bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal stability of medication adherence among adolescent solid organ transplant recipients
Authors: Loiselle Kristin A. , Gutierrez‐Colina Ana M. , Eaton Cyd K. , Simons Laura E. , Devine Katie A. , Mee Laura L. , Blount Ronald L. 
Published: April 2015

AbstractSolid organ transplantation requires ongoing adherence to immunosuppressants and other medications. Although adolescence is a risk factor for poor medication‐taking, little is known about the patterns of adherence within individuals over time. This study aimed to examine the stability of adherence over time using three different assessment techniques. Sixty‐six AYA transplant recipients and/or their caregiver completed interviews of adherence at baseline and at least one yr later. Serum immunosuppressant assay levels were collected via medical chart review. Non‐adherence percentages based on AYA report, caregiver report, and bioassay did not differ from Time 1 to Time 2. However, correlations for these measures across time were non‐significant. Further, the majority of AYAs shifted to a different adherence category from Time 1 to Time 2. Overall, these results demonstrate individual variability in non‐adherence over the course of adolescence and young adulthood and highlight the importance of frequent assessment across time for solid organ transplant recipients.
In‐orbit geometric calibration and validation of ZY‐3 three‐line cameras based on CCD‐detector look angles
Authors: Cao Jinshan , Yuan Xiuxiao , Gong Jianya 
Published: April 2015

AbstractA simple and feasible orientation method for the three‐line cameras of the ZiYuan‐3 (ZY‐3) satellite is introduced. The method calibrates the CCD‐detector look angles in the attitude determination reference (ADR) coordinate system rather than modifying the laboratory‐calibrated orientation parameters, which are not necessary for the geometric calibration. Additionally, the unknown parameters of the model are virtually uncorrelated. Experimental results show that the direct georeferencing accuracy of ZY‐3 nadir images have been improved from the kilometre level to better than 9 m in planimetry, and that of the forward‐and‐backward stereopair was also raised to better than 18 m in plan and 4 m in height. After a bundle adjustment using four ground control points, a higher accuracy of about 3·4 m in plan and 1·6 m in height was achieved.
Using dynamics of forced expiration to identify COPD where conventional criteria for the FEV1/FVC ratio do not match
Authors: Topalovic Marko , Exadaktylos Vasileios , Decramer Marc , Berckmans Daniel , Troosters Thierry , Janssens Wim 
Published: April 2015

AbstractBackground and objectiveThe definition of chronic obstructive pulmonary disease (COPD) based on a fixed forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio or on the lower limits of FEV1/FVC of a healthy reference population is the subject of continuous debate. We explored whether dynamics of forced expiratory flow decline on spirometry can identify subjects with and without COPD when the two key diagnostic criteria are discordant.MethodsFour hundred twenty‐three individuals with a history of ≥15 pack‐years smoking had pulmonary function measurements conducted. A second‐order input–output model was used to describe the dynamics of the forced expiration. The capability of the model parameters to predict presence of disease was explored with a support vector machine classifier. In the discordant individuals, newly classified subjects were validated by other pulmonary function tests.ResultsIn the non‐discordant subjects (n = 370), the second‐order model was able to confirm a diagnosis of COPD in 95% of subjects (n = 351). In the discordant individuals (n = 53), the classification by dynamic flow analysis found 28 patients to be healthy whereas 25 patients were still classified as COPD. Hyperinflation, increased airways resistance and reduced dynamic volumes were observed in the newly identified COPD group of discordant subjects. When using non‐spirometry‐based pulmonary function criteria as a standard for correct diagnoses in the individual discordant subjects, the model allocated 68% (n = 36) of the discordant to a correct diagnosis.ConclusionsExpiratory flow dynamics can detect airflow limitation and indicate the presence of COPD. In discordant subjects, our methodology allows a better identification of subjects with or without characteristics of COPD.
Cyst‐based measurements for assessing lymphangioleiomyomatosis in computed tomography
Authors: Lo P. , Brown M. S. , Kim H. , Kim H. , Argula R. , Strange C. , Goldin J. G. 
Published: April 2015

Purpose:To investigate the efficacy of a new family of measurements made on individual pulmonary cysts extracted from computed tomography (CT) for assessing the severity of lymphangioleiomyomatosis (LAM).Methods:CT images were analyzed using thresholding to identify a cystic region of interest from chest CT of LAM patients. Individual cysts were then extracted from the cystic region by the watershed algorithm, which separates individual cysts based on subtle edges within the cystic regions. A family of measurements were then computed, which quantify the amount, distribution, and boundary appearance of the cysts. Sequential floating feature selection was used to select a small subset of features for quantification of the severity of LAM. Adjusted R2 from multiple linear regression and R2 from linear regression against measurements from spirometry were used to compare the performance of our proposed measurements with currently used density based CT measurements in the literature, namely, the relative area measure and the D measure.Results:Volumetric CT data, performed at total lung capacity and residual volume, from a total of 49 subjects enrolled in the MILES trial were used in our study. Our proposed measures had adjusted R2 ranging from 0.42 to 0.59 when regressing against the spirometry measures, with p < 0.05. For previously used density based CT measurements in the literature, the best R2 was 0.46 (for only one instance), with the majority being lower than 0.3 or p > 0.05.Conclusions:The proposed family of CT‐based cyst measurements have better correlation with spirometric measures than previously used density based CT measurements. They show potential as a sensitive tool for quantitatively assessing the severity of LAM.
The performance of normal‐tissue complication probability models in the presence of confounding factors
Authors: Onjukka Eva , Baker Colin , Nahum Alan 
Published: April 2015

Purpose:This work explores different methods for accounting for patient‐specific factors in normal‐tissue complication probability (NTCP) modeling, and compares the performance of models using pseudoclinical datasets for “lung” and “rectum” complications.Methods:Datasets consisting of dose distributions and resulting normal‐tissue complications were simulated, letting varying levels of confounding factors (i.e., nondosimetric factors) influence the outcome. The simulated confounding factors were patient radiosensitivity and health status. Seven empirical NTCP models were fitted to each dataset; this is analogous to fitting alternative models to datasets from different populations, treated with the same technique. The performance of these models was compared using the area under the ROC curve (AUC) and the impact of confounding factors on the model performance was studied. The patient‐specific factors were then accounted for by (1) stratification and (2) two ways of modifying the traditional NTCP models to include these factors.Results:Confounding factors had a greater impact on model performance than the choice of model. All models performed similarly well on the rectum datasets (except the maximum dose model), while critical‐volume type models were slightly better than the mean dose‐, the Lyman–Kutcher–Burman‐, and the relative seriality models for lung. This difference was more apparent without confounding factors in the dataset. The two alternative functions including patient‐specific factors used in this work (one logistic and one cumulative normal function) were found to be equivalent, and more efficient than stratifying datasets according to patient‐specific factors and fitting models to subgroups individually. For datasets including confounding factors, the performance improved greatly when using models accounting for these; AUC increased from around 0.7 to close to unity.Conclusions:This work shows that identifying confounding factors, and developing methods to quantify them, is more important than the choice of NTCP model. Most dose–volume histogram (DVH)‐based NTCP models can be generalized to include confounding factors.
Population Structure of Klebsiella pneumoniae Causing Bloodstream Infections at a New York City Tertiary Care Hospital: Diversification of Multidrug-Resistant Isolates
Authors: Gomez-Simmonds Angela , Greenman Michelle , Sullivan Sean B. , Tanner Joshua P. , Sowash Madeleine G. , Whittier Susan , Uhlemann Anne-Catrin 
Published: April 2015

ABSTRACT

Despite the growing importance of carbapenem-resistant
Klebsiella pneumoniae
(CRKP), the clonal relationships between CRKP and antibiotic-susceptible isolates remain unclear. We compared the genetic diversity and clinical features of CRKP, third-generation and/or fourth-generation cephalosporin-resistant (Ceph-R)
K. pneumoniae
, and susceptible
K. pneumoniae
isolates causing bloodstream infections at a tertiary care hospital in New York City between January 2012 and July 2013. Drug susceptibilities were determined with the Vitek 2 system. Isolates underwent multilocus sequence typing and PCR sequencing of the
wzi
and
bla
KPC
genes. Clinical and microbiological data were extracted from patient records and correlated with molecular data. Among 223 patients, we identified 272 isolates. Of these, 194 were susceptible, 30 Ceph-R, and 48 CRKP, belonging to 144 sequence types (STs). Susceptible (127 STs) and Ceph-R (20 STs) isolates were highly diverse. ST258 dominated CRKP strains (12 STs, with 63% ST258). There was minimal overlap in STs between resistance groups. The
bla
KPC-3
gene (30%) was restricted to ST258/
wzi
154, whereas
bla
KPC-2
(70%) was observed for several
wzi
allele types. CRKP infections occurred more frequently among solid organ transplant (31%) and dialysis (17%) patients. Mortality rates were high overall (28%) and highest among CRKP-infected patients (59%). In multivariable analyses, advanced age, comorbidities, and disease severity were significant predictors of 30-day mortality rates, whereas the
K. pneumoniae
susceptibility phenotype was not. Among CRKP infections, we observed a borderline significant association of increased mortality rates with ST258 and the
wzi
154 allele. Although the clonal spread of ST258 continues to contribute substantially to the dissemination of CRKP, non-ST258 strains appear to be evolving. Further investigations into the mechanisms promoting CRKP diversification and the effects of clonal backgrounds on outcomes are warranted.
Herpes Simplex Virus 1 US3 Phosphorylates Cellular KIF3A To Downregulate CD1d Expression
Authors: Xiong Ran , Rao Ping , Kim Seil , Li Michelle , Wen Xiangshu , Yuan Weiming 
Published: April 2015

ABSTRACT

Herpes simplex virus 1 (HSV-1) causes one of the most prevalent herpesviral infections in humans and is the leading etiological agent of viral encephalitis and eye infections. Our understanding of how HSV-1 interacts with the host at the cellular and organismal levels is still limited. We and others previously reported that, upon infection, HSV-1 rapidly and efficiently downregulates CD1d cell surface expression and suppresses the function of NKT cells, a group of innate T cells with critical immunoregulatory function. The viral protein kinase US3 plays a major role in this immune evasion mechanism, and its kinase activity is required for this function. In this study, we investigated the cellular substrate(s) phosphorylated by US3 and how it mediates US3 suppression of CD1d recycling. We identified the type II kinesin motor protein KIF3A as a critical kinesin factor in the cell surface expression of CD1d. Interestingly, KIF3A is phosphorylated by US3 both
in vitro
and in infected cells. Mass spectrometry analysis of purified KIF3A showed that it is phosphorylated predominantly at serine 687 by US3. Ablation of this phosphorylation abolished US3-mediated downregulation of CD1d expression, suggesting that phosphorylation of KIF3A is the primary mechanism of HSV-1 suppression of CD1d expression by US3 protein. Understanding of the precise mechanism of viral modulation of CD1d expression will help to develop more efficient vaccines in the future to boost host NKT cell-mediated immune responses against herpesviruses.

IMPORTANCE
Herpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We previously reported that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule CD1d to evade the antiviral function of NKT cells. Here we identified the key cellular motor protein KIF3A as a cellular substrate phosphorylated by US3, and this phosphorylation event mediates US3-induced immune evasion.
Timing Is Everything: Coordinated Control of Host Shutoff by Influenza A Virus NS1 and PA-X Proteins
Authors: Khaperskyy Denys A. , McCormick Craig 
Published: April 2015

ABSTRACT
Like all viruses, influenza viruses (IAVs) use host translation machinery to decode viral mRNAs. IAVs ensure efficient translation of viral mRNAs through host shutoff, a process whereby viral proteins limit the accumulation of host proteins through subversion of their biogenesis. Despite its small genome, the virus deploys multiple host shutoff mechanisms at different stages of infection, thereby ensuring successful replication while limiting the communication of host antiviral responses. In this Gem, we review recent data on IAV host shutoff proteins, frame the outstanding questions in the field, and propose a temporally coordinated model of IAV host shutoff.
Dynasore Disrupts Trafficking of Herpes Simplex Virus Proteins
Authors: Mues Mascha B. , Cheshenko Natalia , Wilson Duncan W. , Gunther-Cummins Leslie , Herold Betsy C. 
Published: April 2015

ABSTRACT
Dynasore, a small-molecule inhibitor of the GTPase activity of dynamin, inhibits the entry of several viruses, including herpes simplex virus (HSV), but its impact on other steps in the viral life cycle has not been delineated. The current study was designed to test the hypothesis that dynamin is required for viral protein trafficking and thus has pleiotropic inhibitory effects on HSV infection. Dynasore inhibited HSV-1 and HSV-2 infection of human epithelial and neuronal cells, including primary genital tract cells and human fetal neurons and astrocytes. Similar results were obtained when cells were transfected with a plasmid expressing dominant negative dynamin. Kinetic studies demonstrated that dynasore reduced the number of viral capsids reaching the nuclear pore if added at the time of viral entry and that, when added as late as 8 h postentry, dynasore blocked the transport of newly synthesized viral proteins from the nucleus to the cytosol. Proximity ligation assays demonstrated that treatment with dynasore prevented the colocalization of VP5 and dynamin. This resulted in a reduction in the number of viral capsids isolated from sucrose gradients. Fewer capsids were observed by electron microscopy in dynasore-treated cells than in control-treated cells. There were also reductions in infectious progeny released into culture supernatants and in cell-to-cell spread. Together, these findings suggest that targeting dynamin-HSV interactions may provide a new strategy for HSV treatment and prevention.

IMPORTANCE
HSV infections remain a global health problem associated with significant morbidity, particularly in neonates and immunocompromised hosts, highlighting the need for novel approaches to treatment and prevention. The current studies indicate that dynamin plays a role in multiple steps in the viral life cycle and provides a new target for antiviral therapy. Dynasore, a small-molecule inhibitor of dynamin, has pleiotropic effects on HSV-1 and HSV-2 infection and impedes viral entry, trafficking of viral proteins, and capsid formation.
American-Indian diabetes mortality in the Great Plains Region 2002–2010
Authors: Kelley Allyson , Giroux Jennifer , Schulz Mark , Aronson Bob , Wallace Debra , Bell Ronny , Morrison Sharon 
Published: April 2015

ObjectiveTo compare American-Indian and Caucasian mortality rates from diabetes among tribal Contract Health Service Delivery Areas (CHSDAs) in the Great Plains Region (GPR) and describe the disparities observed.Research design and methodsMortality data from the National Center for Vital Statistics and Seer*STAT were used to identify diabetes as the underlying cause of death for each decedent in the GPR from 2002 to 2010. Mortality data were abstracted and aggregated for American-Indians and Caucasians for 25 reservation CHSDAs in the GPR. Rate ratios (RR) with 95% CIs were used and SEER*Stat V.8.0.4 software calculated age-adjusted diabetes mortality rates.ResultsAge-adjusted mortality rates for American-Indians were significantly higher than those for Caucasians during the 8-year period. In the GPR, American-Indians were 3.44 times more likely to die from diabetes than Caucasians. South Dakota had the highest RR (5.47 times that of Caucasians), and Iowa had the lowest RR, (1.1). Reservation CHSDA RR ranged from 1.78 to 10.25.ConclusionsAmerican-Indians in the GPR have higher diabetes mortality rates than Caucasians in the GPR. Mortality rates among American-Indians persist despite special programs and initiatives aimed at reducing diabetes in these populations. Effective and immediate efforts are needed to address premature diabetes mortality among American-Indians in the GPR.
Urine lipoarabinomannan to monitor antituberculosis therapy response and predict mortality in an HIV-endemic region: a prospective cohort study
Authors: Drain Paul K , Gounder Lilishia , Grobler Anneke , Sahid Faieza , Bassett Ingrid V , Moosa Mahomed-Yunus S 
Published: April 2015

ObjectiveTo determine if urinary lipoarabinomannan (LAM) may serve as a biomarker to monitor antituberculosis (TB) therapy response, and whether LAM results before and after treatment are predictive of patient outcomes.DesignProspective cohort.SettingOutpatient referral clinic and tertiary hospital in South Africa.ParticipantsAdults (≥18 years) with ≥2 TB-related symptoms (cough, fever, weight loss, night sweats) for ≥2 weeks being initiated on anti-TB therapy.InterventionsOn enrolment, we obtained urine and nebulised sputum specimens, offered HIV testing and started participants on anti-TB therapy for ≥6 months. We collected urine samples after the 2-month intensive treatment phase and at the completion of anti-TB therapy. Positive LAM results were graded from 1 (low) to 5 (high). Participants were followed for >3 years.Outcome measuresThe primary outcome was change in urine LAM results during anti-TB therapy. The secondary outcome was all-cause mortality.ResultsAmong 90 participants, 57 (63%) had culture-confirmed pulmonary TB. Among the 88 participants tested, 82 (93%) were HIV-infected with median CD4 168/mm3(IQR 89–256/mm3). During anti-TB therapy, the percentage of LAM-positive participants decreased from baseline to 2 months (32% to 16%), and from baseline to 6-months (32% to 10%) (p values <0.005). In multivariate longitudinal analyses, urine LAM positivity and grade decreased among those with culture-confirmed pulmonary TB (p<0.0001), and had no change in sputum culture-negative participants. At the 2-month visit, participants with positive laboratory-based LAM or rapid LAM with ≥2+ grade had a significantly greater risk of mortality. In analyses adjusted for age, sex, baseline Karnofsky score and HIV status, participants with a rapid LAM ≥2+ grade after 2 months of anti-TB therapy had a 5.6-fold (95% CI 1.2 to 25.2) greater risk of mortality.ConclusionsRapid urine LAM testing may be a valuable tool to monitor anti-TB therapy response and to assess prognosis of patients being treated for pulmonary TB in HIV-endemic regions.
Factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage: a multicentre retrospective analysis
Authors: Zhao Bing , Zhao Yuanli , Tan Xianxi , Cao Yong , Wu Jun , Zhong Ming , Wang Shuo 
Published: April 2015

ObjectiveTo determine factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage (aSAH).DesignA multicentre retrospective analysis, observational study.SettingHigh-volume teaching hospitals (more than 150 aSAH cases per year).Participants118 patients with World Federation of Neurosurgical Societies (WFNS) grades IV and V underwent surgical treatment. Ultra-early surgery was defined as surgery performed within 24 h of aSAH, and delayed surgery as surgery performed after 24 h. Outcome was assessed by modified Rankin Scale (mRS). The mean time of follow-up was 12.5±3.4 months (range 6–28 months).Results47 (40%) patients underwent ultra-early surgery, and 71 (60%) patients underwent delayed surgery. Patients with WFNS grade V (p=0.011) and brain herniation (p=0.004) more often underwent ultra-early surgery. Postoperative complications were similar in ultra-early and delayed surgery groups. Adjusted multivariate analysis showed the outcomes were similar between the two groups. Multivariate analysis of predictors of poor outcome, ultraearly surgery was not an independent predictor of poor outcome, while advanced age, postresuscitation WFNS V grade, intraventricular haemorrhage, brain herniation and non-middle cerebral artery (MCA) aneurysms were associated with poor outcome.ConclusionsAlthough patients with WFNS grade V and brain herniation more often undergo ultra-early surgery, postoperative complications and outcomes in selected patients were similar in the two groups. Patients of younger age, WFNS grade IV, absence of intraventricular haemorrhage, absence of brain herniation and MCA aneurysms are more likely to have a good outcome. Ultra-early surgery could improve outcomes in carefully selected patients with poor-grade aSAH.
Treatment of direct carotid–cavernous fistulas with a double lumen balloon
Authors: Samaniego Edgar A , Martínez-Galdámez Mario , Abdo German 
Published: April 2015

ObjectiveTo describe the treatment of direct high flow carotid–cavernous sinus fistulas (dCCFs) with the double lumen balloon Scepter C.Materials and methods7 patients with dCCFs were identified and treated with a double lumen balloon Scepter C. 5 patients had post-traumatic dCCFs and two patients had spontaneous dCCFs due to a ruptured cavernous–carotid aneurysm. The double lumen balloon was used in characterizing the angioarchitecture of the fistula in all patients. The best treatment option was then decided based on the characteristics of the carotid wall tear. Embolization of the cavernous sinus was achieved with coils and injection of Onyx liquid embolic material in three patients and with coils alone in four patients. One patient required stent assisted coiling to reconstruct the internal carotid artery.Results7 patients with dCCFs were treated with transarterial embolization. All patients had immediate angiographic and clinical cure. The Scepter C balloon was used for balloon assisted coiling and injection of Onyx liquid embolic material. On follow-up, all patients had clinical symptom resolution.ConclusionsThe Scepter C balloon is a useful tool for the transarterial treatment of dCCFs.