bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Lipid-Modified Estrogen Derivative that Treats Breast Cancer Independent of Estrogen Receptor Expression through Simultaneous Induction of Autophagy and Apoptosis
Authors: Sinha Sutapa , Roy Sayantani , Reddy Bathula Surendar , Pal Krishnendu , Sudhakar Godeshala , Iyer Seethalakshmi , Dutta Shamit , Wang Enfeng , Vohra Pawan Kumar , Roy Karnati Rammohan , Reddanna Pallu , Mukhopadhyay Debabrata , Banerjee Rajkumar 
Published: February 2011

Abstract
It is a challenge to develop a universal single drug that can treat breast cancer at single- or multiple-stage complications, yet remains nontoxic to normal cells. The challenge is even greater when breast cancer–specific, estrogen-based drugs are being developed that cannot act against multistaged breast cancer complications owing to the cells differential estrogen receptor (ER) expression status and their possession of drug-resistant and metastatic phenotypes. We report here the development of a first cationic lipid-conjugated estrogenic derivative (ESC8) that kills breast cancer cells independent of their ER expression status. This ESC8 molecule apparently is nontoxic to normal breast epithelial cells, as well as to other noncancer cells. ESC8 induces apoptosis through an intrinsic pathway in ER-negative MDA-MB-231 cells. In addition, ESC8 treatment induces autophagy in these cells by interfering with the mTOR activity. This is the first example of an estrogen structure–based molecule that coinduces apoptosis and autophagy in breast cancer cells. Further in vivo study confirms the role of this molecule in tumor regression. Together, our results open new perspective of breast cancer chemotherapy through a single agent, which could provide the therapeutic benefit across all stages of breast cancer. Mol Cancer Res; 9(3); 364–74. ©2011 AACR.
Global Assessment of Genetic Variation Influencing Response to Retinoid Chemoprevention in Head and Neck Cancer Patients
Authors: Lee J. Jack , Wu Xifeng , Hildebrandt Michelle A.T. , Yang Hushan , Khuri Fadlo R. , Kim Edward , Gu Jian , Ye Yuanqing , Lotan Reuben , Spitz Margaret R. , Hong Waun Ki 
Published: February 2011

Abstract
Head and neck squamous cell carcinoma (HNSCC) patients are at an increased risk of developing a second primary tumor (SPT) or recurrence following curative treatment. 13-cis-retinoic acid (13-cRA) has been tested in chemoprevention clinical trials, but the results have been inconclusive. We genotyped 9,465 single nucleotide polymorphisms (SNP) in 450 patients from the Retinoid Head and Neck Second Primary Trial. SNPs were analyzed for associations with SPT/recurrence in patients receiving placebo to identify prognosis markers and further analyzed for effects of 13-cRA in patients with these prognostic loci. Thirteen loci identified a majority subgroup of patients at a high risk of SPT/recurrence and in whom 13-cRA was protective. Patients carrying the common genotype of rs3118570 in the retinoid X receptor (RXRA) were at a 3.33-fold increased risk (95% CI, 1.67–6.67) and represented more than 70% of the study population. This locus also identified individuals who received benefit from chemoprevention with a 38% reduced risk (95% CI, 0.43–0.90). Analyses of cumulative effect and potential gene–gene interactions also implicated CDC25C:rs6596428 and JAK2:rs1887427 as 2 other genetic loci with major roles in prognosis and 13-cRA response. Patients with all 3 common genotypes had a 76% reduction in SPT/recurrence (95% CI, 0.093–0.64) following 13-cRA chemoprevention. Carriers of these common genotypes constituted a substantial percentage of the study population, indicating that a pharmacogenetic approach could help select patients for 13-cRA chemoprevention. The lack of any alternatives for reducing risk in these patients highlights the need for future clinical trials to prospectively validate our findings. Cancer Prev Res; 4(2); 185–93. ©2011 AACR.
Gene Expression Profiling Predicts the Development of Oral Cancer
Authors: Saintigny Pierre , Zhang Li , Fan You-Hong , El-Naggar Adel K. , Papadimitrakopoulou Vassiliki A. , Feng Lei , Lee J. Jack , Kim Edward S. , Ki Hong Waun , Mao Li 
Published: February 2011

Abstract
Patients with oral premalignant lesion (OPL) have a high risk of developing oral cancer. Although certain risk factors, such as smoking status and histology, are known, our ability to predict oral cancer risk remains poor. The study objective was to determine the value of gene expression profiling in predicting oral cancer development. Gene expression profile was measured in 86 of 162 OPL patients who were enrolled in a clinical chemoprevention trial that used the incidence of oral cancer development as a prespecified endpoint. The median follow-up time was 6.08 years and 35 of the 86 patients developed oral cancer over the course. Gene expression profiles were associated with oral cancer–free survival and used to develop multivariate predictive models for oral cancer prediction. We developed a 29-transcript predictive model which showed marked improvement in terms of prediction accuracy (with 8% predicting error rate) over the models using previously known clinicopathologic risk factors. On the basis of the gene expression profile data, we also identified 2,182 transcripts significantly associated with oral cancer risk–associated genes (P value &lt; 0.01; univariate Cox proportional hazards model). Functional pathway analysis revealed proteasome machinery, MYC, and ribosomal components as the top gene sets associated with oral cancer risk. In multiple independent data sets, the expression profiles of the genes can differentiate head and neck cancer from normal mucosa. Our results show that gene expression profiles may improve the prediction of oral cancer risk in OPL patients and the significant genes identified may serve as potential targets for oral cancer chemoprevention. Cancer Prev Res; 4(2); 218–29. ©2011 AACR.
A Strong Case for Personalized, Targeted Cancer Prevention
Authors: Dawson Marcia I. 
Published: February 2011

Abstract
The study reported by Lee and colleagues in this issue of the journal (beginning on page 185) incorporated global genetic variation within a new assessment of the outcome of a previously reported phase-III trial of low-dose 13-cis-retinoic acid (13-cRA) for preventing second primary tumors (SPT) or the recurrence of head-and-neck cancer. This analysis identified genotypes of common single-nucleotide polymorphisms (SNP) and cumulative effect and potential gene–gene interactions that were highly associated with increased placebo-arm risk (prognostic) and/or with reduced treatment-arm risk and longer event-free survival (predictive). For example, the wild-type rs3118570 SNP of the retinoid X receptor alpha gene (carried by 71% of the 13-cRA trial population) marked a 3.33-fold increased SPT/recurrence risk in the placebo arm and a 38% reduced risk in the treatment arm. Adding two other informative genotypes strengthened the treatment-arm risk reduction to 76%, although the genotype trio reflected only 13% of the trial population. This report extends the concept of personalized therapy to cancer prevention. Cancer Prev Res; 4(2); 173–6. ©2011 AACR.
Familial History of Stroke Is Associated With Acute Coronary Syndromes in Women
Authors: Banerjee Amitava , Lim Chris C.S. , Silver Louise E. , Welch Sarah J.V. , Banning Adrian P. , Rothwell Peter M. 
Published: February 2011

Background—
Stroke in female first-degree relatives (FDRs) is a powerful risk factor for ischemic stroke in women, but its association with acute coronary syndromes (ACS) is unknown. Family history (FH) of stroke is omitted from existing myocardial infarction risk prediction tools, which perform less well in women than in men. Our objective was to study the sex-of-parent and sex-of-proband interactions for FH of stroke in ACS patients.

Methods and Results—

In a prospective, population-based study (Oxford Vascular Study) of all patients with ACS or stroke/transient ischemic attack, FH data for stroke and myocardial infarction were analyzed by sex of proband and FDRs, and coronary angiograms were reviewed, where available; 942 of 1058 ACS probands and 1015 of 1152 stroke/transient ischemic attack probands had complete FH data; 24.1% of ACS probands and 24.3% of stroke/transient ischemic attack probands had history of stroke in ≥1 FDR. Maternal stroke was more common than paternal stroke in female ACS probands (odds ration [OR], 2.53; 1.39 to 4.61) but not in male probands (OR, 0.92; 0.64 to 1.32) (difference-
P
=0.004). Overall, female ACS probands were more likely to have female than male FDRs with stroke (OR, 2.09; 1.29 to 3.37), whereas the opposite trend was seen in male ACS probands (OR, 0.69; 0.50 to 0.97) (difference-
P
=0.0002). However, there was no association between parental history of stroke and disease localization or presence of multivessel disease on coronary angiography.

Conclusions—
FH of stroke is as common in ACS patients as in stroke/transient ischemic attack patients and sex-of-parent/sex-of-proband interactions are similar. Stroke in female FDRs may help to identify women at increased risk of ACS as well as ischemic stroke.
Can Innate, Modular “Foundations” Explain Morality? Challenges for Haidt's Moral Foundations Theory
Authors: Suhler Christopher L. , Churchland Patricia 
Published: February 2011

AbstractJonathan Haidt's Moral Foundations Theory is an influential scientific account of morality incorporating psychological, developmental, and evolutionary perspectives. The theory proposes that morality is built upon five innate “foundations,” each of which is believed to have been selected for during human evolution and, subsequently, tuned-up by learning during development. We argue here that although some general elements of Haidt's theory are plausible, many other important aspects of his account are seriously flawed. First, innateness and modularity figure centrally in Haidt's account, but terminological and conceptual problems foster confusion and ambiguities. Second, both the theory's proposed number of moral foundations and its taxonomy of the moral domain appear contrived, ignoring equally good candidate foundations and the possibility of substantial intergroup differences in the foundations' contents. Third, the mechanisms (viz., modules) and categorical distinctions (viz., between foundations) proposed by the theory are not consilient with discoveries in contemporary neuroscience concerning the organization, functioning, and development of the brain. In light of these difficulties, we suggest that Haidt's theory is inadequate as a scientific account of morality. Nevertheless, the theory's weaknesses are instructive, and hence, criticism may be useful to psychologists, neuroscientists, and philosophers attempting to advance theories of morality, as well as to researchers wishing to invoke concepts such as innateness and modularity more generally.
Understanding Self-Monitoring of Blood Glucose Among Individuals With Type 1 and Type 2 Diabetes
Authors: Fisher William A. , Kohut Taylor , Schachner Holly , Stenger Patricia 
Published: February 2011

Purpose To evaluate self-monitoring of blood glucose (SMBG) information deficits, motivational obstacles, and behavioral skills limitations in individuals with type 1 and type 2 diabetes, and to assess the relationship of these deficits with SMBG frequency. Methods Individuals with type 1 (n = 208; 103 male, 105 female) and type 2 (n = 218; 107 male, 111 female) diabetes participated in an online survey assessing SMBG information, motivation, behavioral skills, and behavior. Results A substantial proportion of participants scored as SMBG uninformed, unmotivated, and unskilled on specific assessment items. SMBG information, motivation, and behavioral skills deficits were significantly correlated with SMBG frequency, such that individuals with type 1 or type 2 diabetes, who were less informed, less motivated, and less behaviorally skilled, reported lower frequency of SMBG. Conclusion Common and consequential SMBG information, motivation, and behavioral skills deficits were present, and patients with these gaps were less likely to test frequently. Clinical education focusing on relevant SMBG information, motivation to act, and behavioral skills for acting effectively may be a priority.
The ABCs of Diabetes
Authors: Magee Michelle , Bowling Andrea , Copeland James , Fokar Ali , Pasquale Patricia , Youssef Gretchen 
Published: February 2011

Purpose The purpose of the study was to examine the feasibility and impact of a concise community-based program on diabetes self-management education (DSME), according to frequency of emergency department visits and knowledge of, prescriptions for, and control of A1C, blood pressure, and low-density lipoprotein (LDL) cholesterol. Methods A free community-based DSME program was placed in a public library. Adults with diabetes (N, 360) consented to participate in this prospective nonrandomized cohort study with preintervention-postintervention design. The small-group interactive DSME (two 2.5-hour classes) focused on improving cardiovascular disease risk factors and facilitating communication with the primary care physician. Results An increase in knowledge of American Diabetes Association—recommended targets for A1C, blood pressure, and LDL cholesterol from baseline to postintervention was seen among participants. Significant clinical outcomes included reduction in self-reported emergency department visits and reduction in mean A1C. However, despite an increase in prescriptions written for lipid-lowering drugs, blood pressure and LDL cholesterol did not change. Participants who started on insulin were more likely to achieve or maintain A1C < 7% compared to those who either did not take or stopped taking insulin during the study. Conclusions Offering DSME classes for African Americans at a public library was feasible and significantly affected 6-month clinical outcomes, including a reduction in A1C, an increased likelihood of attaining a target A1C of < 7% if insulin was started during the study period, and a two-thirds reduction in emergency department visits for uncontrolled diabetes. Observed results suggest that partnering with community-based organizations such as public libraries offers an accessible and well-received location for offering DSME programs.
Parent Mentor Perspectives on Providing Social Support to Empower Parents
Authors: Sullivan-Bolyai Susan , Lee Mary M. 
Published: February 2011

Purpose To describe the experience of parent mentors providing a social support intervention to parents of children < 13 years old newly diagnosed with type 1 diabetes mellitus. Methods Qualitative descriptive interviews were conducted with 6 parent mentors (all mothers) who provided social support to 34 mothers and 19 fathers of children newly diagnosed with type 1 diabetes mellitus over a 12-month period. The mentors were trained to provide informational, affirmational, and emotional social support through home visits, phone calls, and/or e-mail. Qualitative content analysis was used to identify themes guided by the Ireys social support framework. Findings The parent mentors described support activities that could be categorized into the 3 types of support defined in the Ireys framework. The parent mentors provided informational support, such as tips for travel, school, parties and family get-togethers, camp resources, and how to advocate for the child. Affirmational support was provided by sharing stories and validating parents’ feelings and experiences. Emotional support was provided by “being there” for the parents. No instances were described where parent mentors were pushed to give advice on medical management issues but were more so used for advice on growth and development, sleep, and healthy eating suggestions. Parent mentors also reported being empowered by the role by helping others. Conclusion Careful selection of parent mentors is a strategy for providing social support to parents of children newly diagnosed with type 1 diabetes mellitus, especially in day-to-day management areas that the health care professionals have not experienced.
Quality of Life and Voice Outcomes after Thyroid Ala Graft Laryngotracheal Reconstruction in Young Children
Authors: Tirado Yamilet , Chadha Neil K. , Allegro Jennifer , Forte Vito , Campisi Paolo 
Published: February 2011

Objectives(1) To assess the long‐term impact of thyroid ala cartilage laryngotracheal reconstruction (TAC‐LTR) on health‐related quality of life (QOL) in infants using 4 validated instruments: Health Utility Index version 3 (HUI3), Pediatric Voice‐Related QOL (PVRQOL), Impact on Family Questionnaire, and a visual analog scale and (2) to perform acoustic and perceptual voice assessments to evaluate long‐term voice quality outcomes.Study DesignProspective study.SettingTertiary academic pediatric hospital.SubjectsEligible children who received TAC‐LTR before the age of 24 months between 1995 and 2007.MethodsInterviews with parents and children using 4 validated instruments, voice analyses, and endoscopic evaluation were performed.ResultsTwelve patients (7 male, 5 female, median age 10 years) were enrolled over a 6‐month period. The mean age at LTR was 5 months (range, 1‐20 months), and the mean study follow‐up period was 9 years (range, 2‐14 years). The average speech HUI3, PVRQOL, and Impact on Family scores were 0.83 (95% confidence interval = 0.74, 0.92), 0.93 (interquartile range [IQR] = 0.81, 1.00), and 0.65 (IQR = 0.54, 0.92), respectively. All acoustic scores were either normal or mildly abnormal for the variables jitter, shimmer, noise‐to‐harmonic ratio, peak amplitude variation, and fundamental frequency. The Consensus Auditory‐Perceptual Evaluation of Voice overall severity score was in the normal to mildly abnormal range for 8 of 9 patients.ConclusionThis is the first study to explore and quantify long‐term QOL and voice quality in children following LTR with thyroid ala graft at a very young age. Most patients had very good functional voice outcome as evidenced by the HUI3 and PVRQOL scores. This was corroborated by acoustic and perceptual voice assessments.
Immunomodulatory Role of Histamine H2 Receptor in Allergen‐Specific Immunotherapy
Authors: Shin Ji‐Hyeon , Kim Byung‐Guk , Kim Sung Won , Cho Jin‐Hee , Park Yong‐Jin , Kim Soo Whan 
Published: February 2011

ObjectiveThe purpose of this pilot study was to investigate the effects of HR2 on allergen‐specific immunotherapy in a mouse model of allergic rhinitis.Study DesignAn in vivo study using an animal model.SettingCatholic Research Institutes of Medical Science.MethodsFifty mice were divided into 5 groups: control, allergic rhinitis (AR), immunotherapy (IT), immunotherapy with HR2 agonist (HI), and immunotherapy with HR2 antagonist (HB). All mice except for the control group were sensitized with ovalbumin (OVA). After 1 week, mice in the IT, HI, and HB groups underwent immunotherapy by intradermal injections of OVA. During immunotherapy, the HI group was injected with HR2 agonist, whereas the HB group was injected with HR2 antagonist. All sensitized mice were challenged with intranasal OVA. After the final challenge, allergic behavior was evaluated. Interleukin (IL)–13, interferon‐γ, IL‐10, and transforming growth factor (TGF)–β levels in nasal lavage fluid (NALF), as well as OVA‐specific IgE levels in serum, were measured. The number of eosinophils in lamina propria was evaluated.ResultsThe levels of serum OVA‐specific IgE and IL‐13 in NALF were significantly increased in the HB group compared with the IT group (P <. 05). Also, the tissue eosinophil counts were higher in the HB group than in the IT group (P <. 05).ConclusionHR2 antagonist impaired OVA‐specific immunotherapy in mice. Although confirmation of this preliminary result is needed, these findings suggest that HR2 receptors may have inhibitory effects on immune tolerance. The authors suggest that application of this property could enhance the efficiency of allergen‐specific immunotherapy.
Three‐Dimensional Conformation of the Injected Bolus in Vocal Fold Injections in a Cadaver Model
Authors: Mau Ted , Brewer Jacquelyn M. , Gatzert Samuel T. , Courey Mark S. 
Published: February 2011

ObjectiveTo determine the 3‐dimensional (3D) conformation of the injected bolus in the larynx in vocal fold injections, to understand how the bolus interacts spatially with elements of the laryngeal framework, and to relate the above to clinical observations in performing vocal fold injections.Study DesignExcised cadaveric larynx study.SettingLaboratory.Subjects and MethodsVocal folds of 12 human excised cadaveric larynges were injected with calcium hydroxylapatite. High‐resolution computed tomography scans were obtained of the injected larynges. Densities corresponding to the injected bolus and the laryngeal framework were extracted and processed with MATLAB routines to generate selective 3D reconstructions of the injected bolus within the laryngeal framework. Histology analysis was also performed to correlate with observations from the 3D reconstructions.ResultsBoluses injected into the lateral aspect of the thyroarytenoid muscle tended to be irregularly shaped, appeared to fill up the paraglottic space, and were associated with significant muscle compression. The vertical thickness of the injected boluses averaged 9.5 mm for lateral boluses and 7.6 mm for medial boluses, which were comparable to the vertical thickness of uninjected vocal folds.ConclusionLaterally injected boluses are shaped by spatial constraints imposed by elements of the laryngeal framework. Compression of vocal fold muscle may be a mechanism accounting for stiffness from overinjection. The irregular shapes of some boluses may affect the outcome of subsequent medialization attempts. Injections may enhance the vocal fold contact height as a favorable effect beyond simple medialization.
Risk Factors for Syndesmotic and Medial Ankle Sprain
Authors: Waterman Brian R. , Belmont Philip J. , Cameron Kenneth L. , Svoboda Steven J. , Alitz Curtis J. , Owens Brett D. 
Published: February 2011

Background: Syndesmotic and medial ankle sprains constitute up to 15% of all ankle sprains in athletic populations and can result in significant time lost to injury and long-term disability. Purpose: The objective of this study was to estimate the rate of syndesmotic and medial ankle sprain injuries and identify risk factors associated with these injuries within the physically active cadet population at the United States Military Academy (USMA). Study Design: Cohort study; Level of evidence, 2. Methods: The Cadet Illness and Injury Tracking System (CIITS) database at USMA was queried for all ankle injuries between 2005 and 2009. Sex, level of competition, and exposure to sport were among risk factors analyzed. Results: Among 20 336 person-years, 1206 cadets sustained ankle sprain. Syndesmotic (6.7%) and medial (5.1%) ankle sprains had an incidence rate (IR) of 4.8 and 3.5 per 1000 person-years, respectively. Compared with women, men were 3 times more likely to experience medial ankle sprain (IR ratio [IRR] 3.37; 95% confidence interval [CI]: 1.05, 10.74], but there was no difference in rate of syndesmotic sprains by sex (IRR 1.06; 95% CI: 0.58, 1.95). Athletics accounted for 81% of syndesmotic sprains and 64% of medial sprains. Sprint football (52.3), team handball (men’s, 34.7), soccer (men’s, 30.5; women’s, 6.5), and basketball (men’s, 24.8; women’s, 6.7) had the highest syndesmotic IR per 100 000 athlete-exposures. Medial sprain IR was highest in men’s rugby (16.6) and gymnastics (14.0). When analyzed by athlete-exposure, male intercollegiate athletes had a greater risk of syndesmotic sprain than their female counterparts (3.53; 95% CI: 1.26, 9.83). Furthermore, intercollegiate level of competition had an increased risk of syndesmotic sprain when compared with intramural level (IRR 2.41; 95% CI: 1.03, 5.65). Conclusion: Male athletes have an over threefold greater risk of medial ankle sprain. Male sex and higher level of competition are risk factors for syndesmotic ankle sprain during athletics.