bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of care among patients undergoing lower extremity revascularization
Authors: Slovut David P , Kargoli Faraj , Fletcher Jason J , Etkin Yana , Lipsitz Evan C 
Published: September 2014

Background: Compliance with guidelines for treating patients with peripheral artery disease (PAD) lags compliance for treating patients with coronary artery disease. We assessed the gap between guidelines and practice for patients with PAD who underwent lower extremity revascularization (LER) at our institution from 2007 to 2010. Methods: Quality of care (QoC) was calculated by measuring provider performance on four indicators (antiplatelet therapy, dyslipidemia management, control of hypertension, and diabetes) derived from the ACCF/AHA PAD guidelines. The QoC score was calculated at the time of admission and at time of discharge for each patient, and reflects the proportion of indicated treatments received. Results: Patients ( n = 734, mean age 70±11, female 51%) were followed for a mean of 2.0±1.4 years (range 0–5.7) following LER. The indication for LER was claudication (24.8%), rest pain (16.7%), and tissue loss (58.4%). The percentage of patients with a perfect QoC score increased significantly during hospital admission (11% to 21%, p < 0.001). Significant multivariate predictors of perfect QoC score included race/ethnicity, Charlson score, severity of LE ischemia, and observation period (admission, discharge). Multivariate analysis demonstrated that age>75 years, heart failure, chronic kidney disease, rest pain, and tissue loss—but not compliance with four guideline-based therapies—were associated with decreased freedom from the composite endpoint of major amputation, repeat revascularization, and death. Conclusions: Although adherence to guidelines improved over time, we found a significant gap between guidelines and practice for this cohort of patients at increased risk for adverse cardiovascular events.
Association of echocardiographic left ventricular structure and −344C/T aldosterone synthase gene variant: A meta-analysis
Authors: Wang Lijuan , Zhou Jiapeng , Zhang Bei , Wang Hao , Li Mei , Niu Qiuli , Chen Yubao , Chen Runsheng , Wen Shaojun 
Published: September 2014

Background: Aldosterone synthase (CYP11B2) is one of the most studied candidate genes related to essential hypertension (EH) and left ventricular hypertrophy (LVH). Some studies have focused on the relationship between −344C/T polymorphism (rs1799998) in the CYP11B2 gene and LVH, but the results are controversial. This meta-analysis is purposed to reveal the relationship between the −344C/T and the left ventricular structure and function, including left ventricular end diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular mass/left ventricular mass index (LVM/LVMI), left ventricular posterior wall thickness (LVPWT), and interventricular septal wall thickness (IVS). Methods: A literature search of PubMed and Embase databases was conducted on articles published before January 27, 2014. The odds ratios with 95% confidence intervals were calculated. Heterogeneity analyses were performed using meta-regression. Tests for publication bias were also performed and biased studies should be removed from subsequent analyses. Results: There were 20 studies with a total of 6780 subjects meeting the inclusion criteria. The main finding was that concentration levels of LVEDD and LVESD were higher in CC homozygous individuals than in TT homozygous individuals in the whole group. In the Asian subgroup, TT homozygous individuals had larger IVS than CC homozygous individuals. In the Caucasian normotension subgroup, CC homozygous individuals had larger LVM/LVMI than TT homozygous individuals. In the Asian essential hypertension subgroup, TT homozygous individuals had larger LVPWT values than CC homozygous individuals. Conclusions: The present findings support the hypothesis that CC homozygous individuals may have greater left ventricular diameters (LVEDD and LVESD) regardless of their ethnicities or physical conditions.
Electrocardiogram-based scoring system for predicting secondary pulmonary hypertension: A cross-sectional study
Authors: Pancholy Samir Bipin , Palamaner Subash Shantha Ghanshyam , Patel Nimesh Kirit , Boruah Pranjal , Nanavaty Sukrut , Chandran Sindu , Sethi Arjinder , Sheth Jignesh 
Published: September 2014

Objectives In this study, we have developed an electrocardiogram-based scoring system to predict secondary pulmonary hypertension. Design A cross-sectional study. Setting Single tertiary-care hospital in Scranton, Pennsylvania, USA. Participants Five hundred and fifty-two consecutive patients undergoing right heart catheterization between 2006 and 2009. Main outcome measures Surface electrocardiogram was assessed for R-wave in lead V1 ≥ 6mm, R-wave in V6 ≤ 3mm, S-wave in V6 ≥ 3mm, right atrial enlargement, right axis deviation and left atrial enlargement. Pulmonary hypertension was defined as mean pulmonary artery pressure ≥25 mmHg, determined by right heart catheterization. Results A total of 297 (54%) patients in the study cohort had pulmonary hypertension. In total, 332 patients from the study cohort formed the development cohort and the remaining 220 patients formed the validation cohort. In the development cohort, based on log odds ratios of association, RAE, LAE, RAD, R-wave in V1 ≥ 6 mm were assigned scores of 5, 2, 2 and 1, respectively, to form a 10-point scoring system “Scranton PHT (SP) score”. SP scores of 5 points and 7 points in DC showed C-statistic of 0.83 and 0.89, respectively, for discriminating pulmonary hypertension. C-statistic for RAE alone was significantly lower compared to an SP score of 7 (0.83 vs. 0.89, P = 0.021). The reliability of SP score in the validation cohort was acceptable. Conclusion SP score provides a good point-of-care tool to predict pulmonary hypertension in patients with clinical suspicion of it.
Female community health volunteers service utilization for childhood illness- improving quality of health services only is not enough: a cross-sectional study in mid-western region, Nepal
Authors: Miyaguchi Moe , Yasuoka Junko , Poudyal Amod Kumar , Silwal Ram Chandra , Jimba Masamine 
Published: September 2014

Abstract

Background
Female Community Health Volunteers (FCHVs) are considered service providers for major health problems at the community level in Nepal. However, few studies have been conducted about the roles of FCHVs from the users’ perspective. This study sought to examine the current status of FCHV service utilization and identify the determinants of caregivers’ utilization of FCHVs’ health services in the mid-western region of Nepal.

Methods
This cross-sectional study targeted 446 caregivers of children under five years of age and whose children had ever fallen ill in the study village development committees (VDCs) of three districts of Nepal. Caregivers were asked about their usual health practices for childhood illness, health service utilization for childhood illness, children’s health condition, satisfaction with health services, and socio-demographic status. Descriptive statistics and multiple logistic regression were used for analysis.

Results
Among 446 caregivers, 66.8% had never sought care from FCHVs for their children’s illnesses in their lifetime, and more than 50% of them were unaware of FCHVs’ services for acute respiratory infection and diarrhea. Among 316 caregivers whose child had an illness during the last seven months, 92.3% of them (n = 293) did not take their child to FCHVs. The main reasons were the lack of medicine available from them and their incompetency in providing care. Among the 446 caregivers, those who participated in a mothers’ group (n = 82) were more likely to use FCHVs’ services in their lifetime (AOR = 3.23, 95% CI =1.81-5.76).

Conclusions
Caregivers can gain benefit by using FCHV’s health services, but a majority of the caregivers did not seek care from FCHVs due to its limited quality. Raising caregivers’ awareness on FCHV is equally important at community level.
HCOR: a high-throughput coding-aware opportunistic routing for inter-flow network coding in wireless mesh networks
Authors: Hai Long , Wang Hongyu , Wang Jie , Tang Zhenzhou 
Published: September 2014

Abstract
Coding-aware routing is an effective approach to create more coding opportunities in inter-flow network coding. To the best of our knowledge, most of the coding-aware routing schemes focus on maximizing the coding opportunities. However, for opportunistic transmission, the throughput is not always increased with the increase of coding opportunities. In this paper, we explore why this case will happen and how to measure the benefits of network coding in the opportunistic routing. According to the above conclusions, we propose a novel high-throughput coding-aware opportunistic routing (HCOR) to achieve the maximal throughput gain in wireless mesh networks. HCOR is based on anypath routing and takes advantage of the network coding gain to find out the route with minimal anypath cost reasonably. Meanwhile, it is also a ‘multihop’ network coding and changes the route with dynamical data loads adaptively. Simulation results demonstrate that HCOR has better performance than coding opportunity-aware routing and also obtains a significant throughput gain in wireless mesh networks.
Penicillium sp. as an organism that degrades endosulfan and reduces its genotoxic effects
Authors: Romero-Aguilar Mariana , Tovar-Sánchez Efrain , Sánchez-Salinas Enrique , Mussali-Galante Patricia , Sánchez-Meza Juan Carlos , Castrejón-Godínez María Luisa , Dantán-González Edgar , Trujillo-Vera Miguel Ángel , Ortiz-Hernández Ma Laura 
Published: September 2014

Abstract
Endosulfan is an organochloride and persistent pesticide that has caused concern because of its impact in the environment and its toxicity to and bioaccumulation in living organisms. In this study, we isolated an endosulfan-degrading fungus from the activated sludge from an industrial wastewater treatment plant. Through repetitive enrichment and successive subculture in media containing endosulfan as the sole carbon source, a fungus designated CHE 23 was isolated. Based on a phylogenetic analysis, strain CHE 23 was assigned to the genus Penicillium sp. In a mineral salt medium with 50 mg/l endosulfan as the sole source carbon, CHE 23 removed the added endosulfan in a period of six days. To verify the decrease in endosulfan toxicity due to the activity of the fungus, we performed genotoxicity tests trough the single cell gel electrophoresis assay or comet assay, with Eisenia fetida as the bioindicator species. This organism was exposed to the supernatants of the culture of the fungus and endosulfan. Our results indicated that the genotoxicity of endosulfan was completely reduced due the activity of this fungus. These results suggest that the Penicillium sp. CHE 23 strain can be used to degrade endosulfan residues and/or for water and soil bioremediation processes without causing toxicity problems, which are probably due to the generation of no-toxic metabolites during biodegradation.
Positive end-expiratory airway pressure does not aggravate ventilator-induced diaphragmatic dysfunction in rabbits
Authors: Sassoon Catherine SH , Zhu Ercheng , Fang Liwei , Sieck Gary C , Powers Scott K 
Published: September 2014

Abstract
Introduction
Immobilization of hindlimb muscles in a shortened position results in an accelerated rate of inactivity-induced muscle atrophy and contractile dysfunction. Similarly, prolonged controlled mechanical ventilation (CMV) results in diaphragm inactivity and induces diaphragm muscle atrophy and contractile dysfunction. Further, the application of positive end-expiratory airway pressure (PEEP) during mechanical ventilation would result in shortened diaphragm muscle fibers throughout the respiratory cycle. Therefore, we tested the hypothesis that, compared to CMV without PEEP, the combination of PEEP and CMV would accelerate CMV-induced diaphragm muscle atrophy and contractile dysfunction. To test this hypothesis, we combined PEEP with CMV or with assist-control mechanical ventilation (AMV) and determined the effects on diaphragm muscle atrophy and contractile properties.

Methods
The PEEP level (8 cmH2O) that did not induce lung overdistension or compromise circulation was determined. In vivo segmental length changes of diaphragm muscle fiber were then measured using sonomicrometry. Sedated rabbits were randomized into seven groups: surgical controls and those receiving CMV, AMV or continuous positive airway pressure (CPAP) with or without PEEP for 2 days. We measured in vitro diaphragmatic force, diaphragm muscle morphometry, myosin heavy-chain (MyHC) protein isoforms, caspase 3, insulin-like growth factor 1 (IGF-1), muscle atrophy F-box (MAFbx) and muscle ring finger protein 1 (MuRF1) mRNA.

Results
PEEP shortened end-expiratory diaphragm muscle length by 15%, 14% and 12% with CMV, AMV and CPAP, respectively. Combined PEEP and CMV reduced tidal excursion of segmental diaphragm muscle length; consequently, tidal volume (VT) decreased. VT was maintained with combined PEEP and AMV. CMV alone decreased maximum tetanic force (Po) production by 35% versus control (P < 0.01). Combined PEEP and CMV did not decrease Po further. Po was preserved with AMV, with or without PEEP. Diaphragm muscle atrophy did not occur in any fiber types. Diaphragm MyHC shifted to the fast isoform in the combined PEEP and CMV group. In both the CMV and combined PEEP and CMV groups compared to controls, IGF-1 mRNAs were suppressed, whereas Caspase-3, MAFbx and MuRF1 mRNA expression were elevated.

Conclusions
Two days of diaphragm muscle fiber shortening with PEEP did not exacerbate CMV-induced diaphragm muscle dysfunction.
In-hospital mortality following treatment with red blood cell transfusion or inotropic therapy during early goal-directed therapy for septic shock: a retrospective propensity-adjusted analysis
Authors: Mark Dustin G , Morehouse John W , Hung Yun-Yi , Kene Mamata V , Elms Andrew R , Liu Vincent , Ballard Dustin W , Vinson David R 
Published: September 2014

Abstract
Introduction
We sought to investigate whether treatment of subnormal (<70%) central venous oxygen saturation (ScvO2) with inotropes or red blood cell (RBC) transfusion during early goal-directed therapy (EGDT) for septic shock is independently associated with in-hospital mortality.

Methods
Retrospective analysis of a prospective EGDT patient database drawn from 21 emergency departments with a single standardized EGDT protocol. Patients were included if, during EGDT, they concomitantly achieved a central venous pressure (CVP) of ≥8 mm Hg and a mean arterial pressure (MAP) of ≥65 mm Hg while registering a ScvO2 < 70%. Treatment propensity scores for either RBC transfusion or inotrope administration were separately determined from independent patient sub-cohorts. Propensity-adjusted logistic regression analyses were conducted to test for associations between treatments and in-hospital mortality.

Results
Of 2,595 EGDT patients, 572 (22.0%) met study inclusion criteria. The overall in-hospital mortality rate was 20.5%. Inotropes or RBC transfusions were administered for an ScvO2 < 70% to 51.9% of patients. Patients were not statistically more likely to achieve an ScvO2 of ≥70% if they were treated with RBC transfusion alone (29/59, 49.2%, P = 0.19), inotropic therapy alone (104/226, 46.0%, P = 0.15) or both RBC and inotropic therapy (7/12, 58.3%, P = 0.23) as compared to no therapy (108/275, 39.3%). Following adjustment for treatment propensity score, RBC transfusion was associated with a decreased adjusted odds ratio (aOR) of in-hospital mortality among patients with hemoglobin values less than 10 g/dL (aOR 0.42, 95% CI 0.18 to 0.97, P = 0.04) while inotropic therapy was not associated with in-hospital mortality among patients with hemoglobin values of 10 g/dL or greater (aOR 1.16, 95% CI 0.69 to 1.96, P = 0.57).

Conclusions
Among patients with septic shock treated with EGDT in the setting of subnormal ScvO2 values despite meeting CVP and MAP target goals, treatment with RBC transfusion may be independently associated with decreased in-hospital mortality.
Overcoming endocrine resistance due to reduced PTEN levels in estrogen receptor-positive breast cancer by co-targeting mammalian target of rapamycin, protein kinase B, or mitogen-activated protein kinase kinase
Authors: Fu Xiaoyong , Creighton Chad J , Biswal Nrusingh C , Kumar Vijetha , Shea Martin , Herrera Sabrina , Contreras Alejandro , Gutierrez Carolina , Wang Tao , Nanda Sarmistha , Giuliano Mario , Morrison Gladys , Nardone Agostina , Karlin Kristen L , Westbrook Thomas F , Heiser Laura M , Anur Pavana , Spellman Paul , Guichard Sylvie M , Smith Paul D , Davies Barry R , Klinowska Teresa , Lee Adrian V , Mills Gordon B , Rimawi Mothaffar F , Hilsenbeck Susan G , Gray Joe W , Joshi Amit , Osborne C Kent , Schiff Rachel 
Published: September 2014

Abstract
Introduction
Activation of the phosphatidylinositol 3-kinase (PI3K) pathway in estrogen receptor α (ER)-positive breast cancer is associated with reduced ER expression and activity, luminal B subtype, and poor outcome. Phosphatase and tensin homolog (PTEN), a negative regulator of this pathway, is typically lost in ER-negative breast cancer. We set out to clarify the role of reduced PTEN levels in endocrine resistance, and to explore the combination of newly developed PI3K downstream kinase inhibitors to overcome this resistance.

Methods
Altered cellular signaling, gene expression, and endocrine sensitivity were determined in inducible PTEN-knockdown ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer cell and/or xenograft models. Single or two-agent combinations of kinase inhibitors were examined to improve endocrine therapy.

Results
Moderate PTEN reduction was sufficient to enhance PI3K signaling, generate a gene signature associated with the luminal B subtype of breast cancer, and cause endocrine resistance in vitro and in vivo. The mammalian target of rapamycin (mTOR), protein kinase B (AKT), or mitogen-activated protein kinase kinase (MEK) inhibitors, alone or in combination, improved endocrine therapy, but the efficacy varied by PTEN levels, type of endocrine therapy, and the specific inhibitor(s). A single-agent AKT inhibitor combined with fulvestrant conferred superior efficacy in overcoming resistance, inducing apoptosis and tumor regression.

Conclusions
Moderate reduction in PTEN, without complete loss, can activate the PI3K pathway to cause endocrine resistance in ER-positive breast cancer, which can be overcome by combining endocrine therapy with inhibitors of the PI3K pathway. Our data suggests that the ER degrader fulvestrant, to block both ligand-dependent and -independent ER signaling, combined with an AKT inhibitor is an effective strategy to test in patients.
The forkhead transcription factor FOXM1 promotes endocrine resistance and invasiveness in estrogen receptor-positive breast cancer by expansion of stem-like cancer cells
Authors: Bergamaschi Anna , Madak-Erdogan Zeynep , Kim Yu Jin , Choi Yoon-La , Lu Hailing , Katzenellenbogen Benita S 
Published: September 2014

Abstract
Introduction
The forkhead transcription factor FOXM1 coordinates expression of cell cycle-related genes and plays a pivotal role in tumorigenesis and cancer progression. We previously showed that FOXM1 acts downstream of 14-3-3ζ signaling, the elevation of which correlates with a more aggressive tumor phenotype. However, the role that FOXM1 might play in engendering resistance to endocrine treatments in estrogen receptor-positive (ER+) patients when tumor FOXM1 is high has not been clearly defined yet.

Methods
We analyzed FOXM1 protein expression by immunohistochemistry in 501 ER-positive breast cancers. We also mapped genome-wide FOXM1, extracellular signal-regulated kinase 2 and ERα binding events by chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in hormone-sensitive and resistant breast cancer cells after tamoxifen treatment. These binding profiles were integrated with gene expression data derived from cells before and after FOXM1 knockdown to highlight specific FOXM1 transcriptional networks. We also modulated the levels of FOXM1 and newly discovered FOXM1-regulated genes and examined their impact on the cancer stem-like cell population and on cell invasiveness and resistance to endocrine treatments.

Results
FOXM1 protein expression was high in 20% of the tumors, which correlated with significantly reduced survival in these patients (P = 0.003 by logrank Mantel-Cox test). ChIP-seq analyses revealed that FOXM1 binding sites were enriched at the transcription start site of genes involved in cell-cycle progression, maintenance of stem cell properties, and invasion and metastasis, all of which are associated with a poor prognosis in ERα-positive patients treated with tamoxifen. Integration of binding profiles with gene expression highlighted FOXM1 transcriptional networks controlling cell proliferation, stem cell properties, invasion and metastasis. Increased expression of FOXM1 was associated with an expansion of the cancer stem-like cell population and with increased cell invasiveness and resistance to endocrine treatments. Use of a selective FOXM1 inhibitor proved very effective in restoring endocrine therapy sensitivity and decreasing breast cancer aggressiveness.

Conclusions
Collectively, our findings uncover novel roles for FOXM1 and FOXM1-regulated genes in promoting cancer stem-like cell properties and therapy resistance. They highlight the relevance of FOXM1 as a therapeutic target to be considered for reducing invasiveness and enhancing breast cancer response to endocrine treatments.
Pro: Are we ready to translate Alzheimer's disease modifying therapies to people with Down syndrome?
Authors: Rafii Michael S 
Published: September 2014

Abstract
Background
Down Syndrome (DS) is caused by trisomy of chromosome 21, which includes the gene for the amyloid precursor protein (APP) and leads to overproduction of beta-amyloid. Clinical-pathological studies indicate that individuals with DS begin demonstrating Alzheimer’s disease (AD) pathology during adolescence and that 100% exhibit such changes by age 40. Individuals with DS therefore represent a highly enriched population for AD. Additionally, owing to their baseline intellectual disability, people with DS represent a more vulnerable group of individuals as compared with other populations. Given the recent developments in AD biomarkers, combined with the prospect of achieving greater efficacy with earlier therapeutic intervention, it is logical to include adults with DS in prevention trials for AD.

Discussion
The US Food and Drug Administration has released draft guidance on drug development for early-stage AD, based on the understanding that AD is a progressive disease with symptoms developing decades after the disease process has begun. New biomarkers now permit detection of AD pathology in asymptomatic individuals such that there now exists an opportunity to conduct clinical trials of potentially disease-modifying drugs in the earliest stages of the disease and perhaps have the greatest chance of demonstrating efficacy. As such, clinical trials are being actively planned or conducted in individuals with causative mutations in the APP, presenilin-1 (PSEN1), and presenilin-2 (PSEN2) genes.

Summary
Individuals with DS comprise perhaps the largest group of people with genetically determined AD, with a worldwide population of about 6 million people. Only by inclusion can we provide access to rational therapies that offer the greatest chance of benefiting this highly at-risk population.