bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis
Authors: Chen Yuan , Toffaletti Dena L. , Tenor Jennifer L. , Litvintseva Anastasia P. , Fang Charles , Mitchell Thomas G. , McDonald Tami R. , Nielsen Kirsten , Boulware David R. , Bicanic Tihana , Perfect John R. 
Published: February 2014

ABSTRACTCryptococcus neoformansis the leading cause of fungal meningitis worldwide. Previous studies have characterized the cryptococcal transcriptome under various stress conditions, but a comprehensive profile of theC. neoformanstranscriptome in the human host has not been attempted. Here, we extracted RNA from yeast cells taken directly from the cerebrospinal fluid (CSF) of two AIDS patients with cryptococcal meningitis prior to antifungal therapy. The patients were infected with strains ofC. neoformansvar.grubiiof molecular type VNI and VNII. Using RNA-seq, we compared the transcriptional profiles of these strains under three environmental conditions (in vivoCSF,ex vivoCSF, and yeast extract-peptone-dextrose [YPD]). Although we identified a number of differentially expressed genes, single nucleotide variants, and novel genes that were unique to each strain, the overall expression patterns of the two strains were similar under the same environmental conditions. Specifically, yeast cells obtained directly from each patient’s CSF were more metabolically active than cells that were incubatedex vivoin CSF. Compared with growth in YPD, some genes were identified as significantly upregulated in bothin vivoandex vivoCSF, and they were associated with genes previously recognized for contributing to pathogenicity. For example, genes with known stress response functions, such asRIM101,ENA1, andCFO1, were regulated similarly in the two clinical strains. Conversely, many genes that were differentially regulated between the two strains appeared to be transporters. These findings establish a platform for further studies of how this yeast survives and produces disease.IMPORTANCECryptococcus neoformans, an environmental, opportunistic yeast, is annually responsible for an estimated million cases of meningitis and over 600,000 deaths, mostly among HIV-infected patients in sub-Saharan Africa and Asia. Using RNA-seq, we analyzed the gene expression of two strains ofC. neoformansobtained from the cerebrospinal fluid (CSF) of infected patients, thus creating a comprehensive snapshot of the yeasts’ genetic responses within the human body. By comparing the gene expression of each clinical strain under three conditions (in vivoCSF,ex vivoCSF, and laboratory culture), we identified genes and pathways that were uniquely regulated by exposure to CSF and likely crucial for the survival ofC. neoformansin the central nervous system. Further analyses revealed genetic diversity between the strains, providing evidence for cryptococcal evolution and strain specificity. This ability to characterize transcriptionin vivoenables the elucidation of specific genetic responses that promote disease production and progression.
Rationale and study design of the Prospective comparison of Angiotensin Receptor neprilysin inhibitor with Angiotensin receptor blocker MEasuring arterial sTiffness in the eldERly (PARAMETER) study
Authors: Williams Bryan , Cockcroft John R , Kario Kazuomi , Zappe Dion H , Cardenas Pamela , Hester Allen , Brunel Patrick , Zhang Jack 
Published: February 2014

IntroductionHypertension in elderly people is characterised by elevated systolic blood pressure (SBP) and increased pulse pressure (PP), which indicate large artery ageing and stiffness. LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is being developed to treat hypertension and heart failure. The Prospective comparison of Angiotensin Receptor neprilysin inhibitor with Angiotensin receptor blocker MEasuring arterial sTiffness in the eldERly (PARAMETER) study will assess the efficacy of LCZ696 versus olmesartan on aortic stiffness and central aortic haemodynamics.Methods and analysisIn this 52-week multicentre study, patients with hypertension aged ≥60 years with a mean sitting (ms) SBP ≥150 to <180 and a PP>60 mm Hg will be randomised to once daily LCZ696 200 mg or olmesartan 20 mg for 4 weeks, followed by a forced-titration to double the initial doses for the next 8 weeks. At 12–24 weeks, if the BP target has not been attained (msSBP <140  and ms diastolic BP <90 mm Hg), amlodipine (2.5–5 mg) and subsequently hydrochlorothiazide (6.25–25 mg) can be added. The primary and secondary endpoints are changes from baseline in central aortic systolic pressure (CASP) and central aortic PP (CAPP) at week 12, respectively. Other secondary endpoints are the changes in CASP and CAPP at week 52. A sample size of 432 randomised patients is estimated to ensure a power of 90% to assess the superiority of LCZ696 over olmesartan at week 12 in the change from baseline of mean CASP, assuming an SD of 19 mm Hg, the difference of 6.5 mm Hg and a 15% dropout rate. The primary variable will be analysed using a two-way analysis of covariance.Ethics and disseminationThe study was initiated in December 2012 and final results are expected in 2015. The results of this study will impact the design of future phase III studies assessing cardiovascular protection.Clinical trials identifierEUDract number 2012-002899-14 and ClinicalTrials.govNCT01692301.
The Surgical Safety Checklist and Teamwork Coaching Tools: a study of inter-rater reliability
Authors: Huang Lyen C , Conley Dante , Lipsitz Stu , Wright Christopher C , Diller Thomas W , Edmondson Lizabeth , Berry William R , Singer Sara J 
Published: February 2014

ObjectiveTo assess the inter-rater reliability (IRR) of two novel observation tools for measuring surgical safety checklist performance and teamwork.Summary backgroundData surgical safety checklists can promote adherence to standards of care and improve teamwork in the operating room. Their use has been associated with reductions in mortality and other postoperative complications. However, checklist effectiveness depends on how well they are performed.MethodsAuthors from the Safe Surgery 2015 initiative developed a pair of novel observation tools through literature review, expert consultation and end-user testing. In one South Carolina hospital participating in the initiative, two observers jointly attended 50 surgical cases and independently rated surgical teams using both tools. We used descriptive statistics to measure checklist performance and teamwork at the hospital. We assessed IRR by measuring percent agreement, Cohen's κ, and weighted κ scores.ResultsThe overall percent agreement and κ between the two observers was 93% and 0.74 (95% CI 0.66 to 0.79), respectively, for the Checklist Coaching Tool and 86% and 0.84 (95% CI 0.77 to 0.90) for the Surgical Teamwork Tool. Percent agreement for individual sections of both tools was 79% or higher. Additionally, κ scores for six of eight sections on the Checklist Coaching Tool and for two of five domains on the Surgical Teamwork Tool achieved the desired 0.7 threshold. However, teamwork scores were high and variation was limited. There were no significant changes in the percent agreement or κ scores between the first 10 and last 10 cases observed.ConclusionsBoth tools demonstrated substantial IRR and required limited training to use. These instruments may be used to observe checklist performance and teamwork in the operating room. However, further refinement and calibration of observer expectations, particularly in rating teamwork, could improve the utility of the tools.
Sharing knowledge, saving time: an online toolbox to aid junior doctors
Authors: Houston James , Barker William , Clarke Jonathan , Mew Ed 
Published: February 2014

AbstractJunior doctors are too often frustrated by not being able to quickly find information for how to make referrals, book investigations and contact other professionals at hospital. To make matters worse, much of the knowledge gained by doctors throughout the year is lost during the August rotation. There is an unmet need for retaining such knowledge, in order to facilitate a smoother and safer handover.We set up the “Doctors Directory” at our trust; a website run by junior doctors, providing specific, up-to-date information relevant to other junior doctors within the trust. Whilst providing day-to-day information, it also contains a "survival guide" for each hospital firm.We surveyed junior doctors before and after the implementation of this site. 81% of FY1s surveyed have used the site. Of the doctors that had used the site, 94% found it helpful with a mean self reported time saving of 39 minutes a day. Whilst still in its infancy, the site now has mobile access, and has an average of 60 hits a day. Quality improvement projects such as this are readily scalable to other hospitals and have enabled junior doctors to waste less time finding how to do jobs and more time actually getting them done.
Improving the management of Acute Kidney Injury in a District General Hospital: Introduction of the DONUT bundle
Authors: Bhagwanani Anisha , Carpenter Rory , Yusuf Aqeelah 
Published: February 2014

AbstractThe NCEPOD report (2009) on Acute Kidney Injury (AKI) found 20% of post-admission AKIs were avoidable and only 50% of AKI care was considered 'good'. The DONUT bundle comprises of six interventions aimed at improving the management of AKI.Baseline data was collected prospectively using the biochemistry eAlert system, identifying 50 patients with Stage 1 AKI over a two week period. Management was assessed 24 hours after the eAlert using a standardised proforma. After data analysis, a DONUT sticker was introduced within the Emergency Admissions Unit, providing an efficient method of recording interventions in the notes. Education sessions outlining the DONUT bundle and stickers were delivered via Foundation Program teaching, along with summary flash cards. A re-audit assessed these interventions.Of the initial cohort (n=50), only 8% of cases had all components of the care bundle completed. Following introduction of the education programme and AKI sticker, re-audit showed a rise in full compliance to 17% (n=42). Only 7% of cases used the AKI sticker but where it was used, there was 100% compliance with the bundle.In conclusion, AKI management is sub-standard. An education program and the use of a simple sticker can improve management. Further education regarding AKI is needed and work is ongoing to improve compliance with sticker use.
On H-Supplemented Modules
Authors: Keskin Tütüncü Derya , Nematollahi Mohammad Javad , Talebi Yahya 
Published: February 2014

Let [Formula: see text]be a finite direct sum of modules. We prove: (i) If Mi is radical Mj-projective for all j > i and each Mi is H-supplemented, then M is H-supplemented. (ii) If all the Mi are relatively projective and N is H-supplemented, then each Mi is H-supplemented. Let ρ be the preradical for a cohereditary torsion theory. Let M be a module such that ρ (M) has a unique coclosure and every direct summand of ρ (M) has a coclosure in M. Then M is H-supplemented if and only if there exists a decomposition M=M1⊕M2 such that M2 ⊆ ρ(M), ρ(M)/M2 ≪ M/M2, and M1, M2 are H-supplemented.
The Zero Curvature Form of Integrable Hierarchies in the ℤ × ℤ-Matrices
Authors: Helminck G. F. , Opimakh A. V. 
Published: February 2014

In this paper it is shown how one can associate to a finite number of commuting directions in the Lie algebra of upper triangular ℤ × ℤ-matrices an integrable hierarchy consisting of a set of evolution equations for perturbations of the basic directions inside the mentioned Lie algebra. They amount to a tower of differential and difference equations for the coefficients of these perturbed matrices. The equations of the hierarchy are conveniently formulated in so-called Lax equations for these perturbations. They possess a minimal realization for which it is shown that the relevant evolutions of the perturbation commute. These Lax equations are shown in a purely algebraic way to be equivalent with zero curvature equations for a collection of finite band matrices, that are the components of a formal connection form. One concludes with the linearization of the hierarchies and the notion of wave matrices at zero, which is the algebraic substitute for a basis of the horizontal sections of the formal connection corresponding to this connection form.
Navigating the Challenge of Tumor Heterogeneity in Cancer Therapy
Authors: Fedele Clare , Tothill Richard W. , McArthur Grant A. 
Published: February 2014

Abstract
Summary: The future of cancer treatment lies in personalized strategies designed to specifically target tumorigenic cell populations present in an individual. Although recent advances in directed therapies have greatly improved patient outcomes in some cancers, intuitive drug design is proving more difficult than expected owing largely to the complexity of human cancers. Intratumoral heterogeneity, the presence of multiple genotypically and/or phenotypically distinct cell subpopulations within a single tumor, is a likely cause of drug resistance. Advances in systems biology are helping to unravel the mysteries of cancer progression. In this issue of Cancer Discovery, Zhao and colleagues define a path for functional validation of computational modeling in the context of heterogeneous tumor populations and their potential for drug response and resistance. Cancer Discov; 4(2); 146–8. ©2014 AACR.
See related article by Zhao et al., p. 166
End-Diastolic Fractional Flow Reserve
Authors: Chalyan David A. , Zhang Zhang , Takarada Shigeho , Molloi Sabee 
Published: February 2014

Background—
Diastolic fractional flow reserve (dFFR) has been shown to be highly sensitive for detection of inducible myocardial ischemia. However, its reliance on measurement of left-ventricular pressure for zero-flow pressure correction, as well as manual extraction of the diastolic interval, has been its major limitation. Given previous reports of minimal zero-flow pressure at end-diastole, we compared instantaneous ECG-gated end-diastolic FFR with conventional full-cardiac cycle FFR and other diastolic indices in the porcine model.

Methods and Results—

Measurements of FFR in the left anterior descending and left circumflex arteries were performed in an open-chest swine model with an external occluder device on the coronary artery used to produce varying degrees of epicardial stenosis. An ultrasound flow-probe that was placed proximal to the occluder measured absolute blood flow in ml/min, and it was used as a gold standard for FFR measurement. A total of 17 measurements at maximal hyperemia were acquired in 5 animals. Correlation coefficient between conventional mean hyperemic FFR with pressure-wire and directly measured FFR with flow-probe was 0.876 (standard error estimate=0.069;
P
<0.0001). The hyperemic end-diastolic FFR with pressure-wire correlated better with FFR measured directly with flow-probe (
r
=0.941, standard error estimate=0.050;
P
<0.0001).

Conclusions—
Instantaneous hyperemic ECG-gated FFR acquired at end-diastole, as compared with conventional full-cardiac cycle FFR, has an improved correlation with FFR measured directly with ultrasound flow-probe.
Age‐Dependent Sex Effects on Outcomes After Pediatric Cardiac Surgery
Authors: Kochilas Lazaros K. , Vinocur Jeffrey M. , Menk Jeremiah S. 
Published: February 2014

Background
Sex has been linked to differential outcomes for cardiovascular disease in adults. We examined potential sex differences in outcomes after pediatric cardiac surgery.

Methods and Results

We retrospectively analyzed data from the
P
ediatric
C
ardiac
C
are
C
onsortium (1982–2007) by using logistic regression to evaluate the effects of sex on 30‐day within‐hospital mortality after pediatric (<18 years old) cardiac operations and its interaction with age, risk category, z‐score for weight, and surgical year for the whole cohort. Of 76 312 operations, 55% were in boys. Unadjusted mortality was similar for boys and girls (5.2% versus 5.0%,
P
=0.313), but boys were more likely to have cardiac surgery as a neonate and to have more complex operations. After adjustment, the overall test of any association between postsurgical mortality and sex was significant (
P
=0.002), but the overall test of any interaction was not (
P
=0.503). However, a potential age‐dependent sex effect on postsurgical mortality was observed among infants subjected to high‐risk operations, with girls doing worse during the first 6 months of life.

Conclusions
Patient sex has a significant effect on mortality after pediatric cardiac operations, with an increased risk of death in early infancy for girls after high‐risk cardiac operations. This age‐dependent relationship supports a sex‐related biological effect on postoperative cardiovascular stress.
Role of Preexisting Disability in Patients Treated With Intravenous Thrombolysis for Ischemic Stroke
Authors: Karlinski Michal , Kobayashi Adam , Czlonkowska Anna , Mikulik Robert , Vaclavik Daniel , Brozman Miroslav , Švigelj Viktor , Csiba Laszlo , Fekete Klara , Kõrv Janika , Demarin Vida , Vilionskis Aleksandras , Jatuzis Dalius , Krespi Yakup , Ahmed Niaz , Wahlgren Nils ,   Countries participating in SITS-EAST with national coordinators and number of cases contributed:, Mikulik Robert , Czlonkowska Anna , Brozman Miroslav , Csiba Laszlo , Kõrv Janika , Švigelj Viktor , Demarin Vida , Jatuzis Dalius , Vilionskis Aleksandras , Krespi Yakup , Shamalov Nikolay 
Published: February 2014

Background and Purpose—
Little is known about the effect of thrombolysis in patients with preexisting disability. Our aim was to evaluate the impact of different levels of prestroke disability on patients’ profile and outcome after intravenous thrombolysis.

Methods—
We analyzed the data of all stroke patients admitted between October 2003 and December 2011 that were contributed to the Safe Implementation of Treatments in Stroke–Eastern Europe (SITS-EAST) registry. Patients with no prestroke disability at all (modified Rankin Scale [mRS] score, 0) were used as a reference in multivariable logistic regression.

Results—
Of 7250 patients, 5995 (82%) had prestroke mRS 0, 791 (11%) had prestroke mRS 1, 293 (4%) had prestroke mRS 2, and 171 (2%) had prestroke mRS ≥3. Compared with patients with mRS 0, all other groups were older, had more comorbidities, and more severe neurological deficit on admission. There was no clear association between preexisting disability and the risk of symptomatic intracranial hemorrhage. Prestroke mRS 1, 2, and ≥3 were associated with increased risk of death at 3 months (odds ratio, 1.3, 2.0, and 2.6, respectively) and lower chance of achieving favorable outcome (achieving mRS 0–2 or returning to the prestroke mRS; 0.80, 0.41, 0.59, respectively). Patients with mRS ≥3 and 2 had similar vascular profile and favorable outcome (34% versus 29%), despite higher mortality (48% versus 39%).

Conclusions—
Prestroke disability does not seem to independently increase the risk of symptomatic intracranial hemorrhage after thrombolysis. Despite higher mortality, 1 in 3 previously disabled patients may return to his/her prestroke mRS. Therefore, they should not be routinely excluded from thrombolytic therapy.
Quadrant Distribution of Tropical Cyclone Inner-Core Kinematics in Relation to Environmental Shear
Authors: DeHart Jennifer C. , Houze Robert A. , Rogers Robert F. 
Published: February 2014

Abstract
Airborne Doppler radar data collected in tropical cyclones by National Oceanic and Atmospheric Administration WP-3D aircraft over an 8-yr period (2003–10) are used to statistically analyze the vertical structure of tropical cyclone eyewalls with reference to the deep-layer shear. Convective evolution within the inner core conforms to patterns shown by previous studies: convection initiates downshear right, intensifies downshear left, and weakens upshear. Analysis of the vertical distribution of radar reflectivity and vertical air motion indicates the development of upper-level downdrafts in conjunction with strong convection downshear left and a maximum in frequency upshear left. Intense updrafts and downdrafts both conform to the shear asymmetry pattern. While strong updrafts occur in the eyewall, intense downdrafts show far more radial variability, particularly in the upshear-left quadrant, though they concentrate along the eyewall edges. Strong updrafts are collocated with low-level inflow and upper-level outflow superimposed on the background flow. In contrast, strong downdrafts occur in association with low-level outflow and upper-level inflow.
Nonstationarity in Intermittent Rainfall: The “Dry Drift”
Authors: Schleiss Marc , Chamoun Sabine , Berne Alexis 
Published: February 2014

Abstract
A particular aspect of the nonstationary nature of intermittent rainfall is investigated. It manifests itself in the fact that the average rain rate varies with the distance to the surrounding dry areas. The authors call this fundamental link between the rainfall intensity and the rainfall occurrence process the “dry drift.” Using high-resolution radar rain-rate maps and disdrometer data, they show how the dry drift affects the structure and the variability of intermittent rainfall fields. They provide a rigorous geostatistical framework to describe it and propose an extension of the concept to more general quantities like the (rain)drop size distribution.
Genesis and Development Mechanisms of a Polar Mesocyclone over the Japan Sea
Authors: Watanabe Shun-ichi I. , Niino Hiroshi 
Published: February 2014

Abstract
A polar mesocyclone (PMC) observed over the Japan Sea on 30 December 2010 was studied using a nonhydrostatic mesoscale numerical model with a horizontal resolution of 2 km. The numerical simulation successfully reproduced the observed life cycle of the PMC. The results of the numerical simulation suggest that the life cycle of the PMC may be divided into three stages: an early development stage, in which a number of small vortices appear in a shear zone; a late development stage, which is characterized by the merger of vortices and the formation of a few larger vortices; and a mature stage, in which only a single PMC is present. During the early development stage, vortices are generated in the shear zones of strong updrafts in discrete cumulus convection cells. In contrast, during the late development stage, the vortices develop as a result of barotropic instability in the shear zone. A cloud-free eye and spiral cloud bands accompany the mature stage of a simulated PMC. A warm core structure also forms at the center of the PMC on account of adiabatic warming associated with downdrafts. The structures in the PMC during the mature stage resemble those of a tropical cyclone. Sensitivity experiments, in which sensible and latent heat fluxes from the sea surface and condensational heating were switched on/off, demonstrate that condensational heating is critical to the development of the PMC at all stages, and that sensible and latent heat fluxes play secondary roles.