bluuebunny/crossref_metadata_2025_split huggingface dataset:
Function of the Borrelia burgdorferi FtsH Homolog Is Essential for Viability both
In Vitro
and
In Vivo
and Independent of HflK/C
Authors: Chu Chen-Yi , Stewart Philip E. , Bestor Aaron , Hansen Bryan , Lin Tao , Gao Lihui , Norris Steven J. , Rosa Patricia A. 
Published: April 2016

ABSTRACT

In many bacteria, the FtsH protease and its modulators, HflK and HflC, form a large protein complex that contributes to both membrane protein quality control and regulation of the cellular response to environmental stress. Both activities are crucial to the Lyme disease pathogen
Borrelia burgdorferi
, which depends on membrane functions, such as motility, protein transport, and cell signaling, to respond to rapid changes in its environment. Using an inducible system, we demonstrate that FtsH production is essential for both mouse and tick infectivity and for
in vitro
growth of
B. burgdorferi
. FtsH depletion in
B. burgdorferi
cells resulted in membrane deformation and cell death. Overproduction of the protease did not have any detectable adverse effects on
B. burgdorferi
growth
in vitro
, suggesting that excess FtsH does not proteolytically overwhelm its substrates. In contrast, we did not observe any phenotype for cells lacking the protease modulators HflK and HflC (ΔHflK/C), although we examined morphology, growth rate, growth under stress conditions, and the complete mouse-tick infectious cycle. Our results demonstrate that FtsH provides an essential function in the life cycle of the obligate pathogen
B. burgdorferi
but that HflK and HflC do not detectably affect FtsH function.

IMPORTANCE
Lyme disease is caused by
Borrelia burgdorferi
, which is maintained in nature in an infectious cycle alternating between small mammals and
Ixodes
ticks.
B. burgdorferi
produces specific membrane proteins to successfully infect and persist in these diverse organisms. We hypothesized that
B. burgdorferi
has a specific mechanism to ensure that membrane proteins are properly folded and biologically active when needed and removed if improperly folded or dysfunctional. Our experiments demonstrate that FtsH, a protease that fulfills this role in other microorganisms, is essential to
B. burgdorferi
viability. Cells depleted of FtsH do not survive in laboratory culture medium and cannot colonize mice or ticks, revealing an absolute requirement for this protease. However, the loss of two potential modulators of FtsH activity, HflK and HflC, does not detectably affect
B. burgdorferi
physiology. Our results provide the groundwork for the identification of FtsH substrates that are critical for the bacterium’s viability.
Influence of Cr deficiency on sintering, thermal expansion and electrical properties of La0.75Sr0.25Cr1−xO3−δ as a SOFC interconnect material
Authors: Ren Yi , Ma Wen , Li Xiaoying , Wang Jun , Bai Yu , Dong Hongying 
Published: April 2016

The SOFC interconnect materials La[Formula: see text]Sr[Formula: see text]Cr[Formula: see text]O[Formula: see text] [Formula: see text]–[Formula: see text] were prepared using an auto-ignition process. The influences of Cr deficiency on their sintering, thermal expansion and electrical properties were investigated. All the samples were pure perovskite phase after sintering at 1400[Formula: see text]C for 4 h. The cell volume of La[Formula: see text]Sr[Formula: see text]Cr[Formula: see text]O[Formula: see text] decreased with increasing Cr deficient content. The relative density of the sintered bulk samples increased from 93.2% [Formula: see text] to a maximum value of 94.7% [Formula: see text] and then decreased to 87.7% [Formula: see text]. The thermal expansion coefficients of the sintered bulk samples were in the range of [Formula: see text]–[Formula: see text] (30–1000[Formula: see text]C), which are compatible with that of YSZ. Among the investigated samples, the sample with 0.02 Cr deficiency had a maximum conductivity of 40.4 Scm[Formula: see text] and the lowest Seebeck coefficient of 154.8 [Formula: see text]VK[Formula: see text] at 850[Formula: see text]C in pure He. The experimental results indicate that La[Formula: see text]Sr[Formula: see text]Cr[Formula: see text]O[Formula: see text] has the best properties and is much suitable for SOFC interconnect material application.
Reproductive Risk Factors and Coronary Heart Disease in the Women’s Health Initiative Observational Study
Authors: Parikh Nisha I. , Jeppson Rebecca P. , Berger Jeffrey S. , Eaton Charles B. , Kroenke Candyce H. , LeBlanc Erin S. , Lewis Cora E. , Loucks Eric B. , Parker Donna R. , Rillamas-Sun Eileen , Ryckman Kelli K. , Waring Molly E. , Schenken Robert S. , Johnson Karen C. , Edstedt-Bonamy Anna-Karin , Allison Matthew A. , Howard Barbara V. 
Published: April 2016

Background—
Reproductive factors provide an early window into a woman’s coronary heart disease (CHD) risk; however, their contribution to CHD risk stratification is uncertain.

Methods and Results—

In the Women’s Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C statistic, net reclassification index (or net reclassification index with risk categories of <5%, 5 to <10%, and ≥10% 10-year risk of CHD), and integrated discriminatory index were assessed. Among 72 982 women (CHD events, n=4607; median follow-up,12.0 [interquartile range, 8.3–13.7] years; mean [standard deviation] age, 63.2 [7.2] years), an age-adjusted reproductive risk factor model had a C statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages, and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C statistic increased from 0.726 to 0.730; integrated discriminatory index, 0.0013;
P
<0.0001). Net reclassification for women with events was not improved (net reclassification index events, 0.007;
P
=0.18); and, for women without events, net reclassification was marginally improved (net reclassification index nonevents, 0.002;
P
=0.04)

Conclusions—
Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination, and do not materially improve net reclassification.
Outcomes following Pediatric Auditory Brainstem Implant Surgery
Authors: Puram Sidharth V. , Barber Samuel R. , Kozin Elliott D. , Shah Parth , Remenschneider Aaron , Herrmann Barbara S. , Duhaime Ann‐Christine , Barker Fred G. , Lee Daniel J. 
Published: April 2016

There are no approved Food and Drug Administration indications for pediatric auditory brainstem implant (ABI) surgery in the United States. Our prospective case series aims to determine the safety and feasibility of ABI surgery in pediatric patients <5 years old with congenital deafness at a tertiary North American center. The inclusion criterion was pre‐ or postlinguistic deafness in children not eligible for cochlear implantation. Seventeen candidates were evaluated (mean ± SD: age, 2.52 ± 0.39 years). Four patients underwent ABI surgery (age, 19.2 ± 3.43 months), including 4 primary procedures and 1 revision for device failure. Spontaneous device failure occurred in another subject postoperatively. No major/minor complications occurred, including cerebrospinal fluid leak, facial nerve injury, hematoma, and nonauditory stimulation. All subjects detected sound with environmental awareness, and several demonstrated babbling and mimicry. Poor durability of older implants underscores need for updated technology.
Clinician Prediction of Future Suicide Attempts
Authors: Wang Yunqiao , Bhaskaran Joanna , Sareen Jitender , Bolton Shay-Lee , Chateau Dan , Bolton James M. 
Published: April 2016

Objective: Established risk assessment tools are often inaccurate at predicting future suicide risk. We therefore investigated whether clinicians are able to predict individuals’ suicide risk with greater accuracy. Method: We used the SAFE Database, which included consecutive adult (age ≥18 years) presentations ( N = 3818) over a 22-month period to the 2 tertiary care hospitals in Manitoba, Canada. Medical professionals assessed each individual and recorded his or her predicted risk for future suicide attempt (SA) on a 0-10 scale—the clinician prediction scale. The SAD PERSONS scale was completed as a comparison. SAs within 6 months, assessed using the Columbia Classification Algorithm for Suicide Assessment, were the primary outcome measure. Receiver operating characteristic curve and logistic regression analyses were conducted to determine the accuracy of both scales to predict SAs, and the scales were compared with z scores. Clinician prediction scale performance was stratified based on level of training. Results: Clinicians were able to predict future SAs with significantly greater accuracy (area under the curve [AUC] = 0.73; 95% CI, 0.68 to 0.77; P < 0.001) compared with the SAD PERSONS scale ( z = 3.79, P < 0.001). Both scales nonetheless showed positive predictive value of less than 7%. Analyses by level of training showed that junior psychiatric residents and non–psychiatric residents did not accurately predict SAs, whereas senior psychiatric residents and staff psychiatrists demonstrated greater accuracy (AUC = 0.76 and 0.78, respectively). Conclusions: Clinicians are able to predict future attempts with fewer false positives than a conventional risk assessment scale, and this skill appears related to training level. Predicting future suicidal behaviour remains very challenging.
Effects of Carvedilol Compared to Nebivolol on Insulin Resistance and Lipid Profile in Patients With Essential Hypertension
Authors: Ozyıldız Ali Gokhan , Eroglu Serpil , Bal Ugur , Atar Ilyas , Okyay Kaan , Muderrisoglu Haldun 
Published: April 2016

Background and aim: Beta-blockers have unfavorable effects on metabolic parameters in hypertensive treatment. New generation beta-blockers with vasodilatory capabilities are superior to traditional beta-blockers, but studies examining their effects on metabolic parameters are still lacking. This study aimed to compare the effects of 2 new generation beta-blockers, carvedilol and nebivolol, on insulin resistance (IR) and lipid profiles in patients with essential hypertension. Methods: This was a prospective, randomized, open-label, single-center clinical trial. A total of 80 patients were randomized into 2 groups: the carvedilol group (n = 40, 25 mg of carvedilol daily) and the nebivolol group (n = 40, 5 mg of nebivolol daily). Follow-up was performed for 4 months. Fasting plasma glucose, insulin levels, and the lipid profile (high-density lipoprotein [HDL], low-density lipoprotein [LDL], total cholesterol, triglyceride, apolipoprotein AI, and apolipoprotein B levels) were measured and IR was calculated by the homeostasis model assessment (HOMA) index. These variables were compared before and 4 months after treatment. Results: Blood pressure and heart rate were significantly and similarly reduced in the carvedilol and nebivolol groups after treatment compared to those before treatment (both P < .001). Serum glucose ( P < .001), insulin ( P < .01), HOMA-IR (P < .01), HDL ( P < .001), LDL ( P < .001), total cholesterol ( P < .001), and apolipoprotein B ( P < .05) levels decreased in a similar manner in the carvedilol and nebivolol groups after treatment compared to those before treatment. Serum triglyceride and apolipoprotein AI levels did not change after treatment with both drugs. Conclusion: New generation beta-blockers, carvedilol and nebivolol, efficiently and similarly decrease blood pressure. They have similar favorable effects on glucose, insulin, IR, and the lipid profile.
Diagnostic utility of cerebrospinal fluid immunocytochemistry for diagnosis of feline infectious peritonitis manifesting in the central nervous system
Authors: Gruendl Stefanie , Matiasek Kaspar , Matiasek Lara , Fischer Andrea , Felten Sandra , Jurina Konrad , Hartmann Katrin 
Published: April 2016

Objectives The aim of the study was to evaluate whether an ante-mortem diagnosis of central nervous system (CNS) feline infectious peritonitis (FIP) is possible via immunocytochemical staining (ICC) of feline coronavirus antigen (FCoV) within macrophages of cerebrospinal fluid (CSF). Methods Prospectively, CSF samples of 41 cats were investigated, including cats with histopathologically confirmed FIP and neurological signs (n = 10), cats with confirmed FIP without CNS involvement (n = 11), cats with neurological signs but another confirmed CNS disease (n = 17), and cats without neurological signs and a disease other than FIP (n = 3). ICC staining of CSF macrophages was performed in all cats. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of CSF ICC were calculated. Results Of 10 samples from cats with CNS FIP, eight had detectable CSF macrophages, seven of which were positive for FCoV. Ten of 11 samples from cats with confirmed FIP without neurological signs had macrophages in the CSF, with all 10 being ICC-positive. In cats with other CNS disorders, 11/17 had macrophages, two of which stained positively. In cats with diseases other than FIP and without neurological disorders, 2/3 revealed macrophages, with one cat showing positive ICC staining. Diagnosis of FIP via CSF ICC had a sensitivity of 85.0% and a specificity of 83.3%. PPV and NPV were 85.0% and 83.3%. Conclusions and relevance CSF ICC is a highly sensitive test for ante-mortem diagnosis of FIP manifesting in the CNS. However, CNS ICC specificity is too low to confirm FIP and the method should only be applied in conjunction with other features such as CSF cytology. CNS ICC could be helpful to discover pre-neurological stages of CNS FIP.
L/T-type calcium channel blocker reduces non-Gaussianity of heart rate variability in chronic kidney disease patients under preceding treatment with ARB
Authors: Fukuda Michio , Ogiyama Yoshiaki , Sato Ryo , Miura Toshiyuki , Fukuta Hidekatsu , Mizuno Masashi , Kiyono Ken , Yamamoto Yoshiharu , Hayano Junichiro , Ohte Nobuyuki 
Published: April 2016

Introduction: Increased sympathetic nerve activity has been suggested in patients with chronic kidney disease (CKD). Pathologic sympathetic activity can alter heart rate variability (HRV), and the altered HRV has prognostic importance, so that reducing sympathetic activity may be an important strategy. Novel nonlinear HRVs, including deceleration capacity (DC), have greater predictive power for mortality. We have recently proposed an increase in a non-Gaussianity index of HRV, λ25s, which indicates the probability of volcanic heart rate deviations of departure from each standard deviation level, as a marker of sympathetic cardiac overdrive. L/T-type calcium channel blocker (L/T-CCB), azelnidipine, decreases sympathetic nerve activity in experimental and clinical studies. Methods: In 43 hypertensive patients with CKD under treatment with an angiotensin receptor blocker (ARB), we investigated whether 8-week add-on L/T-CCB treatment could restore HRV. Results: Means of all normal-to-normal intervals over 24 h ( p<0.0001) and DC ( p=0.002) increased, and λ25s ( p=0.001) decreased regardless of gender, age, renal function or blood pressure, while no significant changes were observed in the other HRVs. Conclusions: Reduction of λ25s is useful to assess the effect of sympathoinhibitory treatment. Further studies are needed to investigate if the restoration of HRV is directly associated with the improvement of prognosis in patients with CKD.
Aspirations to Great Power Status: Russia’s Path to Assertiveness in the International Arena under Putin
Authors: Nitoiu Cristian 
Published: April 2016

This article focuses on the literature developed in the last few years on Russia’s foreign policy by exploring six books which can be thought as representative: two general books on Russian foreign policy, one that focuses on security and intervention, another on Russia’s soft power and influence in the post-Soviet space, and two others on Russia’s relationship with the West. There is an underlying idea in the six books that Russian foreign policy has been deeply marked by Putin’s leadership. Russia’s foreign policy has been continuously evolving since 2000 towards assertiveness, through which Putin has aimed to regain Russia’s lost status of being a great power. In the last few years and especially since Putin came to power for the third time, there has been a proliferation of books on Russian foreign policy. The value of the six books lies in the way they chart the path towards assertiveness in Putin’s quest to put Russia again on the map as a great power. Allison R (2013) Russia, the West, and Military Intervention. Oxford: Oxford University Press. De Haas M (2011) Russia’s Foreign Security Policy in the 21st Century: Putin, Medvedev and Beyond. Abingdon: Routledge. Gvosdev NK and Marsh C (2013) Russian Foreign Policy: Interests, Vectors, and Sectors. Los Angeles, CA: CQ Press. Leichtova M (2014) Misunderstanding Russia: Russian Foreign Policy and the West. Farnham, MD: Ashgate. Sherr J (2013) Hard Diplomacy and Soft Coercion: Russia’s Influence Abroad. London: Royal Institute for International Affairs/Chatham House. Tsygankov AP (2012) Russia and the West from Alexander to Putin: Honor in International Relations. Cambridge: Cambridge University Press.
Subpopulation Treatment Effect Pattern Plot (STEPP) analysis for continuous, binary, and count outcomes
Authors: Yip Wai-Ki , Bonetti Marco , Cole Bernard F , Barcella William , Wang Xin Victoria , Lazar Ann , Gelber Richard D 
Published: April 2016

Background: For the past few decades, randomized clinical trials have provided evidence for effective treatments by comparing several competing therapies. Their successes have led to numerous new therapies to combat many diseases. However, since their conclusions are based on the entire cohort in the trial, the treatment recommendation is for everyone, and may not be the best option for an individual. Medical research is now focusing more on providing personalized care for patients, which requires investigating how patient characteristics, including novel biomarkers, modify the effect of current treatment modalities. This is known as heterogeneity of treatment effects. A better understanding of the interaction between treatment and patient-specific prognostic factors will enable practitioners to expand the availability of tailored therapies, with the ultimate goal of improving patient outcomes. The Subpopulation Treatment Effect Pattern Plot (STEPP) approach was developed to allow researchers to investigate the heterogeneity of treatment effects on survival outcomes across values of a (continuously measured) covariate, such as a biomarker measurement. Methods: Here, we extend the Subpopulation Treatment Effect Pattern Plot approach to continuous, binary, and count outcomes, which can be easily modeled using generalized linear models. With this extension of Subpopulation Treatment Effect Pattern Plot, these additional types of treatment effects within subpopulations defined with respect to a covariate of interest can be estimated, and the statistical significance of any observed heterogeneity of treatment effect can be assessed using permutation tests. The desirable feature that commonly used models are applied to well-defined patient subgroups to estimate treatment effects is retained in this extension. Results: We describe a simulation study to confirm that the proper Type I error rate is maintained when there is no treatment heterogeneity, and a power study to show that the statistics have power to detect treatment heterogeneity under alternative scenarios. As an illustration, we apply the methods to data from the Aspirin/Folate Polyp Prevention Study, a clinical trial evaluating the effect of oral aspirin, folic acid, or both as a chemoprevention agent against colorectal adenomas. The pre-existing R software package stepp has been extended to handle continuous, binary, and count data using Gaussian, Bernoulli, and Poisson models, and it is available on the Comprehensive R Archive Network. Conclusion: The extension of the method and the availability of new software now permit STEPP to be applied to the full range of clinical trial end points.
Generalized estimating equations in cluster randomized trials with a small number of clusters: Review of practice and simulation study
Authors: Huang Shuang , Fiero Mallorie H , Bell Melanie L 
Published: April 2016

Background/aims: Generalized estimating equations are a common modeling approach used in cluster randomized trials to account for within-cluster correlation. It is well known that the sandwich variance estimator is biased when the number of clusters is small (≤40), resulting in an inflated type I error rate. Various bias correction methods have been proposed in the statistical literature, but how adequately they are utilized in current practice for cluster randomized trials is not clear. The aim of this study is to evaluate the use of generalized estimating equation bias correction methods in recently published cluster randomized trials and demonstrate the necessity of such methods when the number of clusters is small. Methods: Review of cluster randomized trials published between August 2013 and July 2014 and using generalized estimating equations for their primary analyses. Two independent reviewers collected data from each study using a standardized, pre-piloted data extraction template. A two-arm cluster randomized trial was simulated under various scenarios to show the potential effect of a small number of clusters on type I error rate when estimating the treatment effect. The nominal level was set at 0.05 for the simulation study. Results: Of the 51 included trials, 28 (54.9%) analyzed 40 or fewer clusters with a minimum of four total clusters. Of these 28 trials, only one trial used a bias correction method for generalized estimating equations. The simulation study showed that with four clusters, the type I error rate ranged between 0.43 and 0.47. Even though type I error rate moved closer to the nominal level as the number of clusters increases, it still ranged between 0.06 and 0.07 with 40 clusters. Conclusions: Our results showed that statistical issues arising from small number of clusters in generalized estimating equations is currently inadequately handled in cluster randomized trials. Potential for type I error inflation could be very high when the sandwich estimator is used without bias correction.