bluuebunny/crossref_metadata_2025_split huggingface dataset:
GB Virus C Coinfections in West African Ebola Patients
Authors: Lauck Michael , Bailey Adam L. , Andersen Kristian G. , Goldberg Tony L. , Sabeti Pardis C. , O'Connor David H. 
Published: December 2014

ABSTRACT

In 49 patients with known Ebola virus disease outcomes during the ongoing outbreak in Sierra Leone, 13 were coinfected with the immunomodulatory pegivirus GB virus C (GBV-C). Fifty-three percent of these GBV-C
+
patients survived; in contrast, only 22% of GBV-C
−
patients survived. Both survival and GBV-C status were associated with age, with older patients having lower survival rates and intermediate-age patients (21 to 45 years) having the highest rate of GBV-C infection. Understanding the separate and combined effects of GBV-C and age on Ebola virus survival may lead to new treatment and prevention strategies, perhaps through age-related pathways of immune activation.
Mutations across Murine Hepatitis Virus nsp4 Alter Virus Fitness and Membrane Modifications
Authors: Beachboard Dia C. , Anderson-Daniels Jordan M. , Denison Mark R. 
Published: December 2014

ABSTRACT
A common feature of infection by positive-sense RNA virus is the modification of host cell cytoplasmic membranes that serve as sites of viral RNA synthesis. Coronaviruses induce double-membrane vesicles (DMVs), but the role of DMVs in replication and virus fitness remains unclear. Coronaviruses encode 16 nonstructural proteins (nsps), three of which, nsp3, nsp4, and nsp6, are necessary and sufficient for DMV formation. It has been shown previously that mutations in murine hepatitis virus (MHV) nsp4 loop 1 that alter nsp4 glycosylation are associated with disrupted DMV formation and result in changes in virus replication and RNA synthesis. However, it is not known whether DMV morphology or another function of nsp4 glycosylation is responsible for effects on virus replication. In this study, we tested whether mutations across nsp4, both alone and in combination with mutations that abolish nsp4 glycosylation, affected DMV formation, replication, and fitness. Residues in nsp4 distinct from glycosylation sites, particularly in the endoplasmic reticulum (ER) luminal loop 1, independently disrupted both the number and morphology of DMVs and exacerbated DMV changes associated with loss of glycosylation. Mutations that altered DMV morphology but not glycosylation did not affect virus fitness while viruses lacking nsp4 glycosylation exhibited a loss in fitness. The results support the hypothesis that DMV morphology and numbers are not key determinants of virus fitness. The results also suggest that nsp4 glycosylation serves roles in replication in addition to the organization and stability of MHV-induced double-membrane vesicles.

IMPORTANCE
All positive-sense RNA viruses modify host cytoplasmic membranes for viral replication complex formation. Thus, defining the mechanisms of virus-induced membrane modifications is essential for both understanding virus replication and development of novel approaches to virus inhibition. Coronavirus-induced membrane changes include double-membrane vesicles (DMVs) and convoluted membranes. Three viral nonstructural proteins (nsps), nsp3, nsp4, and nsp6, are known to be required for DMV formation. It is unknown how these proteins induce membrane modification or which regions of the proteins are involved in DMV formation and stability. In this study, we show that mutations across nsp4 delay virus replication and disrupt DMV formation and that loss of nsp4 glycosylation is associated with a substantial fitness cost. These results support a critical role for nsp4 in DMV formation and virus fitness.
Induction of an Embryonic Mouse Innate Immune Response following Inoculation In Utero with Minute Virus of Mice
Authors: Rostovsky Irina , Davis Claytus 
Published: December 2014

ABSTRACTWe used an embryonic-infection model system to show that MVMp, the prototypic minute virus of mice (MVM) serotype and a member of the genusProtoparvovirus, triggers a comprehensive innate immune response in the developing mouse embryo. Direct inoculation of the midtrimester embryoin uterowith MVMp results in a widespread, productive infection. During a 96-h infection course, embryonic beta interferon (IFN-β) and IFN-γ transcription were induced 90- and 60-fold, respectively. IFN-β levels correlated with the embryo viral burden, while IFN-γ levels first increased and then decreased. Production of proinflammatory cytokines, interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α), also increased, but by smaller amounts, approximately 7-fold each. We observed increased levels of downstream antiviral effector molecules, PKR and phosphorylated STAT2. Finally, we showed that there is an immune cell response to the virus infection. Infected tissues in the embryo exhibited an increased density of mature leukocytes compared to the same tissues in uninfected embryos. The responses we observed were almost completely restricted to the infected embryos. Uninfected littermates routinely exhibited small increases in innate immune components that rarely reached statistical significance compared to negative controls. Similarly, the placentae of infected embryos did not show any significant increase in transcription of innate immune cytokines. Since the placenta has both embryonic and maternal components, we suggest there is minimal involvement of the dam in the response to infection.IMPORTANCEInteraction between the small single-stranded vertebrate DNA viruses, the protoparvoviruses, and the host innate immune system has been unclear. The issue is important practically given the potential use of these viruses as oncotherapeutic agents. The data reported here stand in contrast to studies of innate immune response during protoparvovirus infection of adult hosts, which invariably reported no or minimal and sporadic induction of an interferon response during infection. We conclude that under conditions of robust and productive MVM infection, a normal murine host is able to mount a significant and broad innate immune response.
Deletion of the ORF9p Acidic Cluster Impairs the Nuclear Egress of Varicella-Zoster Virus Capsids
Authors: Riva Laura , Thiry Marc , Lebrun Marielle , L'homme Laurent , Piette Jacques , Sadzot-Delvaux Catherine 
Published: December 2014

ABSTRACT

The protein encoded by ORF9 is essential for varicella-zoster virus (VZV) replication. Previous studies documented its presence in the
trans
-Golgi network and its involvement in secondary envelopment. In this work, we deleted the ORF9p acidic cluster, destroying its interaction with ORF47p, and this resulted in a nuclear accumulation of both proteins. This phenotype results in an accumulation of primary enveloped capsids in the perinuclear space, reflecting a capsid de-envelopment defect.
Organizational Predictors of Colonoscopy Follow-up for Positive Fecal Occult Blood Test Results: An Observational Study
Authors: Partin Melissa R. , Burgess Diana J. , Burgess James F. , Gravely Amy , Haggstrom David , Lillie Sarah E. , Nugent Sean , Powell Adam A. , Shaukat Aasma , Walter Louise C. , Nelson David B. 
Published: December 2014

Abstract
Background: This study assessed the contribution of organizational structures and processes identified from facility surveys to follow-up for positive fecal occult blood tests [FOBT-positive (FOBT+)].
Methods: We identified 74,104 patients with FOBT+ results from 98 Veterans Health Administration (VHA) facilities between August 16, 2009 and March 20, 2011, and followed them until September 30, 2011, for completion of colonoscopy. We identified patient characteristics from VHA administrative records, and organizational factors from facility surveys completed by primary care and gastroenterology chiefs. We estimated predictors of colonoscopy completion within 60 days and six months using hierarchical logistic regression models.
Results: Thirty percent of patients with FOBT+ results received colonoscopy within 60 days and 49% within six months. Having gastroenterology or laboratory staff notify gastroenterology providers directly about FOBT+ cases was a significant predictor of 60-day [odds ratio (OR), 1.85; P = 0.01] and six-month follow-up (OR, 1.25; P = 0.008). Additional predictors of 60-day follow-up included adequacy of colonoscopy appointment availability (OR, 1.43; P = 0.01) and frequent individual feedback to primary care providers about FOBT+ referral timeliness (OR, 1.79; P = 0.04). Additional predictors of six-month follow-up included using guideline-concordant surveillance intervals for low-risk adenomas (OR, 1.57; P = 0.01) and using group appointments and combined verbal–written methods for colonoscopy preparation instruction (OR, 1.48; P = 0.0001).
Conclusion: Directly notifying gastroenterology providers about FOBT+ results, using guideline-concordant adenoma surveillance intervals, and using colonoscopy preparations instruction methods that provide both verbal and written information may increase overall follow-up rates. Enhancing follow-up within 60 days may require increased colonoscopy capacity and feedback to primary care providers.
Impact: These findings may inform organizational-level interventions to improve FOBT+ follow-up. Cancer Epidemiol Biomarkers Prev; 24(2); 422–34. ©2014 AACR.
Differential Platelet Levels Affect Response to Taxane-Based Therapy in Ovarian Cancer
Authors: Bottsford-Miller Justin , Choi Hyun-Jin , Dalton Heather J. , Stone Rebecca L. , Cho Min Soon , Haemmerle Monika , Nick Alpa M. , Pradeep Sunila , Zand Behrouz , Previs Rebecca A. , Pecot Chad V. , Crane Erin King , Hu Wei , Lutgendorf Susan K. , Afshar-Kharghan Vahid , Sood Anil K. 
Published: December 2014

Abstract
Purpose: We hypothesized that platelet levels during therapy could serve as a biomarker for response to therapy and that manipulation of platelet levels could impact responsiveness to chemotherapy.
Experimental Design: The medical records of patients with recurrent or progressive ovarian cancer were retrospectively queried for changes in platelet and CA-125 levels during primary therapy. In vitro coculture experiments and in vivo orthotopic models of human ovarian cancer in mice were used to test the effect of modulating platelet levels on tumor growth and responsiveness to docetaxel.
Results: Thrombocytosis at the diagnosis of ovarian cancer was correlated with decreased interval to progression (P = 0.05) and median overall survival (P = 0.007). Mean platelet levels corrected during primary therapy and rose at recurrence. Contrary to treatment-responsive patients, in a cohort of patients refractory to primary therapy, platelet levels did not normalize during therapy. In A2780, HeyA8, and SKOV3-ip1 ovarian cancer cell lines, platelet coculture protected against apoptosis (P &lt; 0.05). In orthotopic models of human ovarian cancer, platelet depletion resulted in 70% reduced mean tumor weight (P &lt; 0.05). Compared with mice treated with docetaxel, mice treated with both docetaxel and platelet-depleting antibody had a 62% decrease in mean tumor weight (P = 0.04). Platelet transfusion increased mean aggregate tumor weight 2.4-fold (P &lt; 0.05), blocked the effect of docetaxel on tumor growth (P = 0.55) and decreased tumor cell apoptosis. Pretransfusion aspirinization of the platelets blocked the growth-promoting effects of transfusion.
Conclusions: Platelet-driven effects of chemotherapy response may explain clinical observations. Clin Cancer Res; 21(3); 602–10. ©2014 AACR.
Tolerability and outcome of once weekly liposomal amphotericin B for the prevention of invasive fungal infections in hematopoietic stem cell transplant patients with graft-versus-host disease
Authors: Luu Tran Huong , Mahmoudjafari Zahra , Rockey Michelle , Henry Dave , Grauer Dennis , Aljitawi Omar , Abhyankar Sunil , Ganguly Siddhartha , Lin Tara , McGuirk Joseph 
Published: December 2014

Background Invasive fungal infections remain problematic in immunosuppressed allogeneic stem cell transplant recipients and the use of corticosteroids for the treatment of graft-versus-host-disease can increase the risk threefold. Although antifungal prophylaxis has been shown to decrease the incidence of infection, the optimal antifungal prophylactic regimen in this patient population has yet to be identified. Since early diagnosis of fungal infections might not be possible and the treatment of established fungal infections might be difficult and associated with high infection-related mortality, prevention has become an important strategy in reducing overall morbidity and mortality. While triazoles are the preferred agents, some patients are unable to tolerate them and an alternative drug is warranted. Objectives To assess the tolerability of once weekly liposomal amphotericin B as a prophylactic strategy in patients undergoing stem cell transplantation by evaluating any adverse events leading to its discontinuation. In terms of efficacy, to also compare the outcome and incidence of invasive fungal infections in patients who received amphotericin B, triazoles, and echinocandins. Results A total of 101 allogeneic transplant recipients receiving corticosteroids for the treatment of graft-versus-host-disease and antifungal prophylaxis were evaluated from August 2009 to September 2012. Liposomal amphotericin B 3 mg/kg intravenous once weekly was found to be well tolerated. The incidence of invasive fungal infections was 19%, 17%, and 7% in the liposomal amphotericin B, echinocandin, and triazole groups, respectively. Two deaths occurred in the liposomal amphotericin B group and one death occurred in the echinocandin group. None of the deaths were fungal infection related. Conclusion Antifungal prophylaxis with liposomal amphotericin B was well tolerated, but the incidence of invasive fungal infections in patients receiving liposomal amphotericin B was higher than other antifungal agents in this study. The optimal dose and schedule of liposomal amphotericin B for antifungal prophylaxis in this patient population are still not known and considering its broad spectrum activity, prospective trials in comparison to triazoles are warranted.
Corrective Realignment Arthrodesis of the First Tarsometatarsal Joint Without Wedge Resection
Authors: McAlister Jeffrey E. , Peterson Kyle S. , Hyer Christopher F. 
Published: December 2014

Moderate to severe hallux valgus (HV) has traditionally been treated with a corrective osteotomy or a tarsometatarsal arthrodesis. Tarsometatarsal arthrodesis can be performed as a planar wedge resection or using a joint curettage technique. Little is known about whether adequate correction can be obtained with purely a joint curettage technique. The purpose of this study is to evaluate the corrective power of a first tarsometatarsal joint (TMTJ) arthrodesis using a nonplanar wedge curettage technique. A retrospective radiograph and chart review was performed on 99 consecutive patients (110 feet) who underwent a first TMTJ arthrodesis for primary HV correction utilizing a curettage technique. The radiographic measurements collected were the first intermetatarsal angle, HV angle, and tibial sesamoid position and were obtained at the following intervals: preoperative, immediate postoperative, and 6 months postoperative. In all, 91 patients (100 feet) qualified for statistical analysis. There was a significant decrease in all 3 measurements from the preoperative throughout the entire postoperative time period ( P < .001). The authors demonstrate the ability to achieve significant angular correction with a joint curettage method for a tarsometatarsal arthrodesis. Levels of Evidence: Therapeutic, Level IV: Case series
Combination of a geolocation database access with infrastructure sensing in TV bands
Authors: Dionísio Rogério , Ribeiro Jorge , Marques Paulo , Rodriguez Jonathan 
Published: December 2014

Abstract
This paper describes the implementation and the technical specifications of a geolocation database assisted by a spectrum-monitoring outdoor network. The geolocation database is populated according to Electronic Communications Committee (ECC) report 186 methodology. The application programming interface (API) between the sensor network and the geolocation database implements an effective and secure connection to successfully gather sensing data and sends it to the geolocation database for post-processing. On the other hand, the testbed allows authorized TV white space devices to gain access to the services of the geolocation database, according to a draft implementation of Internet Engineering Task Force (IETF) Protocol to Access White Space (PAWS) Two experimental methodologies are available with the testbed: one focused on coexistence studies with commercial wireless microphones, when the testbed is used for sensing only, and another for demonstration purposes, when the testbed is also used to emulate wireless microphone signals. Overall, this hybrid approach is a promising solution for the effective use of TV white spaces and for the coexistence with digital TV broadcast signals, or dynamic incumbent systems, such as unregistered wireless microphones.
No Association of Polymorphisms in the Serotonin Transporter Gene with Thermal Pain Sensation in Healthy Individuals
Authors: Schaldemose Ellen Lund , Horjales-Araujo Emilia , Demontis Ditte , Eørglum Anders D , Svensson Peter , Finnerup Nanna Brix 
Published: December 2014

Background: Recent studies have suggested an association between genotypes affecting the expression of the serotonin transporter and thermal pain perception and the thermal grill. The aim of this study was to investigate differences in thermal and mechanical pain perception and the thermal grill in two groups of healthy volunteers according to their genotype, associated with either high (n = 40) or low (n = 40) expression of the serotonin transporter and according to gender. Cold and warm detection and pain thresholds, pressure pain threshold and cold, warm and pain sensations to single or alternating stimuli with cold (20°C) and warm (40°C) temperatures (known as the thermal grill) were determined. In addition, intensity of ongoing pain and area and intensity of pinprick hyperalgesia in the secondary hyperalgesic area following topical application of capsaicin and vehicle control (ethanol) were determined. Results: No significant differences in detection and pain thresholds for cold and warm temperatures, presence of paradoxical heat sensation, pressure pain threshold and pain responses to suprathreshold thermal stimuli were observed. There was also no difference in capsaicin-evoked ongoing pain and secondary hyperalgesia between the two genotype groups (p >0.4), also when subdivided by gender (p >0.17). In addition, there were no significant differences in the perception of the thermal grill between the two genotypes (p >0.5), also when subdivided by gender. Conclusions: Genotypes associated with high or low expression of the serotonin transporter were not associated with thermal pain thresholds, pressure pain threshold, pain after capsaicin application or responses to the thermal grill. The present results do not support that the investigated genotypes play a major role in thermal pain perception among healthy individuals.
Jugular vein distensibility predicts fluid responsiveness in septic patients
Authors: Guarracino Fabio , Ferro Baldassarre , Forfori Francesco , Bertini Pietro , Magliacano Luana , Pinsky Michael R 
Published: December 2014

Abstract
Introduction
The purpose of the study was to verify the efficacy of using internal jugular vein (IJV) size and distensibility as a reliable index of fluid responsiveness in mechanically ventilated patients with sepsis.

Methods
Hemodynamic data of mechanically ventilated patients with sepsis were collected through a radial arterial indwelling catheter connected to continuous hemodynamic monitoring system (Most Care®, Vytech Health, Padova, Italy), including cardiac index (CI) (L/min/M2), heart rate (beats/min), mean arterial pressure (MAP) (mmHg), central venous pressure (CVP) (mmHg) and arterial pulse pressure variation (PPV), coupled with ultrasound evaluation of IJV distensibility (%), defined as a ratio of the difference between IJV maximal antero-posterior diameter during inspiration and minimum expiratory diameter to minimum expiratory diameter x100. Patients were retrospectively divided into two groups; fluid responders (R), if CI increase of more than or equal to 15% after a 7 ml/kg crystalloid infusion, and non-responders (NR) if CI increased more than 15%. We compared differences in measured variables between R and NR groups and calculated receiver-operator-characteristic (ROC) curves of optimal IJV distensibility and PPV sensitivity and specificity to predicting R. We also calculated a combined inferior vena cava distensibility-PPV ROC curve to predict R.

Results
We enrolled 50 patients, of these, 30 were R. Responders presented higher IJV distensibility and PPV before fluid challenge than NR (P <0.05). An IJV distensibility more than 18% prior to volume challenge had an 80% sensitivity and 85% specificity to predict R. Pairwise comparison between IJV distensibility and PPV ROC curves revealed similar ROC area under the curve results. Interestingly, combining IJV distensibility more than 9.7% and PPV more than 12% predicted fluid responsiveness with a sensitivity of 100% and specificity of 95%.

Conclusion
IJV distensibility is an accurate, easily acquired non-invasive parameter of fluid responsiveness in mechanically ventilated septic patients with performance similar to PPV. The combined use of IJV distensibility with left-sided indexes of fluid responsiveness improves their predictive value.
Decreasing the time to achieve therapeutic vancomycin concentrations in critically ill patients: developing and testing of a dosing nomogram
Authors: Baptista João Pedro , Roberts Jason A , Sousa Eduardo , Freitas Ricardo , Deveza Nuno , Pimentel Jorge 
Published: December 2014

Abstract
Introduction
Achievement of optimal vancomycin exposure is crucial to improve the management of patients with life-threatening infections caused by susceptible Gram-positive bacteria and is of particular concern in patients with augmented renal clearance (ARC). The aim of this study was to develop a dosing nomogram for the administration of vancomycin by continuous infusion for the first 24 hours of therapy based on the measured urinary creatinine clearance (8 h CLCR).

Methods
This single-center study included all critically ill patients treated with vancomycin over a 13-month period (group 1), in which we retrospectively assessed the correlation between vancomycin clearance and 8 h CLCR. This data was used to develop a formula for optimised drug dosing. The efficiency of this formula was prospectively evaluated in a second cohort of 25 consecutive critically ill patients (group 2). Vancomycin serum concentrations between 20 to 30 mg/L were considered adequate. ARC was defined as 8 h CLCR more than 130 ml/min/1.73 m2.

Results
The incidence of ARC was 36% (n = 29/79) and 40% (10/25) in group 1 (n = 79) and 2 (n = 25), respectively. The mean serum vancomycin concentration on day 1 was 21.5 (6.4) and 24.5 (5.2) mg/L, for both groups respectively. On the treatment day, vancomycin plasma clearance was 5.12 (1.9) L/h in group 1 and correlated significantly with the 8 h CLCR (r2 = 0.66; P <0.001). The achievement of adequate vancomycin serum concentrations in group 2 was 84% (n = 21/25) versus 51% (n = 40/79) – P <0.005.

Conclusions
This new vancomycin nomogram enabled the achievement of adequate serum concentrations in 84% of the patients on the first day of treatment.