bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in hospital admissions and surgical procedures for degenerative lumbar spine disease in England: a 15-year time-series study
Authors: Sivasubramaniam Vinothan , Patel Hitesh C , Ozdemir Baris A , Papadopoulos Marios C 
Published: December 2015

ObjectivesLow back pain (LBP), from degenerative lumbar spine disease, represents a significant burden on healthcare resources. Studies worldwide report trends attributable to their country's specific demographics and healthcare system. Considering England's specific medico-socioeconomic conditions, we investigate recent trends in hospital admissions and procedures for LBP, and discuss the implications for the allocation of healthcare resources.DesignRetrospective cohort study using Hospital Episode Statistics data relating to degenerative lumbar spine disease in England, between 1999 and 2013. Regression models were used to analyse trends.Outcome measuresTrends in the number of admissions and procedures for LBP, mean patient age, gender and length of stay.ResultsHospital admissions and procedures have increased significantly over the study period, from 127.09 to 216.16 and from 24.5 to 48.83 per 100 000, respectively, (p<0.001). The increase was most marked in the oldest age groups with a 1.9 and 2.33-fold increase in admissions for patients aged 60–74 and ≥75 years, respectively, and a 2.8-fold increase in procedures for those aged ≥60 years. Trends in hospital admissions were characterised by a widening gender gap, increasing mean patient age, and decreasing mean hospital stay (p<0.001). Trends in procedures were characterised by a narrowing gender gap, increasing mean patient age (p=0.014) and decreasing mean hospital stay (p<0.001). Linear regression models estimate that each hospital admission translates to 0.27 procedures, per 100 000 (95% CI 0.25 to 0.30, r 0.99, p<0.001; r, Pearson's correlation coefficient). Hospital admissions are increasing at 3.5 times the rate of surgical procedures (regression gradient 7.63 vs 2.18 per 100 000/year).ConclusionsLBP represents a significant and increasing workload for hospitals in England. These trends demonstrate an increasing demand for specialists involved in the surgical and non-surgical management of this disease, and highlight the need for services capable of dealing with the increased comorbidity burden associated with an ageing patient group.
Bloodstream infections, antibiotic resistance and the practice of blood culture sampling in Germany: study design of a Thuringia-wide prospective population-based study (AlertsNet)
Authors: Karch André , Schmitz Roland P , Rißner Florian , Castell Stefanie , Töpel Sandra , Jakob Matthias , Brunkhorst Frank M , Mikolajczyk Rafael T 
Published: December 2015

IntroductionBloodstream infections are a major cause of death worldwide; blood culture (BC) sampling remains the most important tool for their diagnosis. Current data suggest that BC rates in German hospitals are considerably lower than recommended; this points to shortfalls in the application of microbiological analyses. Since early and appropriate BC diagnostics are associated with reduced case fatality rates and a shorter duration of antimicrobial therapy, a multicomponent study for the improvement of BC diagnostics was developed.Methods and analysisAn electronic BC registry established for the German Federal state of Thuringia is the structural basis of this study. The registry includes individual patient data (microbiological results and clinical data) and institutional information for all clinically relevant positive BCs at the participating centres. First, classic result quality indicators for bloodstream infections (eg, sepsis rates) will be studied using Poisson regression models (adjusted for institutional characteristics) in order to derive relative ranks for feedback to clinical institutions. Second, a target value will be established for the process indicator BC rate. On the basis of this target value, recommendations will be made for a given combination of institutional characteristics as a reference for future use in quality control. An interventional study aiming at the improvement of BC rates will be conducted thereafter. On the basis of the results of a survey in the participating institutions, a targeted educational intervention will be developed. The success of the educational intervention will be measured by changes in the process indicator and the result indicators over time using a pre–post design.Ethics and disseminationEthics approval was obtained from the Ethics committee of the University Hospital Jena and from the Ethics committee of the State Chamber of Physicians of Thuringia. Findings of AlertsNet will be disseminated through public media releases and publications in peer-reviewed journals.Trial registration numberDRKS00004825.
Estimating the probability of demonstrating vaccine efficacy in the declining Ebola epidemic: a Bayesian modelling approach
Authors: Camacho Anton , Eggo Rosalind M , Funk Sebastian , Watson Conall H , Kucharski Adam J , Edmunds W John 
Published: December 2015

ObjectivesWe investigate the chance of demonstrating Ebola vaccine efficacy in an individually randomised controlled trial implemented in the declining epidemic of Forécariah prefecture, Guinea.MethodsWe extend a previously published dynamic transmission model to include a simulated individually randomised controlled trial of 100 000 participants. Using Bayesian methods, we fit the model to Ebola case incidence before a trial and forecast the expected dynamics until disease elimination. We simulate trials under these forecasts and test potential start dates and rollout schemes to assess power to detect efficacy, and bias in vaccine efficacy estimates that may be introduced.ResultsUnder realistic assumptions, we found that a trial of 100 000 participants starting after 1 August had less than 5% chance of having enough cases to detect vaccine efficacy. In particular, gradual recruitment precludes detection of vaccine efficacy because the epidemic is likely to go extinct before enough participants are recruited. Exclusion of early cases in either arm of the trial creates bias in vaccine efficacy estimates.ConclusionsThe very low Ebola virus disease incidence in Forécariah prefecture means any individually randomised controlled trial implemented there is unlikely to be successful, unless there is a substantial increase in the number of cases.
PLAC8 Localizes to the Inner Plasma Membrane of Pancreatic Cancer Cells and Regulates Cell Growth and Disease Progression through Critical Cell-Cycle Regulatory Pathways
Authors: Kaistha Brajesh P. , Lorenz Holger , Schmidt Harald , Sipos Bence , Pawlak Michael , Gierke Berthold , Kreider Ramona , Lankat-Buttgereit Brigitte , Sauer Melanie , Fiedler Lisa , Krattenmacher Anja , Geisel Bettina , Kraus Johann M. , Frese Kristopher K. , Kelkenberg Sabine , Giese Nathalia A. , Kestler Hans A. , Gress Thomas M. , Buchholz Malte 
Published: December 2015

Abstract
Pancreatic ductal adenocarcinoma (PDAC) carries the most dismal prognosis of all solid tumors and is generally strongly resistant to currently available chemo- and/or radiotherapy regimens, including targeted molecular therapies. Therefore, unraveling the molecular mechanisms underlying the aggressive behavior of pancreatic cancer is a necessary prerequisite for the development of novel therapeutic approaches. We previously identified the protein placenta-specific 8 (PLAC8, onzin) in a genome-wide search for target genes associated with pancreatic tumor progression and demonstrated that PLAC8 is strongly ectopically expressed in advanced preneoplastic lesions and invasive human PDAC. However, the molecular function of PLAC8 remained unclear, and accumulating evidence suggested its role is highly dependent on cellular and physiologic context. Here, we demonstrate that in contrast to other cellular systems, PLAC8 protein localizes to the inner face of the plasma membrane in pancreatic cancer cells, where it interacts with specific membranous structures in a temporally and spatially stable manner. Inhibition of PLAC8 expression strongly inhibited pancreatic cancer cell growth by attenuating cell-cycle progression, which was associated with transcriptional and/or posttranslational modification of the central cell-cycle regulators CDKN1A, retinoblastoma protein, and cyclin D1 (CCND1), but did not impact autophagy. Moreover, Plac8 deficiency significantly inhibited tumor formation in genetically engineered mouse models of pancreatic cancer. Together, our findings establish PLAC8 as a central mediator of tumor progression in PDAC and as a promising candidate gene for diagnostic and therapeutic targeting. Cancer Res; 76(1); 96–107. ©2015 AACR.
Establishment and Characterization of an In Vitro Model of Ovarian Cancer Stem-like Cells with an Enhanced Proliferative Capacity
Authors: Ishiguro Tatsuya , Sato Ai , Ohata Hirokazu , Ikarashi Yoshinori , Takahashi Ryou-u , Ochiya Takahiro , Yoshida Masayuki , Tsuda Hitoshi , Onda Takashi , Kato Tomoyasu , Kasamatsu Takahiro , Enomoto Takayuki , Tanaka Kenichi , Nakagama Hitoshi , Okamoto Koji 
Published: December 2015

Abstract
The establishment of cancer stem-like cell (CSC) culture systems may be instrumental in devising strategies to fight refractory cancers. Inhibition of the Rho kinase ROCK has been shown to favorably affect CSC spheroid cultures. In this study, we show how ROCK inhibition in human serous ovarian cancer (SOC) cells can help establish a CSC system, which illuminates cancer pathophysiology and its treatment in this setting. In the presence of a ROCK kinase inhibitor, spheroid cultures of SOC cells expressed characteristic CSC markers including ALDH1A1, CD133, and SOX2, along with differentiation and tumorigenic capabilities in mouse xenograft models of human SOC. High expression levels of ALDH, but not CD133, correlated with spheroid formation CSC marker expression and tumor forming capability. In clinical specimens of SOC, high levels of ALDH1A1 correlated with advanced stage and poor prognosis. Pharmacologic or genetic blockade of ALDH blocked cell proliferation and reduced expression of SOX2, the genetic ablation of which abolished spheroid formation, whereas SOX2 overexpression inhibited ALDH1A1 expression and blocked spheroid proliferation. Taken together, our findings illustrated a new method to culture human ovarian CSC, and they defined a reciprocal regulatory relationship between ALDH1A1 and SOX2, which impacts ovarian CSC proliferation and malignant progression. Cancer Res; 76(1); 150–60. ©2015 AACR.
Molecular Pathways: Targeting Cancer Stem Cells Awakened by Chemotherapy to Abrogate Tumor Repopulation
Authors: Chan Keith Syson 
Published: December 2015

Abstract
Cytotoxic chemotherapy remains the first-line therapy for many advanced solid tumors; hence, understanding the underlying mechanisms to overcome chemoresistance remains a top research priority. In the clinic, chemotherapy is administered in multiple cycles that are spaced out to allow the recovery or repopulation of normal tissues and tissue stem cells between treatment cycles. However, residual surviving cancer cells and cancer stem cells can also repopulate tumors during the gap periods between chemotherapy cycles. Tumor repopulation is a phenomenon that has not been well studied; it is often overlooked due to current customized experimental study strategies. Recent findings reveal an alarming role for dying cells targeted by chemotherapy in releasing mitogens to stimulate active repopulation of quiescent cancer stem cells. Therefore, new therapeutic options to abrogate tumor repopulation will provide new avenues to improve chemotherapeutic response and clinical outcome. Clin Cancer Res; 22(4); 802–6. ©2015 AACR.
Profiling Non–Small Cell Lung Cancer: From Tumor to Blood
Authors: Tsui Dana W.Y. , Berger Michael F. 
Published: December 2015

Abstract
Circulating cell-free tumor DNA has shown great promise for noninvasive genomic profiling to guide the administration of targeted therapies in non–small cell lung cancer. With advancements in molecular technology, it is now possible to interrogate multiple clinically actionable genetic drivers in the blood with a single assay. Clin Cancer Res; 22(4); 790–2. ©2015 AACR.
See related article by Paweletz et al., p. 915
Characterization of White Matter Injury in a Rat Model of Chronic Cerebral Hypoperfusion
Authors: Choi Bo-Ryoung , Kim Dong-Hee , Back Dong Bin , Kang Chung Hwan , Moon Won-Jin , Han Jung-Soo , Choi Dong-Hee , Kwon Kyoung Ja , Shin Chan Young , Kim Bo-Ram , Lee Jongmin , Han Seol-Heui , Kim Hahn Young 
Published: December 2015

Background and Purpose—
Chronic cerebral hypoperfusion can lead to ischemic white matter injury resulting in vascular dementia. To characterize white matter injury in vascular dementia, we investigated disintegration of diverse white matter components using a rat model of chronic cerebral hypoperfusion.

Methods—
Chronic cerebral hypoperfusion was modeled in Wistar rats by permanent occlusion of the bilateral common carotid arteries. We performed cognitive behavioral tests, including the water maze task, odor discrimination task, and novel object test; histological investigation of neuroinflammation, oligodendrocytes, myelin basic protein, and nodal or paranodal proteins at the nodes of Ranvier; and serial diffusion tensor imaging. Cilostazol was administered to protect against white matter injury.

Results—
Diverse cognitive impairments were induced by chronic cerebral hypoperfusion. Disintegration of white matter was characterized by neuroinflammation, loss of oligodendrocytes, attenuation of myelin density, structural derangement at the nodes of Ranvier, and disintegration of white matter tracts. Cilostazol protected against cognitive impairments and white matter disintegration.

Conclusions—
White matter injury induced by chronic cerebral hypoperfusion can be characterized by disintegration of diverse white matter components. Cilostazol might be a therapeutic strategy against white matter disintegration in patients with vascular dementia.
Accession of the Russian Federation to the World Trade Organization: A New Player Joins the Trade Game
Authors: Van der Borght Kim 
Published: December 2015

To date, no country has taken longer to join the World Trade Organization than the Russian Federation despite the fact that the ussr (of which the Russian Federation is the legal successor) participated in the drafting conference of the Charter to the International Trade Organization, i.e., the original source of the rules of the General Agreement on Tariffs and Trade and the later wto.
While the ussr never joined the ito, Russia finally joined the wto in 2012, eighteen years after its first application had been made. The reasons for the lengthy accession process were partially economic, as the wto was established to remove trade impediments; however, the context also was highly politicized. The economic aspects of the wto accession process are the concessions made to existing members. These entail removing the cover offered to domestic producers by opening up to international competition. This process also has political aspects, as domestic lobbies representing economic sectors likely to suffer from an increasingly competitive international environment seek compensation. The politicization is facilitated by a custom contra legem in wto decision-making procedures that gives a de facto veto to existing members. Georgia used this to reassert its position on South Osetiia and Abkhaziia. China brought a border dispute into the process, and the us entangled the process in a broad-ranging debate linked to human rights.
In joining the wto, a dual process of domestic and international negotiations results in the final package of commitments to which an acceding member needs to agree as it joins the wto. Part of our focus in this article will be on key economic and political obligations that the Russian Federation took upon itself by becoming a member of the wto.
Checklist of water bugs (Hemiptera: Heteroptera: Nepomorpha, Gerromorpha) of Slovakia
Authors: KLEMENTOVÁ BARBORA REDUCIENDO , KMENT PETR , SVITOK MAREK 
Published: December 2015

The water bugs represent a significant component of the freshwater biota, play an important role in trophic webs, and may have considerable economic importance. Nevertheless, systematic research of this group has been underdeveloped in Slovakia (central Europe) for decades. This work presents a list of water bug species of Slovakia based on an exhaustive review of the literature (time span: 1808–2013) and on more than 14,000 individuals collected during extensive field campaigns (2010–2014) or obtained from insect collections. Fifty-six species belonging to 11 families of Heteroptera were recorded from a total of 767 sites. Seven species were recorded for the first time from Slovakia during our research. Among those, the first exact records of Corixa panzeri Fieber, 1848, Sigara (Subsigara) distincta (Fieber, 1848), Notonecta (Notonecta) lutea Müller, 1776, Notonecta (Notonecta) maculata Fabricius, 1794 and Microvelia (Microvelia) buenoi Drake, 1920 are provided here. Confusion concerning the records of two additional species, Arctocorisa carinata carinata (C. R. Sahlberg, 1819) and Hesperocorixa parallela (Fieber, 1860) is clarified. The water bugs species inventory appears to be nearly complete (~97 %) given an asymptotic richness estimate. The occurrence of other species is discussed taking into account their habitat requirements and distribution in neighbouring countries. Recommendations for future research are provided.
In Situ–Based Reanalysis of the Global Ocean Temperature and Salinity with ISAS: Variability of the Heat Content and Steric Height
Authors: Gaillard Fabienne , Reynaud Thierry , Thierry Virginie , Kolodziejczyk Nicolas , von Schuckmann Karina 
Published: December 2015

Abstract
The In Situ Analysis System (ISAS) was developed to produce gridded fields of temperature and salinity that preserve as much as possible the time and space sampling capabilities of the Argo network of profiling floats. Since the first global reanalysis performed in 2009, the system has evolved, and a careful delayed-mode processing of the 2002–12 dataset has been carried out using version 6 of ISAS and updating the statistics to produce the ISAS13 analysis. This last version is now implemented as the operational analysis tool at the Coriolis data center. The robustness of the results with respect to the system evolution is explored through global quantities of climatological interest: the ocean heat content and the steric height. Estimates of errors consistent with the methodology are computed. This study shows that building reliable statistics on the fields is fundamental to improve the monthly estimates and to determine the absolute error bars. The new mean fields and variances deduced from the ISAS13 reanalysis and dataset show significant changes relative to the previous ISAS estimates, in particular in the Southern Ocean, justifying the iterative procedure. During the decade covered by Argo, the intermediate waters appear warmer and saltier in the North Atlantic and fresher in the Southern Ocean than in World Ocean Atlas 2005 long-term mean. At interannual scale, the impact of ENSO on the ocean heat content and steric height is observed during the 2006/07 and 2009/10 events captured by the network.
Partial splenic embolization of patients with hypersplenism by transradial or transfemoral approach: a prospective randomized controlled trial
Authors: Wu Tao , Sun Ruimin , Huang Yinuo , Wang Zhixue , He Jue , Shen Songhe , Yin Xiaoxiang , Zhu Zhixiang , Yang Wenyi , Zhao Zhijun 
Published: December 2015

Background Partial splenic artery embolization (PSE) is an effective treatment modality for patients with hypersplenism. It is less invasive and has a quicker recovery compared with surgical procedures. PSE is usually performed using a femoral artery approach that requires bedrest for a few hours, which is rarely the case for transradial PSE. Purpose To compare the transradial and transfemoral approaches for embolization of spleen in patients with hypersplenism. Material and Methods In all, 84 patients with hypersplenism who required PSE were recruited. They were randomly divided into two groups on the basis of the procedure followed: the transradial approach (R-PSE, n = 39) or transfemoral approach (F-PSE, n = 45). Technical success, puncture rate, total procedure time, X-ray exposure time, length of stay in hospital (LOS), and complications of the two groups were recorded. Results The procedure time, X-ray exposure time, and LOS were found to be lower in the R-PSE group than in the F-PSE. However, this difference was not statistically significant. Conclusion The transradial artery approach for PSE in patients with hypersplenism is feasible with no major complications as compared to the femoral approach.
Anti-Ro/SSA autoantibody-positive women’s experience of information given on the risk of congenital heart block
Authors: Tingström J , Hjelmstedt A , Welin Henriksson E , Ambrosi A , Sonesson S-E , Wahren-Herlenius M 
Published: December 2015

Objective Congenital heart block (CHB) may develop in fetuses of women with anti-Ro/SSA autoantibodies, and carries substantial morbidity and mortality. The aim was to evaluate how information on CHB is imparted and identify areas of improvement. Methods A questionnaire was distributed to anti-Ro/SSA antibody-positive women who had either participated in a surveillance programme but whose expected child did not develop CHB ( n = 100, denoted Doppler-Assessed Pregnancies (DAP) group) or given birth to a child with CHB ( n = 88, denoted CHB-Affected Pregnancies (CAP) group). Results The response rate was 83% (157/188). Most women received the information on CHB when they were already pregnant (DAP group 60%, CAP group 83%). However, a majority of them would have wanted the information before pregnancy (DAP group 52%, CAP group 56%), and most stated that it would not have influenced their decision to have a child (DAP group 77%, CAP group 58%). The ability to both understand the information and to perceive the information as sufficient were significantly higher when someone trained in paediatric cardiology gave the information. Conclusions Our findings indicate that information on CHB should be given to women before pregnancy. The data further highlight the importance of having specific knowledge for giving relevant and understandable, yet sufficient information.
Role of angiotensin II in stem cell therapy of cardiac disease
Authors: Ahmadian Elham , Jafari Samira , Yari Khosroushahi Ahmad 
Published: December 2015

Introduction: The renin angiotensin system (RAS) is closely related to the cardiovascular system, body fluid regulation and homeostasis. Materials and methods: Despite common therapeutic methods, stem cell/progenitor cell therapy is daily increasing as a term of regenerative medicine. RAS and its pharmacological inhibitors are not only involved in physiological and pathological aspects of the cardiovascular system, but also affect the different stages of stem cell proliferation, differentiation and function, via interfering cell signaling pathways. Results: This study reviews the new role of RAS, in particular Ang II distinct from other common roles, by considering its regulating impact on the different signaling pathways involved in the cardiac and endothelial tissue, as well as in stem cell transplantation. Conclusions: This review focuses on the impact of stem cell therapy on the cardiovascular system, the role of RAS in stem cell differentiation, and the role of RAS inhibition in cardiac stem cell growth and development.