bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrosis worsens chronic lymphedema in rodent tissues
Authors: Lynch Laura L. , Mendez Uziel , Waller Anna B. , Gillette Amani A. , Guillory Roger J. , Goldman Jeremy
Published: March 2015

Secondary lymphedema in humans is a common consequence of lymph node dissection (LND) to treat breast cancer. A peculiar characteristic of the disease is that lifelong swelling often precipitously appears several years after the surgical treatment, often due to an inflammatory stimulus. Although the incidence of secondary lymphedema dramatically increases after radiation therapy, the relationship between fibrotic scarring and the eventual appearance of lymphedema remains unclear. To clarify the role of fibrosis in secondary lymphedema initiation, we chemically increased fibrosis in rodent tissues with bleomycin and assessed the ability of the local lymphatic system to prevent lymphedema, either acutely or in a chronic state induced by inflammation. We found that bleomycin injections exacerbated fibrotic matrix deposition in an acute mouse tail lymphedema model ( P < 0.005), reduced wound closure ( P < 0.005), and impaired the ability of tail lymphatics to regenerate ( P < 0.005) and reduce the swelling ( P < 0.05). When fibrosis was worsened with bleomycin after axillary LND in the rat foreleg, the ability of the foreleg lymphatic system to reduce the chronic state swelling induced by stimulated inflammation was severely impaired ( P < 0.005). Indocyanine green lymphography in axillary LND-recovered rat forelegs revealed a worsened lymphatic drainage due to inflammation and bleomycin pretreatment. Although inflammation reduced the drainage of dextran fluid tracer from control forelegs ( P < 0.05), the reduction in fluid drainage was more severe after axillary LND when fibrosis was first increased ( P < 0.005). These findings demonstrate that fibrosis reduces the lymphatic capacity to functionally regenerate and prevent the chronic appearance of lymphedema.
Targeting Nodal in Conjunction with Dacarbazine Induces Synergistic Anticancer Effects in Metastatic Melanoma
Authors: Hardy Katharine M. , Strizzi Luigi , Margaryan Naira V. , Gupta Kanika , Murphy George F. , Scolyer Richard A. , Hendrix Mary J.C.
Published: March 2015

Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. Despite a complete response in fewer than 5% of patients, the chemotherapeutic agent dacarbazine (DTIC) remains the reference drug after almost 40 years. More recently, FDA-approved drugs have shown promise but patient outcome remains modest, predominantly due to drug resistance. As such, combinatorial targeting has received increased attention, and will advance with the identification of new molecular targets. One attractive target for improving melanoma therapy is the growth factor Nodal, whose normal expression is largely restricted to embryonic development, but is reactivated in metastatic melanoma. In this study, we sought to determine how Nodal-positive human melanoma cells respond to DTIC treatment and to ascertain whether targeting Nodal in combination with DTIC would be more effective than monotherapy. A single treatment with DTIC inhibited cell growth but did not induce apoptosis. Rather than reducing Nodal expression, DTIC increased the size of the Nodal-positive subpopulation, an observation coincident with increased cellular invasion. Importantly, clinical tissue specimens from patients with melanomas refractory to DTIC therapy stained positive for Nodal expression, both in pre- and post-DTIC tumors, underscoring the value of targeting Nodal. In vitro, anti-Nodal antibodies alone had some adverse effects on proliferation and apoptosis, but combining DTIC treatment with anti-Nodal antibodies decreased cell growth and increased apoptosis synergistically, at concentrations incapable of producing meaningful effects as monotherapy.

Implications: Targeting Nodal in combination with DTIC therapy holds promise for the treatment of metastatic melanoma. Mol Cancer Res; 13(4); 670–80. ©2015 AACR.
Light to Moderate Alcohol Consumption Is Associated With Lower Risk of Aortic Valve Sclerosis
Authors: Markus Marcello Ricardo Paulista , Lieb Wolfgang , Stritzke Jan , Siewert Ulrike , Troitzsch Paulina , Koch Manja , Dörr Marcus , Felix Stephan Burkhard , Völzke Henry , Schunkert Heribert , Baumeister Sebastian Edgar
Published: March 2015

Objective—

In developed countries, sclerotic and calcific degeneration of the aortic valve is a common disorder showing pathophysiologic similarities with atherothrombotic coronary disease. Light to moderate alcohol consumption has been associated with a lower risk for atherothrombotic coronary disease and mortality. Whether alcohol consumption affects the development of aortic valve sclerosis (AVS) is not well known. In the present study, we aim to analyze the cross-sectional association between average daily alcohol consumption and AVS in the general population.

Approach and Results—

We analyzed cross-sectional data from 2022 men and women, aged 45 to 81 years, from the population-based Study of Health in Pomerania. We used a computer-assisted interview that included beverage-specific questions about quantity and frequency of alcohol over the last 30 days to calculate the average quantity of alcohol consumption (in grams of ethanol per day). AVS was ascertained by echocardiography. The prevalence of AVS was 32.3%. Average daily alcohol intake displayed a J-type relation with AVS (fully adjusted
P
value: 0.005). Compared with individuals with an average consumption of 10 g of alcohol per day, multivariable-adjusted odds ratios were 1.60 (95% confidence interval, 1.19–2.14) among current abstainers and 1.56 (95% confidence interval, 1.01–2.41) among individuals with an average consumption of 60 g per day.

Conclusions—

Our findings indicate that light to moderate alcohol consumption was associated with a lower odd of having AVS. Prospective data need to address whether alcohol consumption and related changes over time in several biological markers affect the progression of AVS.
Collectivization of Vascular Smooth Muscle Cells via TGF-β–Cadherin-11–Dependent Adhesive Switching
Authors: Balint Brittany , Yin Hao , Chakrabarti Subrata , Chu Michael W.A. , Sims Stephen M. , Pickering J. Geoffrey
Published: March 2015

Objective—

Smooth muscle cells (SMCs) in healthy arteries are arranged as a collective. However, in diseased arteries, SMCs commonly exist as individual cells, unconnected to each other. The purpose of this study was to elucidate the events that enable individualized SMCs to enter into a stable and interacting cell collective.

Approach and Results—

Human SMCs stimulated to undergo programmed collectivization were tracked by time-lapse microscopy. We uncovered a switch in the behavior of contacting SMCs from semiautonomous motility to cell–cell adherence. Central to the cell-adherent phenotype was the formation of uniquely elongated adherens junctions, up to 60 μm in length, which appeared to strap adjacent SMCs to each other. Remarkably, these junctions contained both N-cadherin and cadherin-11. Ground-state depletion super-resolution microscopy revealed that these hybrid assemblies were comprised of 2 parallel nanotracks of each cadherin, separated by 50 nm. Blocking either N-cadherin or cadherin-11 inhibited collectivization. Cell–cell adhesion and adherens junction elongation were associated with reduced transforming growth factor-β signaling, and exogenous transforming growth factor-β1 suppressed junction elongation via the noncanonical p38 pathway. Imaging of fura-2–loaded SMCs revealed that SMC assemblies displayed coordinated calcium oscillations and cell–cell transmission of calcium waves which, together with increased connexin 43–containing junctions, depended on cadherin-11 and N-cadherin function.

Conclusions—

SMCs can self-organize, structurally and functionally, via transforming growth factor-β–p38–dependent adhesive switching and a novel adherens junction architecture comprised of hybrid nanotracks of cadherin-11 and N-cadherin. The findings define a mechanism for the assembly of SMCs into networks, a process that may be relevant to the stability and function of blood vessels.
Cold-Inducible RNA-Binding Protein Regulates Cardiac Repolarization by Targeting Transient Outward Potassium Channels
Authors: Li Jun , Xie Duanyang , Huang Jian , Lv Fei , Shi Dan , Liu Yi , Lin Li , Geng Li , Wu Yufei , Liang Dandan , Chen Yi-Han
Published: March 2015

Rationale:

Cold-inducible RNA-binding protein (CIRP) is constitutively expressed at low levels across various tissues. It is rapidly upregulated by multiple stresses, underlying a general role for CIRP in organic adaptations to pathophysiological conditions. However, the role of CIRP in the heart remains unclear.

Objective:

To examine the biofunctions of CIRP in the mammalian heart.

Methods and Results:

Rats with targeted disruption of
Cirp
were generated using the TALEN (transcription activator-like effector nucleases)-based genome editing technique. The
Cirp
-knockout rats had structurally and functionally normal hearts. Resting ECG recordings revealed a short rate-corrected QT (QTc) interval in
Cirp
-null rats without any abnormalities in PR interval, RR interval or QRS waves as compared to wild-type animals. The shortened QTc interval from
Cirp
ablation was tightly linked to an abbreviated action potential duration in cardiac myocytes, which was attributable to increased transient outward potassium current (
I
to
). Furthermore, our findings uncovered that CIRP protein selectively bonded to
KCND2
and
KCND3
mRNAs encoding the functional α-subunits of
I
to
channel proteins. CIRP deficiency did not change the transcriptional activity of
KCND2
or
KCND3
, but it facilitated their translation.
Cirp
knockout had no effect on the functional expression of ion channels other than
I
to
channels.

Conclusions:

CIRP modulates cardiac repolarization by negatively adjusting the expression and function of
I
to
channels. Our study may open a window to decipher the potential function of RNA-binding proteins in bioelectric activity.
A Multiple-Goal Investment Strategy for Sovereign Wealth Funds: An Application to China
Authors: Xie Li , Woo Wing Thye , Zhang Zhichao , Zhang Zhuang
Published: March 2015

This paper develops a multiple-goal investment strategy for sovereign wealth funds. In our investment strategy, we embed the Black-Litterman (B-L) model into the mean variance mental accounting (MVMA) approach. The B-L method provides a means of modeling return expectations, and the MVMA framework allows the derivation of the optimal asset allocation from a global investment perspective, in a response to a specific macroeconomic environment.
Further findings from Daveli Cave (Attica, Greece) enhancing the establishment of the genus Oculatella (Pseudanabaenaceae, Cyanobacteria)
Authors: Christodoulou Maria , Meletiou-Christou Maria-Sonia , Parmakelis Aristeidis , Economou-Amilli Athena , Pantazidou Adriani
Published: March 2015

In this study, cyanobacterial assemblages were collected from the limestone cave Daveli (Attica, Greece) during an annual survey (2010–2011). Four sampling areas were selected from the cave entrance inwards, and the main abiotic parameters (PAR, T, RH) were measured at each site. A portion of the collected material was fixed with formaldehyde solution and another part was maintained alive for culturing and microscopic observations. XRD analysis was applied for analyzing the chemical composition of the limestone substrate. Microscopic observation (LM) revealed the presence of a wealth of Cyanobacteria including a brownish-violet colored filamentous morphotype with a large granulated ‘ocellus’ in the apical cell, features resembling the newly (2012) established genus Oculatella of the family Pseudanabaenaceae. This morphotype was isolated in unialgal cultures for a further morphological (SEM and TEM), molecular (16S rRNA) and biochemical analysis (FAME). The 16S rRNA sequence generated from the specimen revealed a 99% similarity with Leptolyngbya sp. VRUC135 (GenBank–X84809), a strain now recognized as the type species (Oculatella subterranea) of Oculatella. Taking a step forward, we proceeded to the determination of fatty acid composition by Gas Chromatography which revealed the dominance of palmitic acid (16:0) in all isolates followed by palmitoleic acid (16:1), linoleic acid (18:2), and oleic acid (18:1), while tridecylic acid (13:0), myristic acid (14:0), isomers of C15, C17, C20 and C22, stearic acid (18:0), linolenic acid (18:3), as well as an unknown fatty acid were found in traces. These new findings corroborate the establishment of the new genus Oculatella and provide information on the fatty acid composition of the species Oculatella subterranea.
    Ophiorrhiza sahyadriensis (Rubiaceae), a new species from southern Western Ghats, Kerala, India
Authors: Sankaran HAREESH Vadakkoot , Balakrishnan Sreekumar Vadakkethil , Mambetta PRABHU KUMAR Konikkal , Kureekadu NIRMESH Thankappan , Ashtamoorthy Sreejith Kalpuzha
Published: March 2015

A new species of Ophiorrhiza (Rubiaceae) is described from southern Western Ghats, Kerala, India. The new species, Ophiorrhiza sahyadriensis, is similar to Ophiorrhiza brunonis, an endangered species endemic to Western Ghats, to which is compared. Detailed description, distribution, ecology, phenology and relevant taxonomic notes are provided along with colour photographs and illustrations.
Typification of the names and taxonomic status of selected vascular plant taxa described by Max Eugen Heinrich Grütter
Authors: Pliszko Artur , Heise Waldemar
Published: March 2015

Max Eugen Heinrich Grütter (30 March 1865–31 March 1897) was a German botanist interested in floristics and taxonomy of vascular plants and mosses (Abromeit 1897). He conducted intensive floristic studies on the territory of the former West and East Prussia, especially in the former West Prussian Province Schwetz (now north-central Poland) where he lived in the small village of Luschkowko (Grütter 1892, 1895a, 1895b, 1895c, 1897). His numerous findings had been frequently cited in “Flora von Ost‑ und Westpreussen” by Abromeit et al. (1898–1940). In 1890–1891, in the course of the floristic expeditions in the former West Prussian Province Schwetz, Grütter found interesting vascular plants which he deemed as new to science. The names of these taxa were validly published in Deutsche botanische Monatsschrift (Grütter 1892).
Nurses’ Involvement in Patients’ Dying and Death
Authors: Kondo Makiko , Nagata Hiroshi
Published: March 2015

This study reports the development of a measurement scale, The Nurses’ Involvement in Patients’ Dying and Death Scale (NIPDYDS), which fully captures the experiences of nurses caring for patients’ dying and death. Potential items were extracted from narrative data gathered systematically and comprehensively from in-depth interviews with nurses engaged in caring for patients’ dying and death. Factor analyses revealed four factors, consisting of 40 total items, with two factors related to the positive aspects of the experience ( Deep involvement in facing dying and death and Increased competence in facing dying and death) and two factors related to the negative aspects of the experience ( Uncertainty and difficulty dealing with dying and death and Accustomed to dying and death). Validity and reliability of the scale were found to be acceptable. The factorial structure of the NIPDYDS was contrasted to Frommelt’s (1991) FATCOD (The Frommelt Attitude Toward Care of the Dying Scale), and the usefulness and limitations of the NIPDYDS were discussed.
Incidence of Secondary Intra-articular Injuries With Time to Anterior Cruciate Ligament Reconstruction
Authors: Ralles Steven , Agel Julie , Obermeier Michael , Tompkins Marc
Published: March 2015

Background:

Precise locations of chondral and meniscal damage with increased time to anterior cruciate ligament reconstruction (ACLR) have not been well described.

Purpose/Hypothesis:

The purpose of the study was to determine the relationship between delay in primary ACLR and incidence of secondary intra-articular injury. The hypothesis was that patients with increased time between initial injury and ACLR will exhibit greater incidence of secondary intra-articular injury when compared with those who receive surgical intervention promptly after injury. A second hypothesis was that patients with higher preinjury activity levels or older age will exhibit greater secondary injury when compared with those with minimal preinjury activity levels and younger age.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

A retrospective review was performed on 1434 patients with an anterior cruciate ligament deficiency who underwent primary ACLR at a single institution between 2009 and 2013. Patients were grouped according to time to surgery after initial injury: 0-3, 4-12, and >12 months. Operative notes were used to analyze 10 variables across time-to-surgery groups: cartilage damage in the patella, trochlea, medial femoral condyle, lateral femoral condyle, medial tibial plateau, and lateral tibial plateau; medial and lateral meniscal injury; and the incidence of procedures involving either the meniscus or cartilage. Patient age and preinjury activity level were also analyzed for the 10 variables based on time-to-surgery groups.

Results:

An association was noted between time to surgery and increased incidence of injury in the trochlea, lateral femoral condyle, medial tibial plateau, and medial meniscus ( P < .001). Different significant findings within each age group were observed, but overall positive findings were seen in the same 4 locations described above. On the basis of preinjury activity level, the less active patients were most at risk for medial meniscal and trochlear injury, while the more active patients were most at risk for medial tibial plateau injury with increased time from injury to ACLR.

Conclusion:

Increasing time from injury to ACLR was associated with increased incidence of secondary injury seen in the trochlea, lateral femoral condyle, medial tibial plateau, and medial meniscus. Separate analyses of patient age and preinjury activity level showed similar findings, thus supporting the primary analysis.
Expectations, Status Value, and Group Structure
Authors: Hysom Stuart J. , Webster Murray , Walker Lisa Slattery
Published: March 2015

We report a replication and extension of theory and experimental tests reported by Stuart J. Hysom. That earlier work added status value of rewards to established theories of status generalization processes. We extend that work to cases in which both the status positions of actors and the status value of their rewards function in status generalization. Overall experimental results show confirmation of the theory, but fine-grained analyses reveal some weaknesses in experimental operations. Besides improving the experimental techniques, future work might explore effects of multiple statuses and rewards, and legitimacy effects that may be raised by inconsistent combinations of status and rewards.
The Construct Validity of Attitudes Toward Career Counseling Scale for Korean College Students
Authors: Nam Suk Kyung , In Park Hyung
Published: March 2015

This study aimed to examine the construct validity of the Attitudes Toward Career Counseling Scale (ATCCS) in Korea. In Study 1, confirmatory factor analysis (CFA) was used for testing the factor structure of the scale. The results supported a two-factor (value and stigma) model, which was theoretically driven from the original study. Results of Study 2 showed that ATCCS-Value and ATCCS-Stigma were differently related to self-disclosure, attitudes toward seeking professional help, self-stigma, public stigma, work-exploration, self-exploration, intention to seeking help, and career decision self-efficacy. Group differences were also examined to demonstrate whether previous experience of counseling was related to current attitudes toward career counseling. Overall, the results indicated that ATCCS would be an adequate assessment of measuring attitudes toward career counseling for Korean college students. The implication of cultural differences and additional limitations were discussed.
Masculinity and medicalization: Gender and vocabularies of motive in the narrative of a sex offender
Authors: Rickard Diana
Published: March 2015

This paper explores the tension between vocabularies of motive provided by a serial sex offender in his narrative construction of his nonconsensual sexual activity. Current discourses on the topic emphasize the efficacy of social control measures and behavioral and pharmacological interventions. There is a dearth of sociological literature exploring the social meanings of sexual offense. Employing a symbolic interactionist approach to a sex offender’s account of self provides an opportunity for making visible the discursive construction of social processes. Deploying broad gender stereotypes in depictions of the women against whom he offended, the case presented here also relied on three dominant therapeutic constructions of the sexual deviant, the psychosocial, the addiction/compulsion model, and the bio-psychiatric—all of which neglect the gendered aspect of his offenses. Positing himself as a “true sex offender” and voluntarily taking hormonal suppressants that rendered him impotent, he was the ideal subject of bio-psychiatric discourse. The paper analyses his narrative in terms of contrasting notions of gender and deviance, masculinity and medicalization, and explores the ways language of institutionally supported interventions are used to make meaningful both normal and deviant identities, while disengaging from gender discourses.
Pleasure, disaffection, ‘conversion’ or rejection? The (limited) role of prefiguration in shaping audience engagement and response
Authors: Michelle Carolyn , Davis Charles H. , Hardy Ann L. , Hight Craig
Published: March 2015

This article examines the extent to which prefigurative ‘horizons of expectations’ shaped audience engagements with Peter Jackson’s 2012 film The Hobbit: An Unexpected Journey ( AUJ). Whereas previous research often focuses on examining prefigurative materials, discussions and debates themselves, this article draws on audience surveys conducted before and after the film’s release to illustrate the impact of prior hopes and expectations on post-viewing responses. While Hobbit pre-viewers were often deeply familiar with various prefigurative materials and intertextual resources, AUJ nonetheless retained the capacity to delight, confound, impress and distress viewers in ways that superseded pre-existing structures of meaning. Thus, while our findings illustrate that processes of reception potentially begin prior to and continue beyond initial moments of viewing, they also affirm the need to engage – theoretically and empirically – with the complex specificity and fluidity of actual reception experiences.
Ruled by attention: A case study of professional digital attention agents at Sina.com and the Chinese blogosphere
Authors: Guo Shaohua
Published: March 2015

Much has been written about the crucial role attention plays in the digital economy and how to enhance technological features to better sustain user attention for commercial applications. However, we know very little about how myriad factors other than technological ones shape the structure and flow of online attention, and what significant implications the attention economy bears for such authoritarian regimes as China that heavily censor the web. This article fills the gap by investigating how Sina.com – the leading news and entertainment web portal in China – innovatively capitalizes on the attention economy and plays a leading role in popularizing blogging in China. This article proposes the concept of ‘professional digital attention agents’ and investigates in detail the role that these agents play in structuring, directing and publicizing online content. It argues that professional digital attention agents not only effectively popularize blogs as a new self-publishing medium in China, but also foster the ascent of critical voices from a commercially oriented Chinese blogosphere.
At home in Asia? Sydney’s Chinatown and Australia’s ‘Asian Century’
Authors: Ang Ien
Published: March 2015

It is widely recognised that the 21st century is seeing a geopolitical shift in global power relations towards Asia, particularly China. This has led Australia to officially embrace Asia as its regional home. But the neoliberal economic logic underpinning this embrace leads to a narrowly transactional conception of Australia’s relationship to Asia, governed by an opportunity/threat dichotomy. By contrast, this article describes Sydney’s Chinatown today as an increasingly hybrid, porous and transnational space of uneven and mixed-up, embodied Asian-Australianness. Juxtaposing the dynamic on-the-ground reality of this contemporary Chinatown with government discourse on Australia’s relationship to Asia, as exemplified by the 2012 White Paper Australia in the Asian Century, illuminates that Australia is not yet at home in Asia.
Citizenship management: On the politics of being included-out
Authors: Erni John Nguyet
Published: March 2015

Many in Hong Kong have identified the city as ‘half-sovereign’ or ‘conditionally sovereign’, as postcoloniality has brought about new ruptures and shifting boundaries of citizenship in economic, cultural and legal terms. The work of deciphering questions of belonging is still ongoing, and has in fact intensified in recent times. Increasingly, who qualifies as a citizen and where their sense of home is have become vital questions for two visible groups: the Chinese Mainlanders whose personal and cultural fortunes have been transformed by opportunities presented by the permeability of the city-border, and the foreign domestic helpers whose right of belonging has been caught up in discriminatory immigration laws. My argument is that their fates are conjoined by what I call the state of being ‘included-out’, something augmented by nebulous doctrines of citizenship rights as well as by legalized and informal forms of cultural racialism. Through an analysis of the landscape of human rights struggles concerning the right of abode for people caught in half-sovereignty, I hope to outline the biopolitical continuum of those ‘included-out’ in Hong Kong’s citizenship management regime.
The conceptual articulation of the reality of life: Max Weber’s theoretical constitution of sociological ideal types
Authors: Rosenberg M Michael
Published: March 2015

Max Weber’s theoretical constitution of sociological ideal types is examined, and a number of key elements and characteristics of such types are identified. Additionally, several common misconceptions with respect to Weber’s sociological types are clarified, including the erroneous assumption that his sociological ideal types were formulated on an ad hoc basis, as well as the common complaint that these types are overly abstract and more suited to classification than explanation. By combining Weber’s methodological discussions of the ideal type with examples taken from his substantive studies, Weber’s sociological ideal types are shown to have been constructed as integrated components of theoretical schemes which, when applied to an empirical context, provide comprehensive explanations.
Neo-liberal educational reform and the role of teachers’ unions in the context of private schools in Nepal: Possibility or paralysis?
Authors: Sharma Poudyal Chandra
Published: March 2015

Nepal experienced political change from absolute monarchy to constitutional monarchy in 1990 and finally to a republic in 2008. These changes in the political climate were followed by subsequent change in the educational policy as the incoming regimes tried to incorporate its ideology in the educational policy. This paper analyses the role of teachers’ unions in the educational reform in Nepal since the 1990s with special focus on private schooling context. This paper draws information collected through qualitative interviews with teachers, administrators and principals of two private schools in Kathmandu, the capital city of Nepal. It also uses documentary sources including newspaper articles and other documents related to private schooling in general and teachers’ unions in particular. This study found that teachers’ unions in the context of private schools in Nepal are still struggling for survival due to lack of support from the stakeholders of private schools.
Development of a Synthetic Adaptive Neuro-Fuzzy Prediction Model for Tumor Motion Tracking in External Radiotherapy by Evaluating Various Data Clustering Algorithms
Authors: Ghorbanzadeh Leila , Torshabi Ahmad Esmaili , Nabipour Jamshid Soltani , Arbatan Moslem Ahmadi
Published: March 2015

In image guided radiotherapy, in order to reach a prescribed uniform dose in dynamic tumors at thorax region while minimizing the amount of additional dose received by the surrounding healthy tissues, tumor motion must be tracked in real-time. Several correlation models have been proposed in recent years to provide tumor position information as a function of time in radiotherapy with external surrogates. However, developing an accurate correlation model is still a challenge. In this study, we proposed an adaptive neuro-fuzzy based correlation model that employs several data clustering algorithms for antecedent parameters construction to avoid over-fitting and to achieve an appropriate performance in tumor motion tracking compared with the conventional models. To begin, a comparative assessment is done between seven nuero-fuzzy correlation models each constructed using a unique data clustering algorithm. Then, each of the constructed models are combined within an adaptive sevenfold synthetic model since our tumor motion database has high degrees of variability and that each model has its intrinsic properties at motion tracking. In the proposed sevenfold synthetic model, best model is selected adaptively at pre-treatment. The model also updates the steps for each patient using an automatic model selectivity subroutine. We tested the efficacy of the proposed synthetic model on twenty patients (divided equally into two control and worst groups) treated with CyberKnife synchrony system. Compared to Cyberknife model, the proposed synthetic model resulted in 61.2% and 49.3% reduction in tumor tracking error in worst and control group, respectively. These results suggest that the proposed model selection program in our synthetic neuro-fuzzy model can significantly reduce tumor tracking errors. Numerical assessments confirmed that the proposed synthetic model is able to track tumor motion in real time with high accuracy during treatment.
Half-Year Retest-Reliability of the Barratt Impulsiveness Scale–Short Form (BIS-15)
Authors: Meule Adrian , Mayerhofer Martina , Gründel Tilman , Berker Jasmin , Beck Teran Carina , Platte Petra
Published: March 2015

One of the most widely used instruments for the measurement of impulsivity is the Barratt Impulsiveness Scale (BIS-11). The short form of the BIS-11, the BIS-15, consists of 15 items representing the three subscales Attentional, Motor, and Non-Planning Impulsivity. In the current study, retest-reliabilities of BIS-15 scores were examined. Female university students completed the BIS-15 at the beginning of the first ( n = 133) and second ( n = 120) semesters. Half-year retest-reliability was rtt = .79 for the BIS-15 total score and ranged between rtt = .61 and .78 for the subscales. Considering the long time span of almost half a year between measurements, the total score of the BIS-15 has high retest-reliability and, thus, measures impulsivity as a stable personality trait.
Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina
Authors: Wang Jianxiang , Shen Zhi-Xiang , Saglio Giuseppe , Jin Jie , Huang He , Hu Yu , Du Xin , Li Jianyong , Meng Fanyi , Zhu Huanling , Hu Jianda , Wang Jianmin , Hou Ming , Hertle Sabine , Menssen Hans D. , Ortmann Christine-Elke , Tribouley Catherine , Yuan Ye , Baccarani Michele , Huang Xiaojun
Published: March 2015

Key Points

Chinese patients with newly diagnosed CML-CP achieved higher rates of MMR with nilotinib vs imatinib. Nilotinib was well tolerated, and no new safety signals were observed.
A novel method to fabricate CoFe2O4/SrFe12O19 composite ferrite nanofibers with enhanced exchange coupling effect
Authors: Pan Lining , Cao Derang , Jing Panpan , Wang Jianbo , Liu Qingfang
Published: March 2015

Nanocomposite of CoFe2O4/SrFe12O19 has been synthesized by the electrospinning and calcination process. A novel method that cobalt powder was used to replace traditional cobalt salt in the precursor sol-gel for electrospinning was proposed. The crystal structures, morphologies, and magnetic properties of these samples have been characterized in detail. Moreover, when the average crystallite size of the hard/soft phases reached up to an optimal value, the CoFe2O4 have an enhanced saturation magnetization of 62.8 emu/g and a coercivity of 2,290 Oe. Significantly, the hysteresis loops for the nanocomposites show a single-phase magnetization behavior, and it has been found that the exchange coupling interaction strongly exists in the CoFe2O4/SrFe12O19 magnetic nanocomposite nanofibers.
Small Organic Molecule Disruptors of Cav3.2 - USP5 Interactions Reverse Inflammatory and Neuropathic Pain
Authors: Gadotti Vinicius M , Caballero Agustin Garcia , Berger N Daniel , Gladding Clare M , Chen Lina , Pfeifer Tom A , Zamponi Gerald W
Published: March 2015

Background

Cav3.2 channels facilitate nociceptive transmission and are upregulated in DRG neurons in response to nerve injury or peripheral inflammation. We reported that this enhancement of Cav3.2 currents in afferent neurons is mediated by deubiquitination of the channels by the deubiquitinase USP5, and that disrupting USP5/Cav3.2 channel interactions protected from inflammatory and neuropathic pain.

Results

Here we describe the development of a small molecule screening assay for USP5- Cav3.2 disruptors, and report on two hits of a ~5000 compound screen - suramin and the flavonoid gossypetin. In mouse models of inflammatory pain and neuropathic pain, both suramin and gossypetin produced dose-dependent and long-lasting mechanical anti-hyperalgesia that was abolished or greatly attenuated in Cav3.2 null mice. Suramin and Cav3.2/USP5 Tat-disruptor peptides were also tested in models of diabetic neuropathy and visceral pain, and provided remarkable protection.

Conclusions

Overall, our findings provide proof of concept for a new class of analgesics that target T-type channel deubiquitination.
Estimated dietary dioxin exposure and breast cancer risk among women from the French E3N prospective cohort
Authors: Danjou Aurélie MN , Fervers Béatrice , Boutron-Ruault Marie-Christine , Philip Thierry , Clavel-Chapelon Françoise , Dossus Laure
Published: March 2015

Introduction

Dioxins are environmental and persistent pollutants mostly emitted from combustion facilities (e.g. waste incinerators, metal and cement industries). Known to be endocrine disrupting chemicals, dioxins are suspected to increase breast cancer (BC) risk. Although diet is considered the primary source of dioxin exposure, no previous study has been published on dietary dioxin exposure in relation to BC risk. We aimed to assess dietary dioxin exposure among women from the E3N cohort and estimate BC risk associated with this exposure.

Methods

The study included 63,830 women from the E3N cohort who completed a diet history questionnaire (DHQ) in 1993 and were followed until 2008. Dietary dioxin exposure was estimated by combining consumption data from the E3N DHQ and food dioxin contamination data from a French national monitoring program. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox models adjusted for BC risk factors.

Results

Mean dietary dioxin exposure was estimated at 1.3 ± 0.4 pg/kg body weight (BW)/day. A 0.4 pg/kg BW/d increase in dioxin intake was not associated with overall BC risk (HR = 1.00; 95% CI: 0.96, 1.05). A significant decrease in risk of estrogen receptor negative (ER-)/progesterone receptor negative (PR-) tumors was observed among post-menopausal women in the upper quartile of estimated dioxin intake (HR for Q4 vs. Q1: 0.65; 95% CI: 0.45, 0.96; P for trend across quartiles = 0.0463).

Conclusions

Overall, no association between estimated dietary dioxin exposure and BC risk was found among E3N women. Further studies should include both dietary and environmental exposures to determine whether low-dose dioxin exposure is associated with BC risk.
Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice
Authors: Decock Julie , Hendrickx Wouter , Thirkettle Sally , Gutiérrez-Fernández Ana , Robinson Stephen D , Edwards Dylan R
Published: March 2015

Introduction

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity that has oncosuppressive actions in numerous tumor types.

Methods

We have intercrossed Mmp8-null mice with the Polyoma virus middle T oncogene-driven (MMTV-PyMT) mouse model of mammary cancer to explore the effects of loss of MMP-8 on the incidence and progression of mammary carcinomas.

Results

In this aggressive mouse model of breast cancer, loss of MMP-8 accelerated tumor onset even further, such that 90% of MMTV-PyMT; Mmp8-null female mice were tumor-bearing at the time of weaning. Throughout the 14 weeks of the model, tumor burden increased in homozygous Mmp8-null mice compared to Mmp8-wild-type and -heterozygote animals. Likewise, lung metastasis dramatically increased in the MMTV-PyMT; Mmp8-null mice. Immunohistochemistry revealed that tumors in wild-type, Mmp8-heterozygotes and -null animals had similar vascular density at 8 weeks, but at 10 weeks Mmp8-wild-type tumors had a lower vascularity than their heterozygote and null counterparts. No differences in macrophage infiltration were apparent throughout primary tumor development, though at 10 weeks a drop in neutrophil infiltrates was observed in Mmp8-wild-type tumors. Using quantitative real-time RT-PCR, we tracked the expression of the entire Mmp and Timp gene families, observing a significant decrease in Mmp3 expression in Mmp8-null tumors compared to wild-type and heterozygotes throughout the time course of the model, which was confirmed at the protein level.

Conclusions

These findings provide novel insight into the suppressive action of MMP-8 on mammary tumorigenesis and metastasis, and indicate that the loss of MMP-8 likely has pleiotropic effects on innate immunity and angiogenesis that are reflected in changes in the protease web.
MUSiCC: a marker genes based framework for metagenomic normalization and accurate profiling of gene abundances in the microbiome
Authors: Manor Ohad , Borenstein Elhanan
Published: March 2015

Functional metagenomic analyses commonly involve a normalization step, where measured levels of genes or pathways are converted into relative abundances. Here, we demonstrate that this normalization scheme introduces marked biases both across and within human microbiome samples, and identify sample- and gene-specific properties that contribute to these biases. We introduce an alternative normalization paradigm, MUSiCC, which combines universal single-copy genes with machine learning methods to correct these biases and to obtain an accurate and biologically meaningful measure of gene abundances. Finally, we demonstrate that MUSiCC significantly improves downstream discovery of functional shifts in the microbiome.

MUSiCC is available at http://elbo.gs.washington.edu/software.html.
HLAreporter: a tool for HLA typing from next generation sequencing data
Authors: Huang Yazhi , Yang Jing , Ying Dingge , Zhang Yan , Shotelersuk Vorasuk , Hirankarn Nattiya , Sham Pak Chung , Lau Yu Lung , Yang Wanling
Published: March 2015

Human leukocyte antigen (HLA) typing from next generation sequencing (NGS) data has the potential for widespread applications. Here we introduce a novel tool (HLAreporter) for HLA typing from NGS data based on read-mapping using a comprehensive reference panel containing all known HLA alleles, followed by de novo assembly of the gene-specific short reads. Accurate HLA typing at high-digit resolution was achieved when it was tested on publicly available NGS data, outperforming other newly developed tools such as HLAminer and PHLAT. HLAreporter can be downloaded from http://paed.hku.hk/genome/.
Heterogeneity of intratumoral 111In-ibritumomab tiuxetan and 18F-FDG distribution in association with therapeutic response in radioimmunotherapy for B-cell non-Hodgkin’s lymphoma
Authors: Hanaoka Kohei , Hosono Makoto , Tatsumi Yoichi , Ishii Kazunari , Im Sung-Woon , Tsuchiya Norio , Sakaguchi Kenta , Matsumura Itaru
Published: March 2015

Background

The purpose of this study was to quantitatively evaluate the tumor accumulation and heterogeneity of 111In-ibritumomab tiuxetan (Zevalin®) and tumor accumulation of 18F-fluoro-deoxyglucose (FDG) and compare them to the tumor response in B-cell non-Hodgkin’s lymphoma patients receiving 90Y-ibritumomab tiuxetan (Zevalin®) therapy.

Methods

Sixteen patients with histologically confirmed non-Hodgkin’s B-cell lymphoma who underwent 90Y-ibritumomab tiuxetan therapy along with 111In-ibritumomab tiuxetan single-photon emission computerized tomography (SPECT)/CT and FDG positron emission tomography (PET)/CT were enrolled in this retrospective study. On pretherapeutic FDG PET/CT images, the maximum standardized uptake value (SUVmax) was measured. On SPECT/CT images, a percentage of the injected dose per gram (%ID/g) and SUVmax of 111In-ibritumomab tiuxetan were measured at 48 h after its administration. The skewness and kurtosis of the voxel distribution were calculated to evaluate the intratumoral heterogeneity of tumor accumulation. As another intratumoral heterogeneity index, cumulative SUV-volume histograms describing the percentage of the total tumor volume above the percentage thresholds of pretherapeutic FDG and 111In-ibritumomab tiuxetan SUVmax (area under the curve of the cumulative SUV histograms (AUC-CSH)) were calculated. All lesions (n = 42) were classified into responders and non-responders lesion-by-lesion on pre- and post-therapeutic CT images.

Results

A positive correlation was observed between the FDG SUVmax and accumulation of 111In-ibritumomab tiuxetan in lesions. A significant difference in pretherapeutic FDG SUVmax was observed between responders and non-responders, while no significant difference in 111In-ibritumomab tiuxetan SUVmax was observed between the two groups. In contrast, voxel distribution of FDG demonstrated no significant differences in the three heterogeneity indices between responders and non-responders, while 111In-ibritumomab tiuxetan demonstrated skewness of 0.58 ± 0.16 and 0.73 ± 0.24 (p < 0.05), kurtosis of 2.39 ± 0.32 and 2.78 ± 0.53 (p < 0.02), and AUC-CSH of 0.37 ± 0.04 and 0.34 ± 0.05 (p < 0.05) for responders and non-responders.

Conclusions

Pretherapeutic FDG accumulation was predictive of the tumor response in 90Y-ibritumomab tiuxetan therapy. The heterogeneity of the intratumoral distribution rather than the absolute level of 111In-ibritumomab tiuxetan was correlated with the tumor response.
What is the influence of a reduction of planktivorous and benthivorous fish on water quality in temperate eutrophic lakes? A systematic review
Authors: Bernes Claes , Carpenter Stephen R , Gårdmark Anna , Larsson Per , Persson Lennart , Skov Christian , Speed James DM , Van Donk Ellen
Published: March 2015

Background

In recent decades, many attempts have been made to restore eutrophic lakes through biomanipulation. Reducing the populations of planktivorous and benthivorous fish (either directly or through stocking of piscivorous fish) may induce ecosystem changes that increase water transparency and decrease the risk of algal blooms and fish kills, at least in the short term. However, the generality of biomanipulation effects on water quality across lake types and geographical regions is not known. Therefore, we have undertaken a systematic review of such effects in eutrophic lakes in temperate regions throughout the world.

Methods

Searches for literature were made using online publication databases, search engines, specialist websites and bibliographies of literature reviews. Search terms were developed in English, Danish, Dutch and Swedish. Identified articles were screened for relevance using inclusion criteria set out in an a priori protocol. To reduce the risk of bias, we then critically appraised the combined evidence found on each biomanipulation. Data were extracted on outcomes such as Secchi depth and chlorophyll a concentration before, during and/or after manipulation, and on effect modifiers such as lake properties and amounts of fish removed or stocked.

Results

Our searches identified more than 14,500 articles. After screening for relevance, 233 of them remained. After exclusions based on critical appraisal, our evidence base included useful data on 128 biomanipulations in 123 lakes. Of these interventions, 85% had been made in Europe and 15% in North America. Meta-analysis showed that removal of planktivores and benthivores (with or without piscivore stocking) leads to increased Secchi depth and decreased chlorophyll a concentration during intervention and the first three years afterwards. Piscivore stocking alone has no significant effect. The response of chlorophyll a levels to biomanipulation is stronger in lakes where fish removal is intense, and in lakes which are small and/or have high pre-manipulation concentrations of total phosphorus.

Conclusions

Our review improves on previous reviews of biomanipulation in that we identified a large number of case studies from many parts of the world and used a consistent, repeatable process to screen them for relevance and susceptibility to bias. Our results indicate that removal of planktivorous and benthivorous fish is a useful means of improving water quality in eutrophic lakes. Biomanipulation tends to be particularly successful in relatively small lakes with short retention times and high phosphorus levels. More thorough fish removal increases the efficacy of biomanipulation. Nonetheless successes and failures have occurred across a wide range of conditions.
Anticancer effect of black tea extract in human cancer cell lines
Authors: Koňariková Katarína , Ježovičová Miriam , Keresteš Ján , Gbelcová Helena , Ďuračková Zdeňka , Žitňanová Ingrid
Published: March 2015

In this study we investigated effects of natural extract from the black tea Camellia sinensis (BTE) against human colon carcinoma cell line HT-29, human breast carcinoma cell line MCF-7, human alveolar carcinoma cell line A549 and healthy cell line NIH-3T3. We identified concentration range for cytotoxic/antiproliferative effects using MTT assay and the trypan blue assay, gel electrophoresis we employed to determine the type of cell death induced by BTE and DNA damage we determined by comet assay. Different concentrations of the extract (0.00078 - 5 μg/mL) we added to the cultured cells and incubated for 216 h. BTE showed cytotoxic effects against all carcinoma cell lines, however HT-29 and MCF-7 cells were more sensitive than A549. BTE showed no antiproliferative effect against healthy cells NIH-3T3 at tested concentrations. We found no apoptotic cell death in HT-29 and MCF-7 cells after 72 h of incubation in case of single administration of BTE but in case of repetitive administration of BTE (BTE was added to the cells each day) we found apoptotic cell death in HT-29 after 72 h incubation. BTE induced also DNA strand breaks and oxidative damage to DNA in carcinoma cells HT-29 and MCF-7.