.09]). Results were consistent when the population was restricted to personnel who had deployed to a war zone. Problems controlling violent behavior were less common in this cohort than has been documented in other studies. Associations of violent behavior with risk and protective factors are consistent with prior research.
A New Treatment Strategy for Parkinson's Disease through the Gut–Brain Axis
Authors: Kim Dong Seok , Choi Ho-Il , Wang Yun , Luo Yu , Hoffer Barry J. , Greig Nigel H.
Published: November 2017

Molecular communications in the gut–brain axis, between the central nervous system and the gastrointestinal tract, are critical for maintaining healthy brain function, particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD, and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing, and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut–brain axis could provide an effective treatment option for neurodegenerative diseases. Glucagon-like peptide-1 (GLP-1)-based antidiabetic drugs have drawn particular attention as an effectual new strategy to not only regulate blood glucose but also decrease body weight by reducing appetite, which implies that GLP-1 could affect the gut–brain axis in normal and pathological conditions. The neurotrophic and neuroprotective effects of GLP-1 receptor (R) stimulation have been characterized in numerous in vitro and in vivo preclinical studies using GLP-1R agonists and dipeptidyl peptidase-4 inhibitors. Recently, the first open label clinical study of exenatide, a long-acting GLP-1 agonist, in the treatment of PD showed long-lasting improvements in motor and cognitive function. Several double-blind clinical trials of GLP-1R agonists including exenatide in PD and other neurodegenerative diseases are already underway or are about to be initiated. Herein, we review the physiological role of the GLP-1R pathway in the gut–brain axis and the therapeutic strategy of GLP-1R stimulation for the treatment of neurodegenerative diseases focused on PD, for which age is the major risk factor.
The Importance of Handwriting Experience on the Development of the Literate Brain
Authors: James Karin H.
Published: November 2017

Handwriting experience can have significant effects on the ability of young children to recognize letters. Why handwriting has this facilitative effect and how this is accomplished were explored in a series of studies using overt behavioral measures and functional neuroimaging of the brain in 4- to 5-year-old children. My colleagues and I showed that early handwriting practice affects visual symbol recognition because it results in the production of variable visual forms that aid in symbol understanding. Further, the mechanisms that support this understanding lay in the communication between visual and motor systems in the brain: Handwriting serves to link visual processing with motor experience, facilitating subsequent letter recognition skills. These results are interpreted in the larger context of the facilitatory effect that learning through action has on perceptual capabilities.
The interplay between accounting professionals and political ideologies: The emergence of Chinese accounting standards from 1978 to 1992
Authors: Xu Lina , Cortese Corinne , Zhang Eagle
Published: November 2017

This article explores the role of accounting professionals in the emergence of the first set of accounting standards – Accounting Standards for Business Enterprises (ASBE) – in China between 1978 and 1992. Based on a variety of sources drawn from the archives of Chinese language accounting textbooks and highly ranked academic journals, this article reveals how accounting professionals adapted accounting thoughts and practice to fit the demands of the prevailing political ideologies, which facilitated the social conditions essential for the development of ASBE. Drawing on theoretical perspectives on the interplay between accounting and its social context, as pronounced and advocated by Hopwood and his collaborators, this article provides evidence that further demonstrates the social nature of accounting as it was implicated in the broader economic and political transformations in China between 1978 and 1992.
Pleuroparenchymal Fibroelastosis With Long History of Asbestos and Silicon Exposure
Authors: Xu Liyan , Rassaei Negar , Caruso Carla
Published: November 2017

Pleuroparenchymal fibroelastosis (PPFE) is an uncommon interstitial lung disease. PPFE is characterized by fibroelastosis involving the pleura and subjacent parenchyma with a predominantly upper lobe distribution. While different possible environmental and familial etiologies have been postulated in the literature, the etiology of this disease remains essentially unclear and most cases are considered as idiopathic. In this report, we describe a rare case of PPFE with multiple lung lobe involvements and prolonged asbestos and silica exposure. Our goal is to investigate the exposure of asbestos and silica and try to identify their possible association with PPFE.
Language of ADHD in Adults on Social Media
Authors: Guntuku Sharath Chandra , Ramsay J. Russell , Merchant Raina M. , Ungar Lyle H.
Published: November 2017

Objective: We computationally analyze the language of social media users diagnosed with ADHD to understand what they talk about, and how their language is correlated with users’ characteristics such as personality and temporal orientation. Method: We analyzed approximately 1.3 million tweets written by 1,399 Twitter users with self-reported diagnoses of ADHD, comparing their posts with those used by a control set matched by age, gender, and period of activity. Results: Users with ADHD are found to be less agreeable, more open, to post more often, and to use more negations, hedging, and swear words. Posts are suggestive of themes of emotional dysregulation, self-criticism, substance abuse, and exhaustion. A machine learning model can predict which of these Twitter users has ADHD with an out-of-sample AUC of .836. Conclusion: Based on this emerging technology, conjectures of future uses of social media by researchers and clinicians to better understand the naturalistic manifestations and sequelae of ADHD.
Endogenous Plasma Peptide Detection and Identification in the Rat by a Combination of Fractionation Methods and Mass Spectrometry
Authors: Bertile Fabrice , Robert Flavie , Delval-Dubois Véronique , Sanglier Sarah , Schaeffer Christine , Van Dorsselaer Alain
Published: November 2017

Mass spectrometry-based analyses are essential tools in the field of biomarker research. However, detection and characterization of plasma low abundance and/or low molecular weight peptides is challenged by the presence of highly abundant proteins, salts and lipids. Numerous strategies have already been tested to reduce the complexity of plasma samples. The aim of this study was to enrich the low molecular weight fraction of rat plasma. To this end, we developed and compared simple protocols based on membrane filtration, solid phase extraction, and a combination of both. As assessed by UV absorbance, an albumin depletion >99% was obtained. The multistep fractionation strategy (including reverse phase HPLC) allowed detection, in a reproducible manner (CV < 30%-35%), of more than 450 peaks below 3000 Da by MALDI-TOF/MS. A MALDI-TOF/MS-determined LOD as low as 1 fmol/μL was obtained, thus allowing nanoLC-Chip/MS/MS identification of spiked peptides representing ~10–6% of total proteins, by weight. Signal peptide recovery ranged between 5%-100% according to the spiked peptide considered. Tens of peptide sequence tags from endogenous plasma peptides were also obtained and high confidence identifications of low abundance fibrinopeptide A and B are reported here to show the efficiency of the protocol. It is concluded that the fractionation protocol presented would be of particular interest for future differential (high throughput) analyses of the plasma low molecular weight fraction.
Recursive Partitioning Analysis of Mediastinal N2 Lymph Node Involvement with Selected Biological Markers in Operable Non-small Cell Lung Cancer: A Correlative Study
Authors: Bozcuk H , Gumus A , Ozbilim G , Sarper A , Kucukosmanoglu I , Ozdogan M , Demircan A
Published: November 2017

Background

Expressions of various biomarkers in non-small cell lung cancer (NSCLC) have been linked with the prognosis and involvement of mediastinal lymph nodes.

Methods

In this study, we utilized recursive partitioning analysis (RPA) by using P53, c-erb-B2, and P-glycoprotein (PGP) expressions evaluated by immunohistochemistry to estimate retrospectively the likelihood of the occult N2 mediastinal lymph node involvement in patients with operable NSCLC.

Results

In univariate tests, immunohistochemical staining of the primary tumor for these 3 markers in 61 patients undergoing surgery revealed no direct relationship with the N2 involvement. However, RPA demonstrated in patients aged <75 and with ≥4 mediastinal lymph nodes removed that, high PGP expression frequency (≥20%) predicted an increased likelihood of the N2 involvement (46.7%, R2 = 0.25). Univariate nominal logistic regression analysis revealed that RPA group affiliation, and the number of mediastinal lymph nodes resected (logarithmic transformation) were associated with the metastasis to N2 lymph nodes (χ2 = 17.59, p = 0.0005, and χ2 = 2.40, p = 0.0654, respectively). Multivariate analysis confirmed that only RPA group affiliation predicted the N2 involvement (χ2 = 14.63, p = 0.0022).

Conclusion

This study shows for the first time that PGP expression of the primary tumor may help to predict the occult N2 mediastinal lymph node involvement in NSCLC. Thus, further research is required to understand whether PGP expression may aid in the decision process for preoperative mediastinoscopy.
Changes in Metallothionein Levels in Freshwater Mussels Exposed to Urban Wastewaters: Effects from Exposure to Heavy Metals?
Authors: Gagné F. , Gagnon C. , Turcotte P. , Blaise C.
Published: November 2017

Municipal effluents are complex mixtures of compounds such as heavy metals, aromatic and aliphatic hydrocarbons, and micro-organisms and are released in aquatic ecosystems. The purpose of this study was to verify whether changes in metallothioneins (MT) were associated with the accumulation of labile metals in tissue of freshwater mussels exposed to the dispersion plume of a major municipal effluent. Mussels were placed in experimental cages deployed at sites 1.5 km upstream, 8 km downstream and 12 km downstream of the outfall of a major, primary-treated municipal effluent in the St. Lawrence River (Québec, Canada). Mussels were analysed for MT and labile zinc levels in their gonads, gills and digestive glands. Lipogenic enzyme (isocitrate and glucose-6-phosphate dehydrogenase) and arachidonic acid cyclooxygenase (COX) activities were also measured in gonad and gill tissues. Although MT was induced in all the tissues examined, the results showed that labile zinc levels were significantly reduced in gill and gonad tissues, with an increase observed only at the 12 km downstream site in the digestive gland. COX activity was readily induced in gills and gonads. Glucose-6-phosphate dehydrogenase activity was reduced at both downstream sites, but isocitrate dehydrogenase activity was significantly induced at the farthest (12 km) site. Analysis of covariance revealed that MT levels in gills were more influenced by COX activity than with distance in the dispersion plume and was negatively correlated with labile zinc levels. In conclusion, MT induction was inversely related to the levels of labile zinc but positively so with the inflammation biomarker COX. Hence, the induction of MT in mussels exposed to the municipal effluent of a large city appears to be associated with either inflammatory processes or as compensation for the loss of labile essential metals. We propose that the simple and complimentary parameters of labile zinc and COX evaluations be used to link MT induction with divalent heavy metal exposure in environmental studies dealing with various type of contaminants in such complex contaminant mixture effluents.
Microvessel Density and Clinicopathologic Characteristics in Hepatocellular Carcinoma with and without Cirrhosis
Authors: Chebib Ivan , Shabani-Rad Meer Taher , Chow Michelle S. , Zhang James , Gao Zu-hua
Published: November 2017

Angiogenesis is essential to the survival, growth, invasion, and metastasis of various human solid tumors. We compared the microvessel density (MVD) and clinicopathologic features of two different groups of hepatocellular carcinoma (HCC), namely HCC with cirrhosis (HCC-C) and without cirrhosis (HCC-NC). A tissue microarray composed of 20 normal livers, 20 cirrhotic livers, tumor and adjacent background non-neoplastic liver tissues from 20 HCC-C and 20 HCC-NC were constructed and stained immunohistochemically with antibodies against the antigen CD34. The MVD was determined by the measurement of the area and density of CD34 positive sinusoidal endothelial cells using the Image Pro Plus software. There was a trend of increased MVD in cirrhotic liver compared to normal liver and in cirrhotic background non-neoplastic liver adjacent to the tumor compared to the non-cirrhotic background non-neoplastic liver. Tumor tissue of HCC-C and HCC-NC both showed significantly higher MVD than their adjacent background non-neoplastic liver tissue. There was no statistical difference in MVD between HCC-C and HCC-NC. A higher value of MVD was seen in tumors of intermediate size (5–10 cm), high histologic grade, the presence of lymphvascular space invasion, and the underlying etiology of hepatitis C and alcoholic steatohepatitis. This data indicates that MVD may play an important role in liver carcinogenesis and neoplastic progression. The difference in clinical behavior between HCC-C and HCC-NC does not seem to be associated with differences in tumor MVD. Objective measurement of MVD using standardized computer software could potentially be used as a clinical marker to predict patients’ prognosis.
Biomarkers in Bladder Cancer: Present Status and Perspectives
Authors: Kim Wun-Jae , Park Soongang , Kim Yong-June
Published: November 2017

Bladder cancers are a mixture of heterogeneous cell populations, and numerous factors are likely to be involved in dictating their recurrence, progression and the patient's survival. For any candidate prognostic marker to have considerable clinical relevance, it must add some predictive capacity beyond that offered by conventional clinical and pathologic parameters. Here, the current situation in bladder cancer research with respect to identification of suitable prognostic markers is reviewed. A number of individual molecular markers that might predict bladder cancer recurrence and progression have been identified but many are not sufficiently sensitive or specific for the whole spectrum of bladder cancer diseases seen in routine clinical practice. These limitations have led to interest in other molecular parameters that could enable more accurate prognosis for bladder cancer patients. Of particular interest is the epigenetic silencing of tumor suppressor genes. Since the methylation of these genes can correlate with a poor prognosis, the methylation profile may represent a new biomarker that indicates the risk of transitional cell carcinoma development. In addition, bladder cancer research is likely to be revolutionized by high-throughput molecular technologies, which allow rapid and global gene expression analysis of thousands of tumor samples. Initial studies employing these technologies have considerably expanded our ability to classify bladder cancers with respect to their survivability. Future microarray analyses are likely to reveal particular gene expression signatures that predict the likelihood of bladder cancer progression and recurrence, as well as patient's survival and responsiveness to different anti-cancer therapies, with great specificity and sensitivity.
Molecular Markers for Biomass Traits: Association, Interaction and Genetic Divergence in SilkwormBombyx mori
Authors: Pradeep Appukuttannair R , Jingade Anuradha H , Urs Raje S
Published: November 2017

Improvement of high yielding, disease resistant silkworm strains became imminent to increase production of silk, which is a major revenue earner for sericulturists. Since environment interacts with phenotype, conventional breeding did not result in commendable yield improvement in synthetic strains of silkworm, Bombyx mori. Identification of DNA markers associated with different economically important biomass traits and its introgression could assist molecular breeding and expression of stabilized high yielding characters, but genetic basis of most quantitative traits in silkworm is poorly understood due to its polygenic control. Correlation analysis (R = 0.9) revealed significant interrelation among biomass traits viz., larval duration (TLD), larval weight (LWT), cocoon weight (CWT), shell weight (SWT), shell ratio (SR) and floss content. PCR using inter simple sequence repeat (ISSR) primers revealed 92% polymorphism among 14 tropical and temperate strains of B. mori, with average diversity index of 0.747. Stepwise multiple regression analysis (MRA) selected 35 ISSR markers positively or negatively correlated with different biomass traits, illustrated polygenic control. ISSR marker 830.81050bpwas significantly associated with LWT, CWT, SWT, SR and floss content, indicated its pleiotropic role. Two ISSR markers, 835.51950bpand 825.9710bpshowed significant association with floss content and TLD. These markers were segregated in F2generation and Chi-square test confirmed (χ2= ~45; P < 0.05) its genetic contribution to the associated biomass traits. Strains, with both positively and negatively correlated markers, had intermediate mean value for biomass traits (eg. SWT = 0.17 ± 0.014 g in GNM and Moria) indicated interaction of loci in natural populations. Low yielding Indian strains grouped together by Hierarchical clustering. Chinese and Japanese strains were distributed in the periphery of ALSCAL matrix indicated convergence of genetic characters in Indian strains. Average genetic distance between Chinese strains and Indian strains (0.193) significantly ( P < 0.01) varied from that between Chinese and Japanese strains. Interaction of loci and allelic substitutions induced phenotypic plasticity in temperate B. mori populations on tropic adaptation in India. These outcomes show possibility to combine favorable alleles at different QTL to increase larval, cocoon and shell weight.
An EGFR and AKT Signaling Pathway was Identified with Mediation Model in Osteosarcomas Clinical Study
Authors: Wu Huiyun , Muscato Nicole E. , Gonzalez Adriana , Shyr Yu
Published: November 2017

Identification of correlation pattern and signal pathway among biomarkers in patients has become increasingly interesting for its potential values in diagnosis, treatment and prognosis. EGFR and p-AKT signaling in osteosarcoma (OS) patients were analyzed for its relationship with cancer cell proliferation maker, Ki-67, using causal procedures and statistical tests. A total of 69 patients were collected who present to Vanderbilt University Medical Center with newly diagnosed, previously untreated osteosarcomas during the clinical study period 1994 through 2003. Tissue microarrays were constructed for EGFR, p-AKT and Ki-67. The mediation model was constructed with structural equation model (SEM) for the causal analysis of the three biomarkers in osteosarcoma patients. The results suggested a mediating effect of p-AKT for the causal relationship between EGFR and Ki-67. The study also found significant associations between EGFR and Ki-67 (p = 0.002), EGFR and p-AKT (p = 0.027), and p-AKT and Ki-67 controlling EGFR (p = 0.004). After the impact of EGFR on Ki-67 was accounted for by p-AKT, the relation between EGFR and Ki-67 was no longer significant (p = 0.381). The mediating effect was confirmed with Sobel test (p < 0.001) and Goodman (I) test (p < 0.001). The study indicated that a mediation model could be an approach to exploring the correlation pattern of EGFR and AKT signal pathway for cancer cell proliferation in OS patients in clinical study.
The Sample Type used Affects the Levels of Gelatinases (MMP-2 and -9) and their Inhibitors (TIMP-1 and -2) in Circulating Blood of Healthy Controls and Breast Cancer Patients
Authors: Paula Kuvaja , Anne Talvensaari-Mattila , Taina Turpeenniemi-Hujanen
Published: November 2017

New potential tumor markers such as matrix metalloproteinases and their inhibitors have been extensively studied during the last decades. The aim is to find prognostic markers that are measurable in easily available samples, such as serum or plasma. The proper sample type to use when measuring the levels of gelatinases and their inhibitors from blood samples is currently under critical evaluation. In this study, the effect of sample type is studied in 26 healthy controls, and the result is confirmed in a series of 80 breast carcinoma patients.

Sample type had the most evident effect on the levels of TIMP-1 and MMP-9. Serum samples gave about two-fold levels of TIMP-1 compared to plasma samples (p < 0.001), with a strong linear correlation between these two (r = 0.79). Pro-MMP-9 levels were significantly affected by the presence of a blood coagulation activator in the serum sample, or a different anticoagulant in the plasma sample. The serum and plasma values had only a weak correlation (r = 0.37).

In conclusion, sample type should be carefully considered, especially when measuring proMMP-9, and plasma should be preferred for this measurement. For TIMP-1 the correlation of serum and plasma values is good; the use of serum samples can therefore be justified as long as the generally higher levels in the serum are acknowledged.
Pharmacodynamic Effects of an Angiotensin II Receptor-Antagonist in Phase I—Comparison between Healthy Subjects and Patients with Hypertension
Authors: Wensing Georg , Ochmann Klaus , Boettcher Michael , Schäfer Anja , Kuhlmann Jochen
Published: November 2017

Biomarkers are increasingly used to provide decision making data early in phase I by showing Proof of Mechanism or Proof of Concept (PoM/PoC). For antihypertensive agents, the administration of multiple doses (md) to hypertensive patients is assumed to be necessary for an early go/no-go decision. We compared the effects of an Angiotensin II receptor antagonist (ARA) on Plasma Renin and blood pressure (BP) following an oral single dose (sd) and once daily md for seven days to healthy volunteers and patients with essential hypertension (diastolic BP 95 mmHg to 114 mmHg; systolic BP 130 mmHg to 200 mmHg). Methods: 5–12 healthy male subjects/dose received 10 mg to 300 mg ARA sd and 50 to 300 mg md for 7 days; patients (9–10/dose) received 20 mg–400 mg ARA for 7 days. The studies were designed as randomized, single blind, placebo-controlled, group comparison or crossover dose-escalation studies. Plasma Renin and BP were monitored up to 24 hours after dosing. Results: Plasma Renin showed a high interindividual variability in both healthy volunteers and patients. Healthy subjects showed a dose- and time-related increase in plasma Renin after sd from 40 mg to 300 mg and md of 50 mg to 300 mg (p < 0.05 for doses of 200 mg and 300 mg). In patients, increases in plasma Renin occurred at 8 hours and beyond starting at sd of 100 mg and md of 50 mg (p < 0.05 for the dose of 400 mg). While healthy volunteers showed no relevant decrease in BP, in hypertensive patients a reduction in BP in doses of 100 mg to 400 mg occurred (p < 0.05); effects were more pronounced after md compared to sd. Conclusion: Early PoM for an antihypertensive agent can be shown by use of laboratory biomarkers following sd to healthy subjects. PoC can be achieved after sd in hypertensive patients. Administration of sd to healthy volunteers is sufficient for an early go/no-decision.
TLR2 and TLR4 as Potential Biomarkers of Environmental Particulate Matter Exposed Human Myeloid Dendritic Cells
Authors: Williams Marc A. , Cheadle Chris , Watkins Tonya , Tailor Anitaben , Killedar Smruti , Breysse Patrick , Barnes Kathleen C. , Georas Steve N.
Published: November 2017

In many subjects who are genetically susceptible to asthma, exposure to environmental stimuli may exacerbate their condition. However, it is unknown how the expression and function of a family of pattern-recognition receptors called toll-like receptors (TLR) are affected by exposure to particulate pollution. TLRs serve a critical function in alerting the immune system of tissue damage or infection—the so-called “danger signals”. We are interested in the role that TLRs play in directing appropriate responses by innate immunity, particularly dendritic cells (DC), after exposing them to particulate pollution. Dendritic cells serve a pivotal role in directing host immunity. Thus, we hypothesized that alterations in TLR expression could be further explored as potential biomarkers of effect related to DC exposure to particulate pollution. We show some preliminary data that indicates that inhaled particulate pollution acts directly on DC by down-regulating TLR expression and altering the activation state of DC. While further studies are warranted, we suggest that alterations in TLR2 and TLR4 expression should be explored as potential biomarkers of DC exposure to environmental particulate pollution.
Expression of Osteoarthritis Marker YKL-39 is Stimulated by Transforming Growth Factor Beta (TGF-beta) and IL-4 in Differentiating Macrophages
Authors: Gratchev Alexei , Schmuttermaier Christina , Mamidi Srinivas , Gooi LiMing , Goerdt Sergij , Kzhyshkowska Julia
Published: November 2017

YKL-39 is a Glyco_18 domain containing chitinase-like protein which is currently recognized as a biomarker for the activation of chondrocytes and the progress of the osteoarthritis in human. YKL-39 was identified as an abundantly secreted protein in primary culture of human articular chondrocytes. Two biological activities of YKL-39 might contribute to the disease progression. One is the induction of autoimmune response and second is the participation in tissue remodeling. Other mammalian chitinase-like proteins including chitotriosidase, SI-CLP, YKL-40 and YM1 are expressed by macrophages in various pathological conditions. In contrast, YKL-39 was never reported to be produced by macrophages. We used in vitro model of human monocyte-derived macrophage differentiation to analyse regulation of YKL-39 expression. Expression of YKL-39 was examined by real-time RT-PCR. CD14+ MACS sorted human monocytes differentiated for 6 days under different stimulations including IFNγ, IL-4, dexamethasone and TGF-β. We found that both IL-4 and TGF-β have weak stimulatory effect on YKL-39 expression in all donors tested (3.2 ± 1.7 fold, p = 0.006 and 6.3 ± 3.1 fold, p = 0.014 respectively). However the combination of IL-4 and TGF-β had strong stimulatory effect on the expression of YKL-39 in all analysed individual macrophage cultures (34 ± 36 fold, p = 0.05). IFN-γ did not show statistically significant effect of YKL-39 mRNA expression. Presence of dexamethasone almost completely abolished the stimulatory effects of IL-4 and TGF-β. In summary, we show here for the first time, that human cells of monocyte origin are able to produce YKL-39. Maturation of monocyte derived macrophages in the presence of Th2 cytokine IL-4 and TGF-β leads to the strong activation of YKL-39 expression. Thus elevated levels of YKL-39 observed during chronic inflammations can not be attributed solely to the activity of chondrocytes. In perspective, YKL-39 might serve as a useful biomarker to detect macrophage-specific response in pathologies like tumour, atherosclerosis and Alzheimer disease.
Neuromodulation in multiple sclerosis
Authors: Abboud Hesham , Hill Eddie , Siddiqui Junaid , Serra Alessandro , Walter Benjamin
Published: November 2017

Neuromodulation, or the utilization of advanced technology for targeted electrical or chemical neuronal stimulation or inhibition, has been expanding in several neurological subspecialties. In the past decades, immune-modulating therapy has been the main focus of multiple sclerosis (MS) research with little attention to neuromodulation. However, with the recent advances in disease-modifying therapies, it is time to shift the focus of MS research to neuromodulation and restoration of function as with other neurological subspecialties. Preliminary research supports the value of intrathecal baclofen pump and functional electrical stimulation in improving spasticity and motor function in MS patients. Deep brain stimulation can improve MS-related tremor and trigeminal neuralgia. Spinal cord stimulation has been shown to be effective against MS-related pain and bladder dysfunction. Bladder overactivity also responds to sacral neuromodulation and posterior tibial nerve stimulation. Despite limited data in MS, transcranial magnetic stimulation and brain–computer interface are promising neuromodulatory techniques for symptom mitigation and neurorehabilitation of MS patients. In this review, we provide an overview of the available neuromodulatory techniques and the evidence for their use in MS.
Hamstring Injuries in Professional Soccer Players: Extent of MRI-Detected Edema and the Time to Return to Play
Authors: Crema Michel D. , Godoy Ivan R. B. , Abdalla Rene J. , de Aquino Jose Sanchez , Ingham Sheila J. McNeill , Skaf Abdalla Y.
Published: November 2017

Background:

Discrepancies exist in the literature regarding the association of the extent of injuries assessed on magnetic resonance imaging (MRI) with recovery times.

Hypothesis:

MRI-detected edema in grade 1 hamstring injuries does not affect the return to play (RTP).

Study Design:

Retrospective cohort study.

Level of Evidence:

Level 4.

Methods:

Grade 1 hamstring injuries from 22 professional soccer players were retrospectively reviewed. The extent of edema-like changes on fluid-sensitive sequences from 1.5-T MRI were evaluated using craniocaudal length, percentage of cross-sectional area, and volume. The time needed to RTP was the outcome. Negative binomial regression analysis tested the measurements of MRI-detected edema-like changes as prognostic factors.

Results:

The mean craniocaudal length was 7.6 cm (SD, 4.9 cm; range, 0.9-19.1 cm), the mean percentage of cross-sectional area was 23.6% (SD, 20%; range, 4.4%-89.6%), and the mean volume was 33.1 cm3 (SD, 42.6 cm3; range, 1.1-161.3 cm3). The mean time needed to RTP was 13.6 days (SD, 8.9 days; range, 3-32 days). None of the parameters of extent was associated with RTP.

Conclusion:

The extent of MRI edema in hamstring injuries does not have prognostic value.

Clinical Relevance:

Measuring the extent of edema in hamstring injuries using MRI does not add prognostic value in clinical practice.
Ideas for Teaching Vision and Visioning
Authors: Quijada Maria Alejandra
Published: November 2017

In teaching leadership, a key element to include should be a discussion about vision: what it is, how to communicate it, and how to ensure that it is effective and shared. This article describes a series of exercises that rely on videos to illustrate different aspects of vision and visioning, both in the positive and in the negative. The article also shares the videos and supporting materials that build these exercises. The exercises can be used in undergraduate or graduate leadership classes and can be easily used in an online class.