bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of antithrombotic nanoconjugate blocking integrin α2β1-collagen interactions
Authors: Zhang Chao , Zhang Lin , Zhang Youcai , Sun Na , Jiang Shaoyi , Fujihara Timothy J. , Sun Yan 
Published: May 2016

AbstractAn antithrombotic nanoconjugate was designed in which a designed biomimetic peptide LWWNSYY was immobilized to the surface of poly(glycidyl methacrylate) nanoparticles (PGMA NPs). Our previous work has demonstrated LWWNSYY to be an effective inhibitor of integrin α2β1-collagen interaction and subsequent thrombus formation, however its practical application suffered from the formation of clusters in physiological environment caused by its high hydrophobicity. In our present study, the obtained LWWNSYY-PGMA nanoparticles (L-PGMA NPs) conjugate, with an improved dispersibility of LWWNSYY by PGMA NPs, have shown binding to collagen receptors with a Kd of 3.45 ± 1.06 μM. L-PGMA NPs have also proven capable of inhibiting platelet adhesion in vitro with a reduced IC50 of 1.83 ± 0.29 μg/mL. High inhibition efficiency of L-PGMA NPs in thrombus formation was further confirmed in vivo with a 50% reduction of thrombus weight. Therefore, L-PGMA NPs were developed as a high-efficiency antithrombotic nanomedicine targeted for collagen exposed on diseased blood vessel wall.
MAXI observations of long-term variations of Cygnus X-1 in the low/hard and the high/soft states
Authors: Sugimoto Juri , Mihara Tatehiro , Kitamoto Shunji , Matsuoka Masaru , Sugizaki Mutsumi , Negoro Hitoshi , Nakahira Satoshi , Makishima Kazuo 
Published: May 2016

Abstract
The long-term X-ray variability of the black hole binary Cygnus X-1 was studied with five years of MAXI data from 2009 to 2014, which include substantial periods of the high/soft state, as well as the low/hard state. In each state, normalized power spectrum densities (NPSDs) were calculated in three energy bands of 2–4 keV, 4–10 keV, and 10–20 keV. The NPSDs for frequencies from 10−7 Hz to 10−4 Hz are all approximated by a power-law function with an index −1.35–1.29. The fractional RMS variation η, calculated in the above frequency range, was found to show the following three properties: (1) η slightly decreases with energy in the low/hard state; (2) η increases towards higher energies in the high/soft state; and (3) in the 10–20 keV band, η is three times higher in the high/soft state than in the low/hard state. These properties were confirmed through studies of intensity-correlated changes of the MAXI spectra. Of these three findings, the first one is consistent with that seen in the short-term variability during the low/hard state. The latter two can be understood as a result of high variability of the hard-tail component seen in the high/soft state with the above very low frequency range, although the origin of the variability remains inconclusive.
“Silent Sinus Syndrome” Following Orbital Trauma: A Case Series and Review of the Literature
Authors: Brown Sebastian J. , Hardy Thomas G. , McNab Alan A. 
Published: May 2016

Purpose:
To describe the demographics, presentation, and treatment of “silent sinus syndrome” (SSS) diagnosed following orbital trauma and review the literature on this topic.

Methods:
A retrospective review of 6 consecutive cases of SSS following trauma seen by the authors from 2004 to 2015. Data collected included patient demographics, details of previous trauma, clinical presentation, imaging findings, surgery performed, outcome, and follow up.

Results:
Six patients were identified presenting with SSS following orbital floor fracture. All cases developed progressive enophthalmos due to maxillary sinus atelectasis on average 8 months after their initial trauma (range, 3–16 months). The appearance of the maxillary sinus on CT was indistinguishable from the changes seen in spontaneous SSS. All 6 patients had surgical repair, which included maxillary sinus reventilation and surgery to build up the orbital floor and correct the enophthalmos in 4 patients, maxillary sinus reventilation surgery only in 1 patient and surgery to build up the orbital floor only in 1 patient. There was a reduction of enophthalmos and globe dystopia in all cases with no significant complications.

Conclusions:
Changes in the maxillary sinus after orbital floor fracture may occur in the months following the initial trauma and the changes are indistinguishable from those seen in spontaneous SSS. The mechanism is presumed to be obstruction of the natural ostium of the maxillary sinus, accumulation of secretions and the development of negative pressure within the sinus leading to its collapse.
Deriving shape-based features for C. elegans locomotion using dimensionality reduction methods
Authors: Gyenes Bertalan , Brown André E.X. 
Published: May 2016

AbstractHigh-throughput analysis of animal behavior has become a reality with the advance of recording technology, leading to large high-dimensional data sets. This dimensionality can sometimes be reduced while still retaining relevant information. In the case of the nematode worm Caenorhabditis elegans, more than 90% of the shape variance can be captured using just four principal components. However, it remains unclear if other methods can achieve a more compact representation or contribute further biological insight to worm locomotion. Here we take a data-driven approach to worm shape analysis using independent component analysis (ICA), non-negative matrix factorization (NMF), a cosine series, and jPCA and confirm that the dimensionality of worm shape space is close to four. Projecting worm shapes onto the bases derived using each method gives interpretable features ranging from head movements to tail oscillation. We use these as a comparison method to find differences between the wild type N2 worms and various mutants. The different bases provide complementary views of worm behavior and we expect that closer examination of the time series of projected amplitudes will lead to new results in the future.
Nostalgia in online brand communities
Authors: Koetz Clara , Tankersley John Daniel 
Published: May 2016

Purpose
The purpose of this paper is to analyze the characteristics of a subculture of consumption organized toward a nostalgic brand on a social media platform. More specifically, the authors examine the role of these nostalgic feelings in the development of a community identity and the benefits they promote in the creation and perpetuation of this group.

Design/methodology/approach
The authors conducted a netnographic study to examine the case of Caloi 10 on Facebook. The data collection was carried out by following interactions among members of this community for seven months. Besides this, field observations and interviews were also considered in the analysis.

Findings
Four categories emerged from the analysis: Identity and nostalgia, the subculture’s ethos, consumption habits and hierarchical social structure. Nostalgia was shown to have a collective dimension, connecting the group around the brand, and positively affecting the ties between members and members and the brand.

Practical implications
On-line brand communities can be promoted to strengthen connections between consumers and a brand, and between consumers with each other. For that, it is important to understand the characteristics and specificities of these groups.

Originality/value
Few studies have dealt with the characteristics of brand communities in social media, as well as the role of nostalgia in these groups. This research fills these gaps, exploring aspects related to consumption as a way of transmitting symbolic meanings and expressing nostalgic feelings in on-line brand communities.
Development and feasibility testing of an oral hygiene intervention for stroke unit care
Authors: Smith Craig J. , Horne Maria , McCracken Giles , Young David , Clements Ian , Hulme Sharon , Ardron Claire , Hamdy Shaheen , Vail Andy , Walls Angus , Tyrrell Pippa J. 
Published: May 2016

ObjectiveTo develop an oral hygiene complex intervention and evaluate its feasibility in a single UK stroke centre.BackgroundOral hygiene interventions might improve clinical outcomes after stroke but evidence‐based practice is lacking.Materials and methodsWe used a sequential mixed methods approach and developed an oral hygiene complex intervention comprising: (i) web‐based education and ‘hands‐on’ practical training for stroke unit nursing staff, (ii) a pragmatic oral hygiene protocol consisting of twice‐daily powered (or manual if preferred) brushing with chlorhexidine gel (or non‐foaming toothpaste) ± denture care. We evaluated feasibility of (i) the staff education and training and (ii) the oral hygiene protocol in consenting inpatients with confirmed stroke, requiring assistance with at least one aspect of personal care.ResultsThe staff education and training were feasible, acceptable and raised knowledge and awareness. Several barriers to completing the education and training were identified. The oral hygiene protocol was feasible and well‐tolerated. 22% of eligible patients screened declined participation in the study. Twenty‐nine patients (median age = 78 year; National Institutes of Health Stroke Scale score = 8.5; 73% dentate) were recruited at a median of 7 days from stroke onset. 97% of participants chose the default chlorhexidine‐based protocol; the remainder chose the non‐foaming toothpaste‐based protocol. The mouth hygiene protocol was administered as prescribed on 95% of occasions, over a median duration of 28 days. There were no adverse events attributed to the oral hygiene protocol.ConclusionOur oral hygiene complex intervention was feasible in a single UK stroke centre. Further studies to optimise patient selection, model health economics and explore efficacy are now required.
Patterns of lymph node metastasis identified following bilateral mandibular and medial retropharyngeal lymphadenectomy in 31 dogs with malignancies of the head
Authors: Skinner Owen T. , Boston Sarah E. , Souza Carlos H. de M. 
Published: May 2016

AbstractVariable pathways of lymphatic drainage have been described in the dog head and neck. The aim of this study was to retrospectively assess the patterns of lymph node metastasis in dogs with malignancies of the head following bilateral mandibular and medial retropharyngeal lymphadenectomy. Thirty‐one dogs were included. Median age at surgery was 10 years (range: 5 months to 14 years) and mean bodyweight was 21.4 ± 11.9 kg. Lymph node metastasis occurred in 14 dogs (45%), with spread to mandibular lymph nodes in 14 dogs and medial retropharyngeal metastasis in 11 dogs. Eight of 13 dogs (62%) with lymphatic metastasis and a lateralised lesion showed contralateral dissemination, while 12/13 (92%) showed ipsilateral metastasis. Of 13 dogs with oral malignant melanoma, four showed metastasis to all four lymph centres. Contralateral metastasis may occur in dogs with malignancies of the head and should be considered during staging and management.
Abstract C190: Potent and selective inhibition of CDK7 by novel covalent inhibitors
Authors: Poddutoori Ramulu , Satyam Leena K. , Daginakatte Girish , Mukherjee Subhendu , Marappan Sivapriya , Gopinath Sreevalsam , Ramachandra Raghuveer , Lakshminarasimhan Anirudha , Pothuganti Manoj , Nayak Shilpa , C Nandish , Naik Chandranath , MV Ravindra , Dabbeeru Madhu , Antony Thomas , Pandit Chetan , Ramachandra Murali , Chelur Shekar , Samajdar Susanta 
Published: May 2016

Abstract
Cyclin-dependent kinase 7 (CDK7) is an important constituent of the cellular transcriptional machinery, where it phosphorylates the C-terminal domain (CTD) of RNAP polymerase II (RNAPII). Because many tumor types are critically dependent on transcription for maintenance of their oncogenic state, pharmacological modulation of CDK7 kinase activity is considered as an approach to treat cancer. Multiple series of CDK7 inhibitors were identified by iterative medicinal chemistry efforts and SAR based approach. Early compounds were optimized towards attaining good physicochemical properties, high potency, good selectivity and desirable pharmacokinetic profile to achieve anti-tumor activity. We have identified compounds from two distinct chemical series that are highly potent in inhibiting CDK7 in biochemical assays. These inhibitors demonstrate time-dependent inhibition of CDK7 indicating covalent nature of binding. The compounds showed potent anti-proliferative activity in cell lines derived from various tumor types and this was accompanied by CDK7 modulation in cells as monitored by pS5RNAPII levels. They have excellent drug-like characteristics including solubility, permeability, metabolic stability and good oral bioavailability. In a broad panel of kinases (332 kinase), selected compounds from both series showed good selectivity profile. Tolerability and efficacy studies are ongoing with selected early leads to test their impact on tumor growth inhibition in xenograft models. We have identified novel and selective CDK7 covalent inhibitors from two series with desirable drug-like properties, which are being evauated for anti-tumor activity in xenograft models.
Citation Format: Ramulu Poddutoori, Leena K. Satyam, Girish Daginakatte, Subhendu Mukherjee, Sivapriya Marappan, Sreevalsam Gopinath, Raghuveer Ramachandra, Anirudha Lakshminarasimhan, Manoj Pothuganti, Shilpa Nayak, Nandish C, Chandranath Naik, Ravindra MV, Madhu Dabbeeru, Thomas Antony, Chetan Pandit, Murali Ramachandra, Shekar Chelur, Susanta Samajdar. Potent and selective inhibition of CDK7 by novel covalent inhibitors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C190.
Abstract P4-09-09: Verification of the breast cancer progression-associated miRNA hsa-miR-199a-5p using NanoString® platform
Authors: Fehm T , Schultz S , Bartsch H , Petat-Dutter K , Kahlert S , Sotlar K , Niederacher D , Neubauer H 
Published: May 2016

Abstract
A fundamental and clinically important step during breast tumourigenesis is the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Improved knowledge of this transition from pre-invasive to invasive breast cancer will pave the way for novel preventative and therapeutic strategies.
We have previously reported on differential expression of the miRNA hsa-miR-199a-5p in 15 matched pairs of DCIS and IDC areas isolated by laser capture microdissection (LCM) from formalin fixed and paraffin embedded (FFPE) breast cancer tissues using Illumina miRNA BeadChip microarray platform. Differential expression of hsa-miR-199a-5p was validated by quantitative RT-PCR in additional independent DCIS/IDC sample pairs from 25 breast cancer patients. Knock down of hsa-miR-199a-5p in invasive MDA-MB-231 and TMX2-28 breast cancer cells using a specific inhibitor significantly reduced invasiveness by approx. 73% and 71%, respectively (P &lt;0.01 and P&lt;0.05).
Now we report on experiments to validate differential expression of hsa-miR-199a-5p using a new platform – NanoString® (nCounter® miRNA Expression Assay, NanoString Technologies®). The NanoString® System is an automated, digital detection and counting system which uses a novel barcoding technology to directly profile up to 800 miRNAs simultaneously from a single sample. Total RNA from 6 DCIS/IDC FFPE tumours was used for miRNA expression analysis.
This analysis resulted in 10 differentially expressed miRNAs including hsa-miR-199a-5p which is upregulated in IDC (P &lt;0.05). Besides hsa-mir-199a-5p, hsa-miR-222 is significantly differentially expressed between DCIS and IDC which could be found in both expression data sets (Illumina® and NanoString®).
In this project we identified candidate progression-associated miRNAs which are differentially expressed between DCIS and IDC. Hsa-miR-199a-5p was validated in an independent sample cohort and its expression was further verified using the new miRNA expression analysis platform NanoString®. Hsa-miR-199a5-p is influencing in vitro cell invasiveness and may therefore be a potential drugable regulator of tumour progression and invasion in breast cancer.
Citation Format: Fehm T, Schultz S, Bartsch H, Petat-Dutter K, Kahlert S, Sotlar K, Niederacher D, Neubauer H. Verification of the breast cancer progression-associated miRNA hsa-miR-199a-5p using NanoString® platform. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-09.
Abstract P6-05-03: Genomic diversity of ductal carcinoma in situ (DCIS) as a driver of invasion and metastasis
Authors: King LM , Marks JR , Hall AH , Temko D , Graham TA , Mardis ER , Maley CC , Hwang E 
Published: May 2016

Abstract
Background: Recent evidence indicates that breast cancers may have high levels of heterogeneity. Based on principles of tumor evolution, we are investigating whether DCIS with higher levels of intra-tumoral genetic heterogeneity are more likely to progress to invasive and/or metastatic disease.
Methods: Cases (DCIS with co-existing invasive or metastatic cancer) and controls (pure DCIS) are identified from Duke Pathology archives. From cases and controls, we are analyzing two areas of DCIS separated by &gt;1cm with germ line DNA from the same subject to measure allele frequencies of somatic mutations and copy number variation (CNV). Small amounts of FFPE derived DNA are made into NGS libraries for full exome sequencing and hybridization to a 4.2 million element SNP array. Comparison of allele frequencies and CNV is made between specimens from the same cancer to assess heterogeneity.
Results: We identified a series of pure DCIS (controls for this study) and generated high coverage sequencing data from 20ng of FFPE DNA from 12 samples (4 subjects, germline + 2 DCIS containing areas from each subject) as proof of principle. We compared the occurrence of deletions, insertions and SNP's after a 20X coverage filtration. From these data, we identified between 50 to greater than 600 sequence changes in these DCIS compared to normal DNA. Present/absent calls and allele frequencies indicate both significant and variable degrees of heterogeneity even in these pure DCIS samples. Additional data is now being gathered and analyzed based on this established technical approach.
Conclusion: We have demonstrated the feasibility of acquiring high quality NGS data from archival DCIS specimens allowing us to test the hypothesis that genetic heterogeneity is a driving force in breast cancer progression. The degree and nature of this heterogeneity will be assessed in a panel of pure DCIS and DCIS co-existing with invasive and/or metastatic cancer. We are now generating and analyzing these data for Symposium presentation.
Citation Format: King LM, Marks JR, Hall AH, Temko D, Graham TA, Mardis ER, Maley CC, Hwang E. Genomic diversity of ductal carcinoma in situ (DCIS) as a driver of invasion and metastasis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-05-03.
Abstract A18: Expression of the tumor suppressor gene RARRES1 in the differentiation hierarchy of breast cancer is regulated by DNA methylation
Authors: Coyle Krysta Mila , Vidovic Dejan , Dean Cheryl A. , Thomas Margaret Lois , Sultan Mohammad , Clements Derek , Vaghar-Kashani Ahmad , Wallace Melissa , Weaver Ian , Giacomantonio Carman A. , Helyer Lucy , Marcato Paola 
Published: May 2016

Abstract
The tumor-suppressive function of the retinoic acid (RA)-inducible gene, retinoic acid receptor responder 1 (RARRES1), has been reported in many cancer types; however, in inflammatory breast cancer, RARRES1 is pro-tumorigenic. Furthermore, high transcript levels of RARRES1 are associated with more aggressive triple-negative breast cancers (TNBCs) and poorer patient outcomes. This suggests that RARRES1 may also be oncogenic and requires investigation to determine its role in breast cancer.
Expression analyses of 20 breast cancer cell lines (including 18 TNBC and two estrogen-receptor-positive cell lines) revealed that RARRES1 is predominantly expressed in basal-like breast cancer cells, but is often methylated and silenced in claudin-low breast cancer cells. We have identified possible sites of regulation by methylation in RARRES1 using Illumina 450K methylation arrays and 5-methylcytosine ChIP.
Basal-like cells express higher levels of the cancer stem cell (CSC) marker ALDH1A3. Expression of RARRES1 is dependent on, and strongly correlates with ALDH1A3 expression in fixed breast cancer patient samples. Immunohistochemistry of the same patient tumor samples revealed RARRES1 expression is localized to the endoplasmic reticulum.
Finally, knockdown of RARRES1 in claudin-low MDA-MB-231 and basal-like MDA-MB-468 and HCC1937 significantly increased cell proliferation and tumor growth, suggesting RARRES1 has a tumor suppressive function regardless of position on the differentiation hierarchy. We conclude that RARRES1 is a tumor suppressor in TNBC with methylation and expression profiles distinct to the differentiation hierarchy observed in breast cancer.
Citation Format: Krysta Mila Coyle, Dejan Vidovic, Cheryl A. Dean, Margaret Lois Thomas, Mohammad Sultan, Derek Clements, Ahmad Vaghar-Kashani, Melissa Wallace, Ian Weaver, Carman A. Giacomantonio, Lucy Helyer, Paola Marcato. Expression of the tumor suppressor gene RARRES1 in the differentiation hierarchy of breast cancer is regulated by DNA methylation. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A18.