bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial investigation of the blood-brain barrier in MS lesions at 7 tesla
Authors: Gaitán María I , Sati Pascal , Inati Souheil J , Reich Daniel S 
Published: December 2012

Background: We previously described two dynamics of contrast enhancement in scans of active multiple sclerosis lesions: Medium-sized, early lesions enhance centrifugally, whereas larger, slightly older lesions enhance centripetally. Due to technical limitations, our previous study did not characterize lesions < 5 mm in diameter, cortical enhancement, and anatomical structures within lesions. Objective: The objective of this paper is to obtain initial observations of these important aspects of lesion development on a 7 tesla scanner at high spatial resolution. Methods: We scanned eight patients, acquiring precontrast T2*-weighted scans, T1-weighted scans before and after contrast, and high-resolution dynamic contrast-enhanced scans during and up to 30 min after contrast. Results: We detected 15 enhancing lesions, obtaining dynamic data in 10: Five lesions < 4 mm enhanced centrifugally (initial central enhancement expanded outward), and five lesions > 4 mm enhanced centripetally (initial peripheral enhancement gradually filled the lesion). A leukocortical lesion initially showed enhancement in its white matter portion, which gradually spread into the cortex. Seventy-three percent of lesions were clearly perivenular. Conclusion: Most active lesions are perivenular, and the smallest lesions enhance centrifugally. This supports the idea that lesions grow outward from a central vein.
Overview, hurdles, and future work in adaptive designs: perspectives from a National Institutes of Health-funded workshop
Authors: Coffey Christopher S , Levin Bruce , Clark Christina , Timmerman Cate , Wittes Janet , Gilbert Peter , Harris Sara 
Published: December 2012

Background The clinical trials community has a never-ending search for dependable and reliable ways to improve clinical research. This exploration has led to considerable interest in adaptive clinical trial designs, which provide the flexibility to adjust trial characteristics on the basis of data reviewed at interim stages. Statisticians and clinical investigators have proposed or implemented a wide variety of adaptations in clinical trials, but specific approaches have met with differing levels of support. Within industry, investigators are actively exploring the benefits and pitfalls associated with adaptive designs (ADs). For example, a Drug Information Association (DIA) working group on ADs has engaged regulatory agencies in discussions. Many researchers working on publicly funded clinical trials, however, are not yet fully engaged in this discussion. We organized the Scientific Advances in Adaptive Clinical Trial Designs Workshop to begin a conversation about using ADs in publicly funded research. Held in November of 2009, the 1½-day workshop brought together representatives from the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the European Medicines Agency (EMA), the pharmaceutical industry, nonprofit foundations, the patient advocacy community, and academia. The workshop offered a forum for participants to address issues of ADs that arise at the planning, designing, and execution stages of clinical trials, and to hear the perspectives of influential members of the clinical trials community. The participants also set forth recommendations for guiding action to promote the appropriate use of ADs. These recommendations have since been presented, discussed, and vetted in a number of venues including the University of Pennsylvania Conference on Statistical Issues in Clinical Trials and the Society for Clinical Trials annual meeting. Purpose To provide a brief overview of ADs, describe the rationale behind conducting the workshop, and summarize the main recommendations that were produced as a result of this workshop. Conclusions There is a growing interest in the use of adaptive clinical trial designs. However, a number of logistical barriers need to be addressed in order to obtain the potential advantages of an AD. Currently, the pharmaceutical industry is well ahead of academic trialists with respect to addressing these barriers. Academic trialists will need to address important issues such as education, infrastructure, modifications to existing funding models, and the impact on Data and Safety Monitoring Boards (DSMB) in order to achieve the possible benefits of adaptive clinical trial designs.
Ocular symptoms secondary to meningeal carcinomatosis in a patient with lung adenocarcinoma: a case report
Authors: Sabater Alfonso L , Sadaba Luis M , de Nova Elisa 
Published: December 2012

Abstract

Background
Meningeal carcinomatosis (MC) is a rare complication associated with hematologic and solid tumors. MC develops when malignant cells gain access to the leptomeningeal space, producing several clinical symptoms. Loss of vision and ocular motility deficit are the most frequent ocular symptoms reported. Fundus examination usually appears normal, although optic nerve alterations like optic atrophy or papilledema have been described. MC diagnosis is usually completed by magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis. Indicated treatment for MC usually involves intrathecal chemotherapy combined with radiotherapy, although survival rate is extremely low.

Case presentation
A 66-year old man with stage IV metastatic lung adenocarcinoma, presented to the Ophthalmology Department with a two-month history of double vision, soft headaches and dizziness episodes. The patient presented a best visual corrected acuity of 0.7 in his right eye and 0.8 in his left eye. Diplopia was corrected with 6-prism diopters base-out prism in right eye. Funduscopy showed a bilateral papilledema, juxtapapillary exudates and splinter hemorrhages. Brain MRI showed a diffuse leptomeningeal enhancement in cortical sulcus. Lumbar puncture was performed and cerebrospinal fluid (CSF) cytology revealed malignant cells compatible with a diagnosis of MC. Intrathecal chemotherapy was administered.

Conclusion
MC is a serious complication of systemic cancer patients, involving a poor prognosis. Early diagnosis is extremely important, although treatment is frequently aimed to reduce the symptoms and extend survival. Eye symptoms may be the chief complaint, so MC should be considered in any patient with vision loss or diplopia accompanied by neurologic symptoms and in the absence of an intraocular cause, especially in the context of systemic cancer.
Effectiveness of a psycho-educational group program for major depression in primary care: a randomized controlled trial
Authors: Casañas Rocío , Catalán Rosa , del Val Jose Luis , Real Jordi , Valero Sergi , Casas Miquel 
Published: December 2012

Abstract

Background
Studies show the effectiveness of group psychoeducation in reducing symptoms in people with depression. However, few controlled studies that have included aspects of personal care and healthy lifestyle (diet, physical exercise, sleep) together with cognitive-behavioral techniques in psychoeducation are proven to be effective.
The objective of this study is to assess the effectiveness of a psychoeducational program, which includes aspects of personal care and healthy lifestyle, in patients with mild/moderate depression symptoms in Primary Care (PC).

Methods
In a randomized, controlled trial, 246 participants over 20 years old with ICD-10 major depression were recruited through nurses/general practitioners at 12 urban Primary Care Centers (PCCs) in Barcelona. The intervention group (IG) (n=119) received a group psychoeducational program (12 weekly, 1.5 h sessions led by two nurses) and the control group (CG) (n=112) received usual care. Patients were assessed at baseline and at, 3, 6 and 9 months. The main outcome measures were the BDI, EQ-5D and remission based upon the BDI.

Results
231 randomized patients were included, of whom 85 had mild depression and 146 moderate depression. The analyses showed significant differences between groups in relation to remission of symptoms, especially in the mild depression group with a high rate of 57% (p=0.009) at post-treatment and 65% (p=0.006) at 9 month follow up, and only showed significant differences on the BDI at post-treatment (p=0.016; effect size Cohen’s d’=.51) and at 6 and 9 month follow-up (p= 0.048; d’=.44).
In the overall and moderate sample, the analyses only showed significant differences between groups on the BDI at post-treatment, p=0.02 (d’=.29) and p=0.010 (d’=.47), respectively.
The psychoeducation group improved significantly on the EQ-5D at short and long-term.

Conclusions
This psychoeducational intervention is a short and long-term effective treatment for patients with mild depression symptoms. It results in a high remission rate, is recommended in PC and can be carried out by nurses with previous training. In moderate patients, group psychoeducation is effective in the short-term.

Trial registration
Clinical Trials.gov identifier NCT00841737
RETRACTED ARTICLE: Synthesis, characterization and in vitro studies of doxorubicin-loaded magnetic nanoparticles grafted to smart copolymers on A549 lung cancer cell line
Authors: Akbarzadeh Abolfazl , Samiei Mohammad , Joo Sang Woo , Anzaby Maryam , Hanifehpour Younes , Nasrabadi Hamid Tayefi , Davaran Soodabeh 
Published: December 2012

Abstract

Background
The aim of present study was to develop the novel methods for chemical and physical modification of superparamagnetic iron oxide nanoparticles (SPIONs) with polymers via covalent bonding entrapment. These modified SPIONs were used for encapsulation of anticancer drug doxorubicin.

Method
At first approach silane–grafted magnetic nanoparticles was prepared and used as a template for polymerization of the N-isopropylacrylamide (NIPAAm) and methacrylic acid (MAA) via radical polymerization. This temperature/pH-sensitive copolymer was used for preparation of DOX–loaded magnetic nanocomposites. At second approach Vinyltriethoxysilane-grafted magnetic nanoparticles were used as a template to polymerize PNIPAAm-MAA in 1, 4 dioxan and methylene-bis-acrylamide (BIS) was used as a cross-linking agent. Chemical composition and magnetic properties of Dox–loaded magnetic hydrogel nanocomposites were analyzed by FT-IR, XRD, and VSM.

Results
The results demonstrate the feasibility of drug encapsulation of the magnetic nanoparticles with NIPAAm–MAA copolymer via covalent bonding. The key factors for the successful prepardtion of magnetic nanocomposites were the structure of copolymer (linear or cross-linked), concentration of copolymer and concentration of drug. The influence of pH and temperature on the release profile of doxorubicin was examined. The in vitro cytotoxicity test (MTT assay) of both magnetic DOx–loaded nanoparticles was examined. The in vitro tests showed that these systems are no toxicity and are biocompatible.

Conclusion
IC50 of DOx–loaded Fe3O4 nanoparticles on A549 lung cancer cell line showed that systems could be useful in treatment of lung cancer.
Differential Lumbar Spinal Cord Responses among Wild Type, CD4 Knockout, and CD40 Knockout Mice in Spinal Nerve L5 Transection-Induced Neuropathic Pain
Authors: Cao Ling , Beaulac Holly , Eurich Adriana 
Published: December 2012

Background: Our previous studies have indicated that both lumbar spinal cord-infiltrating CD4+ T cells and microglial CD40 contribute to the maintenance of mechanical hypersensitivity in a murine model of neuropathic pain spinal nerve L5 transection (L5Tx). To further delineate the CD4 and CD40-mediated mechanisms involved in the development of L5Tx-induced neuropathic pain behaviors, we examined the lumbar spinal cord mononuclear cells of wild type (WT) BALB/c, BALB/c-CD4 knockout (KO), and BALB/c-CD40 KO mice via flow cytometry. Results: In WT mice, L5Tx induced significant but transient (at day 3 and/or day 7) increases of the total numbers of mononuclear cells, microglial cells (CD45loCD11b+), and infiltrating leukocytes (CD45hi) in the ipsilateral side of the spinal cord. In CD4 KO mice, significant elevation of microglia was detected only on day 7 post-L5Tx, while no significant increase in infiltrating leukocytes post-L5Tx was observed. CD40 KO mice did not exhibit any of the changes observed in WT mice. Furthermore, neutralizing CD40 antibody treatment indicated an early involvement of CD40 signaling in the development of L5Tx-induced mechanical hypersensitivity. Conclusions: Altogether, data indicate that both CD4 and CD40 play a role in L5Tx-induced leukocyte infiltration into the lumbar spinal cord but have differential contributions to spinal cord microglial activation following peripheral nerve injury.
The utility of FDG-PET for assessing outcomes in oligometastatic cancer patients treated with stereotactic body radiotherapy: a cohort study
Authors: Solanki Abhishek A , Weichselbaum Ralph R , Appelbaum Daniel , Farrey Karl , Yenice Kamil M , Chmura Steven J , Salama Joseph K 
Published: December 2012

Abstract

Background
Studies suggest that patients with metastases limited in number and destination organ benefit from metastasis-directed therapy. Stereotactic body radiotherapy (SBRT) is commonly used for metastasis directed therapy in this group. However, the characterization of PET response following SBRT is unknown in this population. We analyzed our cohort of patients to describe the PET response following SBRT.

Methods
Patients enrolled on a prospective dose escalation trial of SBRT to all known sites of metastatic disease were reviewed to select patients with pre- and post-therapy PET scans. Response to SBRT was characterized on PET imaging based on standard PET response criteria and compared to CT based RECIST criteria for each treated lesion.

Results
31 patients had PET and CT data available before and after treatment for analysis in this study. In total, 58 lesions were treated (19 lung, 11 osseous, 11 nodal, 9 liver, 6 adrenal and 2 soft tissue metastases). Median follow-up was 14 months (range: 3–41). Median time to first post-therapy PET was 1.2 months (range; 0.5-4.1). On initial post-therapy PET evaluation, 96% (56/58) of treated metastases responded to therapy. 60% (35/58) had a complete response (CR) on PET and 36% (21/58) had a partial response (PR). Of 22 patients with stable disease (SD) on initial CT scan, 13 had CR on PET, 8 had PR, and one had SD. Of 21 metastases with PET PR, 38% became CR, 52% remained PR, and 10% had progressive disease on follow-up PET. 10/35 lesions (29%) with an initial PET CR progressed on follow-up PET scan with median time to progression of 4.11 months (range: 2.75-9.56). Higher radiation dose correlated with long-term PET response.

Conclusions
PET response to SBRT enables characterization of metastatic response in tumors non-measurable by CT. Increasing radiation dose is associated with prolonged complete response on PET.
Modulation of γ-secretase by EVP-0015962 reduces amyloid deposition and behavioral deficits in Tg2576 mice
Authors: Rogers Kathryn , Felsenstein Kevin M , Hrdlicka Lori , Tu Zhiming , Albayya Faris , Lee Winnie , Hopp Sarah , Miller Mary-Jo , Spaulding Darcie , Yang Zhiyong , Hodgdon Hilliary , Nolan Scott , Wen Melody , Costa Don , Blain Jean-Francois , Freeman Emily , De Strooper Bart , Vulsteke Veerle , Scrocchi Louise , Zetterberg Henrik , Portelius Erik , Hutter-Paier Birgit , Havas Daniel , Ahlijanian Michael , Flood Dorothy , Leventhal Liza , Shapiro Gideon , Patzke Holger , Chesworth Richard , Koenig Gerhard 
Published: December 2012

Abstract

Background
A hallmark of Alzheimer’s disease is the presence of senile plaques in human brain primarily containing the amyloid peptides Aβ42 and Aβ40. Many drug discovery efforts have focused on decreasing the production of Aβ42 through γ-secretase inhibition. However, identification of γ-secretase inhibitors has also uncovered mechanism-based side effects. One approach to circumvent these side effects has been modulation of γ-secretase to shift Aβ production to favor shorter, less amyloidogenic peptides than Aβ42, without affecting the overall cleavage efficiency of the enzyme. This approach, frequently called γ-secretase modulation, appears more promising and has lead to the development of new therapeutic candidates for disease modification in Alzheimer’s disease.

Results
Here we describe EVP-0015962, a novel small molecule γ-secretase modulator. EVP-0015962 decreased Aβ42 in H4 cells (IC50 = 67 nM) and increased the shorter Aβ38 by 1.7 fold at the IC50 for lowering of Aβ42. AβTotal, as well as other carboxyl-terminal fragments of amyloid precursor protein, were not changed. EVP-0015962 did not cause the accumulation of other γ-secretase substrates, such as the Notch and ephrin A4 receptors, whereas a γ-secretase inhibitor reduced processing of both. A single oral dose of EVP-0015962 (30 mg/kg) decreased Aβ42 and did not alter AβTotal peptide levels in a dose-dependent manner in Tg2576 mouse brain at an age when overt Aβ deposition was not present. In Tg2576 mice, chronic treatment with EVP-0015962 (20 or 60 mg/kg/day in a food formulation) reduced Aβ aggregates, amyloid plaques, inflammatory markers, and cognitive deficits.

Conclusions
EVP-0015962 is orally bioavailable, detected in brain, and a potent, selective γ-secretase modulator in vitro and in vivo. Chronic treatment with EVP-0015962 was well tolerated in mice and lowered the production of Aβ42, attenuated memory deficits, and reduced Aβ plaque formation and inflammation in Tg2576 transgenic animals. In summary, these data suggest that γ-secretase modulation with EVP-0015962 represents a viable therapeutic alternative for disease modification in Alzheimer’s disease.
Lower short- and long-term mortality associated with overweight and obesity in a large cohort study of adult intensive care unit patients
Authors: Abhyankar Swapna , Leishear Kira , Callaghan Fiona M , Demner-Fushman Dina , McDonald Clement J 
Published: December 2012

Abstract
Introduction
Two thirds of United States adults are overweight or obese, which puts them at higher risk of developing chronic diseases and of death compared with normal-weight individuals. However, recent studies have found that overweight and obesity by themselves may be protective in some contexts, such as hospitalization in an intensive care unit (ICU). Our objective was to determine the relation between body mass index (BMI) and mortality at 30 days and 1 year after ICU admission.

Methods
We performed a cohort analysis of 16,812 adult patients from MIMIC-II, a large database of ICU patients at a tertiary care hospital in Boston, Massachusetts. The data were originally collected during the course of clinical care, and we subsequently extracted our dataset independent of the study outcome.

Results
Compared with normal-weight patients, obese patients had 26% and 43% lower mortality risk at 30 days and 1 year after ICU admission, respectively (odds ratio (OR), 0.74; 95% confidence interval (CI), 0.64 to 0.86) and 0.57 (95% CI, 0.49 to 0.67)); overweight patients had nearly 20% and 30% lower mortality risk (OR, 0.81; 95% CI, 0.70 to 0.93) and OR, 0.68 (95% CI, 0.59 to 0.79)). Severely obese patients (BMI ≥ 40 kg/m2) did not have a significant survival advantage at 30 days (OR, 0.94; 95% CI, 0.74 to 1.20), but did have 30% lower mortality risk at 1 year (OR, 0.70 (95% CI, 0.54 to 0.90)). No significant difference in admission acuity or ICU and hospital length of stay was found across BMI categories.

Conclusion
Our study supports the hypothesis that patients who are overweight or obese have improved survival both 30 days and 1 year after ICU admission.
Superior Long-Term Outcome With Idarubicin Compared With High-Dose Daunorubicin in Patients With Acute Myeloid Leukemia Age 50 Years and Older
Authors: Gardin Claude , Chevret Sylvie , Pautas Cécile , Turlure Pascal , Raffoux Emmanuel , Thomas Xavier , Quesnel Bruno , de Revel Thierry , de Botton Stéphane , Gachard Nathalie , Renneville Aline , Boissel Nicolas , Preudhomme Claude , Terré Christine , Fenaux Pierre , Bordessoule Dominique , Celli-Lebras Karine , Castaigne Sylvie , Dombret Hervé 
Published: December 2012

PurposeAlthough standard chemotherapy remains associated with a poor outcome in older patients with acute myeloid leukemia (AML), it is unclear which patients can survive long enough to be considered as cured. This study aimed to identify factors influencing the long-term outcome in these patients.Patients and MethodsThe study included 727 older patients with AML (median age, 67 years) treated in two idarubicin (IDA) versus daunorubicin (DNR) Acute Leukemia French Association trials. Prognostic analysis was based on standard univariate and multivariate models and also included a cure fraction model to focus on long-term outcome.ResultsAge, WBC count, secondary AML, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and adverse-risk and favorable-risk AML subsets (European LeukemiaNet classification) all influenced complete remission (CR) rate and overall survival (OS). IDA random assignment was associated with higher CR rate, but not with longer OS (P = .13). The overall cure rate was 13.3%. Older age and ECOG-PS more than 1 negatively influenced cure rate, which was higher in patients with favorable-risk AML (39.1% v 8.0% in adverse-risk AML; P < .001) and those treated with IDA (16.6% v 9.8% with DNR; P = .018). The long-term impact of IDA was still observed in patients younger than age 65 years, although all of the younger patients in the DNR control arm received high DNR doses (cure rate, 27.4% for IDA v 15.9% for DNR; P = .049). In multivariate analysis, IDA random assignment remained associated with a higher cure rate (P = .04), together with younger age and favorable-risk AML, despite not influencing OS (P = .11).ConclusionIn older patients with AML, younger age, favorable-risk AML, and IDA treatment predict a better long-term outcome.