Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of estrogen receptor-positive breast cancers inBRCA1mutation carriers.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #1105 Background: Invasive breast cancers (IBC) in BRCA1 mutation carriers are usually estrogen receptor (ER) negative (-) and more than 80% have a basal-like molecular phenotype. These tumors are typically poorly differentiated invasive ductal carcinomas with a high mitotic rate and frequently show a prominent lymphoid infiltrate, pushing or circumscribed margins, and geographic necrosis or a central fibrotic focus. However, some women with BRCA1 germline mutations develop ER positive (+) cancers; little is known about the characteristics of the ER+ tumors in this group. Design: We identified 41 ER+ IBC that developed in women with BRCA1 germline mutations with available pathologic material for review. The histologic features were analyzed in detail and compared with those of 45 ER- IBC that developed among BRCA1 mutation carriers. Results: Mean patient age was 46y for ER+ and 45y for ER- cases. Ninety percent of the ER+ cases and all the ER- cases were invasive ductal carcinomas or invasive carcinomas with ductal and lobular features. There were 2 mucinous and 2 tubular carcinomas in the ER+ group. The ER+ cancers exhibited a range of histologic grades: 12 (29.3%) were grade I, 10 (24.4%) grade II, and 18 (43.9%) grade III (1 case of microinvasive carcinoma could not be graded). In contrast, 43 of the 45 ER- cancers were grade III (95.6%) and 1 (2.2%) grade II (1 case of microinvasive carcinoma could not be graded). Histologic features commonly seen in association with ER- BRCA1 mutation-associated IBC were compared between the two groups and the results are summarized in the table. [][1] Of note, a brisk mitotic rate, pushing margin, and the presence of geographic necrosis/central fibrosis were all significantly more common in ER- than in ER+ tumors. Conclusions: To our knowledge, this study is the first to document in detail the histologic features of the uncommon ER+ IBC occurring in BRCA1 mutation carriers. Our observations suggest that ER+ IBC in BRCA1 mutation carriers represent a morphologically diverse group. This raises the possibility that at least some ER+ IBC that develop in women with germline BRCA1 mutations may be sporadic rather than BRCA1 -associated. We are currently analyzing these lesions with a panel of biomarkers and assays for loss of heterozygosity at the BRCA1 mutation sites to further address this important issue. This work was supported by a grant from the Breast Cancer Research Foundation. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1105. [1]: /embed/graphic-1.gif
An update review on risk factors and scales for prediction of deep sternal wound infections

Surgical site infections are the most common nosocomial infections in surgical patients. The preventable and the unmodifiable risk factors for deep sternal wound infections (DSWI) have been amply assessed in the literature. The aim of this review was to describe the results of the numerous published studies to describe all the DSWI risk factors and the scales devised to predict SWI, with a view to providing an update on this issue. A comprehensive search of the Medline and Embase databases was performed (considering studies from January 1995 to April 2011); and a manual search was also conducted using references cited in original publications and relevant review articles. There are several risk factors associated with DSWI, which could be classified in four categories as demographic (e.g. sex and age), behavioural (e.g. smoking and obesity), baseline clinical conditions (e.g. diabetes, hypertension and COPD) and surgical operative risk factors (e.g. duration of operation and emergency operation). Six scales for predicting the risk of DSWI are described in the literature: they vary not only in accuracy but also in ease of application and they are applied at different times (some only preoperatively and others also postoperatively). This study provides a broad update on our knowledge of the risk factors for DSWI and the scales for prediction with a view to improving the management of infections at cardiosurgery units.
Efficacy of Internet and Group-Administered Cognitive Behavioral Therapy for Insomnia in Adolescents: A Pilot Study

Research indicates that adolescents are at risk for insomnia, but are reluctant to seek help. Treatment of insomnia has been extensively examined in adults, but studies with adolescents are sparse. The purpose of this pilot study was to assess feasibility and efficacy of cognitive behavioral therapy for insomnia (CBT–i) for adolescents in both group and Internet settings. Twenty-six adolescents received 6 weekly sessions of CBT–i in a group (N = 13) or individual Internet setting (N = 13). Their sleep was measured with actigraphy, sleep logs, and questionnaires at baseline, posttreatment, and a 2-month follow up. For both treatments, results show a significant improvement, with medium to large effect sizes (ESs) of sleep onset latency, wake after sleep onset, and sleep efficiency. There was also a small ES increase of total sleep time in sleep log measures, but not in actigraphy measures. On questionnaires measuring symptoms of insomnia and chronic sleep reduction, significant improvements occurred either at posttreatment or at follow up. No differences were found between the groups. This study indicates CBT–i, either in group or in Internet formats, is an effective treatment for insomnia in adolescents. Further studies in a randomized controlled design are warranted.
Meeting the Challenge of New Graduate Role Transition: Clinical Nurse Educators Leading the Change

The transition from new graduate to professional nurse can be a challenging process. In some cases, more than 50% of new graduates have left their first position within the first year. One strategy that has been shown to yield positive results in facilitating new graduate role transition is nurse internship programs. All studies of internship programs in this review demonstrated lower turnover at 1 year after hire when compared with traditional clinical orientation programs.
B cells set trends: Lessons from multiple sclerosis

Until relatively recently, B cells were viewed as relatively passive recipients of T cell help, serving the primary normal function of protective antibody production. Similarly, their role in immune‐mediated diseases, including multiple sclerosis (MS), was traditionally ascribed to production of pathogenic autoantibodies. However, new insights gained from both animal models and in humans, including studies of selective B cell targeting in patients, have shed light on non‐antibody‐mediated functions of B cells as immune regulators in both health and disease. Here, we consider the significance of the recent success of B cell depletion in patients with MS. We submit that it is no longer a question of whether B cells contribute to MS, but how B cells do so. In this review, we consider concepts of the different antibody‐dependent and ‐independent biological roles that B cells might play in MS pathophysiology. Important data from the commonly used animal model of MS, experimental autoimmune encephalomyelitis (EAE), continues to contribute to our understanding of the molecular cascades involved in peripheral immune regulation and in immune‐neural interactions that might be relevant to inflammatory events of multiple sclerosis. We focus this review on results from human‐based studies, occasionally drawing on observations from animal models to highlight specific principles.
Intra-Articular Injection of Tenoxicam in the Treatment of Osteoarthritis of the Knee

Objectives: The aim of this study was to determine whether tenoxicam, administered by the intra-articular route, is useful for the treatment of osteoarthritis [OA] of the knee. Methods: Patients with knee OA were placed into three groups. Patients with no evidence of inflammation were randomized into Groups 1 and 2. Group 3 consisted of patients with knee OA with associated signs of inflammation. Groups 1 and 3 received three weekly intra-articular injections of tenoxicam, whereas only physical exercise was applied to Group 2. The Western Ontario McMaster Universities Index [WOMAC], the Lequesne Index for knee OA, and physical examination findings of the knee joint were used in the clinical and functional evaluations at baseline and months 1, 3, and 6. Results: A total of 63 subjects participated in this study. Statistically significant improvements from baseline were detected in Group 1 and Group 3, but not in Group 2. There was no lasting benefit from tenoxicam therapy since Groups 1 and 2 showed no significant differences at the six-month conclusion of the study. Similarly, Group 1 and Group 3 did not differ significantly. Conclusions: Intra-articular tenoxicam therapy seemed to show greater efficacy for pain and improvement of functional performance than exercise therapy alone, but the effects were no longer present. Tenoxicam, given intra-articularly, may provide benefit from the symptoms of OA, but the effects are transient.
Male Aggression in Dating-Courtship Relations

Approximately 62 per cent of a group of university Freshmen women reported experiencing offensive male sexual aggresion during the year prior to university entrance. Proneness to sexual aggression appears associated with a lack of parental sex guidance and the absence of older male siblings. Certain characteristics of the pair relationship also increase the probability of aggression. The adjustive reactions of the offended female are strongly influenced by prior parental guidance and the severity and provocation of the aggresive episode.
Capsaicin-sensitive Aδ Fibers in Cat Tooth Pulp

How close a correlation there is between the conduction velocity and receptive properties of pulpal nerve fibers is still unclear. Our specific aims were to confirm whether: (1) capsaicin affects not only polymodal C fibers but A8 fibers as well, and (2) Aδ polymodal nociceptors exist in the tooth pulp. A total of 139 functional single cat tooth pulp nerve fibers was isolated for analysis, of which 21 were Ap, 37 C, and 81 AS fibers. The A8 fibers were divided into two groups: One (n = 38) consisted of those fibers whose conduction velocities were more than 2.0 m/s both inside and outside the tooth pulp, and the other (n = 43) consisted of those fibers whose intrapulpal conduction velocities were less than 2.0 m/s, with extrapulpal conduction velocities greater than 2.0 m/s. We used 82 fibers to record the neural response following the topical application of capsaicin for 60 min at increasing concentrations (1 nM, 100 nM, 10 μM) through thin dentin. Six of 25 slow Aδ, 10/20 C, and no Ap (0/11) or fast AS (0/26) fibers responded to 1 nM or 100 nM of capsaicin. When the three concentrations of capsaicin solution were applied in turn, the electrical threshold and latency of Aβ and fast AS fibers did not change, whereas those of slow AS and C fibers gradually increased. In 0/11 Ap, 0/26 fast AS, 13/25 slow AS, and 18/20 C fibers, the conduction was blocked reversibly or irreversibly following the application of 10 uM of capsaicin. The amplitude of the late component of antidromic action potential of fast AS fibers decreased after the capsaicin application. No neural discharge could be recorded from 19 (3 Aβ, 5 fast AS, 6 slow AS, and 5C) fibers following the application of a single high concentration of capsaicin (10 μM). A single low concentration of capsaicin (100 nM) activated only some slow-conducting fibers (0/4 Ap, 0/4 FAS, 3/6 SAS, and 4/6 C). Response properties recorded from the remaining 18 fibers (3 Ap, 3 fast AS, 6 slow Aδ, and 6 C) were not changed following the application of the control vehicle. These results confirm that a low concentration of capsaicin has an excitatory effect on the response of slow pulpal AS as well as C fibers, and that a high concentration of capsaicin blocks the conduction of slow Aδ and C fibers as well as the terminals of fast AS fibers in the pulp.
INTRODUCTION TO MENTAL HEALTH

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Phenotyping Before Starting Treatment in COPD?

ABSTRACT Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous and complex disease with great morbidity and mortality. Despite the new developments in the managements of COPD, it was recognized that not all patients benefit from the available medications. Therefore, efforts to identify subgroups or phenotypes had been made in order to predict who will respond to a class of drugs for COPD. This review will discuss phenotypes, endotypes, and subgroups such as the frequent exacerbator, the one with systemic inflammation, the fast decliner, ACOS, and the one with co-morbidities and their impact on therapy. It became apparent, that the “inflammatory” phenotypes: frequent exacerbator, chronic bronchitic, and those with a number of co-morbidities need inhaled corticosteroids; in contrast, the emphysematous type with dyspnea and lung hyperinflation, the fast decliner, need dual bronchodilation (deflators). However, larger, well designed studies clustering COPD patients are needed, in order to identify the important subgroups and thus, to lead to personalize management in COPD.
The Association of Lung Clearance Index with COPD and FEV1 Reduction in ‘Men Born in 1914’

ABSTRACT Lung Clearance Index (LCI) provides an overall measurement of ventilation inhomogeneity. This population-based study examines whether LCI predicts pulmonary obstruction and incidence of chronic obstructive pulmonary disease (COPD) events over a long-term follow-up. Multiple breath nitrogen washout and spirometry were performed in 674 men from the cohort “Men born in 1914” at age 55 years. Subjects were classified into quartiles (Q) of LCI and according to LCI above and below upper limit of normal (ULN). Incidence of COPD events (COPD hospitalisations or COPD-related deaths) were monitored over the remaining life span of the men, by linkage with national hospital registers. In addition, development of pulmonary obstruction (i.e., FEV1/vital capacity below lower limit of normal (LLN)) was studied in 387 men who were re-examined with spirometry at 68 years of age. Over 44 years of follow-up, there were 85 incident COPD events. Hazards ratios (HRs) for COPD across quartiles of LCI were: Q1 1.00 (reference), Q2 1.30 (95% confidence interval: 0.61–2.74), Q3 1.97 (0.97–3.98) and Q4 3.99 (2.06–7.71) (p value for trend <0.001). This relationship remained significant after adjustments for confounding factors, including smoking and FEV1 (HR, Q4 vs Q1: 2.34 (1.17–4.69); p value for trend: 0.006). Reduction of FEV1 between 55 and 68 years of age and incidence of pulmonary obstruction was highest in those with high LCI. High LCI is associated with future development of pulmonary obstruction and incidence of COPD hospitalisations in men from the general population.
Facile synthesis of spinel CuCo2O4 nanocrystals as high-performance cathode catalysts for rechargeable Li-air batteries.

CuCo2O4 nanoparticles have been synthesized by a simple and low-cost urea combustion method and characterized as bifunctional catalysts for non-aqueous Li-air batteries. The resulting CuCo2O4 catalyst has been demonstrated to effectively reduce the charge-discharge polarization of Li-air batteries in a simulated air environment (80% Ar : 20% O2).
Excess S‐adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis

Methionine adenosyltransferase 1A (MAT1A) and glycine N‐methyltransferase (GNMT) are the primary genes involved in hepatic S‐adenosylmethionine (SAMe) synthesis and degradation, respectively. Mat1a ablation in mice induces a decrease in hepatic SAMe, activation of lipogenesis, inhibition of triglyceride (TG) release, and steatosis. Gnmt‐deficient mice, despite showing a large increase in hepatic SAMe, also develop steatosis. We hypothesized that as an adaptive response to hepatic SAMe accumulation, phosphatidylcholine (PC) synthesis by way of the phosphatidylethanolamine (PE) N‐methyltransferase (PEMT) pathway is stimulated in Gnmt−/− mice. We also propose that the excess PC thus generated is catabolized, leading to TG synthesis and steatosis by way of diglyceride (DG) generation. We observed that Gnmt−/− mice present with normal hepatic lipogenesis and increased TG release. We also observed that the flux from PE to PC is stimulated in the liver of Gnmt−/− mice and that this results in a reduction in PE content and a marked increase in DG and TG. Conversely, reduction of hepatic SAMe following the administration of a methionine‐deficient diet reverted the flux from PE to PC of Gnmt−/− mice to that of wildtype animals and normalized DG and TG content preventing the development of steatosis. Gnmt−/− mice with an additional deletion of perilipin2, the predominant lipid droplet protein, maintain high SAMe levels, with a concurrent increased flux from PE to PC, but do not develop liver steatosis. Conclusion: These findings indicate that excess SAMe reroutes PE towards PC and TG synthesis and lipid sequestration. (Hepatology 2013;58:1296–1305)
Genomic profiling of cell lines for personalized targeted therapy for hepatocellular carcinoma

Although a cancer cell line has limitations in modeling the physiological complexity in human cancer, it has shown to be useful as a convenient tool to interrogate the molecular mechanism of action of cancer therapeutics. Finn et al. tested an intriguing idea to use a human hepatocellular carcinoma (HCC) gene signature to probe genomic profiles of hepatoma cell lines to evaluate sensitivity to a molecular targeted agent, dasatinib, although more work is needed to determine its mechanism of action. The authors identified two groups of cell lines according to the presence of a gene signature of “progenitor/HB” subtype linked to a distinct median inhibitory concentration (IC50) profile as well as cell cycle arrest and apoptosis induced by dasatinib. Of note, the classification looks concordant with positivity of alpha-fetoprotein (AFP), which has been repeatedly reported as the major determinant of global transcriptome landscape in hepatoma cells. We previously annotated the AFP-based subtypes of hepatoma cell lines with various molecular features and clinical phenotypes by using the gene signature assessment. In the analysis, AFPnegative cells, corresponding “S1” subclass identified in our metaanalysis of human HCC cohorts, were characterized by activation of transforming growth factor beta (TGF-b) and Met pathways, suppression of the p53 pathway, overexpression of canonical Wnt pathway target genes, more disseminative phenotype, and in fact enrichment of the “progenitor/HB” signature. These may represent clues to the mechanism. In addition, these findings may collectively suggest that AFP is a predictive biomarker of dasatinib sensitivity. If this is confirmed and the drug shows a clinically meaningful effect in the subset of patients with non-AFP-producing HCC, this could have huge implications in the personalized HCC treatment because AFP is already available in clinics worldwide.
Building a Community With Your Advisees

Few faculty members have received specific orientation, guidance, or training for academic advising. The author describes the advisor-advisee relationship, the responsibilities of both parties, the goals of advising, expectations that students have of their advisors, and tips for advising a student with poor academic performance. Resources for advising are included, as well as recommendations for using technology effectively to strengthen the advising role and create a community with your advisees.
STUDIES ON PNEUMOCOCCUS GROWTH INHIBITION

Using the method described in an earlier publication for testing the growth-inhibitory and bactericidal activity of serum-leucocyte mixtures for the pneumococcus, a study has been made of the action of antipneumococcus serum added to the serum and leucocytes of the rabbit, which alone lack the power to inhibit pneumococcus growth. It was found that the additiori of relatively small quantities of immune serum to a mixture of rabbit serum and washed rabbit leucocytes conferred on this mixture marked growth-inhibitory and pneumococcidal powers. The effect of the immune serum was found to be quantitative in nature. Beyond a certain point progressive dilution of the serum resulted in a corresponding decrease in the degree of growth inhibition, but this property of the immune serum did not disappear until a high dilution was reached. The leucocytes were also found to exert their effect quantitatively. Within certain limits the number of pneurnococci killed was dependent on the quantity of them present. Tests comparing the action of immune serum in the rabbit serum-leucocyte tubes with their protective action in mice showed a close parallelism between these two effects; that is to say, an immune serum showing marked protective properties for mice was likewise effective in high dilution in the in vitro test, and vice versa.
The Mommy and Me Play Program: A Pilot Play Intervention for Low-Income, African American Preschool Families

In this study the author examined the effects of a dyadic, mother-paired play intervention—The Mommy and Me Play Program—an innovative intervention program designed using a live-action modeling technique in which mothers serve as “natural helpers” to each other. By identifying natural strengths in mothers and employing opportunities for scaffolded learning, this intervention aimed to enhance mother–child play interactions and children's social and emotional competence. Fifty mother–child dyads from a single, low-income, African American, urban community were assessed in this study on measures of mother–child play interactions and children's social and emotional competency. Results from this pilot were not statistically significant, but provide important information regarding future research with this intervention program. These preliminary findings indicated that mothers with fewer play skills pre-intervention demonstrated improvement in their play skills post-intervention beyond other intervention participants; and children of those same mothers showed the greatest decrease in angry and aggressive behaviors in the classroom when compared to other participating children from pre- to post-intervention. Implications for research and practice in community-based, intervention work with low-income, ethnic-minority families are discussed.
Effect of L-000845704, an αVβ3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women

The αVβ3 integrin (vitronectin receptor) plays a pivotal role in bone resorption. We hypothesized that L-000845704, an αVβ3 integrin antagonist, would potently inhibit bone resorption, thereby increasing bone mass as assessed by bone mineral density (BMD) in women with postmenopausal osteoporosis. In a multicenter, randomized, double-blind, placebo-controlled, 12-month study, 227 women (average 63 yr) with low lumbar spine or femoral neck BMD were randomly assigned to receive 100 or 400 mg L-000845704 once daily (qd), 200 mg L-000845704 twice daily (bid), or placebo. L-000845704 increased lumbar spine BMD (2.1, 3.1, and 3.5% for the 100-mg-qd, 400-mg-qd, and 200-mg-bid treatment groups, respectively, vs. −0.1% for placebo; P < 0.01 all treatments vs. placebo). Only 200 mg L-000845704 bid significantly increased BMD at the hip (1.7 vs. 0.3% for placebo; P < 0.03) and femoral neck (2.4 vs. 0.7% for placebo; P < 0.05). No L-000845704 group increased total body BMD. All doses of L-000845704 resulted in a simi.