bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of the Influence of Test Characteristics on the Clinical and Cost Impacts of Methicillin-ResistantStaphylococcus aureusScreening Programs in US Hospitals
Authors: Olchanski Natalia , Mathews Charles , Fusfeld Lauren , Jarvis William 
Published: February 2011

Objective.To compare the impacts of different methicillin-resistantStaphylococcus aureus(MRSA) screening test options (eg, polymerase chain reaction [PCR], rapid culture) and program characteristics on the clinical outcomes and budget of a typical US hospital.Methods.We developed an Excel-based decision-analytic model, using published literature to calculate and compare hospital costs and MRSA infection rates for PCR- or culture-based MRSA screening and then used multivariate sensitivity analysis to evaluate key variables. Same-day PCR testing for a representative 370-bed teaching hospital in the United States was assessed in different populations (high-risk patients, intensive care unit [ICU] patients, or all patients) and compared with other test options.Results.Different screening program populations (all patients, high-risk patients, ICU patients, or patients with previous MRSA colonization or infection only) represented a potential savings of $12,158-$76,624 per month over no program ($188,618). Analysis of multiple test options in high-risk population screening indicated that same-day PCR testing of high-risk patients resulted in fewer infections over 1,720 patient-days (2.9, compared with 3.5 for culture on selective media and 3.8 for culture on nonselective media) and the lowest total cost ($112,012). The costs of other testing approaches ranged from $113,742 to $123,065. Sensitivity analysis revealed that variations in transmission rate, conversion to infection, prevalence increases, and hospital size are important to determine program impact. Among test characteristics, turnaround time is highly influential.Conclusion.All screening options showed reductions in infection rates and cost impact improvement over no screening program. Among the options, same-day PCR testing for high-risk patients slightly edges out the others in terms of fewest infections and greatest potential cost savings.
MPID-T2: a database for sequence–structure–function analyses of pMHC and TR/pMHC structures
Authors: Khan Javed Mohammed , Cheruku Harish Reddy , Tong Joo Chuan , Ranganathan Shoba 
Published: February 2011

Abstract
Summary: Sequence–structure–function information is critical in understanding the mechanism of pMHC and TR/pMHC binding and recognition. A database for sequence–structure–function information on pMHC and TR/pMHC interactions, MHC-Peptide Interaction Database-TR version 2 (MPID-T2), is now available augmented with the latest PDB and IMGT/3Dstructure-DB data, advanced features and new parameters for the analysis of pMHC and TR/pMHC structures.
Availability: http://biolinfo.org/mpid-t2.
Contact: shoba.ranganathan@mq.edu.au
Supplementary Information: Supplementary data are available at Bioinformatics online.
The KEEP ON GOING Protein of Arabidopsis Recruits the ENHANCED DISEASE RESISTANCE1 Protein to Trans-Golgi Network/Early Endosome Vesicles
Authors: Gu Yangnan , Innes Roger W. 
Published: February 2011

AbstractLoss-of-function mutations in the Arabidopsis (Arabidopsis thaliana) ENHANCED DISEASE RESISTANCE1 (EDR1) gene confer enhanced resistance to powdery mildew infection, enhanced senescence, and enhanced programmed cell death under both abiotic and biotic stress conditions. All edr1-mediated phenotypes can be suppressed by a specific missense mutation (keg-4) in the KEEP ON GOING (KEG) gene, which encodes a multidomain protein that includes a RING E3 ligase domain, a kinase domain, ankyrin repeats, and HERC2-like (for HECT and RCC1-like) repeats. The molecular and cellular mechanisms underlying this suppression are poorly understood. Using confocal laser scanning microscopy and fluorescent protein fusions, we determined that KEG localizes to trans-Golgi network/early endosome (TGN/EE) vesicles. Both the keg-4 mutation, which is located in the carboxyl-terminal HERC2-like repeats, and deletion of the entire HERC2-like repeats reduced endosomal localization of KEG and increased localization to the endoplasmic reticulum and cytosol, indicating that the HERC2-like repeats facilitate the TGN/EE targeting of KEG. EDR1 colocalized with KEG to the TGN/EE when coexpressed but localized primarily to the endoplasmic reticulum when expressed alone. Yeast two-hybrid and coimmunoprecipitation analyses revealed that EDR1 and KEG physically interact. Deletion of the HERC2-like repeats abolished the interaction between KEG and EDR1 as well as the KEG-induced TGN/EE localization of EDR1, indicating that the recruitment of EDR1 to the TGN/EE is based on a direct interaction between EDR1 and KEG mediated by the HERC2-like repeats. Collectively, these data suggest that EDR1 and KEG function together to regulate endocytic trafficking and/or the formation of signaling complexes on TGN/EE vesicles during stress responses.
The J-Domain Protein J3 Mediates the Integration of Flowering Signals in Arabidopsis
Authors: Shen Lisha , Kang Yin Ga Germain , Liu Lu , Yu Hao 
Published: February 2011

Abstract
The timing of the switch from vegetative to reproductive development in Arabidopsis thaliana is controlled by an intricate network of flowering pathways, which converge on the transcriptional regulation of two floral pathway integrators, FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1). SHORT VEGETATIVE PHASE (SVP) acts as a key flowering regulator that represses the expression of FT and SOC1. Here, we report the identification of another potent flowering promoter, Arabidopsis DNAJ HOMOLOG 3 (J3), which mediates the integration of flowering signals through its interaction with SVP. J3 encodes a type I J-domain protein and is ubiquitously expressed in various plant tissues. J3 expression is regulated by multiple flowering pathways. Loss of function of J3 results in a significant late-flowering phenotype, which is partly due to decreased expression of SOC1 and FT. We further show that J3 interacts directly with SVP in the nucleus and prevents in vivo SVP binding to SOC1 and FT regulatory sequences. Our results suggest a flowering mechanism by which J3 integrates flowering signals from several genetic pathways and acts as a transcriptional regulator to upregulate SOC1 and FT through directly attenuating SVP binding to their regulatory sequences during the floral transition.
Alloantigen specific deletion of primary human T cells by Fas ligand (CD95L)‐transduced monocyte‐derived killer‐dendritic cells
Authors: Schütz Christian , Hoves Sabine , Halbritter Dagmar , Zhang Huang‐Ge , Mountz John D. , Fleck Martin 
Published: February 2011

SummaryNumerous studies have been performed in vitro and in various animal models to modulate the interaction of dendritic cells (DC) and T cells by Fas (CD95/Apo‐1) signalling to delete activated T cells via induction of activation‐induced cell death (AICD). Previously, we could demonstrate that Fas ligand (FasL/CD95L)‐expressing ‘killer‐antigen‐presenting cells’ can be generated from human monocyte‐derived mature DC (mDC) using adenoviral gene transfer. To evaluate whether these FasL‐expressing mDC (mDC‐FasL) could eliminate alloreactive primary human T cells in vitro, co‐culture experiments were performed. Proliferation of human T cells was markedly reduced in primary co‐cultures with allogeneic mDC‐FasL, whereas a strong proliferative T‐cell response could be observed in co‐cultures with enhanced green fluorescent protein‐transduced mDC. Inhibition of T‐cell proliferation was related to the transduction efficiency, and the numbers of mDC‐FasL present in co‐cultures. In addition, proliferation of pre‐activated alloreactive CD4+ and CD8+ T cells could be almost completely inhibited in secondary co‐cultures using mDC‐FasL as stimulatory cells, which was the result of induction of apoptosis in the majority of preactivated T cells. The specific deletion of alloreactive T cells by mDC‐FasL was confirmed by an unaffected proliferative response of surviving T cells towards allogeneic ‘third‐party’ peripheral blood mononuclear cells in a third stimulation, or upon unspecific stimulation with anti‐CD3/CD28 beads. The results of this study demonstrate that allospecifically activated T cells are efficiently eliminated by mDC‐FasL, supporting further investigations to apply FasL‐expressing ‘killer‐DC’ as a novel strategy for the treatment of allograft rejection.
Review: The neurobiology of varicella zoster virus infection
Authors: Gilden D. , Mahalingam R. , Nagel M. A. , Pugazhenthi S. , Cohrs R. J. 
Published: February 2011

D. Gilden, R. Mahalingam, M. A. Nagel, S. Pugazhenthi and R. J. Cohrs (2011) Neuropathology and Applied Neurobiology37, 441–463 The neurobiology of varicella zoster virus infection Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV‐specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to one to three dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV‐specific immunity, the role of apoptosis in VZV‐induced cell death and the development of an animal model provided by simian varicella virus infection of monkeys.
Assessing the role of root plasma membrane and tonoplast Na+/H+ exchangers in salinity tolerance in wheat: in planta quantification methods
Authors: CUIN TRACEY A. , BOSE JAYAKUMAR , STEFANO GIOVANNI , JHA DEEPA , TESTER MARK , MANCUSO STEFANO , SHABALA SERGEY 
Published: February 2011

ABSTRACTThis work investigates the role of cytosolic Na+ exclusion in roots as a means of salinity tolerance in wheat, and offers in planta methods for the functional assessment of major transporters contributing to this trait. An electrophysiological protocol was developed to quantify the activity of plasma membrane Na+ efflux systems in roots, using the microelectrode ion flux estimation (MIFE) technique. We show that active efflux of Na+ from wheat root epidermal cells is mediated by a SOS1‐like homolog, energized by the plasma membrane H+‐ATPase. SOS1‐like efflux activity was highest in Kharchia 65, a salt‐tolerant bread wheat cultivar. Kharchia 65 also had an enhanced ability to sequester large quantities of Na+ into the vacuoles of root cells, as revealed by confocal microscopy using Sodium Green. These findings were consistent with the highest level of expression of both SOS1 and NHX1 transcripts in plant roots in this variety. In the sensitive wheat varieties, a greater proportion of Na+ was located in the root cell cytosol. Overall, our findings suggest a critical role of cytosolic Na+ exclusion for salinity tolerance in wheat and offer convenient protocols to quantify the contribution of the major transporters conferring this trait, to screen plants for salinity tolerance.
Possible association of Henoch–Schönlein purpura in adults with odontogenic focal infection
Authors: Igawa Ken , Satoh Takahiro , Yokozeki Hiroo 
Published: February 2011

AbstractBackground  Odontogenic focal infection (OFI) is considered to be an important precipitating factor in some cases of palmoplantar pustulosis and psoriasis. In Henoch–Schönlein purpura (HSP), it is clear that acute bacterial infection is one of the causes. However, it remains unclear how OFI participates in the pathogenesis of HSP.Methods  To clarify how OFI is related to the disease activity of HSP in terms of skin lesions and organ involvement, we conducted a retrospective study of 28 cases of adult‐type HSP.Results  Panoramic x‐ray screening detected OFI in 14 of the 28 patients. Patients with OFI had higher incidences of renal and gastrointestinal complications than those without OFI. Seven patients had severe OFI and underwent tooth extraction, resulting in a marked improvement of their skin lesions. Five of those seven patients exhibited transient flare‐up after the tooth extraction.Conclusions  Latent OFI is an important infectious focus that is involved in the pathogenesis of HSP and influences its disease activity.
Photodamaging effects of porphyrins and chitosan on primary human keratinocytes and carcinoma cell cultures
Authors: Susan Mirela , Baldea Ioana , Senila Simona , Macovei Victorina , Dreve Simina , Ion Rodica Mariana , Cosgarea Rodica 
Published: February 2011

AbstractBackground  Photodynamic therapy (PDT) is a non‐surgical method for treating non‐melanoma skin cancer and precancerous lesions which involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in the destruction of the latter. The present study evaluates the effect of PDT on primary normal and basal cell carcinoma cultures in vitro.Methods  Primary human keratinocytes and carcinoma cell cultures were exposed to various concentrations of 5,10,15,20‐tetra‐(para‐methoxyphenyl) porphyrin (TMP) and its zinc compound (Zn‐TMP) for 24 hours, with or without chitosan, and then irradiated using a PDT lamp (630 nm, 6 J/cm2). The effects of PDT were assessed using a 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium inner salt (MTS) assay and an immunocytochemical method with Annexin V‐FITC for detecting apoptosis.Results  Both tested substances, TMP and Zn‐TMP, had a phototoxic effect on primary human carcinoma cell cultures in concentrations of 1–100 μg/ml, which positively correlated with the concentration of the photosensitizer. There was no phototoxic effect on primary keratinocytes, probably because of the preferential accumulation of photosensitizing substances in tumoral cells. Administration of chitosan in association with photosensitizing substances increased cell viability compared with photosensitizers alone, exerting a cytoprotective effect.Conclusions  The study demonstrates that the photodynamic activity of TMP and its metalloporphyrin derivative is limited to primary human carcinoma cells and suggests that these porphyrins could be efficiently used in PDT in vivo.
Cutaneous sarcoidosis developing after treatment with pegylated interferon and ribavirin: a new case and review of the literature
Authors: López Verónica , Molina Inmaculada , Monteagudo Carlos , Jordá Esperanza 
Published: February 2011

AbstractSarcoidosis is a multisystem granulomatous disease that affects multiple organs in adults between 20 and 50 years old. Interferon alpha (IFN‐α) is an immunomodulator that has been used in a wide range of diseases, including hepatitis C virus infection, multiple sclerosis, and other types of neoplasias, including leukemia, lymphoma, Kaposi’s sarcoma, and melanoma. Standard IFN‐α‐induced sarcoidosis has been reported, but there are few reports of cutaneous sarcoidosis with pegylated IFN‐α therapy. We present a new case of cutaneous sarcoidosis after treatment with pegylated IFN, and a review of the literature.
Research of UL54‐specific siRNA on herpes simplex virus type II replication
Authors: Qing Guo , Weili Weng , Fanqin Zeng , Rongchang Zheng , Yijin Luo , Jianqun Du 
Published: February 2011

AbstractTo determine how UL54‐specific siRNA affects virus replication and protection of host cells, we examined virus titer and the activity of the cells at 12 hours, 24 hours, 36 hours, 48 hours, 60 hours and 72 hours after process of RNAi, including: four UL54‐specific siRNAs and the positive/negative control siRNAs synthesized in vitro by chemical processes. The Vero cells were transfected with siRNAs using lipofectamine 2000 followed by infection by HSV‐II. Our studies reveal that the groups with UL54‐specific siRNA decreased significantly in virus titer at 12–24 hours, and only slightly decreased after that; groups with UL54‐specific siRNA had higher OD values shown by MTT colorimetric assay than blank cells and survived better; R2 and R4 groups had lower virus titer and better survival than other groups. UL54‐specific siRNA can inhibit HSV‐II replication, while protecting host cells. There are effective and ineffective siRNA, which were synthesized in accordance with the same principles.
Nanoparticles: small and mighty
Authors: Wiesenthal Alison , Hunter Lindsey , Wang Shuguang , Wickliffe Jeffrey , Wilkerson Michael 
Published: February 2011

AbstractThe properties of engineered nanomaterials and nanoparticles such as zinc oxide and titanium dioxide may differ substantially from naturally occurring materials and particles. Nanoparticles have unique physical properties making them ideal for use in various skin care products currently on the market. Nano‐preparations are currently under investigation as novel treatments of acne vulgaris, recurrent condyloma accuminata, atopic dermatitis, hyperpigmented skin lesions, and other non‐dermatologic diseases. Because of their increased surface area, nanoparticles have increased reactivity and a small size allowing for enhanced mobility through the human body and environment. As their use becomes more prevalent, nanoparticles are being scrutinized for their safety and long‐term effects. This review discusses the benefits of nanoparticles in dermatological therapies and skin care products as well as potential disadvantages and possible mechanisms of toxicity.
Turning signals into meaning –‘Shared decision making’ meets communication theory
Authors: Kasper Jürgen , Légaré France , Scheibler Fülöp , Geiger Friedemann 
Published: February 2011

AbstractShared decision making (SDM) is being increasingly challenged for promoting an innovative role model while adhering to an archaic approach to patient‐clinician communication, both in clinical practice and the research field. Too often, SDM has been studied at the individual level, which ignores the interpersonal system between patients and physicians. We aimed to encourage debate by reflecting on the essentials of SDM in terms of epistemology. We operationalized the SDM core concept of information exchange in terms of social systems theory. An epistemological analysis of the term information refers to its inherent process character. Exchange of information thereby becomes synonymous with social sense construction, indicating that, rather than just being a vehicle, the act of communication itself is the information. We plead for the adoption of existing dyadic analytical methods such as those offered by the interpersonal paradigm. Implications of an updated concept of information for the use of SDM‐evaluation methods, for SDM‐goal setting, and for clinical practice of SDM are described.
A health economic analysis of clinical islet transplantation
Authors: Beckwith Jessica , Nyman John A. , Flanagan Brian , Schrover Rudolf , Schuurman Henk‐Jan 
Published: February 2011

Beckwith J, Nyman JA, Flanagan B, Schrover R, Schuurman H‐J. A health economic analysis of clinical islet transplantation.  Clin Transplant 2012: 26: 23–33.  © 2011 John Wiley & Sons A/S.Abstract: Islet cell transplantation is in clinical development for type 1 diabetes. There are no data on the cost in relationship to its benefits. We performed a cost‐effectiveness analysis and made a comparison with standard insulin therapy, using Markov modeling and Monte Carlo simulations. The patient population was adults aged 20 yr suffering from hypoglycemia unawareness. Data were estimates from literature and clinical trials: costs were based on the situation in the United States. For insulin therapy, cumulative cost per patient during a 20‐yr follow‐up was $663 000, and cumulative effectiveness was 9.3 quality‐adjusted life years (QALY), the average cost‐effectiveness ratio being $71 000 per QALY. Islet transplantation had a cumulative cost of $519 000, a cumulative effectiveness of 10.9 QALY, and an average cost‐effectiveness ratio of $47 800. During the first 10 yr, costs for transplantation were higher, but cumulative effectiveness was higher from the start onwards. In sensitivity analyses, the need for one instead of two transplants during the first year did not affect the conclusions, and islet transplantation remained cost‐saving up to an initial cost of the procedure of $240 000. This exploratory evaluation shows that islet cell transplantation is more effective than standard insulin treatment, and becomes cost‐saving at about 9–10 yr after transplantation.
New transgenic pigs for xenotransplantation, part 2: Strategies to overcome cellular rejection
Authors: Keßler B. , Kurome M. , Klymiuk N. , Wünsch A. , Seissler J. , Wolf E. 
Published: February 2011

The successful generation of α‐1,3 galactosyltransferase knockout (αGal‐KO) pigs and pigs expressing human complement regulators was a crucial step forward in xenotransplantation research. These genetic modifications helped to control hyperacute rejection, but vascular and cellular mechanisms still represent a major hurdle for pig‐to‐primate xenotransplantation.Coagulation incompatibilities between human blood and porcine endothelium lead to thrombotic microangiopathy, which could be observed as a key rejection mechanism in pig‐to‐primate transplantation using αGal‐KO pigs as organ donors. Circulating human thrombin is bound by porcine thrombomodulin, but the resulting heterodimer fails to activate protein C, which inhibits the coagulation cascade. We established a vector for endothelial‐specific expression of human thrombomodulin (hTM) in αGal‐KOxCD46 pigs. The hTM construct was combined with a floxed blasticidin resistance cassette and transfected mixed cell populations were used as donors for somatic cell nuclear transfer (SCNT). Two hundred and ninety‐eight reconstructed embryos were transferred to four recipients, resulting in one pregnancy, which lead to the birth of three living piglets. All of them showed strong endothelial hTM expression.In contrast to vascularised organs, pancreatic islets are not subject to hyperacute rejection, but to cellular rejection, mainly based on T‐cell stimulation as islets of mature pigs express αGal‐epitopes only at a very low level and are vascularized by recipient capillaries after transplantation. Human CTLA4‐Ig is a potent inhibitor of T‐cell activation, excelled by its derivate LEA29Y which has higher binding affinity to the costimulatory B7 receptors. We have established the coding sequence of LEA29Y under the transcriptional control of a regulatory fragment of the porcine insulin gene. The construct also contained a floxed neomycin resistance cassette. Porcine fetal fibroblasts were transfected, followed by selection under geneticin for 7 days. Stably transfected cell clones were pooled and used as donor cells for SCNT. Transfer of 216 reconstructed embryos to three recipients resulted in two pregnancies with nine born piglets, including two stillbirths. Seven piglets were shown to be transgenic. Immunohistochemistry of the pancreata of two transgenic founders showed high expression levels of LEA29Y at an age of 3 months.