bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of fibrocytes in fibrotic diseases of the lungs and heart
Authors: Keeley Ellen C , Mehrad Borna , Strieter Robert M 
Published: January 2011

AbstractFibrosis is the end result of a complex series of events that follow tissue injury and inflammation. Pathophysiologic fibrosis results in permanent scar formation, and can impair organ function. Fibrocytes are circulating, bone-marrow-derived progenitor cells that traffic from the bone marrow to the injured organ via the bloodstream, where they differentiate into fibroblasts and myofibroblasts, and play a pivotal role in both physiologic and aberrant fibrosis. In this review, we focus on the contribution of fibrocytes to fibrotic diseases of the lungs and the heart, including interstitial lung diseases, asthma, pulmonary hypertension, atherosclerosis and ischemic cardiomyopathy.
Building prognostic models for breast cancer patients using clinical variables and hundreds of gene expression signatures
Authors: Fan Cheng , Prat Aleix , Parker Joel S , Liu Yufeng , Carey Lisa A , Troester Melissa A , Perou Charles M 
Published: January 2011

Abstract

Background
Multiple breast cancer gene expression profiles have been developed that appear to provide similar abilities to predict outcome and may outperform clinical-pathologic criteria; however, the extent to which seemingly disparate profiles provide additive prognostic information is not known, nor do we know whether prognostic profiles perform equally across clinically defined breast cancer subtypes. We evaluated whether combining the prognostic powers of standard breast cancer clinical variables with a large set of gene expression signatures could improve on our ability to predict patient outcomes.

Methods
Using clinical-pathological variables and a collection of 323 gene expression "modules", including 115 previously published signatures, we build multivariate Cox proportional hazards models using a dataset of 550 node-negative systemically untreated breast cancer patients. Models predictive of pathological complete response (pCR) to neoadjuvant chemotherapy were also built using this approach.

Results
We identified statistically significant prognostic models for relapse-free survival (RFS) at 7 years for the entire population, and for the subgroups of patients with ER-positive, or Luminal tumors. Furthermore, we found that combined models that included both clinical and genomic parameters improved prognostication compared with models with either clinical or genomic variables alone. Finally, we were able to build statistically significant combined models for pathological complete response (pCR) predictions for the entire population.

Conclusions
Integration of gene expression signatures and clinical-pathological factors is an improved method over either variable type alone. Highly prognostic models could be created when using all patients, and for the subset of patients with lymph node-negative and ER-positive breast cancers. Other variables beyond gene expression and clinical-pathological variables, like gene mutation status or DNA copy number changes, will be needed to build robust prognostic models for ER-negative breast cancer patients. This combined clinical and genomics model approach can also be used to build predictors of therapy responsiveness, and could ultimately be applied to other tumor types.
Cyclooxygenase-2 up-regulates vascular endothelial growth factor via a protein kinase C pathway in non-small cell lung cancer
Authors: Luo Honghe , Chen Zhenguang , Jin Hui , Zhuang Mei , Wang Tao , Su Chunhua , Lei Yiyan , Zou Jianyong , Zhong Beilong 
Published: January 2011

Abstract

Background
Vascular endothelial growth factor (VEGF) expression is up-regulated via a cyclooxygenase-2 (COX-2)-dependent mechanism in non-small cell lung cancer (NSCLC), but the specific signaling pathway involved is unclear. Our aim was to investigate the signaling pathway that links COX-2 with VEGF up-regulation in NSCLC.

Material and methods
COX-2 expression in NSCLC samples was detected immunohistochemically, and its association with VEGF, microvessel density (MVD), and other clinicopathological characteristics was determined. The effect of COX-2 treatment on the proliferation of NSCLC cells (A549, H460 and A431 cell lines) was assessed using the tetrazolium-based MTT method, and VEGF expression in tumor cells was evaluated by flow cytometry. COX-2-induced VEGF expression in tumor cells was monitored after treatment with inhibitors of protein kinase C (PKC), PKA, prostaglandin E2 (PGE2), and an activator of PKC.

Results
COX-2 over-expression correlated with MVD (P = 0.036) and VEGF expression (P = 0.001) in NSCLC samples, and multivariate analysis demonstrated an association of VEGF with COX-2 expression (P = 0.001). Exogenously applied COX-2 stimulated the growth of NSCLCs, exhibiting EC50 values of 8.95 × 10-3, 11.20 × 10-3, and 11.20 × 10-3 μM in A549, H460, and A431 cells, respectively; COX-2 treatment also enhanced tumor-associated VEGF expression with similar potency. Inhibitors of PKC and PGE2 attenuated COX-2-induced VEGF expression in NLCSCs, whereas a PKC activator exerted a potentiating effect.

Conclusion
COX-2 may contribute to VEGF expression in NSCLC. PKC and downstream signaling through prostaglandin may be involved in these COX-2 actions.
Finding a cure for HIV: will it ever be achievable?
Authors: Lewin Sharon R , Evans Vanessa A , Elliott Julian H , Spire Bruno , Chomont Nicolas 
Published: January 2011

Combination antiretroviral therapy (cART) has led to a major reduction in HIV‐related mortality and morbidity. However, HIV still cannot be cured. With the absence of an effective prophylactic or therapeutic vaccine, increasing numbers of infected people, emerging new toxicities secondary to cART and the need for life‐long treatment, there is now a real urgency to find a cure for HIV.There are currently multiple barriers to curing HIV. The most significant barrier is the establishment of a latent or “silent” infection in resting CD4+ T cells. In latent HIV infection, the virus is able to integrate into the host cell genome, but does not proceed to active replication. As a consequence, antiviral agents, as well as the immune system, are unable to eliminate these long‐lived, latently infected cells. Reactivation of latently infected resting CD4+ T cells can then re‐establish infection once cART is stopped. Other significant barriers to cure include residual viral replication in patients receiving cART, even when the virus is not detectable by conventional assays. In addition, HIV can be sequestered in anatomical reservoirs, such as the brain, gastrointestinal tract and genitourinary tract.Achieving either a functional cure (long‐term control of HIV in the absence of cART) or a sterilizing cure (elimination of all HIV‐infected cells) remains a major challenge. Several studies have now demonstrated that treatment intensification appears to have little impact on latent reservoirs. Some potential and promising approaches that may reduce the latent reservoir include very early initiation of cART and the use of agents that could potentially reverse latent infection.Agents that reverse latent infection will promote viral production; however, simultaneous administration of cART will prevent subsequent rounds of viral replication. Such drugs as histone deacetylase inhibitors, currently used and licensed for the treatment of some cancers, or activating latently infected resting cells with cytokines, such as IL‐7 or prostratin, show promising results in reversing latency in vitro when used either alone or in combination. In order to move forward toward clinical trials that target eradication, there needs to be careful consideration of the risks and benefits of these approaches, agreement on the most informative endpoints for eradication studies and greater engagement of the infected community.
Development and implementation of a performance improvement project in adult intensive care units: overview of the Improving Medicine Through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) study
Authors: Mangino Julie E , Peyrani Paula , Ford Kimbal D , Kett Daniel H , Zervos Marcus J , Welch Verna L , Scerpella Ernesto G , Ramirez Julio A ,   the IMPACT-HAP Study Group
Published: January 2011

Abstract
Introduction
In 2005 the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) published guidelines for managing hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and healthcare-associated pneumonia (HCAP). Although recommendations were evidence based, collective guidelines had not been validated in clinical practice and did not provide specific tools for local implementation. We initiated a performance improvement project designated Improving Medicine Through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) at four academic centers in the United States. Our objectives were to develop and implement the project, and to assess compliance with quality indicators in adults admitted to intensive care units (ICUs) with HAP, VAP, or HCAP.

Methods
The project was conducted in three phases over 18 consecutive months beginning 1 February 2006: 1) a three-month planning period for literature review to create the consensus pathway for managing nosocomial pneumonia in these ICUs, a data collection form, quality performance indicators, and internet-based repository; 2) a six-month implementation period for customizing ATS/IDSA guidelines into center-specific guidelines via educational forums; and 3) a nine-month post-implementation period for continuing education and data collection. Data from the first two phases were combined (pre-implementation period) and compared with data from the post-implementation period.

Results
We developed a consensus pathway based on ATS/IDSA guidelines and customized it at the local level to accommodate formulary and microbiologic considerations. We implemented multimodal educational activities to teach ICU staff about the guidelines and continued education throughout post-implementation. We registered 432 patients (pre- vs post-implementation, 274 vs 158). Diagnostic criteria for nosocomial pneumonia were more likely to be met during post-implementation (247/257 (96.1%) vs 150/151 (99.3%); P = 0.06). Similarly, empiric antibiotics were more likely to be compliant with ATS/IDSA guidelines during post-implementation (79/257 (30.7%) vs 66/151 (43.7%); P = 0.01), an effect that was sustained over quarterly intervals (P = 0.0008). Between-period differences in compliance with obtaining cultures and use of de-escalation were not statistically significant.

Conclusions
Developing a multi-center performance improvement project to operationalize ATS/IDSA guidelines for HAP, VAP, and HCAP is feasible with local consensus pathway directives for implementation and with quality indicators for monitoring compliance with guidelines.
Polymorphism of the 5-HT transporter and response to
antidepressants: randomised controlled trial
Authors: Lewis Glyn , Mulligan Jean , Wiles Nicola , Cowen Philip , Craddock Nick , Ikeda Masashi , Grozeva Detelina , Mason Victoria , Nutt David , Sharp Deborah , Tallon Debbie , Thomas Laura , O'Donovan Michael C. , Peters Tim J. 
Published: January 2011

BackgroundAntidepressants exhibit a variety of pharmacological actions including
inhibition of the serotonin and noradrenaline transporters. We wished to
investigate whether genetic variation could be used to target or
personalise treatment, in a comparison of selective serotonin reuptake
inhibitors (SSRIs) with noradrenaline reuptake inhibitors (NARIs).AimsTo test the hypothesis that patients homozygous for the long (insertion)
polymorphism of the serotonin transporter (5-HTTLPR) have an increased
response to SSRI antidepressants but not to NARI antidepressants.MethodIn an individually randomised, parallel-group controlled trial, people
meeting criteria for a depressive episode who were referred by their
general practitioner were randomised to receive either citalopram (an
SSRI) or reboxetine (an NARI). Randomisation was by means of a remote
automated system accessed by telephone. The main outcome was depressive
symptoms, measured by Beck Depression Inventory (BDI) total score 6 weeks
after randomisation. The trial was registered with the International
Standard Randomised Controlled Trials Number registry
(ISRCTN31345163).ResultsAltogether 298 participants were randomised to receive citalopram and 303
were randomised to reboxetine. At 6 weeks follow-up, complete data were
available for 258 participants taking citalopram and 262 taking
reboxetine. We found no evidence to support an influence of 5-HTTLPR on
outcome following antidepressant treatment. The interaction term for BDI
score at 6 weeks was 0.50 (95% CI −2.04 to 3.03, P =
0.70), which indicated that responses to the SSRI and NARI were similar
irrespective of 5-HTTLPR genotype.ConclusionsIt is unlikely that the 5-HTTLPR polymorphism alone will be clinically
useful in predicting response to antidepressants in people with
depression.
Treatment of suicidal people around the world
Authors: Bruffaerts R. , Demyttenaere K. , Hwang I. , Chiu W.-T. , Sampson N. , Kessler R. C. , Alonso J. , Borges G. , de Girolamo G. , de Graaf R. , Florescu S. , Gureje O. , Hu C. , Karam E. G. , Kawakami N. , Kostyuchenko S. , Kovess-Masfety V. , Lee S. , Levinson D. , Matschinger H. , Posada-Villa J. , Sagar R. , Scott K. M. , Stein D. J. , Tomov T. , Viana M. C. , Nock M. K. 
Published: January 2011

BackgroundSuicide is a leading cause of death worldwide; however, little
information is available about the treatment of suicidal people, or about
barriers to treatment.AimsTo examine the receipt of mental health treatment and barriers to care
among suicidal people around the world.MethodTwenty-one nationally representative samples worldwide
(n=55 302; age 18 years and over) from the World
Health Organization's World Mental Health Surveys were interviewed
regarding past-year suicidal behaviour and past-year healthcare use.
Suicidal respondents who had not used services in the past year were
asked why they had not sought care.ResultsTwo-fifths of the suicidal respondents had received treatment (from 17%
in low-income countries to 56% in high-income countries), mostly from a
general medical practitioner (22%), psychiatrist (15%) or
non-psychiatrist (15%). Those who had actually attempted suicide were
more likely to receive care. Low perceived need was the most important
reason for not seeking help (58%), followed by attitudinal barriers such
as the wish to handle the problem alone (40%) and structural barriers
such as financial concerns (15%). Only 7% of respondents endorsed stigma
as a reason for not seeking treatment.ConclusionsMost people with suicide ideation, plans and attempts receive no
treatment. This is a consistent and pervasive finding, especially in
low-income countries. Improving the receipt of treatment worldwide will
have to take into account culture-specific factors that may influence the
process of help-seeking.
Palliative Cancer Care: An Epidemiologic Study
Authors: Becker Gerhild , Hatami Isaak , Xander Carola , Dworschak-Flach Bettina , Olschewski Manfred , Momm Felix , Deibert Peter , Higginson Irene J. , Blum Hubert E. 
Published: January 2011

Purpose To analyze the need for palliative care in hospital patients who have cancer. Palliative care is an essential component of comprehensive cancer care and identification of palliative care needs (PCNs) of patients with cancer is a topic that has not been thoroughly studied. Patients and Methods Data were collected prospectively from inpatients of University Medical Center Freiburg in Freiburg, Germany, with 982 hospital beds included in the study. During the observation period of 17 months, each patient discharged from a hospital ward was screened by surveying the treating physician who was responsible for dismissal about patients' PCNs based on the WHO 1990 definition of palliative care. To complete obligatory electronic discharge management, a modified dismissal form asking to classify the patient as having PCN “yes/no” had to be filled out for each patient discharged. Results The response rate was 96% with data for 39,849 patients that could be analyzed. A total of 6.9% of all hospital patients and 9.1% of patients older than age 65 years were considered to have PCNs. Of the 2,757 patients with PCNs, 67% (n = 1,836) had cancer. Among the 11,584 patients with cancer, 15.8% were classified as having PCNs. PCNs were particularly high in patients with head and neck cancer (28.3%), malignant melanoma (26.0%), and brain tumors (18.2%). Suffering from cancer increases the probability of developing PCNs by a factor of 3.63 (95% CI, 3.27 to 4.04). For patients with metastatic cancer, the risk of developing PCNs is increased 12-fold (odds ratio, 12.27; 95% CI, 11.07 to 13.60). Conclusion Structures to provide palliative care for patients with cancer are needed.
Phase III Trial of Weekly Methotrexate or Pulsed Dactinomycin for Low-Risk Gestational Trophoblastic Neoplasia: A Gynecologic Oncology Group Study
Authors: Osborne Raymond J. , Filiaci Virginia , Schink Julian C. , Mannel Robert S. , Alvarez Secord Angeles , Kelley Joseph L. , Provencher Diane , Scott Miller David , Covens Allan L. , Lage Janice M. 
Published: January 2011

Purpose There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN). Patients and Methods Two commonly used single-drug regimens were compared with respect to the proportion of patients meeting the criteria for a complete response (CR) in a randomized phase III trial conducted by the Gynecologic Oncology Group. Eligibility was purposefully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease (limited to lung lesions < 2 cm, adnexa, or vagina) or choriocarcinoma. Results Two hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m2 was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m2 (CR: 70% v 53%; P = .01). Similarly, in patients with low-risk GTN as defined before the 2002 WHO risk score revisions (risk score of 0 to 4 and excluding choriocarcinoma), response was 58% and 73% in the methotrexate and dactinomycin arms, respectively (P = .03). Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma (CR: 9% and 42%, respectively). There were two potential recurrences; one at 4 months (dactinomycin) and one at 22 months (methotrexate). Not all patients completed follow-up. Both regimens were well tolerated. Conclusion The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease.
High Survival Rate After Two-Stage Resection of Advanced Colorectal Liver Metastases: Response-Based Selection and Complete Resection Define Outcome
Authors: Brouquet Antoine , Abdalla Eddie K. , Kopetz Scott , Garrett Christopher R. , Overman Michael J. , Eng Cathy , Andreou Andreas , Loyer Evelyne M. , Madoff David C. , Curley Steven A. , Vauthey Jean-Nicolas 
Published: January 2011

Purpose Prolonged survival after two-stage resection (TSR) of advanced colorectal liver metastases (CLM) may be the result of selection of best responders to chemotherapy. The impact of complete resection in this well-selected group is controversial. Patients and Methods Data on 890 patients undergoing resection and 879 patients who received only chemotherapy for CLM were collected prospectively. We used intent-to-treat analysis to evaluate the survival of patients who underwent TSR. Additionally, we evaluated a cohort of nonsurgically treated patients selected to mirror the TSR population: colorectal metastases with liver-only disease, objective response to chemotherapy, and alive 1 year after chemotherapy initiation. Results Sixty-five patients underwent the first stage of TSR; 62 patients fulfilled the inclusion criteria for the medical group. TSR patients had a mean of 6.7 ± 3.4 CLM with mean size of 4.5 ± 3.1 cm. Nonsurgical patients had a mean of 5.9 ± 2.9 CLM with mean size of 5.4 ± 3.4 cm (not significant). Forty-seven TSR patients (72%) completed the second stage. Progression between stages was the main cause of noncompletion of the second stage (61%). After 50 months median follow-up, the 5-year survival rate was 51% in the TSR group and 15% in the medical group (P = .005). In patients who underwent TSR, noncompletion of TSR and major postoperative complications were independently associated with worse survival. Conclusion TSR is associated with excellent outcome in patients with advanced CLM as a result of both selection by chemotherapy and complete resection of metastatic disease.
Clinical Evidence for Predominance of Delta-5 Steroid Production in Women with Polycystic Ovary Syndrome
Authors: Rosencrantz Marcus A. , Coffler Mickey S. , Haggan Annette , Duke Kimberly B. , Donohue Michael C. , Shayya Rana F. , Su H. Irene , Chang R. Jeffrey 
Published: January 2011

AbstractContext:In women with polycystic ovary syndrome (PCOS), the basis for ovarian androgen overproduction involves an overall increase of steroidogenesis, notably in the delta-4 pathway. However, in vitro studies have suggested that excessive androgen production occurs predominantly through the delta-5 pathway.Objective:This study was performed to assess androgen dose-responses after human chorionic gonadotropin (hCG) stimulation in PCOS and normal women.Design:We conducted a prospective study to compare androgen production after iv hCG in PCOS and normal women.Setting:The study was conducted in a General Clinical Research Center in an academic medical center.Participants:Women with PCOS (age, 18–37 yr; n = 10) and normal ovulatory controls (age, 18–37 yr; n = 11) were recruited.Interventions:For dose-response studies, blood samples were obtained before and at 0.5, 24, and 48 h after iv recombinant hCG (1, 10, 25, 100, and 250 μg). A subset of subjects underwent frequent blood sampling over 24 h after iv injection of 25 μg of recombinant hCG.Main Outcome Measure(s):We measured basal and stimulated serum 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T), dehydroepiandrosterone, estradiol, and progesterone responses after hCG administration.Results:In PCOS women, maximal A and T production was observed at the lowest doses of hCG, whereas responses were minimal in normal women. Incremental responses of 17-OHP, estradiol, and progesterone were greater in PCOS compared to normal women.Conclusion:In PCOS women, maximal A and T responses to hCG relative to those of 17-OHP are consistent with ovarian androgen overproduction via the delta-5 pathway.