bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring of therapy in atopic dermatitis – observations with the use of high‐frequency ultrasonography
Authors: Polańska A. , Silny W. , Jenerowicz D. , Knioła K. , Molińska‐Glura M. , Dańczak‐Pazdrowska A. 
Published: June 2014

BackgroundIn reactive and proactive therapy of atopic dermatitis a well established agent is tacrolimus, a member of calcineurin inhibitors' family. The clinical safety and efficacy of this drug were evaluated previously in randomized multicenter trials. However, so far in clinical studies the assessment of its action on the skin has been made only on the basis of different scores and scales. We present the 6‐month observations of tacrolimus therapy in atopic dermatitis patients monitored with the use of noninvasive techniques like high‐frequency ultrasonography and evaporimetry.MethodsThe study consisted of 39 patients withADand their mean age was 26.3 ± 12.8 years. The study lasted 6 months and every 4 weeks patient visited the outpatient clinic (totally 7 visits). The evaluation of disease severity within right antecubital fossa was obtained on the basis of Investigator's Global Assessment (IGA) score. During every control visit noninvasive measurements were carried in the form ofHF‐USG(with determination of subepidermal low echogenic band,SLEB) and evaporimetry.Results39 patients started the study and 22 of them (54.6%) finished it. Out of 39 patients, 31 (79.5%) received at least 4 week long proactive treatment. We observed statistically significant change ofIGA, meanSLEBvalue andTEWLduring underwent therapy. There were also statistically significant differences in meanSLEBandTEWLvalues between lesional and nonlesional measures.ConclusionsThis report shows the usefulness ofHF‐USGin monitoring tacrolimus therapy in atopic dermatitis. It is worth emphasizing, that this tool is easily reproducible and allows clinicians to visualize pathologic changes of all skinin vivo. As a noninvasive and independent of subjective judgment method,HF‐USGshould be included in overall evaluation of atopic dermatitis disease severity together with common scores or scales, especially in the era of evidence based medicine.
An Asian Origin of Virulent Aeromonas hydrophila Responsible for Disease Epidemics in United States-Farmed Catfish
Authors: Hossain Mohammad J. , Sun Dawei , McGarey Donald J. , Wrenn Shannon , Alexander Laura M. , Martino Maria Elena , Xing Ye , Terhune Jeffery S. , Liles Mark R. 
Published: June 2014

ABSTRACT

Since 2009, catfish farming in the southeastern United States has been severely impacted by a highly virulent and clonal population of
Aeromonas hydrophila
causing motile
Aeromonas
septicemia (MAS) in catfish. The possible origin of this newly emerged highly virulent
A. hydrophila
strain is unknown. In this study, we show using whole-genome sequencing and comparative genomics that
A. hydrophila
isolates from diseased grass carp in China and catfish in the United States have highly similar genomes. Our phylogenomic analyses suggest that U.S. catfish isolates emerged from
A. hydrophila
populations of Asian origin. Furthermore, we identified an
A. hydrophila
strain isolated in 2004 from a diseased catfish in Mississippi, prior to the onset of the major epidemic outbreaks in Alabama starting in 2009, with genomic characteristics that are intermediate between those of the Asian and Alabama fish isolates. Investigation of
A. hydrophila
strain virulence demonstrated that the isolate from the U.S. catfish epidemic is significantly more virulent to both channel catfish and grass carp than is the Chinese carp isolate. This study implicates the importation of fish or fishery products into the United States as the source of highly virulent
A. hydrophila
that has caused severe epidemic outbreaks in United States-farmed catfish and further demonstrates the potential for invasive animal species to disseminate bacterial pathogens worldwide.

IMPORTANCE
Catfish aquaculture farming in the southeastern United States has been severely affected by the emergence of virulent
Aeromonas hydrophila
responsible for epidemic disease outbreaks, resulting in the death of over 10 million pounds of catfish. Because the origin of this newly emerged
A. hydrophila
strain is unknown, this study used a comparative genomics approach to conduct a phylogenomic analysis of
A. hydrophila
isolates obtained from the United States and Asia. Our results suggest that the virulent isolates from United States-farmed catfish have a recent common ancestor with
A. hydrophila
isolates from diseased Asian carp. We have also observed that an Asian carp isolate, like recent U.S. catfish isolates, is virulent in catfish. The results from this study suggest that the highly virulent U.S. epidemic isolates emerged from an Asian source and provide another example of the threat that invasive species pose in the dissemination of bacterial pathogens.
Human Genetic Variation and Yellow Fever Mortality during 19th Century U.S. Epidemics
Authors: Blake Lauren E. , Garcia-Blanco Mariano A. 
Published: June 2014

ABSTRACTWe calculated the incidence, mortality, and case fatality rates for Caucasians and non-Caucasians during 19th century yellow fever (YF) epidemics in the United States and determined statistical significance for differences in the rates in different populations. We evaluated nongenetic host factors, including socioeconomic, environmental, cultural, demographic, and acquired immunity status that could have influenced these differences. While differences in incidence rates were not significant between Caucasians and non-Caucasians, differences in mortality and case fatality rates were statistically significant for all epidemics tested (P< 0.01). Caucasians diagnosed with YF were 6.8 times more likely to succumb than non-Caucasians with the disease. No other major causes of death during the 19th century demonstrated a similar mortality skew toward Caucasians. Nongenetic host factors were examined and could not explain these large differences. We propose that the remarkably lower case mortality rates for individuals of non-Caucasian ancestry is the result of human genetic variation in loci encoding innate immune mediators.IMPORTANCEDifferent degrees of severity of yellow fever have been observed across diverse populations, but this study is the first to demonstrate a statistically significant association between ancestry and the outcome of yellow fever (YF). With the global burden of mosquito-borne flaviviral infections, such as YF and dengue, on the rise, identifying and characterizing host factors could prove pivotal in the prevention of epidemics and the development of effective treatments.
Herbal medicines for cancer cachexia: protocol for a systematic review
Authors: Park Bongki , Jun Ji Hee , Jung Jeeyoun , You Sooseong , Lee Myeong Soo 
Published: June 2014

IntroductionTo assess the efficacy of herbal medicines as a treatment of cancer cachexia.Methods and analysisWe will search the following 13 electronic databases from their inception. MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary Medicine Database (AMED), China National Knowledge Infrastructure (CNKI), Wanfang, Journal Integration Platform (VIP) and six Korean Medical Databases (KoreaMed, the Korean Traditional knowledge Portal, OASIS, DBPIA, the Research Information Service System and the Korean Studies Information Service System) without restrictions on time or language. The data will be extracted independently by two authors using predefined criteria. Disagreements will be resolved by discussion between the authors. The risk of bias will be assessed using the Cochrane risk of bias tool.DisseminationThe review will be published in a journal. The review will also be disseminated electronically and in print. An update of the review will be conducted to inform and guide healthcare practice and policy.Trial registration numberPROSPERO 2013:CRD42013006612.
A Functional Variant in NKX3.1 Associated with Prostate Cancer Risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Authors: Martinez Erin E. , Darke Amy K. , Tangen Catherine M. , Goodman Phyllis J. , Fowke Jay H. , Klein Eric A. , Abdulkadir Sarki A. 
Published: June 2014

Abstract
NKX3.1 is an androgen-regulated prostate tumor suppressor protein. We previously found that antioxidant administration (N-acetylcysteine) in the Nkx3.1 knockout mouse model promoted prostate epithelial proliferation, suggesting that NKX3.1 activity modifies the effect of antioxidant administration on prostate carcinogenesis. Interestingly, administration of the antioxidant vitamin E significantly increased prostate cancer risk in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), suggesting that our animal experiments may be relevant to humans. To determine whether NKX3.1 played a role in increased human prostate cancer risk associated with antioxidant administration in SELECT, we investigated the joint risk of antioxidant administration and NKX3.1 genotypes previously found to be associated with decreased NKX3.1 mRNA expression (rs11781886) or DNA-binding activity in vitro (rs2228013) in the SELECT biomarker case–cohort substudy (1,866 cases; 3,135 non-cases). Multivariable COX regression models were developed to determine the joint association of NKX3.1 genotypes with administration of vitamin E, selenium, or the combination, compared with placebo. The CC genotype at rs11781886 combined with selenium administration was associated with increased overall prostate cancer risk [HR, 1.676; 95% confidence interval (CI), 1.011–2.777; P = 0.045] and low-grade prostate cancer risk (HR, 1.811; 95% CI, 1.016–3.228; P = 0.0441). Similarly, the rs11781886 minor allele (CC+CT) combined with vitamin E administration was significantly associated with increased prostate cancer risk (HR, 1.450; 95% CI, 1.117–1.882; P = 0.0052). Our results indicate that variation in NKX3.1 expression combined with selenium or vitamin E treatment modifies the risk of prostate cancer. Genetic background may modulate the effects of antioxidant supplementation thought to act as chemoprevention agents. Cancer Prev Res; 7(9); 950–7. ©2014 AACR.
EGFR Variant Heterogeneity in Glioblastoma Resolved through Single-Nucleus Sequencing
Authors: Francis Joshua M. , Zhang Cheng-Zhong , Maire Cecile L. , Jung Joonil , Manzo Veronica E. , Adalsteinsson Viktor A. , Homer Heather , Haidar Sam , Blumenstiel Brendan , Pedamallu Chandra Sekhar , Ligon Azra H. , Love J. Christopher , Meyerson Matthew , Ligon Keith L. 
Published: June 2014

Abstract
Glioblastomas (GBM) with EGFR amplification represent approximately 50% of newly diagnosed cases, and recent studies have revealed frequent coexistence of multiple EGFR aberrations within the same tumor, which has implications for mutation cooperation and treatment resistance. However, bulk tumor sequencing studies cannot resolve the patterns of how the multiple EGFR aberrations coexist with other mutations within single tumor cells. Here, we applied a population-based single-cell whole-genome sequencing methodology to characterize genomic heterogeneity in EGFR-amplified glioblastomas. Our analysis effectively identified clonal events, including a novel translocation of a super enhancer to the TERT promoter, as well as subclonal LOH and multiple EGFR mutational variants within tumors. Correlating the EGFR mutations onto the cellular hierarchy revealed that EGFR truncation variants (EGFRvII and EGFR carboxyl-terminal deletions) identified in the bulk tumor segregate into nonoverlapping subclonal populations. In vitro and in vivo functional studies show that EGFRvII is oncogenic and sensitive to EGFR inhibitors currently in clinical trials. Thus, the association between diverse activating mutations in EGFR and other subclonal mutations within a single tumor supports an intrinsic mechanism for proliferative and clonal diversification with broad implications in resistance to treatment.
Significance: We developed a novel single-cell sequencing methodology capable of identifying unique, nonoverlapping subclonal alterations from archived frozen clinical specimens. Using GBM as an example, we validated our method to successfully define tumor cell subpopulations containing distinct genetic and treatment resistance profiles and potentially mutually cooperative combinations of alterations in EGFR and other genes. Cancer Discov; 4(8); 956–71. ©2014 AACR.
See related commentary by Gini and Mischel, p. 876
This article is highlighted in the In This Issue feature, p. 855
Acute Changes of Mitral Valve Geometry During Interventional Edge-to-Edge Repair With the MitraClip System Are Associated With Midterm Outcomes in Patients With Functional Valve Disease
Authors: Schueler Robert , Momcilovic Diana , Weber Marcel , Welz Armin , Werner Nikos , Mueller Cornelius , Ghanem Alexander , Nickenig Georg , Hammerstingl Christoph 
Published: June 2014

Background—
Transcatheter mitral valve repair (TMVR) is a treatment option in patients with symptomatic functional or degenerative mitral regurgitation (DMR) at high surgical risk. The acute effect of MitraClip procedure on mitral valve (MV) annular geometry and its relation to functional outcomes is unclear. We sought to assess immediate effect of TMVR on MV annular geometry with 3-dimensional (3D) transesophageal echocardiography and the association of MV diameter reduction with functional response after 6 months.

Methods and Results—

Consecutive patients (n=111; age, 78.3±8.1 years) at high surgical risk (logistic EuroSCORE [European System for Cardiac Operative Risk Evaluation], 29.8±21.5%) underwent TMVR. The procedure was completed successfully in 107 (96%) patients with 3D reconstruction of MV annular geometry immediately before and after clip implantation. Only patients with functional mitral regurgitation (n=71) experienced an acute reduction of anterior-posterior MV diameters (4.0±0.6 and 3.6±0.6 cm;
P
<0.0001), MV annulus areas (2D annulus area, 13.9±3.8 and 12.8±3.4 cm
2
;
P
<0.0001 and 3D annulus area, 14.4±3.9 and 12.9±3.4 cm
2
;
P
<0.0001), and MV annular geometry (MV sphericity index, 0.9±0.1 and 0.8±0.1;
P
<0.0001); the lateral medial MV diameters remained unchanged (4.3±0.7 and 4.4±0.6 cm;
P
=0.13). In subjects with DMR, all MV annular geometry-defining values were not significantly altered after TMVR (n=36;
P
>0.05). Acute anterior-posterior diameter reduction was associated with clinical response to TMVR after 6 months of follow-up (cutoff value, ≥6.4%; area under the curve, 0.81;
P
=0.002; sensitivity, 81.6%; specificity, 81.8%), which was confirmed by additional regression analysis (
P
=0.007).

Conclusions—
Three-dimensional transesophageal echocardiography enables assessment of acute changes of MV geometry in patients undergoing the MitraClip procedure. Only patients with functional mitral regurgitation experienced significant reduction of MV annular dimensions, which was associated with clinical response to TMVR.
Relationship Between Care Gaps and Projected Life Expectancy After Acute Myocardial Infarction
Authors: Ko Dennis T. , Austin Peter C. , Tu Jack V. , Lee Douglas S. , Yun Lingsong , Alter David A. 
Published: June 2014

Background—
Higher-risk patients may not receive evidence-based therapy because of limited life expectancy, which is a composite measure that encompasses many patient factors, including age, frailty, and comorbidities. In this study, we evaluated the extent to which treatment care gaps can be explained by a difference in projected life expectancy.

Methods and Results—

An observational cohort study was conducted on acute myocardial infarction patients hospitalized in Ontario, Canada. Projected life expectancy was estimated using actual survival data with extrapolation using proportional hazard models adjusting for important covariates. The relationship between projected life expectancy with statins and reperfusion therapy was examined using generalized linear models. Among the 7001 acute myocardial infarction patients, 84.3% were prescribed statins and 72.9% were treated with reperfusion therapy. When projected life expectancy was <10 years, the likelihood of receiving either treatment declined progressively with reduction in life expectancy (
P
<0.001). At the 25th percentile of projected life expectancies, the likelihood of receiving a statin decreased by 1.4% (95% confidence interval, 1.0–1.8%), and acute reperfusion therapy decreased by 2.6% (95% confidence interval, 1.8–3.3%) for each year decline in projected life expectancy.

Conclusions—
Life expectancy of a patient strongly influences evidence-based treatment in acute myocardial infarction. It was seen not only among patients with limited life expectancies but also among those with many years to live. Treatment care gaps may reflect clinicians’ synthesis about frailty and life-expectancy gains.
Sex, Socioeconomic Status, Access to Cardiac Catheterization, and Outcomes for Acute Coronary Syndromes in the Context of Universal Healthcare Coverage
Authors: Fabreau Gabriel E. , Leung Alexander A. , Southern Danielle A. , Knudtson Merrill L. , McWilliams J. Michael , Ayanian John Z. , Ghali William A. 
Published: June 2014

Background—
Sex and neighborhood socioeconomic status (nSES) may independently affect the care and outcomes of acute coronary syndrome, partly through barriers in timely access to cardiac catheterization. We sought to determine whether sex modifies the association between nSES and the receipt of cardiac catheterization and mortality after an acute coronary syndrome in a universal healthcare system.

Methods and Results—

We studied 14 012 patients with acute coronary syndrome admitted to cardiology services between April 18, 2004, and December 31, 2011, in Southern Alberta, Canada. We used multivariable logistic regression to compare the odds of cardiac catheterization within 2 and 30 days of admission and the odds of 30-day and 1-year mortality for men and women by quintile of neighborhood median household income. Significant relationships between nSES and the receipt of cardiac catheterization and mortality after acute coronary syndrome were detected for women but not men. When examined by nSES, each incremental decrease in neighborhood income quintile for women was associated with a 6% lower odds of receiving cardiac catheterization within 30 days (
P
=0.01) and a 14% higher odds of 30-day mortality (
P
=0.03). For men, each decrease in neighborhood income quintile was associated with a 2% lower odds of receiving catheterization within 30 days (
P
=0.10) and a 5% higher odds of 30-day mortality (
P
=0.36).

Conclusions—
Associations between nSES and receipt of cardiac catheterization and 30-day mortality were noted for women but not men in a universal healthcare system. Care protocols designed to improve equity of access to care and outcomes are required, especially for low-income women.
Efficacy and Safety of Rivaroxaban Compared With Warfarin Among Elderly Patients With Nonvalvular Atrial Fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)
Authors: Halperin Jonathan L. , Hankey Graeme J. , Wojdyla Daniel M. , Piccini Jonathan P. , Lokhnygina Yuliya , Patel Manesh R. , Breithardt Günter , Singer Daniel E. , Becker Richard C. , Hacke Werner , Paolini John F. , Nessel Christopher C. , Mahaffey Kenneth W. , Califf Robert M. , Fox Keith A.A. 
Published: June 2014

Background—
Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). This prespecified secondary analysis compares outcomes in older and younger patients.

Methods and Results—

There were 6229 patients (44%) aged ≥75 years with atrial fibrillation and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio=2.0–3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance <50 mL/min), double blind. The primary end point was stroke and systemic embolism by intention to treat. Over 10 866 patient-years, older participants had more primary events (2.57% versus 2.05%/100 patient-years;
P
=0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years;
P
<0.0001). Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence interval, 0.63–1.02) and younger patients (2.00% versus 2.10%/100 patient-years; hazard ratio=0.95; 95% confidence interval, 0.76–1.19; interaction
P
=0.313), as were major bleeding rates (≥75 years: 4.86% rivaroxaban versus 4.40% warfarin per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92–1.34; <75 years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence interval, 0.78–1.19; interaction
P
=0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response.

Conclusions—
Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly.
Atrial Fibrillation, Stroke, and Anticoagulation in Medicare Beneficiaries: Trends by Age, Sex, and Race, 1992–2010
Authors: Shroff Gautam R. , Solid Craig A. , Herzog Charles A. 
Published: June 2014

Background

We evaluated temporal trends in ischemic stroke and warfarin use among demographic subsets of the
US
Medicare population that are not well represented in randomized trials of warfarin for stroke prevention in nonvalvular atrial fibrillation (
AF
).

Methods and Results

One‐year cohorts of Medicare–primary payer patients (1992–2010) were created using the Medicare 5% sample.
International Classification of Diseases, Ninth Revision, Clinical Modification
codes were used to identify
AF
and ischemic and hemorrhagic stroke; ≥3 consecutive prothrombin time claims were used to identify warfarin use. Ischemic stroke rates (per 1000 patient‐years) decreased markedly from 1992 to 2010. Among women, rates decreased from 37.1 to 13.6 for ages 65 to 74 years, from 55.2 to 16.5 for ages 74 to 84, and from 66.9 to 22.9 for age ≥85; warfarin use increased 31% to 59%, 27% to 63%, and 15% to 49%, respectively. Among men, rates decreased from 33.8 to 11.7 for ages 65 to 74 years, from 49.2 to 13.8 for ages 75 to 84, and from 51.5 to 18.0 for age ≥ 85; warfarin use increased 34% to 63%, 28% to 66%, and 15% to 55%, respectively. Rates decreased from 47.0 to 14.8 for whites and 73.0 to 29.3 for blacks; warfarin use increased 27% to 61% and 19% to 52%, respectively. In all age categories, the thromboembolic risk (
CHADS
[congestive heart failure, hypertension, age ≥75 years, diabetes, stroke]) score was significantly higher among women (versus men) and blacks (versus whites).

Conclusions

Ischemic stroke rates among Medicare
AF
patients decreased significantly in all demographic subpopulations from 1992–2010, coincident with increasing warfarin use. Ischemic stroke rates remained higher and warfarin use rates remained lower for women and blacks with
AF
, groups whose baseline
CHADS
scores were higher.