bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host-Pathogen-Treatment Triad: Host Factors Matter Most in Methicillin-Resistant Staphylococcus aureus Bacteremia Outcomes
Authors: Guillamet M. Cristina Vazquez , Vazquez Rodrigo , Deaton Benjamin , Shroba Jenny , Vazquez Laia , Mercier Renee-Claude 
Published: December 2017

ABSTRACT

Previous studies have separately emphasized the importance of host, pathogen, and treatment characteristics in determining short-term or in-hospital mortality rates for patients with methicillin-resistant
Staphylococcus aureus
(MRSA) bloodstream infections. Less is known about the relative importance of these factors and their interactions in determining short-, medium-, and long-term mortality rates. This is an observational cohort study in which data for all patients admitted to the University of New Mexico (UNM) Health Sciences Center (HSC) between July 2002 and August 2013 with MRSA-positive blood cultures were recorded. We collected patients' demographics and treatment data, as well as data on genetic markers of the MRSA isolates. Outcomes of interest were determinants of short-term (within 30 days), medium-term (30 to 90 days), and long-term (>90 days) mortality rates. This study included 273 patients with MRSA bacteremia. Short-, medium-, and long-term mortality rates were 18.7%, 26.4%, and 48%, respectively. Thirty-day mortality rates were influenced by host variables and host-pathogen interaction characteristics. Pitt bacteremia scores, malignancy, and health care exposure contributed to 30- to 90-day mortality rates, while treatment duration of >4 weeks had a protective effect. Age remained a significant risk factor for death at >90 days, while admission leukocytosis was protective. Infection represented the most frequent cause of death for all three time frames; rates varied from 72.6% in the first 30 days and 60% for 30 to 90 days to 35.7% for >90 days (
P
= 0.003). Host characteristics affect short-, medium-, and long-term mortality rates for MRSA bloodstream infections more than do pathogen genetic markers and treatment factors.
Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing
Authors: Neely Michael N. , Kato Lauren , Youn Gilmer , Kraler Lironn , Bayard David , van Guilder Michael , Schumitzky Alan , Yamada Walter , Jones Brenda , Minejima Emi 
Published: December 2017

ABSTRACT

We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentration-time curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians targeted trough concentrations of 10 to 20 mg/liter (infection dependent) and controlled dosing. In years 2 and 3, the study team controlled vancomycin dosing with BestDose Bayesian software to achieve a daily, steady-state AUC/MIC ratio of ≥400, with a maximum AUC value of 800 mg · h/liter, regardless of trough concentration. For Bayesian estimation of AUCs, we used trough samples in years 1 and 2 and optimally timed samples in year 3. We enrolled 252 adults who were ≥18 years old with ≥1 available vancomycin concentration. Only 19% of all trough concentrations were therapeutic versus 70% of AUCs (
P
< 0.0001). After enrollment, median trough concentrations by year were 14.4, 9.7, and 10.9 mg/liter (
P
= 0.005), with 36%, 7%, and 6% over 15 mg/liter (
P
< 0.0001). Bayesian AUC-guided dosing in years 2 and 3 was associated with fewer additional blood samples per subject (3.6, 2.0, and 2.4;
P
= 0.003), shorter therapy durations (8.2, 5.4, and 4.7 days;
P
= 0.03), and reduced nephrotoxicity (8%, 0%, and 2%;
P
= 0.01). The median inpatient stay was 20 days among nephrotoxic patients versus 6 days (
P
= 0.002). There was no difference in efficacy by year, with 42% of patients having microbiologically proven infections. Compared to trough concentration targets, AUC-guided, Bayesian estimation-assisted vancomycin dosing was associated with decreased nephrotoxicity, reduced per-patient blood sampling, and shorter length of therapy, without compromising efficacy. These benefits have the potential for substantial cost savings. (This study has been registered at ClinicalTrials.gov under registration no. NCT01932034.)
Mapping Protective Regions on a Three-Dimensional Model of the Moraxella catarrhalis Vaccine Antigen Oligopeptide Permease A
Authors: Perez Antonia C. , Johnson Antoinette , Chen Ziqiang , Wilding Gregory E. , Malkowski Michael G. , Murphy Timothy F. 
Published: December 2017

ABSTRACT

A vaccine against
Moraxella catarrhalis
would reduce tremendous morbidity, mortality, and financial burden by preventing otitis media in children and exacerbations of chronic obstructive pulmonary disease (COPD) in adults. Oligopeptide permease A (OppA) is a candidate vaccine antigen that is (i) a nutritional virulence factor expressed on the bacterial cell surface during infection, (ii) widely conserved among strains, (iii) highly immunogenic, and (iv) a protective antigen based on its capacity to induce protective responses in immunized animals. In the present study, we show that the antibodies to OppA following vaccination mediate accelerated clearance in animals after pulmonary challenge. To identify regions of OppA that bind protective antibodies, truncated constructs of OppA were engineered and studied to map regions of OppA with surface-accessible epitopes that bind high-avidity antibodies following vaccination. Protective epitopes were located in the N and C termini of the protein. Immunization of mice with constructs corresponding to these regions (T5 and T8) induced protective responses. Studies of overlapping peptide libraries of constructs T5 and T8 with OppA immune serum identified two discrete regions on each construct. These potentially protective regions were mapped on a three-dimensional computational model of OppA, where regions with solvent-accessible amino acids were identified as three potentially protective epitopes. In all, these studies revealed two regions with three specific epitopes in OppA that induce potentially protective antibody responses following vaccination. Detection of antibodies to these regions could serve to guide vaccine formulation and as a diagnostic tool for monitoring development of protective responses during clinical trials.
The clinical and prognostic relevance of driver mutations in 203 Taiwanese patients with primary myelofibrosis
Authors: Kuo Ming-Chung , Lin Tung-Huei , Sun Chien-Feng , Lin Tung-Liang , Wu Jin-Hou , Wang Po-Nan , Huang Ying-Jung , Chang Hung , Huang Ting-Yu , Shih Lee-Yung 
Published: December 2017

AimsWe investigated the clinical and prognostic relevance of the mutational status of driver genes with allele burden and endogenous erythroid colony (EEC) growth in 203 Taiwanese patients with primary myelofibrosis (PMF).MethodsPyrosequencing was used to detectJAK2V617Fmutational status and measure allele burden, whileMPL(exon 10) mutations were analysed by PCR assay and then by direct sequencing.CALRexon 9 mutations were first screened for length changes by GeneScan followed by sequencing. The allele burden of the mutatedCALRgene was measured by pyrosequencing. The EEC assay was conducted using a serum-free culture system.ResultsThe frequencies of the three driver mutations and triple-negative status were similarly distributed between pre-PMF and overt PMF patients, except that pre-PMF patients had a higher incidence ofCALRtype 2/type-2 like mutations and a lowerJAK2V617Fallele burden. EEC growth andCALRmutations conferred favourable overall survival (OS). A lowerJAK2V617Fallele burden and grade 3 bone marrow fibrosis were associated with shorter OS and decreased leukaemia-free survival (LFS). Type 2/type 2-likeCALmutations were associated with better LFS compared with type1/type 1-like mutations. Patients with triple-negative mutation status had significantly worse OS and LFS. The allele burden ofCALRmutations remained unchanged, while someJAK2V617Fmutations showed clonal expansion in patients during secondary acute myeloid leukaemia transformation.ConclusionsOur study showed that EEC growth, a higherJAK2V617Fallele burden andCALRmutations, especially type 2, were independent predictors for better outcomes in PMF. The allele burden ofCALRmutations remained stable, but the allele burden ofJAK2V617Fmutations was variable during leukaemia transformation.
Trends in adolescent mental health during economic upturns and downturns: a multilevel analysis of Swedish data 1988-2008
Authors: Kim Yunhwan , Hagquist Curt 
Published: December 2017

BackgroundA long-term trend of increasing mental health problems among adolescents in many Western countries indicates a great need to investigate if and how societal changes have contributed to the reported increase. Using seven waves of repeated cross-sectional data collected between 1988 and 2008 in Sweden, the current study examined if economic factors at the societal level (municipality unemployment rate) and at the individual level (worry about family finances), and their interaction could explain a secular trend in mental health problems.MethodsParticipants were 17 533 students of age 15–16 years (49.3% girls), from 14 municipalities in a county of Sweden. Data on adolescents’ mental health (psychosomatic problems) and worry about family finances were obtained using a self-report questionnaire. A series of multilevel regression analyses were conducted in order to explain the trends in adolescents’ mental health.ResultsThe results indicated that the individual-level predictor (worry about family finances) significantly explained the increasing rates of adolescents’ psychosomatic problems. This was particularly the case during the mid-1990s, which was characterised by a severe recession in Sweden with high unemployment rates. For example, after accounting for adolescents’ worry, a significant increase in psychosomatic symptoms between 1988 and 1998 among girls (b=0.112, P<0.05) disappeared (b=0.018, P>0.05) and a non-significant decrease between 1988 and 1995 among boys (b=−0.017, P>0.05) became significant (b=−0.142, P<0.05). Neither municipality unemployment rate nor its interaction with adolescents’ worry explained psychosomatic problems.ConclusionsThe findings demonstrate the effects of adolescents’ worry about family finances on a secular trend in mental health problems during an economically bleak period of time. The study highlights the need for repeated measurements including a large number of time points over a long time period in order to analyse time-specific putative explanatory factors for trends in adolescent mental health problems.
HIV and herpes simplex virus type 2 epidemiological synergy: misguided observational evidence? A modelling study
Authors: Omori Ryosuke , Nagelkerke Nico , Abu-Raddad Laith J 
Published: December 2017

ObjectivesTo investigate whether observational studies of HIV and herpes simplex virus type 2 (HSV-2) infections have the capacity to assess the HIV/HSV-2 epidemiological synergy.MethodsAn individual-based Monte Carlo model was used to simulate HIV/HSV-2 epidemics in two scenarios: no HIV/HSV-2 biological interaction and HSV-2 seropositivity enhancing HIV acquisition. Cross-sectional observational studies were simulated by sampling individuals from the population to assess resulting crude and adjusted ORs of the HIV/HSV-2 association. Meta-analyses were conducted to estimate the pooled mean ORs. Impact of under-reporting of sexual behaviour and miscapture of high-risk individuals was assessed through sensitivity analyses.ResultsAssuming no HIV/HSV-2 biological interaction, the crude HIV/HSV-2 OR ranged between 1.38 and 9.93, with a pooled mean of 6.45 (95% CI 5.81 to 7.17). Adjustment for the number of sexual partners over last year, over lifetime and for both partner numbers simultaneously reduced the mean OR to 5.45 (95% CI 4.90 to 6.06), 3.70 (95% CI 3.32 to 4.12) and 3.54 (95% CI 3.17 to 3.94), respectively. Assuming HIV/HSV-2 biological interaction, the crude OR ranged between 3.44 and 9.95, with a pooled mean of 8.05 (95% CI 7.14 to 9.07). The adjustments reduced the mean OR to 7.00 (95% CI 6.21 to 7.90), 3.76 (95% CI 3.32 to 4.25) and 3.68 (95% CI 3.25 to 4.17), respectively. Under-reporting of partners reduced the confounder-adjustment effects. Miscapture of high-risk individuals considerably lowered the estimated ORs.ConclusionsIt is difficult to control for sexual-behaviour confounding in observational studies. The observed HIV/HSV-2 association appears more consistent with two infections sharing the same mode of transmission, rather than with HSV-2 enhancing HIV acquisition.
A METHOD FOR ESTIMATING THE RATES OF GASTRIC SECRETION AND EMPTYING
Authors: Hildes J. A. , Dunlop D. L. 
Published: December 2017

The dilution indicator, phenol red, was used to measure rates of gastric secretion and emptying. A test meal containing 2.5 mgm. phenol red was introduced into the stomach through a tube, the stomach contents mixed, and a sample aspirated. The volume of stomach contents was calculated from the immediate dilution of the phenol red. At the end of a 20 min. test period the stomach volume was again estimated by sampling before and after the addition of 1.0 mgm. phenol red. From the known volume of gastric contents and the known concentration of phenol red the rates of gastric secretion and emptying were calculated from the equations (1) [Formula: see text], (2) [Formula: see text]. Q0 and Q are the quantities of dye at the beginning and end of a test period of t minutes' duration; V0 and V are volumes of stomach contents at these times and A and B are the rates of secretion and emptying respectively. The results of 10 experiments are presented.
CIRCULATION PÉRIPHÉRIQUE ET TENEUR DES SURRÉNALES EN ADRÉNALINE ET EN ARTÉRÉNOL (NORADRÉNALINE) CHEZ LE RAT BLANC EXPOSÉ AU FROID
Authors: DesMarais André , Dugal L.-Paul 
Published: December 2017

Experiments made on white rats exposed to cold disclosed the following facts: (1). During the period of resistance and acclimatization to cold, the peripheral circulation shows alternate phases of vasodilation and vasoconstriction, with prevalance of the latter. (2). Complete adaptation to cold is accompanied by the establishment of a new rate of peripheral circulation, which is a light vasodilation. (3). Peripheral circulatory changes which occur during the period of resistance and acclimatization to cold are not accompanied with parallel fluctuations of the adrenaline and arterenol content of the adrenal medulla, but exposure to cold seems to increase gradually the adrenal content in both hormones until adaptation is reached.
INFLUENCE DE L’ADMINISTRATION D’ADRÉNALINE ET D’ARTÉRÉNOL SUR L’HYPERTROPHIE DE LA SURRÉNALE AU FROID
Authors: DesMarais André , Dugal L.-Paul 
Published: December 2017

By experiments made on white rats of the Wistar strain, it was shown that: (1). Injection of either pure adrenaline or pure arterenol has no effect on the hypertrophy of the adrenal cortex during exposure to cold. (2). Injection of adrenaline lowers the adrenal content of this hormone, with out influencing the level of the other hormone, arterenol, in the adrenal medulla. (3). Injection of arterenol is followed by a drop of this substance in the adrenal medulla, while the adrenaline content remains unchanged. (4). Injection of adrenaline in rats exposed to a cold environment seems to enhance their survival.
THE RELATIONSHIP OF DIETARY FACTORS TO RAT SERUM ALKALINE PHOSPHATASE
Authors: Tuba Jules , Jelinek Bohdan , Shaw Ridley K. , Madsen Neil B. 
Published: December 2017

Weanling rats were fed dietary concentrations of 0%, 5%, 10%, 30%, and 91% casein. Complete absence of dietary protein resulted in death of the young animals within five weeks. Activity of serum alkaline phosphatase was at starvation levels during this period. Optimal growth was obtained at 30% dietary level of casein, and alkaline phosphatase activity was in the normal range. No effect on the enzyme could be attributed to the protein. There is a highly significant correlation between daily food consumption and serum phosphatase activity, which is attributed to the fat component of the various diets. Adult male rats were subjected to a three-week period of protein depletion, which was followed by a two-week period of protein repletion. The protein was supplied in the following forms: casein, dried brewer’s yeast, wheat gluten, casein plus wheat gluten, and dried brewer’s yeast plus gluten. Enzyme values at the end of the experiment were typical for the high fat diet (26%) which these animals were receiving. Once more there is a significant correlation between serum alkaline phosphatase activity and daily consumption of fat, whereas the protein component of the diet is without effect on the enzyme.
The Hipster Approach for Improving Cloud System Efficiency
Authors: Nishtala Rajiv , Carpenter Paul , Petrucci Vinicius , Martorell Xavier 
Published: December 2017

In 2013, U.S. data centers accounted for 2.2% of the country’s total electricity consumption, a figure that is projected to increase rapidly over the next decade. Many important data center workloads in cloud computing are interactive, and they demand strict levels of quality-of-service (QoS) to meet user expectations, making it challenging to optimize power consumption along with increasing performance demands.
This article introduces Hipster, a technique that combines heuristics and reinforcement learning to improve resource efficiency in cloud systems. Hipster explores heterogeneous multi-cores and dynamic voltage and frequency scaling for reducing energy consumption while managing the QoS of the latency-critical workloads. To improve data center utilization and make best usage of the available resources, Hipster can dynamically assign remaining cores to batch workloads without violating the QoS constraints for the latency-critical workloads. We perform experiments using a 64-bit ARM big.LITTLE platform and show that, compared to prior work, Hipster improves the QoS guarantee for Web-Search from 80% to 96%, and for Memcached from 92% to 99%, while reducing the energy consumption by up to 18%. Hipster is also effective in learning and adapting automatically to specific requirements of new incoming workloads just enough to meet the QoS and optimize resource consumption.
NAMPT Is a Potent Oncogene in Colon Cancer Progression that Modulates Cancer Stem Cell Properties and Resistance to Therapy through Sirt1 and PARP
Authors: Lucena-Cacace Antonio , Otero-Albiol Daniel , Jiménez-García Manuel P. , Muñoz-Galvan Sandra , Carnero Amancio 
Published: December 2017

Abstract
Purpose: Colorectal cancer is the second most common cancer in women and the third most common in men worldwide. However, despite current progress, many patients with advanced and metastatic tumors still die from the malignancy. Refractory disease often relies on nicotinamide adenine dinucleotide (NAD)-dependent mechanisms. NAD metabolism and a stable NAD regeneration circuit are required to maintain tissue homeostasis and metabolism. However, high levels of NAD confer therapy resistance to tumors.
Experimental Design: Ectopic overexpression of nicotinamide phosphoribosil transferase (NAMPT) and shRNAs in colorectal cancer cell lines, tumorigenic and stemness properties and transcription measurement in culture and in vivo. Transcriptional analysis in public databases. Therapeutic approaches.
Results: NAMPT, the rate-limiting enzyme responsible for the highest source of physiologic NAD biosynthesis, increases tumorigenic properties and induces cancer stem cell–like properties through pathways that control stem cell signaling, thus enriching the cancer-initiating cell (CIC) population. Furthermore, NAMPT expression correlated with high levels of CIC-like cells in colon tumors directly extracted from patients, and transcription meta-analysis revealed that NAMPT is also a key factor that induces cancer stem pathways in colorectal cancer tumors. This effect is mediated by PARP and SIRT1. In addition, we report a novel NAMPT-driven signature that stratifies prognosis from high to low expression groups. The NAMPT signature contained SIRT1 and PARP1 levels as well as other cancer stem cell–related genes. Finally, NAMPT inhibition increased the sensitivity to apoptosis in both NAMPT-expressing cells and tumorspheres.
Conclusions: NAMPT represents a novel therapeutic target in colon cancer progression and relapse, particularly the CIC subset of human colon cancers. Clin Cancer Res; 24(5); 1202–15. ©2017 AACR.
Novel Interactive Data Visualization
Authors: Brigdan Matthew , Hill Michael D. , Jagdev Abhijeet , Kamal Noreen 
Published: December 2017

Background and Purpose—
The ESCAPE (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) randomized clinical trial collected a large diverse data set. However, it is difficult to fully understand the effects of the study on certain patient groups and disease progression. We developed and evaluated an interactive visualization of the ESCAPE trial data.

Methods—
We iteratively designed an interactive visualization using Python’s Bokeh software library. The design was evaluated through a user study, which quantitatively evaluated its efficiency and accuracy against traditional modified Rankin Scalegraphic. Qualitative feedback was also evaluated.

Results—

The novel interactive visualization of the ESCAPE data are publicly available at
http://escapevisualization.herokuapp.com/
. There was no difference in the efficiency and accuracy when comparing the use of the novel with the traditional visualization. However, users preferred the novel visualization because it allowed for greater exploration. Some insights obtained through exploration of the ESCAPE data are presented.

Conclusions—
Novel interactive visualizations can be applied to acute stroke trial data to allow for greater exploration of the results.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01778335.
Autonomic Dysfunction Predicts Clinical Outcomes After Acute Ischemic Stroke
Authors: Xiong Li , Tian Ge , Leung Howan , Soo Yannie O.Y. , Chen Xiangyan , Ip Vincent H.L. , Mok Vincent C.T. , Chu Winnie C.W. , Wong Ka Sing , Leung Thomas W.H. 
Published: December 2017

Background and Purpose—
Central autonomic dysfunction increases stroke morbidity and mortality. We aimed to investigate whether poststroke autonomic dysfunction graded by Ewing battery can predict clinical outcome.

Methods—
In this prospective observational study, we assessed autonomic function of ischemic stroke patients within 7 days from symptom onset by Ewing battery. On the basis of the magnitude of autonomic dysfunction, we stratified patients into significant (definite, severe, or atypical) or minor (normal or early) autonomic function impairment groups and correlated the impairment with the 3-month modified Rankin Scale score (good outcome: modified Rankin Scale score 0≈2; poor outcome: modified Rankin Scale score 3≈6).

Results—

Among the 150 patients enrolled (mean age, 66.4±9.9 years; 70.7% males), minor autonomic dysfunction was identified in 36 patients (24.0%), and significant autonomic dysfunction was identified in 114 patients (76.0%) based on Ewing battery. In 3 months, a poor functional outcome was found in 32.5% of significant group patients compared with 13.9% in the minor group (
P
=0.031). Crude odds ratios of the magnitude of autonomic dysfunction and 3-month unfavorable functional outcome after acute ischemic stroke were 2.979 (95% confidence interval, 1.071–8.284;
P
=0.036). After adjusting for confounding variables with statistical significance between the 2 functional outcome subgroups identified in univariate analysis (including sex and National Institutes of Health Stroke Scale score on admission), the magnitude of autonomic dysfunction still independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141–9.335;
P
=0.027).

Conclusions—
Autonomic dysfunction gauged by Ewing battery predicts poor functional outcome after acute ischemic stroke.