bluuebunny/crossref_metadata_2025_split huggingface dataset:
Findings from a pilot Randomised trial of an Asthma Internet Self-management Intervention (RAISIN)
Authors: Morrison D , Wyke S , Saunderson K , McConnachie A , Agur K , Chaudhuri R , Thomas M , Thomson N C , Yardley L , Mair F S 
Published: May 2016

ObjectiveTo evaluate the feasibility of a phase 3 randomised controlled trial (RCT) of a website (Living Well with Asthma) to support self-management.Design and settingPhase 2, parallel group, RCT, participants recruited from 20 general practices across Glasgow, UK. Randomisation through automated voice response, after baseline data collection, to website access for minimum 12 weeks or usual care.ParticipantsAdults (age≥16 years) with physician diagnosed, symptomatic asthma (Asthma Control Questionnaire (ACQ) score ≥1). People with unstable asthma or other lung disease were excluded.Intervention‘Living Well with Asthma’ is a desktop/laptop compatible interactive website designed with input from asthma/ behaviour change specialists, and adults with asthma. It aims to support optimal medication management, promote use of action plans, encourage attendance at asthma reviews and increase physical activity.Outcome measuresPrimary outcomes were recruitment/retention, website use, ACQ and mini-Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes included patient activation, prescribing, adherence, spirometry, lung inflammation and health service contacts after 12 weeks. Blinding postrandomisation was not possible.ResultsRecruitment target met. 51 participants randomised (25 intervention group). Age range 16–78 years; 75% female; 28% from most deprived quintile. 45/51 (88%; 20 intervention group) followed up. 19 (76% of the intervention group) used the website, for a mean of 18 min (range 0–49). 17 went beyond the 2 ‘core’ modules. Median number of logins was 1 (IQR 1–2, range 0–7). No significant difference in the prespecified primary efficacy measures of ACQ scores (−0.36; 95% CI −0.96 to 0.23; p=0.225), and mini-AQLQ scores (0.38; −0.13 to 0.89; p=0.136). No adverse events.ConclusionsRecruitment and retention confirmed feasibility; trends to improved outcomes suggest use of Living Well with Asthma may improve self-management in adults with asthma and merits further development followed by investigation in a phase 3 trial.Trial registration numberISRCTN78556552; Results.
Mutation screening of theTPOgene in a cohort of 192 Chinese patients with congenital hypothyroidism
Authors: Fu Chunyun , Xie Bobo , Zhang Shujie , Wang Jin , Luo Shiyu , Zheng Haiyang , Su Jiasun , Hu Xuyun , Chen Rongyu , Fan Xin , Luo Jingsi , Gu Xuefan , Chen Shaoke 
Published: May 2016

ObjectivesDefects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to dyshormonogenesis. The aim of this study was to examine theTPOmutation spectrum and prevalence among patients with CH in the Guangxi Zhuang Autonomous Region of China and to define the relationships betweenTPOgenotypes and clinical phenotypes.MethodsBlood samples were collected from 192 patients with CH in the Guangxi Zhuang Autonomous Region, China and genomic DNA was extracted from peripheral blood leucocytes. All exons of the 10 common CH-associated genes includingTPOtogether with their exon-intron boundaries were screened by next-generation sequencing (NGS). The effect of the novelTPOmutation was investigated by ‘in silico’ studies.ResultsNGS analysis ofTPOin 192 patients with CH revealed 3 different variations in 2 individuals (2/192, 1%). Sequencing other CH candidate genes in the patients withTPOvariants revealed that patient 1 was homozygous for c.2422delTTPOmutation combined with double heterozygousDUOX2pathogenic variants (p.R683L/p.L1343F) and patient 2 was triallelic forTPOpathogenic variants (p.R648Q/p.T561M/p.T561M). The present study identified a novelTPOvariation c.1682C>T/p.T561M; and four known mutations: c.2422delT/p.C808Afs×24 and c.1943C>T/p.R648Q inTPO, c.2048G>T/p.R683L and c.4027C>T/p.L1343F inDUOX2.ConclusionsOur study indicated that the prevalence ofTPOmutations was 1% among studied Chinese patients with CH. More than two variations in one or more CH-associated genes can be found in a single patient, and may, in combination, affect the phenotype of the individual. A novelTPOvariation c.1682C>T/p.T561M was found,thereby expanding the mutational spectrum of the gene.
Association between relocation and changes in cardiometabolic risk factors: a longitudinal study in tsunami survivors of the 2011 Great East Japan Earthquake
Authors: Takahashi Shuko , Nakamura Motoyuki , Yonekura Yuki , Tanno Kozo , Sakata Kiyomi , Ogawa Akira , Kobayashi Seiichiro 
Published: May 2016

ObjectivesThe aim of this study is to determine changes in atherosclerotic cardiovascular risk factors with and without serious disaster-related mental and socioeconomic problems represented by relocation (REL).DesignA longitudinal survey.SettingMultiphasic health check-ups for the general population affected by the 2011 Great East Japan Earthquake and Tsunami.ParticipantsA total 6528 disaster survivors in heavily tsunami-damaged municipalities were recruited. Two sequential surveys were conducted and the data were analysed.Main outcome measuresMultiphasic health check-ups including investigation of lifestyle and psychological and socioeconomic measures were performed in two sequential phases (8 and 18 months) after the disaster for tsunami survivors with REL (n=3160) and without REL (n=3368). Longitudinal changes in cardiometabolic risk factors between the two phases were compared in the REL and non-REL groups.ResultsIn sex/age-adjusted analysis, we found increases in body weight and waist circumference between the two phases that were significantly greater in the REL group than in the non-REL group (body weight:+0.31 (0.23∼0.39) versus −0.24 (−0.32∼−0.16) kg, p<0.001; waist circumference:+0.58 (0.48∼0.68) versus+0.05 (−0.05∼0.15) cm, p<0.001)). A decrease in serum HDLC levels was found and again was significantly greater in the REL group than in the non-REL group (−0.65 (−0.96∼−0.34) versus −0.09 (−0.39∼0.21) mg/dL, p=0.009). In addition, deterioration in physical activity, mental health and socioeconomic status was more prevalent in the REL group than in the non-REL group (all p<0.001).ConclusionsThis study suggests that relocation after the devastating tsunami was related to weight gain and decreasing HDLC among survivors, and this change was associated with prolonged psychological distress and socioeconomic problems after the disaster.
‘They shouldn't be coming to the ED, should they?’ A qualitative study of why patients with palliative care needs present to the emergency department
Authors: Green Emilie , Shaw Sara E , Harris Tim 
Published: May 2016

IntroductionAcross the developed world, there are concerns about ‘inappropriate’ use of the emergency department (ED). Patients with palliative care needs frequently attend the ED. Previous studies define the ‘reason’ for presentation as the ‘presenting symptom’, which ignores the perspectives of service users. This paper addresses an acknowledged gap in the literature, which fails to examine the decision-making process that brings patients to the ED.MethodsIn-depth narrative interviews were conducted with 7 patients (known to a specialist palliative care service and presenting to the ED during a 10-week period) and 2 informal caregivers. Analysis drew on ‘Burden of Treatment Theory’ to examine the meaning attributed by participants to their experience of serious acute illness, their capacity for action and the work required to access emergency care.Results5 themes were identified about how and why emergency services were accessed: capacity for action, making sense of local services, making decisions to access emergency services, experience of emergency care and coping with change. All narratives captured concerns surrounding the complexity of services. Participants struggled to piece together the jigsaw of services, and were subsequently more likely to attend the ED. Differences between the ways that patients with chronic obstructive pulmonary disease and cancer accessed the ED were prominent.ConclusionsFurther work is needed to understand and respond to decisions leading patients with palliative care needs to the ED, particularly in the context of locally fragmented services, poor signposting and confusion about available healthcare. The perspectives of service users are essential in shaping emergency care.
A qualitative study of the impact of Crohn's disease from a patient's perspective
Authors: Wilburn Jeanette , Twiss James , Kemp Karen , McKenna Stephen P 
Published: May 2016

ObjectiveTo understand how the lives of people with Crohn's disease (CD) are affected. Most research in CD has focused on symptoms and functioning rather than on how these outcomes influence quality of life (QoL).DesignAs part of a study to develop a CD-specific patient-reported outcome measure, qualitative interviews were conducted with patients from Manchester Royal Infirmary to determine how CD affects QoL. The needs-based model was adopted for the study. The interviews, which took the form of focused conversations covering all aspects of the impact of CD and its treatment, were audio-recorded. Theoretical thematic analysis of the transcripts identified needs affected by CD.ResultsThirty patients (60% female) aged 25–68 years were interviewed. Participants had experienced CD for between 2 and 40 years. Nearly 1300 statements relating to the impact of CD were identified. Thirteen main need themes were identified: nutrition, hygiene, continence, freedom from infection, security, self-esteem, role, attractiveness, relationships, intimacy, clear-mindedness, pleasure and autonomy.ConclusionsThe findings from the interviews indicate that CD has a major impact on need-fulfilment. Such issues should be addressed in CD audit, clinical trials and when evaluating clinical practice.
Diagnosis of lung adenocarcinoma in situ and minimally invasive adenocarcinoma from intraoperative frozen sections: an analysis of 136 cases
Authors: He Ping , Yao Guangyu , Guan Yubao , Lin Yunen , He Jianxing 
Published: May 2016

AimsTo determine the diagnostic accuracy and contraindications for intraoperative diagnosis of lung adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) from frozen sections.MethodsA retrospective analysis of data from 136 patients pathologically diagnosed with early-stage (T1N0M0) AIS or MIA from paraffin-embedded sections. The rate of concordance between the diagnoses from intraoperative frozen sections and paraffin-embedded sections was determined, and the interpretive features that contributed to errors and deferrals in frozen-section diagnoses were identified.ResultsOf the 136 patients, diagnoses from frozen sections and paraffin-embedded sections were concordant in 86 (63.24%) cases intraoperatively diagnosed with AIS or MIA, and 44 (32.35%) cases were intraoperatively diagnosed with adenocarcinoma as the range of infiltration could not be determined from the frozen sections. From the remaining six (4.41%) cases, the frozen section and paraffin-embedded section diagnoses were discordant. The reasons for frozen section errors and deferrals included larger tumour volume, tumour located close to the visceral pleura, interstitial inflammation or fibrosis, absence of prominent atypia and differential morphology in the deeper levels of the paraffin block.ConclusionsDiagnosis of AIS and MIA from intraoperative frozen sections is feasible. We provide several modifications that may improve the diagnostic accuracy of intraoperative frozen sections for early-stage lung adenocarcinoma.
Role of lipocalin 2 in intraventricular haemoglobin-induced brain injury
Authors: Shishido Hajime , Toyota Yasunori , Hua Ya , Keep Richard F , Xi Guohua 
Published: May 2016

ObjectiveOur recent studies have shown that blood components, including haemoglobin and iron, contribute to hydrocephalus development and brain injury after intraventricular haemorrhage (IVH). The current study investigated the role of lipocalin 2 (LCN2), a protein involved in iron handling, in the ventricular dilation and neuroinflammation caused by brain injury in a mouse model of IVH.DesignFemale wild-type (WT) C57BL/6 mice and LCN2-deficient (LCN2−/−) mice had an intraventricular injection of haemoglobin, and control mice received an equivalent amount of saline. MRI was performed presurgery and postsurgery to measure ventricular volume and the brains were used for either immunohistochemistry or western blot.ResultsVentricular dilation was observed in WT mice at 24 h after haemoglobin (25 mg/mL, 20 µL) injection (12.5±2.4 vs 8.6±1.5 mm3in the control, p<0.01). Western blotting showed that LCN2 was significantly upregulated in the periventricular area (p<0.01). LCN2 was mainly expressed in astrocytes, whereas the LCN2 receptor was detected in astrocytes, microglia/macrophages and neurons. Haemoglobin-induced ventricle dilation and glia activation were less in LCN2−/−mice (p<0.01). Injection of high-dose haemoglobin (50 mg/mL) resulted in lower mortality in LCN2−/−mice (27% vs 86% in WT; p<0.05).ConclusionsIntraventricular haemoglobin caused LCN2 upregulation and ventricular dilation. Haemoglobin resulted in lower mortality and less ventricular dilation in LCN2−/−mice. These results suggest that LCN2 has a role in haemoglobin-induced brain injury and may be a therapeutic target for IVH.
Primary peripheral primitive neuroectodermal tumour of the tongue in a peach‐faced lovebird (Agapornis roseicollis)
Authors: Nakano Yumiko , Une Yumi 
Published: May 2016

Ewing's sarcoma and primitive neuroectodermal tumour (PNET) are extraordinarily rare. In human beings, these tumours have a common chromosomal translocation and differ only in their spectrum of neurodifferentiation. A six‐year‐old female peach‐faced lovebird (Agapornis roseicollis) presented with an approximately 7 mm diameter mass on the inferior surface of the tongue. The bird died during cytoreductive surgery. The mass was clearly demarcated and extended broadly from the tip of the tongue to the pharynx without invasion or adhesion. Histopathologically, the mass was composed of small round cells and short spindle‐shaped cells. The neoplastic cells formed Homer‐Wright pseudorosettes and contained glycogen. There were numerous areas of necrosis and haemorrhage. Immunohistochemically, the tumour cells were positive for vimentin and S‐100 and negative for cytokeratin, actin, glial fibrillary acidic protein, osteocalcin and secreted protein acidic and rich in cysteine (SPARC). To the authors’ knowledge, this is the first report of a peripheral primitive neuroectodermal tumour (pPNET) in a bird.
High-Frequency Absorption of the Hybrid Composites with Spindle-like Fe3O4 Nanoparticles and Multiwalled Carbon Nanotubes
Authors: Xia Ruozhou , Yin Yichao , Zeng Min , Dong Hangrong , Yang Haozhe , Zeng Xiaojun , Tang Wukui , Yu Ronghai 
Published: May 2016

The anisotropic spindle-like Fe3O4 hybrid nanocomposites blended with multi-wall carbon nanotubes (MWCNTs) have been prepared to function as an ideal lightweight candidate for electromagnetic (EM) wave absorption with decent performance in high frequency. The microstructure, morphology, magnetic properties, charge-transfer behavior and EM wave absorbing performance have been characterized by powder X-ray diffractometer, transmission electron microscope, vibrating sample magnetometer, Raman spectrometer and vector network analyzer, respectively. A maximum reflection loss reaches around [Formula: see text]40[Formula: see text]dB with 5% MWCNTs loading density. Compared with the monomer Fe3O4, the complex permittivity and permeability of the Fe3O4–MWCNTs nanocomposites are kept in balance, achieving a better impedance matching with a larger dielectric loss and magnetic loss. The optimization may be attributed to the synergistic effect between spindle-like Fe3O4 nanoparticles and MWCNTs. Moreover, the EM microwave absorbing performance can be optimized by tuning the Fe3O4–MWCNTs mass ratio and layer thickness of the samples, indicating promising application prospects for outstanding performance EM attenuation materials in high frequency.
Commentary on Folkman: “How Is Blood Vessel Growth Regulated in Normal and Neoplastic Tissue?”
Authors: Augustin Hellmut G. 
Published: May 2016

Abstract
Angiogenesis is a prerequisite for tumor growth and metastatic progression. The discovery of the first specific angiogenic cytokine, VEGF, in 1989 paved the way for the clinical approval of the first antiangiogenic tumor drug 15 years later. This brief commentary highlights and puts into historical perspective the 1985 G.H.A. Clowes Memorial Award Lecture delivered by Dr. Judah Folkman. Thirty years later, this award lecture is a lively testimony of the visionary mind of Dr. Folkman, whose legacy continues to inspire contemporary angiogenesis research. Cancer Res; 76(10); 2854–6. ©2016 AACR.
See related article by Folkman J, Cancer Res 1986;46:467–73.
Changes in Expression of Genes Representing Key Biologic Processes after Neoadjuvant Chemotherapy in Breast Cancer, and Prognostic Implications in Residual Disease
Authors: Klintman Marie , Buus Richard , Cheang Maggie Chon U. , Sheri Amna , Smith Ian E. , Dowsett Mitch 
Published: May 2016

AbstractPurpose: The primary aim was to derive evidence for or against the clinical importance of several biologic processes in patients treated with neoadjuvant chemotherapy (NAC) by assessing expression of selected genes with prior implications in prognosis or treatment resistance. The secondary aim was to determine the prognostic impact in residual disease of the genes' expression.Experimental Design: Expression levels of 24 genes were quantified by NanoString nCounter on formalin-fixed paraffin-embedded residual tumors from 126 patients treated with NAC and 56 paired presurgical biopsies. The paired t test was used for testing changes in gene expression, and Cox regression and penalized elastic-net Cox Regression for estimating HRs.Results: After NAC, 12 genes were significantly up- and 8 downregulated. Fourteen genes were significantly associated with time to recurrence in univariable analysis in residual disease. In a multivariable model, ACACB, CD3D, MKI67, and TOP2A added prognostic value independent of clinical ER−, PgR−, and HER2− status. In ER+/HER2− patients, ACACB, PAWR, and ERBB2 predicted outcome, whereas CD3D and PAWR were prognostic in ER−/HER2− patients. By use of elastic-net analysis, a 6-gene signature (ACACB, CD3D, DECORIN, ESR1, MKI67, PLAU) was identified adding prognostic value independent of ER, PgR, and HER2.Conclusions: Most of the tested genes were significantly enriched or depleted in response to NAC. Expression levels of genes representing proliferation, stromal activation, metabolism, apoptosis, stemcellness, immunologic response, and Ras–ERK activation predicted outcome in residual disease. The multivariable gene models identified could, if validated, be used to identify patients needing additional post-neoadjuvant treatment to improve prognosis. Clin Cancer Res; 22(10); 2405–16. ©2016 AACR.
High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype
Authors: Dennison Jennifer B. , Shahmoradgoli Maria , Liu Wenbin , Ju Zhenlin , Meric-Bernstam Funda , Perou Charles M. , Sahin Aysegul A. , Welm Alana , Oesterreich Steffi , Sikora Matthew J. , Brown Robert E. , Mills Gordon B. 
Published: May 2016

Abstract
Purpose: The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior.
Experimental Design: Formalin-fixed, paraffin-embedded tissue and matched protein lysates were evaluated from two independent breast cancer patient datasets (TCGA and MD Anderson). Reverse-phase protein arrays (RPPA) were utilized to create a proteomics signature to define breast tumor subtypes. Expression patterns of cell lines and normal breast tissues were utilized to determine markers that were differentially expressed in stroma and cancer cells. Protein localization and stromal contents were evaluated for matched cases by imaging.
Results: A subtype of breast cancers designated “Reactive,” previously identified by RPPA that was not predicted by mRNA profiling, was extensively characterized. These tumors were primarily estrogen receptor (ER)-positive/human EGF receptor (HER)2-negative, low-risk cancers as determined by enrichment of low-grade nuclei, lobular or tubular histopathology, and the luminal A subtype by PAM50. Reactive breast cancers contained high numbers of stromal cells and the highest extracellular matrix content typically without infiltration of immune cells. For ER-positive/HER2-negative cancers, the Reactive classification predicted favorable clinical outcomes in the TCGA cohort (HR, 0.36; P &lt; 0.05).
Conclusions: A protein stromal signature in breast cancers is associated with a highly differentiated phenotype. The stromal compartment content and proteins are an extended phenotype not predicted by mRNA expression that could be utilized to subclassify ER-positive/HER2-negative breast cancers. Clin Cancer Res; 22(20); 5068–78. ©2016 AACR.
Microparticles as new markers of cardiovascular risk in diabetes and beyond
Authors: Santilli Francesca , Marchisio Marco , Lanuti Paola , Boccatonda Andrea , Miscia Sebastiano , Davì Giovanni 
Published: May 2016

SummaryThe term microparticle (MP) identifies a heterogeneous population of vesicles playing a relevant role in the pathogenesis of vascular diseases, cancer and metabolic diseases such as diabetes mellitus. MPs are released by virtually all cell types by shedding during cell growth, proliferation, activation, apoptosis or senescence processes. MPs, in particular platelet- and endothelial-derived MPs (PMPs and EMPs), are increased in a wide range of thrombotic disorders, with an interesting relationship between their levels and disease pathophysiology, activity or progression. EMP plasma levels have been associated with several cardiovascular diseases and risk factors. PMPs are also shown to be involved in the progressive formation of atherosclerotic plaque and development of arterial thrombosis, especially in diabetic patients. Indeed, diabetes is characterised by an increased procoagulant state and by a hyperreactive platelet phenotype, with enhanced adhesion, aggregation, and activation. Elevated MP levels, such as TF+ MPs, have been shown to be one of the procoagulant determinants in patients with type 2 diabetes mellitus. Atherosclerotic plaque constitutes an opulent source of sequestered MPs, called “plaque” MPs. Otherwise, circulating MPs represent a TF reservoir, named “blood-borne” TF, challenging the dogma that TF is a constitutive protein expressed in minute amounts. “Blood-borne” TF is mainly harboured by PMPs, and it can be trapped within the developing thrombus. MP detection and enumeration by polychromatic flow cytometry (PFC) have opened interesting perspectives in clinical settings, particularly for the evaluation of MP numbers and phenotypes as independent marker of cardiovascular risk, disease and outcome in diabetic patients.