bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fulminant pneumococcal infection
Authors: Naito Ryo , Miyazaki Tetsuro , Kajino Kazunori , Daida Hiroyuki 
Published: August 2014

SummaryFulminant pneumococcal infection is a fatal pneumococcal infection that tends to occur in immunocompromised hosts, such as patients who are asplenic or on immunosuppressant therapy. We experienced a case of a 73-year-old Japanese man with a medical history of coronary stent implantation and catheter ablation for atrial flutter who presented with dyspnoea at rest. The patient was diagnosed with streptococcal pneumonia based on a urine antigen test and CT. Despite the use of effective antibiotics and systemic therapies, his clinical course was rapidly progressive and he died 18 h after admission. This case of fulminant pneumococcal infection is reported along with the autopsy findings.
Managing patient complaints in China: a qualitative study in Shanghai
Authors: Jiang Yishi , Ying Xiaohua , Zhang Qian , Tang Sirui Rae , Kane Sumit , Mukhopadhyay Maitrayee , Qian Xu ,   HESVIC team authorship
Published: August 2014

ObjectivesTo examine the handling system for patient complaints and to identify existing barriers that are associated with effective management of patient complaints in China.SettingKey stakeholders of the handling system for patient complaints at the national, Shanghai municipal and hospital levels in China.Participants35 key informants including policymakers, hospital managers, healthcare providers, users and other stakeholders in Shanghai.Primary and secondary outcome measuresSemistructured interviews were conducted to understand the process of handling patient complaints and factors affecting the process and outcomes of patient complaint management.ResultsThe Chinese handling system for patient complaints was established in the past decade. Hospitals shoulder the most responsibility of patient complaint handling. Barriers to effective management of patient complaints included service users’ low awareness of the systems in the initial stage of the process; poor capacity and skills of healthcare providers, incompetence and powerlessness of complaint handlers and non-transparent exchange of information during the process of complaint handling; conflicts between relevant actors and regulations and unjustifiable complaints by patients during solution settlements; and weak enforcement of regulations, deficient information for managing patient complaints and unwillingness of the hospitals to effectively handle complaints in the postcomplaint stage.ConclusionsBarriers to the effective management of patient complaints vary at the different stages of complaint handling and perspectives on these barriers differ between the service users and providers. Information, procedure design, human resources, system arrangement, unified legal system and regulations and factors shaping the social context all play important roles in effective patient complaint management.
Efficacy of a dual-ring wound protector for prevention of incisional surgical site infection after Whipple's procedure (pancreaticoduodenectomy) with preoperatively-placed intrabiliary stents: protocol for a randomised controlled trial
Authors: Bressan Alexsander K , Roberts Derek J , Edwards Janet P , Bhatti Sana U , Dixon Elijah , Sutherland Francis R , Bathe Oliver , Ball Chad G 
Published: August 2014

IntroductionAmong surgical oncology patients, incisional surgical site infection is associated with substantially increased morbidity, mortality and healthcare costs. Moreover, while adults undergoing pancreaticoduodenectomy with preoperative placement of an intrabiliary stent have a high risk of this type of infection, and wound protectors may significantly reduce its risk, no relevant studies of wound protectors yet exist involving this patient population. This study will evaluate the efficacy of a dual-ring wound protector for prevention of incisional surgical site infection among adults undergoing pancreaticoduodenectomy with preoperatively-placed intrabiliary stents.Methods and analysisThis study will be a parallel, dual-arm, randomised controlled trial that will utilise a more explanatory than pragmatic attitude. All adults (≥18 years) undergoing a pancreaticoduodenectomy at the Foothills Medical Centre in Calgary, Alberta, Canada with preoperative placement of an intrabiliary stent will be considered eligible. Exclusion criteria will include patient age <18 years and those receiving long-term glucocorticoids. The trial will employ block randomisation to allocate patients to a commercial dual-ring wound protector (the Alexis Wound Protector) or no wound protector and the current standard of care. The main outcome measure will be the rate of surgical site infection as defined by the Centers for Disease Control and Prevention criteria within 30 days of the index operation date as determined by a research assistant blinded to treatment allocation. Outcomes will be analysed by a statistician blinded to allocation status by calculating risk ratios and 95% CIs and compared using Fisher's exact test.Ethics and disseminationThis will be the first randomised trial to evaluate the efficacy of a dual-ring wound protector for prevention of incisional surgical site infection among patients undergoing pancreaticoduodenectomy. Results of this study are expected to be available in 2016/2017 and will be disseminated using an integrated and end-of-grant knowledge translation strategy.Trial registration numberClinicalTrials.gov identifierNCT01836237.
Developing a service user informed intervention to improve participation and ability to perform daily activities in primary Sjögren's syndrome: a mixed-methods study protocol
Authors: Hackett Katie L , Newton Julia L , Deane Katherine H O , Rapley Tim , Deary Vincent , Kolehmainen Niina , Lendrem Dennis , Ng Wan-Fai 
Published: August 2014

IntroductionA significant proportion of patients with primary Sjögren's syndrome (PSS) is functionally impaired and experience difficulties participating in various aspects of everyday life. There is currently no evidence of efficacy for non-pharmacological interventions aimed specifically at supporting the patients with PSS to improve their participation and ability to perform daily activities. This paper describes a research protocol for a mixed-methods study to develop an intervention to improve these outcomes. The protocol follows the Medical Research Council framework for complex interventions.Methods and analysisWe will use group concept mapping with the patients, adults who live with them and healthcare professionals to identify factors which prevent people with PSS from participating in daily life and performing daily activities. The factors will be prioritised by participants for importance and feasibility and will inform an intervention to be delivered within a National Health Service (NHS) setting. Evidence-based intervention techniques will be identified for the prioritised factors and combined into a deliverable intervention package. Key stakeholders will comment on the intervention content and mode of delivery through focus groups, and the data will be used to refine the intervention. The acceptability and feasibility of the refined intervention will be evaluated in a future study.Ethics and disseminationThe study has been approved by an NHS Research Ethics Committee, REC Reference: 13/NI/0190. The findings of this study will be disseminated in peer-reviewed journals and through presentation at national and international conferences.Trial registration numberUKCRN Study ID: 15939.
Complex Formation and Function of Estrogen Receptor α in Transcription Requires RIP140
Authors: Rosell Meritxell , Nevedomskaya Ekaterina , Stelloo Suzan , Nautiyal Jaya , Poliandri Ariel , Steel Jennifer H. , Wessels Lodewyk F.A. , Carroll Jason S. , Parker Malcolm G. , Zwart Wilbert 
Published: August 2014

Abstract
RIP140 is a transcriptional coregulator involved in energy homeostasis, ovulation, and mammary gland development. Although conclusive evidence is lacking, reports have implicated a role for RIP140 in breast cancer. Here, we explored the mechanistic role of RIP140 in breast cancer and its involvement in estrogen receptor α (ERα) transcriptional regulation of gene expression. Using ChIP-seq analysis, we demonstrate that RIP140 shares more than 80% of its binding sites with ERα, colocalizing with its interaction partners FOXA1, GATA3, p300, CBP, and p160 family members at H3K4me1-demarcated enhancer regions. RIP140 is required for ERα-complex formation, ERα-mediated gene expression, and ERα-dependent breast cancer cell proliferation. Genes affected following RIP140 silencing could be used to stratify tamoxifen-treated breast cancer cohorts, based on clinical outcome. Importantly, this gene signature was only effective in endocrine-treated conditions. Cumulatively, our data suggest that RIP140 plays an important role in ERα-mediated transcriptional regulation in breast cancer and response to tamoxifen treatment. Cancer Res; 74(19); 5469–79. ©2014 AACR.
AEG-1 Promoter–Mediated Imaging of Prostate Cancer
Authors: Bhatnagar Akrita , Wang Yuchuan , Mease Ronnie C. , Gabrielson Matthew , Sysa Polina , Minn Il , Green Gilbert , Simmons Brian , Gabrielson Kathleen , Sarkar Siddik , Fisher Paul B. , Pomper Martin G. 
Published: August 2014

Abstract
We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through a systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single-photon emission computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for noninvasive clinical imaging. Furthermore, the approach compares favorably with accepted and emerging clinical standards, including PET with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer. Cancer Res; 74(20); 5772–81. ©2014 AACR.
SAR405838: An Optimized Inhibitor of MDM2–p53 Interaction That Induces Complete and Durable Tumor Regression
Authors: Wang Shaomeng , Sun Wei , Zhao Yujun , McEachern Donna , Meaux Isabelle , Barrière Cédric , Stuckey Jeanne A. , Meagher Jennifer L. , Bai Longchuan , Liu Liu , Hoffman-Luca Cassandra Gianna , Lu Jianfeng , Shangary Sanjeev , Yu Shanghai , Bernard Denzil , Aguilar Angelo , Dos-Santos Odette , Besret Laurent , Guerif Stéphane , Pannier Pascal , Gorge-Bernat Dimitri , Debussche Laurent 
Published: August 2014

Abstract
Blocking the oncoprotein murine double minute 2 (MDM2)–p53 protein–protein interaction has long been considered to offer a broad cancer therapeutic strategy, despite the potential risks of selecting tumors harboring p53 mutations that escape MDM2 control. In this study, we report a novel small-molecule inhibitor of the MDM2–p53 interaction, SAR405838 (MI-77301), that has been advanced into phase I clinical trials. SAR405838 binds to MDM2 with Ki = 0.88 nmol/L and has high specificity over other proteins. A cocrystal structure of the SAR405838:MDM2 complex shows that, in addition to mimicking three key p53 amino acid residues, the inhibitor captures additional interactions not observed in the p53–MDM2 complex and induces refolding of the short, unstructured MDM2 N-terminal region to achieve its high affinity. SAR405838 effectively activates wild-type p53 in vitro and in xenograft tumor tissue of leukemia and solid tumors, leading to p53-dependent cell-cycle arrest and/or apoptosis. At well-tolerated dose schedules, SAR405838 achieves either durable tumor regression or complete tumor growth inhibition in mouse xenograft models of SJSA-1 osteosarcoma, RS4;11 acute leukemia, LNCaP prostate cancer, and HCT-116 colon cancer. Remarkably, a single oral dose of SAR405838 is sufficient to achieve complete tumor regression in the SJSA-1 model. Mechanistically, robust transcriptional upregulation of PUMA induced by SAR405838 results in strong apoptosis in tumor tissue, leading to complete tumor regression. Our findings provide a preclinical basis upon which to evaluate SAR405838 as a therapeutic agent in patients whose tumors retain wild-type p53. Cancer Res; 74(20); 5855–65. ©2014 AACR.
Folate and Vitamin B12 May Play a Critical Role in Lowering the HPV 16 Methylation–Associated Risk of Developing Higher Grades of CIN
Authors: Piyathilake Chandrika J. , Macaluso Maurizio , Chambers Michelle M. , Badiga Suguna , Siddiqui Nuzhat R. , Bell Walter C. , Edberg Jeffrey C. , Partridge Edward E. , Alvarez Ronald D. , Johanning Gary L. 
Published: August 2014

Abstract
We previously reported that a higher degree of methylation of CpG sites in the promoter (positions 31, 37, 43, 52, and 58) and enhancer site 7862 of human papillomavirus (HPV) 16 was associated with a lower likelihood of being diagnosed with HPV 16–associated CIN 2+. The purpose of this study was to replicate our previous findings and, in addition, to evaluate the influence of plasma concentrations of folate and vitamin B12 on the degree of HPV 16 methylation (HPV 16m). The study included 315 HPV 16-positive women diagnosed with either CIN 2+ or ≤CIN 1. Pyrosequencing technology was used to quantify the degree of HPV 16m. We reproduced the previously reported inverse association between HPV 16m and risk of being diagnosed with CIN 2+. In addition, we observed that women with higher plasma folate and HPV 16m or those with higher plasma vitamin B12 and HPV 16m were 75% (P &lt; 0.01) and 60% (P = 0.02) less likely to be diagnosed with CIN 2+, respectively. With a tertile increase in the plasma folate or vitamin B12, there was a 50% (P = 0.03) and 40% (P = 0.07) increase in the odds of having a higher degree of HPV 16m, respectively. This study provides initial evidence that methyl donor micronutrients, folate and vitamin B12, may play an important role in maintaining a desirably high degree of methylation at specific CpG sites in the HPV E6 promoter and enhancer that are associated with the likelihood of being diagnosed with CIN 2+. Cancer Prev Res; 7(11); 1128–37. ©2014 AACR.
RUC-4
Authors: Li Jihong , Vootukuri Spandana , Shang Yi , Negri Ana , Jiang Jian-kang , Nedelman Mark , Diacovo Thomas G. , Filizola Marta , Thomas Craig J. , Coller Barry S. 
Published: August 2014

Objective—
Treatment of myocardial infarction within the first 1 to 2 hours with a thrombolytic agent, percutaneous coronary intervention, or an αIIbβ3 antagonist decreases mortality and the later development of heart failure. We previously reported on a novel small molecule αIIbβ3 antagonist, RUC-2, that has a unique mechanism of action. We have now developed a more potent and more soluble congener of RUC-2, RUC-4, designed to be easily administered intramuscularly by autoinjector to facilitate its use in the prehospital setting. Here, we report the properties of RUC-4 and the antiplatelet and antithrombotic effects of RUC-2 and RUC-4 in animal models.

Approach and Results—

RUC-4 was ≈20% more potent than RUC-2 in inhibiting human ADP-induced platelet aggregation and much more soluble in aqueous solutions (60–80 mg/mL). It shared RUC-2’s specificity for αIIbβ3 versus αVβ3, did not prime the receptor to bind fibrinogen, or induce changes in β3 identified by a conformation-specific monoclonal antibody. Both RUC-2 and RUC-4 prevented FeCl
3
-induced thrombotic occlusion of the carotid artery in mice and decreased microvascular thrombi in response to laser injury produced by human platelets infused into transgenic mice containing a mutated von Willebrand factor that reacts with human but not mouse platelets. Intramuscular injection of RUC-4 in nonhuman primates at 1.9 and 3.85 mg/kg led to complete inhibition of platelet aggregation within 15 minutes, with dose-dependent return of platelet aggregation after 4.5 to 24 hours.

Conclusions—
RUC-4 has favorable biochemical, pharmacokinetic, pharmacodynamic, antithrombotic, and solubility properties as a prehospital therapy of myocardial infarction, but the possibility of increased bleeding with therapeutic doses remains to be evaluated.
Correlates of Quality of Life in Rural Patients With Heart Failure
Authors: Nesbitt Thomas , Doctorvaladan Sahar , Southard Jeffrey A. , Singh Satinder , Fekete Anne , Marie Kate , Moser Debra K. , Pelter Michelle M. , Robinson Susan , Wilson Machelle D. , Cooper Lawton , Dracup Kathleen 
Published: August 2014

Background—
There is abundant research indicating poor physical, psychological, and social functioning of patients with chronic heart failure (HF), a reality that can lead to poor health-related quality of life (QoL). Little is known about the experience of rural patients with HF.

Methods and Results—
This study was part of a randomized clinical trial titled Rural Education to Improve Outcomes in Heart Failure (REMOTE-HF) designed to test an education and counseling intervention to improve self-care in patients with HF. We evaluated 612 rural patients. Multiple validated questionnaires were administered to assess patient perceptions of health and health literacy. Baseline factors were collected and compared with baseline QoL measures only. Patients’ health-related QoL was assessed using the Minnesota Living with Heart Failure scale. The data were analyzed using a general linear model to test the association of various patient characteristics with QoL in rural patients with HF. Patients were 65.8 (+12.9) years of age. The majority were men (58.7%), married (56.4%), and had completed a high-school education (80.9%). Factors associated with reduced QoL among this population include geographic location, younger age, male sex, higher New York Heart Association class, worse HF knowledge, poorer perceived control, and symptoms of depression or anxiety. The data provided no evidence of an association between left ventricular ejection fraction and QoL.

Conclusions—
This study of rural patients with HF confirms previously identified factors associated with perceptions of QoL. However, further study is warranted with an urban control group.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00415545.
Acute Blood Pressure Reduction in Patients With Intracerebral Hemorrhage Does Not Result in Borderzone Region Hypoperfusion
Authors: Gould Bronwen , McCourt Rebecca , Gioia Laura C. , Kate Mahesh , Hill Michael D. , Asdaghi Negar , Dowlatshahi Dariush , Jeerakathil Thomas , Coutts Shelagh B. , Demchuk Andrew M. , Emery Derek , Shuaib Ashfaq , Butcher Ken 
Published: August 2014

Background and Purpose—
The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT) demonstrated blood pressure (BP) reduction does not affect mean perihematoma or hemispheric cerebral blood flow. Nonetheless, portions of the perihematoma and borderzones may reach ischemic thresholds after BP reduction. We tested the hypothesis that BP reduction after intracerebral hemorrhage results in increased critically hypoperfused tissue volumes.

Methods—
Patients with Intracerebral hemorrhage were randomized to a target systolic BP (SBP) of <150 or <180 mm Hg and imaged with computed tomographic perfusion 2 hours later. The volumes of tissue below cerebral blood flow thresholds for ischemia (<18 mL/100 g/min) and infarction (<12 mL/100 g/min) were calculated as a percentage of the total volume within the internal and external borderzones and the perihematoma region.

Results—

Seventy-five patients with intracerebral hemorrhage were randomized a median (interquartile range) of 7.8 (13.3) hours from onset. Acute hematoma volume was 17.8 (27.1) mL and mean SBP was 183±22 mm Hg. At the time of computed tomographic perfusion (2.3 [1.0] hours after randomization), SBP was lower in the <150 mm Hg (n=37; 140±18 mm Hg) than in the <180 mm Hg group (n=36; 162±12 mm Hg;
P
<0.001). BP treatment did not affect the percentage of total borderzone tissue with cerebral blood flow <18 (14.7±13.6 versus 15.6±13.7%;
P
=0.78) or <12 mL/100 g/min (5.1±5.1 versus 5.8±6.8%;
P
=0.62). Similar results were found in the perihematoma region. Low SBP load (fraction of time with SBP<150 mmHg) did not predict borderzone tissue volume with cerebral blood flow <18 mL/100 g/min (β=0.023 [−0.073, 0.119]).

Conclusions—
BP reduction does not increase the volume of critically hypoperfused borderzone or perihematoma tissue. These data support the safety of early BP reduction in intracerebral hemorrhage.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00963976.
Two Defining Features of Russian Tort Law: Their Rationale and Legal Effect
Authors: Lee Jewoo 
Published: August 2014

There are two aspects of Russian tort law that set it apart from that of other countries: the recognition of a general reversal of the burden of proof regarding fault in delictual obligations, and the existence of a general clause of strict liability. Such features are not only unique to Russian law but, also, constitute the very core of tort law in Russia today.Despite the significance of these two features, this is a gravely understudied area of research. One of the main reasons for this lies in the lack of interest in (and access to) Soviet legal literature and case law. However, without examining such sources, it is impossible to grasp the rationale behind such atypical legislation, which in turn, makes it difficult to understand Russian tort law in general. Therefore, it is necessary to explore the legislative history of Russia’s past era.Equally important is the legal effect that features may have in modern Russian tort law. This article will focus on the impact that a general reversal of the burden of proof has had on the outcome of tort cases in Russia. The author also will compare the general clause of strict liability in the Russian Civil Code with the regulation of sources of heightened danger in selected countries, a topic that deserves special attention, given Russia’s extensive experience in the field. In addition, all these questions will be examined against the backdrop of other contemporary jurisdictions and European harmonization initiatives in the area of tort law.
Daily Cycle of Precipitation over the Northern Coast of Brazil
Authors: Brito Sheila Santana de Barros , Oyama Marcos Daisuke 
Published: August 2014

AbstractThe daily cycle of precipitation (DCP) in the austral autumn on the northern coast of Brazil (NCB) is examined in detail. The Tropical Rainfall Measuring Mission 3B42 dataset was used to obtain the DCP, and the intradaily variability was measured using the coefficient of variation (CV). The DCP data of the NCB were grouped into five regimes. A new regime was found, called the shore regime. It has a minimum CV, and its cycle shows both continental (late afternoon peak) and oceanic features (morning peak). The landside coastal regime was divided into two areas: a continental coast regime, with very high CV, and an inland coast regime, with clear inland phase propagation. The continental regime was divided into two categories: an inland regime with low and high variability. The Forecast and Tracking of the Evolution of Cloud Clusters (ForTraCC) data were used to relate convective systems (CS) and their processes to the DCP. The following processes are studied for the CS: initiation/dissipation, merge/split, area increase/reduction, and advection. Initiation is more concentrated in time, while dissipation is more distributed. Physical mechanisms that generate initiation can promote area expansion and hence CS merge. By considering a simple parameterization, the time scale of the CS area reduction under environmental conditions that are unfavorable to initiation ranges from 6 to 12 h. Therefore, there is upscaling of the CS in the afternoon and slow decay during the night and morning, which leads to a more uniform cycle inland.