bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multistage Genetic Association Study Identifies Breast Cancer Risk Loci at 10q25 and 16q24
Authors: Higginbotham Kathryn S. , Breyer Joan P. , McReynolds Kate M. , Bradley Kevin M. , Schuyler Peggy A. , Plummer W. Dale , Freudenthal Marcia E. , Trentham-Dietz Amy , Newcomb Polly A. , Parl Fritz F. , Sanders Melinda E. , Page David L. , Egan Kathleen M. , Dupont William D. , Smith Jeffrey R. 
Published: September 2012

AbstractBackground: Heritable risk for breast cancer includes an increasing number of common, low effect risk variants. We conducted a multistage genetic association study in a series of independent epidemiologic breast cancer study populations to identify novel breast cancer risk variants.Methods: We tested 1,162 SNPs of greatest nominal significance from stage I of the Cancer Genetic Markers of Susceptibility breast cancer study (CGEMS; 1,145 cases, 1,142 controls) for evidence of replicated association with breast cancer in the Nashville Breast Cohort (NBC; 599 cases, 1,161 controls), the Collaborative Breast Cancer Study (CBCS; 1,552 cases, 1,185 controls), and BioVU Breast Cancer Study (BioVU; 1,172 cases, 1,172 controls).Results: Among these SNPs, a series of validated breast cancer risk variants yielded expected associations in the study populations. In addition, we observed two previously unreported loci that were significantly associated with breast cancer risk in the CGEMS, NBC, and CBCS study populations and had a consistent, although not statistically significant, risk effect in the BioVU study population. These were rs1626678 at 10q25.3 near ENO4 and KIAA1598 (meta-analysis age-adjusted OR = 1.13 [1.07–1.20], P = 5.6 × 10−5), and rs8046508 at 16q23.1 in the eighth intron of WWOX (meta-analysis age-adjusted OR = 1.20 [1.10–1.31], P = 3.5 × 10−5).Conclusions: Our data supports the association of two novel loci, at 10q25.3 and 16q23.1, with risk of breast cancer.Impact: The expanding compendium of known breast cancer genetic risk variants holds increasing power for clinical risk prediction models of breast cancer, improving upon the Gail model. Cancer Epidemiol Biomarkers Prev; 21(9); 1565–73. ©2012 AACR.
HER2 Amplification: A Potential Mechanism of Acquired Resistance to EGFR Inhibition in EGFR-Mutant Lung Cancers That Lack the Second-Site EGFRT790M Mutation
Authors: Takezawa Ken , Pirazzoli Valentina , Arcila Maria E. , Nebhan Caroline A. , Song Xiaoling , de Stanchina Elisa , Ohashi Kadoaki , Janjigian Yelena Y. , Spitzler Paula J. , Melnick Mary Ann , Riely Greg J. , Kris Mark G. , Miller Vincent A. , Ladanyi Marc , Politi Katerina , Pao William 
Published: September 2012

Abstract
EGF receptor (EGFR)–mutant lung cancers eventually become resistant to treatment with EGFR tyrosine kinase inhibitors (TKI). The combination of EGFR-TKI afatinib and anti-EGFR antibody cetuximab can overcome acquired resistance in mouse models and human patients. Because afatinib is also a potent HER2 inhibitor, we investigated the role of HER2 in EGFR-mutant tumor cells. We show in vitro and in vivo that afatinib plus cetuximab significantly inhibits HER2 phosphorylation. HER2 overexpression or knockdown confers resistance or sensitivity, respectively, in all studied cell line models. FISH analysis revealed that HER2 was amplified in 12% of tumors with acquired resistance versus only 1% of untreated lung adenocarcinomas. Notably, HER2 amplification and EGFRT790M were mutually exclusive. Collectively, these results reveal a previously unrecognized mechanism of resistance to EGFR-TKIs and provide a rationale to assess the status and possibly target HER2 in EGFR-mutant tumors with acquired resistance to EGFR-TKIs.
Significance: Because all EGFR-mutant lung adenocarcinomas eventually develop resistance to TKI therapy, understanding mechanisms of acquired resistance may improve clinical outcomes. These results implicate HER2 as a novel protein involved in the sensitivity or resistance of EGFR-mutant lung cancer and provide a rationale to assess the status of and possibly target HER2 in such tumors. Cancer Discov; 2(10); 922–33. ©2012 AACR.
Read the Commentary on this article by Blakely and Bivona, p. 872.
This article is highlighted in the In This Issue feature, p. 857.
The experiences of Australian parents with psychosis: The second Australian national survey of psychosis
Authors: Campbell Linda , Hanlon Mary-Claire , Poon Abner Weng Cheong , Paolini Stefania , Stone Melanie , Galletly Cherrie , Stain Helen J , Cohen Martin 
Published: September 2012

Objective: Being a parent is an important part of one’s identity and role. Previous research outlines many challenges associated with parenting by people with severe mental illness. However, there is a limited research describing parenting experiences of mothers and fathers who have psychosis. Method: The second Australian national survey of psychosis recruited 1825 people living with symptoms of, or a diagnosis of, psychosis. The survey was conducted through face-to-face interviews and included key clinical and demographic information, as well as parenting specific information. Results: Over half of all women and a quarter of men were parents. Almost a quarter of women but only 5.5% of the men had dependent children (own and/or stepchildren) living at home with them. Of parents with dependent children, the most common diagnosis was schizophrenia (48.2% fathers, 28.9% mothers), and there were high rates of comorbidity with substance abuse/dependence (alcohol: fathers 69.2%, mothers 44.3%; cannabis: fathers 69.22%, mothers 47.8%). A substantial proportion of parents with dependent children experienced challenges including low educational attainment, unemployment, poverty, and social isolation. Although many parents living with dependent children functioned in the average range, a significant proportion was moderately to severely disabled on global independent functioning ratings (fathers 49.1%, mothers 35.7%) and some were identified as having obvious/severe impairments in their ability to care for their child(ren) (fathers 28.3%, mothers 21.3%). Conclusions: Most parents living with psychosis function well. However, a significant proportion has impairments in parenting and general functioning that could have adverse consequences for both the parent and children. This study brings into focus the need for interventions to optimise successful parenting outcomes.
Functional Outcomes of Chemoradiation in Patients with Head and Neck Cancer
Authors: Tulunay‐Ugur Ozlem E. , McClinton Christopher , Young Zachary , Penagaricano Jose A. , Maddox Anne‐Marie , Vural Emre 
Published: September 2012

ObjectiveConcurrent chemoradiotherapy (CCRT) has become the treatment of choice for oropharyngeal and hypopharyngolaryngeal cancers in many centers. Although it has increased the rates of organ preservation, there has also been an increase in treatment‐related complications. We aimed to evaluate the functional outcomes of CCRT in head and neck cancer.Study DesignCase series with chart review.SettingTertiary cancer center.Subjects and MethodsA retrospective study of patients treated with CCRT at the University of Arkansas for Medical Sciences was performed. Demographic data and treatment outcomes were extracted, specifically feeding tube and tracheotomy dependence and number of esophageal dilatations.ResultsOf the 243 patients treated with concurrent chemoradiotherapy (5‐flourouracil + cysplatin and radiotherapy), 152 patients received a feeding tube. The median percutaneous gastrostomy tube (PEG) use was 9 months (range, 1‐96 months). More than 70% of the patients who had a PEG more than 6 months had a T3 or T4 tumor. Thirty‐seven patients underwent esophageal dilatations, (median, 1; range, 1‐7). The median use of a tracheotomy was 7 months, and 77% of these patients were treated for hypopharyngolaryngeal cancer.ConclusionsDespite major improvement in locoregional control rates, CCRT has a significant negative impact on the functional outcomes of head and neck cancer patients, with a high number of patients remaining PEG and tracheotomy dependent.
Ambulatory Office Visits and Medical Comorbidities Associated with Obstructive Sleep Apnea
Authors: Bhattacharyya Neil , Kepnes Lynn J. 
Published: September 2012

Objective(1) Understand the epidemiology of obstructive sleep apnea (OSA) ambulatory office visits in the United States. (2) Quantify the prevalence of comorbid illnesses that are likely to occur in the setting of OSA.MethodsFrom the 2008‐2009 National Ambulatory Medical Care Surveys and National Hospital Ambulatory Medical Care Surveys, adult cases with a diagnosis of OSA were extracted. The epidemiology of OSA was determined. The prevalences of comorbid priority illnesses (obesity, asthma, cerebrovascular disease, depression, hypertension, and ischemic heart disease) were also determined.Study DesignCross‐sectional analysis of a national survey database.SettingAmbulatory care settings in the United States.ResultsThere were an estimated 4.1 ± 1.2 million annual visits with a diagnosis of OSA (60% ± 3.2% men; mean age, 56.4 ± 0.9 years). There were 419,000 ± 28,000 visits annually to otolaryngologists for OSA. Comorbid illnesses were obesity (23.8% ± 5.2%), asthma (14.3% ± 3.0%), cerebrovascular disease (2.5% ± 1.5%), depression (23.2% ± 2.6%), hypertension 53.8% ± 3.9%), and ischemic heart disease (10.3% ± 3.0%). Adjusting for age, sex, ethnicity, obesity, and race, statistically significant increased odds for the presence of obesity (3.6, P <. 001), asthma (2.7, P <. 001), depression (2.5, P <. 001), and hypertension (2.0, P <. 001) with OSA were noted. Increased odds for cerebrovascular disease and ischemic heart disease were not identified (P =. 725 and P =. 083, respectively).ConclusionObstructive sleep apnea is a relatively common diagnosis in ambulatory and otolaryngologic care. It is associated with a significantly increased prevalence of several key priority health care conditions in the United States. Otolaryngologists and health care providers should be aware of these associations, understanding the potentially broad impact of OSA on general health.
Does neuromuscular electrical stimulation enhance the effectiveness of an exercise programme in subjects with knee osteoarthritis? A randomized controlled trial
Authors: Elboim-Gabyzon M , Rozen N , Laufer Y 
Published: September 2012

Objective: To determine whether neuromuscular electrical stimulation applied to the quadriceps femoris muscle will enhance the effectiveness of an exercise programme in patients with knee osteoarthritis. Design: A randomized trial with parallel intervention treatment groups. Setting: Outpatient physical therapy clinic. Subjects: Fifty participants (mean age (SD) 68.9 (7.7) years) with symptomatic idiopathic knee osteoarthritis and radiographic evidence (grade ≥II Kelgren’s classification). Interventions: Participants were randomized into one of two groups receiving 12 biweekly treatments: An exercise-only group or an exercise combined with neuromuscular electrical stimulation group (biphasic pulses, at 75 Hz and 250 µs phase duration). Main measures: Knee pain intensity; maximal voluntary isometric contraction and voluntary activation of the quadriceps femoris muscle; measures of functional performance. Results: A significant interaction effect ( P = 0.01) indicated greater improvement in pain for the electrical stimulation group. The mean (SD) change in pain intensity was from 7.5 ± 2 to 5 ± 2.2 and from 7.4 ± 1.9 to 3.3 ± 2.4 in the exercise and electrical stimulation groups, respectively. A significant treatment effect was also noted for the voluntary activation of the quadriceps femoris, which increased by 22.2% in the electrical stimulation group and by 9.6% in the exercise group ( P = 0.045). Significant improvements were observed in both groups in all remaining measures, with no differences between groups. Conclusions: Electrical stimulation treatment to the quadriceps femoris enhanced the effectiveness of an exercise programme in alleviating pain and improving voluntary activation in patients with knee osteoarthritis, but did not enhance its effect on muscle strength or functional performance.
Collapsing glomerulopathy associated lupus in a black female with homozygous APOL1 mutation
Authors: Kofman T , Narjoz C , Raimbourg Q , Loriot M-A , Karras A , Roland M , Hill G , Jacquot C , Nochy D , Thervet E 
Published: September 2012

Collapsing glomerulopathy(CG), characterized by collapse of the glomerular capillary loops onto the mesangial stalks is rarely associated to systemic lupus erythematosus (SLE). Recently a genetic predisposition to HIV associated nephropathy (HIVAN) has been shown in Afro-Americans: MYH9 polymorhism in 2008 and then APOL1 variants (G1 and G2 alleles) in 2010 were shown to be strongly associated with HIVAN. We describe here for the first time the association of CG in a young Afro-American female with SLE having a homozygous mutation of APOL1. The clinical history, laboratory findings and immunofluorescence all confirmed a diagnosis of SLE. However, studies for factors associated with collapsing glomerulopathy in other situations were consistently negative. As this Afro-American patient developed a CG, we performed genotyping of APOL1. It was found that she is homozygotic for the G2 allele of APOL1. Despite
Computational Models of Transcranial Direct Current Stimulation
Authors: Bikson Marom , Rahman Asif , Datta Abhishek 
Published: September 2012

During transcranial direct current stimulation (tDCS), controllable dose parameters are electrode number (typically 1 anode and 1 cathode), position, size, shape, and applied electric current. Because different electrode montages result in distinct brain current flow patterns across the brain, tDCS dose parameters can be adjusted, in an application-specific manner, to target or avoid specific brain regions. Though the tDCS electrode montage often follows basic rules of thumb (increased/decreased excitability “under” the anode/cathode electrode), computational forward models of brain current flow provide more accurate insight into detailed current flow patterns and, in some cases, can even challenge simplified electrode-placement assumptions. With the increased recognized value of computational forward models in informing tDCS montage design and interpretation of results, there have been recent advances in modeling tools and a greater proliferation of publications. In addition, the importance of customizing tDCS for potentially vulnerable populations (eg, skull defects, brain damage/stroke, and extremes of age) can be considered. Finally, computational models can be used to design new electrode montages, for example, to improve spatial targeting such as high-definition tDCS. Pending further validation and dissemination of modeling tools, computational forward models of neuromodulation will become standard tools to guide the optimization of clinical trials and electrotherapy.
Phylogenetic relationships among Staphylococcus species and refinement of cluster groups based on multilocus data
Authors: Lamers Ryan P , Muthukrishnan Gowrishankar , Castoe Todd A , Tafur Sergio , Cole Alexander M , Parkinson Christopher L 
Published: September 2012

Abstract

Background
Estimates of relationships among Staphylococcus species have been hampered by poor and inconsistent resolution of phylogenies based largely on single gene analyses incorporating only a limited taxon sample. As such, the evolutionary relationships and hierarchical classification schemes among species have not been confidently established. Here, we address these points through analyses of DNA sequence data from multiple loci (16S rRNA gene, dnaJ, rpoB, and tuf gene fragments) using multiple Bayesian and maximum likelihood phylogenetic approaches that incorporate nearly all recognized Staphylococcus taxa.

Results
We estimated the phylogeny of fifty-seven Staphylococcus taxa using partitioned-model Bayesian and maximum likelihood analysis, as well as Bayesian gene-tree species-tree methods. Regardless of methodology, we found broad agreement among methods that the current cluster groups require revision, although there was some disagreement among methods in resolution of higher order relationships. Based on our phylogenetic estimates, we propose a refined classification for Staphylococcus with species being classified into 15 cluster groups (based on molecular data) that adhere to six species groups (based on phenotypic properties).

Conclusions
Our findings are in general agreement with gene tree-based reports of the staphylococcal phylogeny, although we identify multiple previously unreported relationships among species. Our results support the general importance of such multilocus assessments as a standard in microbial studies to more robustly infer relationships among recognized and newly discovered lineages.
Profiling microRNAs in lung tissue from pigs infected with Actinobacillus pleuropneumoniae
Authors: Podolska Agnieszka , Anthon Christian , Bak Mads , Tommerup Niels , Skovgaard Kerstin , Heegaard Peter MH , Gorodkin Jan , Cirera Susanna , Fredholm Merete 
Published: September 2012

Abstract

Background
MicroRNAs (miRNAs) are a class of non-protein-coding genes that play a crucial regulatory role in mammalian development and disease. Whereas a large number of miRNAs have been annotated at the structural level during the latest years, functional annotation is sparse. Actinobacillus pleuropneumoniae (APP) causes serious lung infections in pigs. Severe damage to the lungs, in many cases deadly, is caused by toxins released by the bacterium and to some degree by host mediated tissue damage. However, understanding of the role of microRNAs in the course of this infectious disease in porcine is still very limited.

Results
In this study, the RNA extracted from visually unaffected and necrotic tissue from pigs infected with Actinobacillus pleuropneumoniae was subjected to small RNA deep sequencing. We identified 169 conserved and 11 candidate novel microRNAs in the pig. Of these, 17 were significantly up-regulated in the necrotic sample and 12 were down-regulated. The expression analysis of a number of candidates revealed microRNAs of potential importance in the innate immune response. MiR-155, a known key player in inflammation, was found expressed in both samples. Moreover, miR-664-5p, miR-451 and miR-15a appear as very promising candidates for microRNAs involved in response to pathogen infection.

Conclusions
This is the first study revealing significant differences in composition and expression profiles of miRNAs in lungs infected with a bacterial pathogen. Our results extend annotation of microRNA in pig and provide insight into the role of a number of microRNAs in regulation of bacteria induced immune and inflammatory response in porcine lung.
Basic geriatric assessment does not predict in-hospital mortality after PEG placement
Authors: Smoliner Christine , Volkert Dorothee , Wittrich Anke , Sieber Cornel C , Wirth Rainer 
Published: September 2012

Abstract

Background
Percutaneous endoscopic gastrostomy (PEG) is an established procedure for long-term nutrition. However, studies have underlined the importance of proper patient selection as mortality has been shown to be relatively high in acute illness and certain patient groups, amongst others geriatric patients. Objective of the study was to gather information about geriatric patients receiving PEG and to identify risk factors associated with in-hospital mortality after PEG placement.

Methods
All patients from the GEMIDAS database undergoing percutaneous endoscopic gastrostomy in acute geriatric wards from 2006 to 2010 were included in a retrospective database analysis. Data on age, gender, main diagnosis leading to hospital admission, death in hospital, care level, and legal incapacitation were extracted from the main database of the Geriatric Minimum Data Set. Self-care capacity was assessed by the Barthel index, and cognitive status was rated with the Mini Mental State Examination or subjectively judged by the clinician. Descriptive statistics and group comparisons were chosen according to data distribution and scale of measurement, logistic regression analysis was performed to examine influence of various factors on hospital mortality.

Results
A total of 1232 patients (60.4% women) with a median age of 82 years (range 60 to 99 years) were included. The mean Barthel index at admission was 9.5 ± 14.0 points. Assessment of cognitive status was available in about half of the patients (n = 664), with 20% being mildly impaired and almost 70% being moderately to severely impaired. Stroke was the most common main diagnosis (55.2%). In-hospital mortality was 12.8%. In a logistic regression analysis, old age (odds ratio (OR) 1.030, 95% confidence interval (CI) 1.003-1.056), male sex (OR 1.741, 95% CI 1.216-2.493), and pneumonia (OR 2.641, 95% CI 1.457-4.792) or the diagnosis group ‘miscellaneous disease’ (OR 1.864, 95% CI 1.224-2.839) were identified as statistical risk factors for in–hospital death. Cognitive status did not have an influence on mortality (OR 0.447, CI 95% 0.248-1.650).

Conclusion
In a nationwide geriatric database, no component of the basic geriatric assessment emerged as a significant risk factor for mortality after PEG placement, emphasizing individual decision-making.
No-shows to primary care appointments: subsequent acute care utilization among diabetic patients
Authors: Nuti Lynn A , Lawley Mark , Turkcan Ayten , Tian Zhiyi , Zhang Lingsong , Chang Karen , Willis Deanna R , Sands Laura P 
Published: September 2012

Abstract

Background
Patients who no-show to primary care appointments interrupt clinicians’ efforts to provide continuity of care. Prior literature reveals no-shows among diabetic patients are common. The purpose of this study is to assess whether no-shows to primary care appointments are associated with increased risk of future emergency department (ED) visits or hospital admissions among diabetics.

Methods
A prospective cohort study was conducted using data from 8,787 adult diabetic patients attending outpatient clinics associated with a medical center in Indiana. The outcomes examined were hospital admissions or ED visits in the 6 months (182 days) following the patient’s last scheduled primary care appointment. The Andersen-Gill extension of the Cox proportional hazard model was used to assess risk separately for hospital admissions and ED visits. Adjustment was made for variables associated with no-show status and acute care utilization such as gender, age, race, insurance and co-morbid status. The interaction between utilization of the acute care service in the six months prior to the appointment and no-show was computed for each model.

Results
The six-month rate of hospital admissions following the last scheduled primary care appointment was 0.22 (s.d. = 0.83) for no-shows and 0.14 (s.d. = 0.63) for those who attended (p < 0.0001). No-show was associated with greater risk for hospitalization only among diabetics with a hospital admission in the prior six months. Among diabetic patients with a prior hospital admission, those who no-showed were at 60% greater risk for subsequent hospital admission (HR = 1.60, CI = 1.17–2.18) than those who attended their appointment. The six-month rate of ED visits following the last scheduled primary care appointment was 0.56 (s.d. = 1.48) for no-shows and 0.38 (s.d. = 1.05) for those who attended (p < 0.0001); after adjustment for covariates, no-show status was not significantly related to subsequent ED utilization.

Conclusions
No-show to a primary care appointment is associated with increased risk for hospital admission among diabetics recently hospitalized.