bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of family medicine clerkships in undergraduate medical education: a systematic review
Authors: Turkeshi Eralda , Michels Nele R , Hendrickx Kristin , Remmen Roy 
Published: August 2015

ObjectiveSynthesise evidence about the impact of family medicine/general practice (FM) clerkships on undergraduate medical students, teaching general/family practitioners (FPs) and/or their patients.Data sourcesMedline, ERIC, PsycINFO, EMBASE and Web of Knowledge searched from 21 November to 17 December 2013. Primary, empirical, quantitative or qualitative studies, since 1990, with abstracts included. No country restrictions. Full text languages: English, French, Spanish, German, Dutch or Italian.Review methodsIndependent selection and data extraction by two authors using predefined data extraction fields, including Kirkpatrick’s levels for educational intervention outcomes, study quality indicators and Best Evidence Medical Education (BEME) strength of findings’ grades. Descriptive narrative synthesis applied.ResultsSixty-four included articles: impact on students (48), teaching FPs (12) and patients (8). Sample sizes: 16-1095 students, 3-146 FPs and 94-2550 patients. Twenty-six studies evaluated at Kirkpatrick level 1, 26 at level 2 and 6 at level 3. Only one study achieved BEME’s grade 5. The majority was assessed as grade 4 (27) and 3 (33). Students reported satisfaction with content and process of teaching as well as learning in FM clerkships. They enhanced previous learning, and provided unique learning on dealing with common acute and chronic conditions, health maintenance, disease prevention, communication and problem-solving skills. Students’ attitudes towards FM were improved, but new or enhanced interest in FM careers did not persist without change after graduation. Teaching FPs reported increased job satisfaction and stimulation for professional development, but also increased workload and less productivity, depending on the setting. Overall, student’s presence and participation did not have a negative impact on patients.ConclusionsResearch quality on the impact of FM clerkships is still limited, yet across different settings and countries, positive impact is reported on students, FPs and patients. Future studies should involve different stakeholders, medical schools and countries, and use standardised and validated evaluation tools.
‘HeART of Stroke (HoS)’, a community-based Arts for Health group intervention to support self-confidence and psychological well-being following a stroke: protocol for a randomised controlled feasibility study
Authors: Ellis-Hill Caroline , Gracey Fergus , Thomas Sarah , Lamont-Robinson Catherine , Thomas Peter W , Marques Elsa M R , Grant Mary , Nunn Samantha , Cant Robin P I , Galvin Kathleen T , Reynolds Frances , Jenkinson Damian F 
Published: August 2015

IntroductionOver 152 000 people in the UK have strokes annually and a third experience residual disability. Low mood also affects a third of stroke survivors; yet psychological support is poor. While Arts for Health interventions have been shown to improve well-being in people with mild-to-moderate depression post-stroke, their role in helping people regain sense of self, well-being and confidence has yet to be evaluated. The main aim of this study is to explore the feasibility of conducting a pragmatic multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of an Arts for Health group intervention (‘HeART of Stroke’ (HoS)) for stroke survivors. HoS is a 10-session artist-facilitated group intervention held in the community over 14 weeks. It offers a non-judgemental, supportive environment for people to explore sense of self, potentially enhancing well-being and confidence.Methods and analysisSixty-four people, up to 2 years post-stroke, recruited via secondary care research staff or community stroke/rehabilitation teams in two UK centres will be randomised to either HoS plus usual care or usual care only. Self-reported outcomes, measured at baseline and approximately 5 months postrandomisation, will include stroke-related, well-being, mood, self-esteem, quality of life and process measures. Analyses will focus on estimating key feasibility parameters (eg, rates of recruitment, retention, intervention attendance). We will develop outcome and resource use data collection methods to inform an effectiveness and cost-effectiveness analysis in the future trial. Interviews, with a sample of participants, will explore the acceptability of the intervention and study processes, as well as experiences of the HoS group.Ethics and disseminationNational Health Service (NHS), Research and Development and University ethical approvals have been obtained. Two peer-reviewed journal publications are planned plus one service user led publication. Findings will be disseminated at key national conferences, local stakeholder events and via institutional websites.Trial registration numberISRCTN99728983.
Test result communication in primary care: a survey of current practice
Authors: Litchfield Ian , Bentham Louise , Lilford Richard , McManus Richard J , Hill Ann , Greenfield Sheila 
Published: August 2015

BackgroundThe number of blood tests ordered in primary care continues to increase and the timely and appropriate communication of results remains essential. However, the testing and result communication process includes a number of participants in a variety of settings and is both complicated to manage and vulnerable to human error. In the UK, guidelines for the process are absent and research in this area is surprisingly scarce; so before we can begin to address potential areas of weakness there is a need to more precisely understand the strengths and weaknesses of current systems used by general practices and testing facilities.MethodsWe conducted a telephone survey of practices across England to determine the methods of managing the testing and result communication process. In order to gain insight into the perspectives from staff at a large hospital laboratory we conducted paired interviews with senior managers, which we used to inform a service blueprint demonstrating the interaction between practices and laboratories and identifying potential sources of delay and failure.ResultsStaff at 80% of practices reported that the default method for communicating normal results required patients to telephone the practice and 40% of practices required that patients also call for abnormal results. Over 80% had no fail-safe system for ensuring that results had been returned to the practice from laboratories; practices would otherwise only be aware that results were missing or delayed when patients requested results. Persistent sources of missing results were identified by laboratory staff and included sample handling, misidentification of samples and the inefficient system for collating and resending misdirected results.ConclusionsThe success of the current system relies on patients both to retrieve results and in so doing alert staff to missing and delayed results. Practices appear slow to adopt available technological solutions despite their potential for reducing the impact of recurring errors in the handling of samples and the reporting of results. Our findings will inform our continuing work with patients and staff to develop, implement and evaluate improvements to existing systems of managing the testing and result communication process.
Longitudinal study of Asian elephants, Elephas maximus, indicates intermittent shedding of elephant endotheliotropic herpesvirus 1 during pregnancy
Authors: Bennett Laura , Dunham Stephen , Yon Lisa , Chapman Sarah , Kenaghan Megan , Purdie Laura , Tarlinton Rachael 
Published: August 2015

IntroductionEEHV‐1 is a viral infection of elephants that has been associated with a fatal haemorrhagic syndrome in Asian elephants. Previous studies have suggested that pregnant animals may shed more virus than non‐pregnant animals.MethodsThis study examined whether pregnancy affected the frequency or magnitude of shedding of elephant endotheliotropic herpesvirus 1 (EEHV1) using Taq man real‐time PCR on trunk washes from four female elephants from a UK collection over three time periods between 2011 and 2014. These periods included pregnancies in two animals (period 1 and period 3). Behavioural observations made by keepers were also assessed.ResultsDuring period 1 there was a high degree of social hierarchical instability which led to a hierarchy change, and was associated with aggressive behaviour. Also during period 1 EEHV‐1 shedding was of a higher magnitude and frequency than in the latter two time periods.ConclusionsThese results suggest that there is no clear relationship between shedding and pregnancy, and that behavioural stressors may be related to an increase in EEHV‐1 shedding.
Optimal L(j,k)-Edge-Labeling of Regular Grids
Authors: Calamoneri Tiziana 
Published: August 2015

Given a graph [Formula: see text] and two positive integers j and k, an [Formula: see text]-edge-labeling is a function f assigning to edges of E colors from a set [Formula: see text] such that [Formula: see text] if e and e′ are adjacent, i.e. they share a common endpoint, [Formula: see text] if e and e′ are not adjacent and there exists an edge adjacent to both e and e′. The aim of the [Formula: see text]-edge-labeling problem consists of finding a coloring function f such that the value of [Formula: see text] is minimum. This minimum value is called [Formula: see text]. This problem has already been studied on hexagonal, squared and triangular grids, but mostly not coinciding upper and lower bounds on [Formula: see text] have been proposed. In this paper we close some of these gaps or find better bounds on [Formula: see text] in the special cases [Formula: see text] and [Formula: see text]. Moreover, we propose tight [Formula: see text]-edge-labelings for eight-regular grids.
Abstract 1004: Novel adjuvants from seaweed impede autophagy signaling in therapy-resistant residual pancreatic cancer
Authors: Aravindan Sheeja , Ramraj Satish Kumar , Khan Faizan H. , Herman Terence S. , Somasundaram Somasundaram T. , Aravindan Natarajan 
Published: August 2015

Abstract
Background: Identifying the drug-deliverables that target autophagy is crucial to finding a cure for pancreatic cancer (PC), as activated autophagy is associated with poor patient outcomes. Our recent studies recognized the anti-PC potential of an antioxidant-rich collection of seaweed polyphenols and identified potential compounds for the treatment of PC. Accordingly, we investigated whether such compounds could regulate autophagy in therapy-resistant PC cells in vitro and in residual PC in vivo.
Results: Human Panc-3.27 and MiaPaCa-2 cells were exposed to FIR with/without polyphenol from Spatoglossum asperum (SA-EA), Padina tetrastromatica (PT-EA), or Hormophysa triquerta (HT-EA). The cells were subjected to QPCR to examine transcriptional alterations in the following autophagy functional regulators: ATG3, ATG5, ATG7, ATG5, LC3A, LC3B, Beclin, Myd88, HMGB1, Rage, and TLRs 1-9. Using a clinically relevant mouse model of residual PC, we use tissue microarray (TMA) and immunohistochemistry (IHC) procedures to investigate the potential of polyphenol(s) to target ATG3, ATG5, ATG12, LC3A, LC3B, BECN1, and survivin after clinical radiotherapy. Radiation significantly increased the transcription of autophagy functional regulators in both lines. Seaweed polyphenols completely suppressed all investigated regulators in both lines. TMA-IHC analysis revealed the complete regulation of ATG3, ATG5, 12, LC3A, LC3B, BECN1, and survivin in residual PC following SA-EA, PT-EA, and HT-EA treatment.
Conclusions: These data demonstrate the autophagy blue print in therapy-resistant PC cells for the first time. Moreover, the data strongly suggest that the selected polyphenols could serve as effective adjuvants for current PC treatment modalities and may inhibit tumor relapse by comprehensively targeting therapy-orchestrated autophagy in residual cells.
Citation Format: Sheeja Aravindan, Satish Kumar Ramraj, Faizan H. Khan, Terence S. Herman, Somasundaram T. Somasundaram, Natarajan Aravindan. Novel adjuvants from seaweed impede autophagy signaling in therapy-resistant residual pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1004. doi:10.1158/1538-7445.AM2015-1004
Abstract 101: WHSC1L1 as a therapeutic target in squamous cell carcinoma of the head and neck
Authors: Saloura Vassiliki , Vougiouklakis Theodore , Lingen Mark , Seiwert Tanguy , Vokes Everett , Nakamura Yusuke , Hamamoto Ryuji 
Published: August 2015

Abstract
Background: Squamous cell carcinoma of the head and neck (SCCHN) is a common malignancy with high recurrence rates and poor survival, thus new therapies are eagerly awaited. Protein lysine methyltransferases (PKMTs) have recently become one of the most important targets for drug discovery efforts, but only a few studies have explored their role in the pathogenesis of SCCHN. WHSC1L1, a nuclear SET-Suppressor of variegation 3-9, Enhancer of zeste and Trithorax-domain (NSD) PKMT and chromatin modifier, was reported to be amplified (8p11.23) in 6% of SCCHN tumors. This study aims to elucidate the pathophysiological role of WHSC1L1 as an oncogenic force in SCCHN and provide rationale for the development of inhibitors targeting WHSC1L1.
Methods: Cytotoxicity assays (MTTs) were conducted in one HPV-positive and one HPV-negative SCCHN cell line with WHSC1L1-specific siRNAs. Quantitative polymerase chain reaction (qPCR) and Western blotting were performed to examine WHSC1L1 expression levels in 14 SCCHN cell lines in comparison to a normal keratinocyte cell line (KGM). Immunohistochemistry (IHC) for WHSC1L1 in 115 patients with SCCHN and correlation of its expression with H3K36me2 was also performed. To identify candidate substrates that are directly methylated by WHSC1L1, in vitro methyltransferase assays using a recombinant protein library were conducted.
Results: siRNA-mediated knockdown of WHSC1L1 caused significant cell death in 2 SCCHN cell lines. Approximately 30% of SCCHN cell lines overexpressed WHSC1L1 compared to normal keratinocytes. WHSC1L1 expression as evaluated by IHC was significantly stronger in SCCHN compared to normal epithelium (Kruskal-Wallis test, p = 0.002) and 24% of SCCHN sections expressed high levels of WHSC1L1, compared to 6% of dysplastic lesions and 0% of normal epithelium sections. Interestingly, no association between WHSC1L1 expression levels and H3K36me2 was observed.
Conclusions: WHSC1L1 is genetically altered in multiple cancer types. In SCCHN, it is significantly overexpressed in 24% of the tumors and its knockdown caused significant growth suppression of both HPV-positive and HPV-negative SCCHN cell lines. Taken together, WHSC1L1 merits further investigation as a potential therapeutic target in SCCHN.
Citation Format: Vassiliki Saloura, Theodore Vougiouklakis, Mark Lingen, Tanguy Seiwert, Everett Vokes, Yusuke Nakamura, Ryuji Hamamoto. WHSC1L1 as a therapeutic target in squamous cell carcinoma of the head and neck. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 101. doi:10.1158/1538-7445.AM2015-101
Abstract 1018: Role of Stat3 vs Stat5 in the differentiation of HC11, mouse breast epithelial cells
Authors: Cass Jamaica , Niit Maximilian , Arulanandam Rozanne , Elliott Bruce , Raptis Leda 
Published: August 2015

Abstract
The Signal Transducer and Activator of Transcription (Stat)3 and Stat5 are transcription factors involved in normal breast development, and are hyperactivated in 30-50% of breast cancers. Stat5 is required for breast epithelial cell differentiation and is over-expressed in breast cancers with a more differentiated phenotype. On the other hand, constitutive over-activation of Stat3 can drive expression of genes involved in survival, migration and angiogenesis, while mutationally activated Stat3 (Stat3C) can transform cultured cells, indicating that Stat3 may play an important role in cancer etiology. Following activation of a number of growth factor or cytokine receptors such as interleukin-6 or expression of oncogenes such as Src, Stat3 is phosphorylated at tyr-705, dimerizes and migrates to the nucleus where it activates transcription from a number of genes involved in cell division and survival, such as survivin, Bcl-xL, Mcl1 and myc, while it downregulates expresssion of the tumor suppressor p53. We recently discovered a novel pathway of activation of Stat3: Engagement of cadherins (E-, N-cadherin or cadherin-11), cell to cell adhesion proteins induces a dramatic increase in the levels of the Rac1 and Cdc42 small GTPases, and this leads to interleukin-6 transcription, hence Stat3 activation.
The differentiation of HC11, nonneoplastic mouse breast epithelial cells requires prolactin, hydrocortisone and insulin, added at confluence. Since confluence activates Stat3, we examined the role of Stat3 upon breast epithelial cell differentiation, measured by cellular morphology and expression of the milk proteins, β-casein or whey acidic protein. Through pharmacological inhibition with CPA7 or S3I-201, our results demonstrate that Stat3 is, in fact, required for HC11 cell differentiation. In contrast, constitutive expression of mutationally activated Rac1 was found to block differentiation while inducing transformation.
In sharp contrast, our results indicate that Stat5 is upregulated by the differentiation cocktail but is unaffected by cell density, while expression of activated Stat5 promotes a more differentiated phenotype. Taken together, our results demonstrate that Stat3 and Stat5 may constitute independent prognostic markers as well as treatment targets for breast cancer.
Citation Format: Jamaica Cass, Maximilian Niit, Rozanne Arulanandam, Bruce Elliott, Leda Raptis. Role of Stat3 vs Stat5 in the differentiation of HC11, mouse breast epithelial cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1018. doi:10.1158/1538-7445.AM2015-1018
Abstract 102: KDM5B plays a central role in esophageal cancer progression
Authors: Nishida Naohiro , Kano Yoshihiro , Koseki Jun , Konno Masamitsu , Kawamoto Koichi , Doki Yuichiro , Mori Masaki , Ishii Hideshi 
Published: August 2015

Abstract
Esophageal cancer is consists of highly heterogeneous populations, which include cancer initiating cells, so-called cancer stem cells. Although histone modification is shown to be an essential factor for normal stem cell maintenance, the involvement of histone demethylase in cancer progression has been poorly understood. We investigated the functional roles of the Histone H3 lysine 4 (H3K4) demethylase KDM5B, a crucial epigenetic regulator that is required for normal embryonic development and cell growth. KDM5B knockdown resulted in the suppression of esophageal cancer cell growth, sphere formation and invasion ability and was associated with loss of epithelial cell marker expression. These tumor inhibitory effects were reverted subsequent to subcutaneous inoculation of these cells into immune-deficient mice. These results indicated that KDM5B plays an important role in maintaining cancer stem cells and justifies the rationale for studying the effects of continuous inhibition of this epigenetic factor in esophageal cancer.
Citation Format: Naohiro Nishida, Yoshihiro Kano, Jun Koseki, Masamitsu Konno, Koichi Kawamoto, Yuichiro Doki, Masaki Mori, Hideshi Ishii. KDM5B plays a central role in esophageal cancer progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 102. doi:10.1158/1538-7445.AM2015-102
Abstract 1072: DNA methylation profile analysis of gliomas revealed a change in methylation status during malignant progression
Authors: Akitake Mukasa , Saito Kuniaki , Aihara Koki , Nagae Genta , Omata Mayu , Otani Ryohei , Takayangi Shunsaku , Tanaka Shota , Narita Yoshitaka , Ueki Keisuke , Nishikawa Ryo , Nagane Motoo , Aburatani Hiroyuki , Saito Nobuhito 
Published: August 2015

Abstract
Low-grade glioma, especially astrocytomas often undergo malignant progression, and these transformations are a leading cause of death in patients with low-grade gliomas. However, the mechanisms underlying malignant tumor transformation are still not well understood. Recent evidence indicates that epigenetic deregulation is an important cause of gliomagenesis; therefore, we examined the epigenetic changes during malignant progression of gliomas. We used the Illumina Infinium Human Methylation 450K BeadChip to perform genome-wide DNA methylation analysis of 124 gliomas and four normal brains. These tumors comprised 37 grade IV gliomas, 32 grade III gliomas, and 55 grade II gliomas. This study sample included 26 matched-pairs of initial lower grade gliomas and recurrent tumors and 21 of the 26 recurring tumors recurred as malignant progressions.
Analyses of methylation profiles demonstrated that most low-grade gliomas in our sample (84%) had a CpG island methylator phenotype (G-CIMP). Remarkably, approximately 25% of recurrent malignant gliomas that had progressed from low-grade tumors with the G-CIMP status exhibited a characteristic partial demethylation of genomic DNA during malignant progression, but other recurrent gliomas showed no apparent change in DNA methylation pattern. Interestingly, we found that most loci that were demethylated during malignant progression were located outside of CpG islands. The information of histone modifications patterns in normal human astrocytes and embryonal stem cells also showed that the ratio of active marks at the site corresponding to DNA demethylated loci in G-CIMP-demethylated tumors was significantly lower; this finding indicated that most demethylated loci in G-CIMP-demethylated tumors were likely transcriptionally inactive. A small number of the genes that were upregulated and had demethylated CpG islands were associated with cell cycle-related pathway. Here, we demonstrated that partial DNA demethylation occurred during malignant transfomrmation of a subset of lower grade gliomas.
Citation Format: Mukasa Akitake, Kuniaki Saito, Koki Aihara, Genta Nagae, Mayu Omata, Ryohei Otani, Shunsaku Takayangi, Shota Tanaka, Yoshitaka Narita, Keisuke Ueki, Ryo Nishikawa, Motoo Nagane, Hiroyuki Aburatani, Nobuhito Saito. DNA methylation profile analysis of gliomas revealed a change in methylation status during malignant progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1072. doi:10.1158/1538-7445.AM2015-1072