bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-7–producing stromal cells are critical for lymph node remodeling
Authors: Onder Lucas , Narang Priyanka , Scandella Elke , Chai Qian , Iolyeva Maria , Hoorweg Kerim , Halin Cornelia , Richie Ellen , Kaye Paul , Westermann Jürgen , Cupedo Tom , Coles Mark , Ludewig Burkhard 
Published: September 2012

AbstractNonhematopoietic stromal cells of secondary lymphoid organs form important scaffold and fluid transport structures, such as lymph node (LN) trabeculae, lymph vessels, and conduits. Furthermore, through the production of chemokines and cytokines, these cells generate a particular microenvironment that determines lymphocyte positioning and supports lymphocyte homeostasis. IL-7 is an important stromal cell-derived cytokine that has been considered to be derived mainly from T-cell zone fibroblastic reticular cells. We show here that lymphatic endothelial cells (LECs) are a prominent source of IL-7 both in human and murine LNs. Using bacterial artificial chromosome transgenic IL-7–Cre mice, we found that fibroblastic reticular cells and LECs strongly up-regulated IL-7 expression during LN remodeling after viral infection and LN reconstruction after avascular transplantation. Furthermore, IL-7–producing stromal cells contributed to de novo formation of LyveI-positive lymphatic structures connecting reconstructed LNs with the surrounding tissue. Importantly, diphtheria toxin–mediated depletion of IL-7–producing stromal cells completely abolished LN reconstruction. Taken together, this study identifies LN LECs as a major source of IL-7 and shows that IL-7–producing stromal cells are critical for reconstruction and remodeling of the distinct LN microenvironment.
Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection
Authors: Trautmann Lydie , Mbitikon-Kobo Florentin-Martial , Goulet Jean-Philippe , Peretz Yoav , Shi Yu , Van Grevenynghe Julien , Procopio Francesco Andrea , Boulassel Mohamad Rachid , Routy Jean-Pierre , Chomont Nicolas , Haddad Elias K. , Sekaly Rafick-Pierre 
Published: September 2012

AbstractImmediate-early host-virus interactions that occur during the first weeks after HIV infection have a major impact on disease progression. The mechanisms underlying the failure of HIV-specific CD8 T-cell response to persist and control viral replication early in infection are yet to be characterized. In this study, we performed a thorough phenotypic, gene expression and functional analysis to compare HIV-specific CD8 T cells in acutely and chronically infected subjects. We showed that HIV-specific CD8 T cells in primary infection can be distinguished by their metabolic state, rate of proliferation, and susceptibility to apoptosis. HIV-specific CD8 T cells in acute/early HIV infection secreted less IFN-γ but were more cytotoxic than their counterparts in chronic infection. Importantly, we showed that the levels of IL-7R expression and the capacity of HIV-specific CD8 T cells to secrete IL-2 on antigenic restimulation during primary infection were inversely correlated with the viral set-point. Altogether, these data suggest an altered metabolic state of HIV-specific CD8 T cells in primary infection resulting from hyperproliferation and stress induced signals, demonstrate the discordant function of HIV-specific CD8 T cells during early/acute infection, and highlight the importance of T-cell maintenance for viral control.
Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study
Authors: Xu-Monette Zijun Y. , Wu Lin , Visco Carlo , Tai Yu Chuan , Tzankov Alexander , Liu Wei-min , Montes-Moreno Santiago , Dybkær Karen , Chiu April , Orazi Attilio , Zu Youli , Bhagat Govind , Richards Kristy L. , Hsi Eric D. , Zhao X. Frank , Choi William W. L. , Zhao Xiaoying , van Krieken J. Han , Huang Qin , Huh Jooryung , Ai Weiyun , Ponzoni Maurilio , Ferreri Andrés J. M. , Zhou Fan , Kahl Brad S. , Winter Jane N. , Xu Wei , Li Jianyong , Go Ronald S. , Li Yong , Piris Miguel A. , Møller Michael B. , Miranda Roberto N. , Abruzzo Lynne V. , Medeiros L. Jeffrey , Young Ken H. 
Published: September 2012

Abstract
TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP–treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 50% cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP–treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies.
HTLV-1–infected T cells contain a single integrated provirus in natural infection
Authors: Cook Lucy B. , Rowan Aileen G. , Melamed Anat , Taylor Graham P. , Bangham Charles R. M. 
Published: September 2012

AbstractHuman T lymphotropic virus type 1 (HTLV-1) appears to persist in the chronic phase of infection by driving oligoclonal proliferation of infected T cells. Our recent high-throughput sequencing study revealed a large number (often > 104) of distinct proviral integration sites of HTLV-1 in each host that is greatly in excess of previous estimates. Here we use the highly sensitive, quantitative high-throughput sequencing protocol to show that circulating HTLV-1+ clones in natural infection each contain a single integrated proviral copy. We conclude that a typical host possesses a large number of distinct HTLV-1–infected T-cell clones.
Translation and adaption of the interRAI suite to local requirements in Belgian hospitals
Authors: Wellens Nathalie IH , Flamaing Johan , Moons Philip , Deschodt Mieke , Boonen Steven , Milisen Koen 
Published: September 2012

Abstract

Background
The interRAI Suite contains comprehensive geriatric assessment tools designed for various healthcare settings. Although each instrument is developed for a particular population, together they form an integrated health evaluation system. The interRAI Acute Care Minimum Data Set (interRAI AC) is tailored for hospitalized older persons. Our aim in this study was to translate and adapt the interRAI AC to the Belgian hospital context, where it can be used together with the interRAI Home Care (HC) and the interRAI Long Term Care Facility (LTCF).

Methods
A systematic, comprehensive, and rigorous 10-step approach was used to adapt the interRAI AC to local requirements. After linguistic translation by an official translator, five researchers assessed the translation for appropriate hospital jargon. Three researchers double-checked for translation accuracy and proposed additional items. A provisional version was converted into the three official languages of Belgium—Flemish, French, and German. Next, a multidisciplinary panel of nine experts judged item relevance to the Belgian care context and advised which country-specific items should be added. After these suggestions were incorporated into the interRAI AC, hospital staff from nine Flemish hospitals field-tested the tool in their practice. After evaluating field-test results, we compared the interRAI AC with Belgian versions of the interRAI HC and interRAI LTCF. Next, the Flemish, French, and German versions of the Belgian interRAI portfolio were harmonized. Finally, we submitted the Belgian interRAI AC to the interRAI organization for ratification.

Results
Eighteen administrative items of the interRAI AC were adapted to the Belgian healthcare context (e.g., usual residence, formal community services prior to admission). Fourteen items assessing the ‘informal caregiver’, and 17 items, including country-specific items, were added (e.g., advanced directive for euthanasia).

Conclusions
The interRAI AC was adapted to local requirements using a meticulous and recursive 10-step approach. As use of the interRAI Suite continues to grow worldwide and as it continues to expand to other care settings and populations, this procedure can guide future translations. This procedure might also be used by others facing similar challenges of complex translation and adaptation situations, where multidimensional instruments are used across multiple care settings in multiple languages.
Impact of mannose-binding lectin deficiency on radiocontrast-induced renal dysfunction: a post-hoc analysis of a multicenter randomized controlled trial
Authors: Osthoff Michael , Piezzi Vanja , Klima Theresia , Christ Andreas , Marana Ivana , Hartwiger Sabine , Breidthardt Tobias , Marenzi Giancarlo , Trendelenburg Marten , Mueller Christian 
Published: September 2012

Abstract

Background
Local renal ischemia is regarded as an important factor in the development of contrast-induced nephropathy (CIN). Mannose-binding lectin (MBL) is involved in the tissue damage during experimental ischemia/reperfusion injury of the kidneys. The aim of the present study was to investigate the association of MBL deficiency with radiocontrast-induced renal dysfunction in a large prospective cohort.

Methods
246 patients with advanced non–dialysis-dependent renal dysfunction who underwent radiographic contrast procedures were included in the study. Baseline serum MBL levels were analyzed according to the occurrence of a creatinine-based (increase of ≥0.5 mg/dL or ≥25% within 48 hours) or cystatin C-based (increase of ≥10% within 24 hours) CIN.

Results
The incidence of creatinine-based and cystatin C-based CIN was 6.5% and 24%, respectively. MBL levels were not associated with the occurrence of creatinine-based CIN. However, patients that experienced a cystatin C increase of ≥10% showed significantly higher MBL levels than patients with a rise of <10% (median 2885 (IQR 1193–4471) vs. 1997 (IQR 439–3504)ng/mL, p = 0.01). In logistic regression analysis MBL deficiency (MBL levels≤500 ng/ml) was identified as an inverse predictor of a cystatin C increase ≥10% (OR 0.34, 95% CI 0.15-0.8, p = 0.01).

Conclusion
MBL deficiency was associated with a reduced radiocontrast-induced renal dysfunction as reflected by the course of cystatin C. Our findings support a possible role of MBL in the pathogenesis of CIN.
Suboptimal management of central nervous system infections in children: a multi-centre retrospective study
Authors: Kelly Christine , Sohal Aman , Michael Benedict D , Riordan Andrew , Solomon Tom , Kneen Rachel ,   Northwest Neurological Infections Network
Published: September 2012

Abstract

Objective
We aimed to audit the regional management of central nervous system (CNS) infection in children.

Methods
The study was undertaken in five district general hospitals and one tertiary paediatric hospital in the Mersey region of the UK. Children admitted to hospital with a suspected CNS infection over a three month period were identified. Children were aged between 4 weeks and 16 years old. Details were recorded from the case notes and electronic records. We measured the appropriateness of management pathways as outlined by national and local guidelines.

Results
Sixty-five children were identified with a median age of 6 months (range 1 month to 15 years). Ten had a CNS infection: 4 aseptic meningitis, 3 purulent meningitis, 3 encephalitis [2 with herpes simplex virus (HSV) type 1]. A lumbar puncture (LP) was attempted in 50 (77%) cases but only 43 had cerebrospinal fluid (CSF) available for analysis. Of these 24 (57%) had a complete standard set of tests performed. Fifty eight (89%) received a third generation cephalosporin. Seventeen (26%) also received aciclovir with no obvious indication in 9 (53%). Only 11 (65%) of those receiving aciclovir had CSF herpes virus PCR. Seventeen had cranial imaging and it was the first management step in 14. Treatment lengths of both antibiotics and aciclovir were highly variable: one child with HSV encephalitis was only treated with aciclovir for 7 days.

Conclusions
The clinical management of children with suspected CNS infections across the Mersey region is heterogeneous and often sub-optimal, particularly for the investigation and treatment of viral encephalitis. National guidelines for the management of viral encephalitis are needed.
Appropriate use of indwelling urethra catheters in hospitalized patients: results of a multicentre prevalence study
Authors: Jansen Irálice AV , Hopmans Titia EM , Wille Jan C , van den Broek Peterhans J , van der Kooi Tjallie II , van Benthem Birgit HB 
Published: September 2012

Abstract

Background
Although indwelling urethra catheterization is a medical intervention with well-defined risks, studies show that approximately 14–38% of the indwelling urethra catheters (IUCs) are placed without a specific medical indication. In this paper we describe the prevalence of IUCs, including their inappropriate use in the Netherlands. We also determine factors associated with inappropriate use of IUCs in hospitalized patients.

Methods
In 28 Dutch hospitals, prevalence surveys were performed biannually in 2009 and 2010 within the PREZIES-network. All patients admitted to a participating hospital and who had an IUC in place at the day of the survey were included. Pre-determined criteria were used to categorize the indication for catheterization as appropriate or inappropriate.

Results
A total of 14,252 patients was included and 3020 (21.2%) of them had an IUC (range hospitals 13.4-27.3). Initial catheter placement was inappropriate in 5.2% of patients and 7.5% patients had an inappropriate indication at the day of the survey. In multivariate analyses inappropriate catheter use at the time of placement was associated with female sex, older age, admission on a non-intensive care ward, and not having had surgery. Inappropriate catheter use at the time of survey showed comparable associated factors.

Conclusions
Although lower than in many other countries, inappropriate use of IUC is present in Dutch hospitals. To reduce the inappropriate use of IUCs, recommended components of care (bundle for UTI), including daily revision and registration of the indication for catheterization, should be introduced for all patients with an IUC. Additionally, an education and awareness campaign about appropriate indications for IUC should be available.
Rotavirus A-specific single-domain antibodies produced in baculovirus-infected insect larvae are protective in vivo
Authors: Gómez-Sebastián Silvia , Nuñez Maria C , Garaicoechea Lorena , Alvarado Carmen , Mozgovoj Marina , Lasa Rodrigo , Kahl Alan , Wigdorovitz Andres , Parreño Viviana , Escribano José M 
Published: September 2012

Abstract

Background
Single-domain antibodies (sdAbs), also known as nanobodies or VHHs, are characterized by high stability and solubility, thus maintaining the affinity and therapeutic value provided by conventional antibodies. Given these properties, VHHs offer a novel alternative to classical antibody approaches. To date, VHHs have been produced mainly in E. coli, yeast, plants and mammalian cells. To apply the single-domain antibodies as a preventive or therapeutic strategy to control rotavirus infections in developing countries (444,000 deaths in children under 5 years of age) has to be minimized their production costs.

Results
Here we describe the highly efficient expression of functional VHHs by the Improved Baculovirus Expression System (IBES® technology), which uses a baculovirus expression vector in combination with Trichoplusia ni larvae as living biofactories. Two VHHs, named 3B2 and 2KD1, specific for the inner capsid protein VP6 of Group A rotavirus, were expressed in insect larvae. The IBES® technology achieved very high expression of 3B2 and 2KD1, reaching 2.62% and 3.63% of the total soluble protein obtained from larvae, respectively. These expression levels represent up to 257 mg/L of protein extract after insect processing (1 L extract represents about 125 g of insect biomass or about 375 insect larvae). Larva-derived antibodies were fully functional when tested in vitro and in vivo, neutralizing Group A rotaviruses and protecting offspring mice against rotavirus-induced diarrhea.

Conclusions
Our results open up the possibility of using insects as living biofactories (IBES® technology) for the cost-efficient production of these and other fully functional VHHs to be used for diagnostic or therapeutic purposes, thereby eliminating concerns regarding the use of bacterial or mammalian cells. To the best of our knowledge, this is the first time that insects have been used as living biofactories to produce a VHH molecule.
Boundaries and e-health implementation in health and social care
Authors: King Gerry , O’Donnell Catherine , Boddy David , Smith Fiona , Heaney David , Mair Frances S 
Published: September 2012

Abstract

Background
The major problem facing health and social care systems globally today is the growing challenge of an elderly population with complex health and social care needs. A longstanding challenge to the provision of high quality, effectively coordinated care for those with complex needs has been the historical separation of health and social care. Access to timely and accurate data about patients and their treatments has the potential to deliver better care at less cost.

Methods
To explore the way in which structural, professional and geographical boundaries have affected e-health implementation in health and social care, through an empirical study of the implementation of an electronic version of Single Shared Assessment (SSA) in Scotland, using three retrospective, qualitative case studies in three different health board locations.

Results
Progress in effectively sharing electronic data had been slow and uneven. One cause was the presence of established structural boundaries, which lead to competing priorities, incompatible IT systems and infrastructure, and poor cooperation. A second cause was the presence of established professional boundaries, which affect staffs’ understanding and acceptance of data sharing and their information requirements. Geographical boundaries featured but less prominently and contrasting perspectives were found with regard to issues such as co-location of health and social care professionals.

Conclusions
To provide holistic care to those with complex health and social care needs, it is essential that we develop integrated approaches to care delivery. Successful integration needs practices such as good project management and governance, ensuring system interoperability, leadership, good training and support, together with clear efforts to improve working relations across professional boundaries and communication of a clear project vision. This study shows that while technological developments make integration possible, long-standing boundaries constitute substantial risks to IT implementations across the health and social care interface which those initiating major changes would do well to consider before committing to the investment.
Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats
Authors: Lu Jing , Yao Yu-yu , Dai Qi-ming , Ma Gen-shan , Zhang Shu-feng , Cao Lei , Ren Li-qun , Liu Nai-feng 
Published: September 2012

Abstract

Background
Recent studies revealed that erythropoietin (EPO) has tissue-protective effects in the heart by increasing vascular endothelial growth factor (VEGF) expression and attenuating myocardial fibrosis in ischemia models. In this study, we investigated the effect of EPO on ventricular remodeling and blood vessel growth in diabetic rats.

Methods
Male SD rats were randomly divided into 3 groups: control rats, streptozotocin (STZ)-induced diabetic rats, and diabetic rats treated with 1000 U/kg EPO by subcutaneous injection once per week. Twelve weeks later, echocardiography was conducted, and blood samples were collected for counting of peripheral blood endothelial progenitor cells (EPCs). Myocardial tissues were collected, quantitative real-time PCR (RT-PCR) was used to detect the mRNA expression of VEGF and EPO-receptor (EPOR), and Western blotting was used to detect the protein expression of VEGF and EPOR. VEGF, EPOR, transforming growth factor beta (TGF-β), and CD31 levels in the myocardium were determined by immunohistochemistry. To detect cardiac hypertrophy, immunohistochemistry of collagen type I, collagen type III, and Picrosirius Red staining were performed, and cardiomyocyte cross-sectional area was measured.

Results
After 12 weeks STZ injection, blood glucose increased significantly and remained consistently elevated. EPO treatment significantly improved cardiac contractility and reduced diastolic dysfunction. Rats receiving the EPO injection showed a significant increase in circulating EPCs (27.85 ± 3.43%, P < 0.01) compared with diabetic untreated animals. EPO injection significantly increased capillary density as well as EPOR and VEGF expression in left ventricular myocardial tissue from diabetic rats. Moreover, EPO inhibited interstitial collagen deposition and reduced TGF-β expression.

Conclusions
Treatment with EPO protects cardiac tissue in diabetic animals by increasing VEGF and EPOR expression levels, leading to improved revascularization and the inhibition of cardiac fibrosis.
The global pipeline of new medicines for the control and elimination of malaria
Authors: Anthony Melinda P , Burrows Jeremy N , Duparc Stephan , JMoehrle Joerg , Wells Timothy NC 
Published: September 2012

AbstractOver the past decade, there has been a transformation in the portfolio of medicines to combat malaria. New fixed-dose artemisinin combination therapy is available, with four different types having received approval from Stringent Regulatory Authorities or the World Health Organization (WHO). However, there is still scope for improvement. The Malaria Eradication Research agenda identified several gaps in the current portfolio. Simpler regimens, such as a single-dose cure are needed, compared with the current three-day treatment. In addition, new medicines that prevent transmission and also relapse are needed, but with better safety profiles than current medicines. There is also a big opportunity for new medicines to prevent reinfection and to provide chemoprotection. This study reviews the global portfolio of new medicines in development against malaria, as of the summer of 2012. Cell-based phenotypic screening, and ‘fast followers’ of clinically validated classes, mean that there are now many new classes of molecules starting in clinical development, especially for the blood stages of malaria. There remain significant gaps for medicines blocking transmission, preventing relapse, and long-duration molecules for chemoprotection. The nascent pipeline of new medicines is significantly stronger than five years ago. However, there are still risks ahead in clinical development and sustainable funding of clinical studies is vital if this early promise is going to be delivered.