bluuebunny/crossref_metadata_2025_split huggingface dataset:
4-Aminopyridine for symptomatic treatment of multiple sclerosis: a systematic review
Authors: Jensen Henrik Boye , Ravnborg Mads , Dalgas Ulrik , Stenager Egon 
Published: December 2013

This systematic review summarizes the existing evidence on the effect of 4-aminopyridine (4-AP) as a symptomatic treatment of decreased walking capacity in patients with multiple sclerosis (MS) when administered as an immediate release compound and a slow release compound. It summarizes existing evidence on the basic mechanisms of 4-AP from experimental studies and evidence on the clinical use of the compound. A systematic literature search was conducted of the following databases: PubMed and EMBASE. Thirty-five studies were included in the review divided into 16 experimental studies, two clinical studies with paraclinical endpoints and 17 clinical studies with clinical endpoints. Animal studies show that 4-AP can improve impulse conduction through demyelinated lesions. In patients with MS this translates into improved walking speed and muscle strength of the lower extremities in a subset of patients at a level that is often of clinical relevance. Phase III trials demonstrate approximately 25% increase in walking speed in roughly 40% and improved muscle strength in the lower extremities. Furthermore, 4-AP might have an effect on other domains such as cognition, upper extremity function and bowel and bladder, but this warrants further investigation. Side effects are mainly mild to moderate, consisting primarily of paraesthesia, dizziness, nausea/vomiting, falls/balance disorders, insomnia, urinary tract infections and asthenia. Side effects are worse when administered intravenously and when administered as an immediate release compound. Serious adverse events are rarely seen in the marketed clinical dosages. In conclusion, 4-AP is easy and safe to use. Slow release 4-AP shows more robust clinical effects and a more beneficial side-effect profile than immediate release 4-AP.
Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients
Authors: Rapin Nicolas , Bagger Frederik Otzen , Jendholm Johan , Mora-Jensen Helena , Krogh Anders , Kohlmann Alexander , Thiede Christian , Borregaard Niels , Bullinger Lars , Winther Ole , Theilgaard-Mönch Kim , Porse Bo T. 
Published: December 2013

Key Points
This study describes a method for the comparison of gene expression data of any type of cancer cells with their corresponding normal cells. Our analyses reveal novel disease entities, identify common deregulated transcriptional networks, and predict survival.
IL-17 protects T cells from apoptosis and contributes to development of ALPS-like phenotypes
Authors: Boggio Elena , Clemente Nausicaa , Mondino Anna , Cappellano Giuseppe , Orilieri Elisabetta , Gigliotti Casimiro L. , Toth Erika , Ramenghi Ugo , Dianzani Umberto , Chiocchetti Annalisa 
Published: December 2013

Key Points
In vitro, IL-17 inhibits Fas-induced cell death and IL-17 neutralization improves lymphocyte apoptosis in patients with ALPS and DALD. Treatment of MRLlpr/lpr mice with anti–IL-17A antibodies decreases the severity of autoimmune/lymphoproliferative disease.
Fluorescent tagging of VP22 in N-terminus reveals that VP22 favors Marek’s disease virus (MDV) virulence in chickens and allows morphogenesis study in MD tumor cells
Authors: Rémy Sylvie , Blondeau Caroline , Vern Yves Le , Lemesle Monique , Vautherot Jean-François , Denesvre Caroline 
Published: December 2013

Abstract
Marek’s disease virus (MDV) is an alpha-herpesvirus causing Marek’s disease in chickens, mostly associated with T-cell lymphoma. VP22 is a tegument protein abundantly expressed in cells during the lytic cycle, which is essential for MDV spread in culture. Our aim was to generate a pathogenic MDV expressing a green fluorescent protein (EGFP) fused to the N-terminus of VP22 to better decipher the role of VP22 in vivo and monitor MDV morphogenesis in tumors cells. In culture, rRB-1B EGFP22 led to 1.6-fold smaller plaques than the parental virus. In chickens, the rRB-1B EGFP22 virus was impaired in its ability to induce lymphoma and to spread in contact birds. The MDV genome copy number in blood and feathers during the time course of infection indicated that rRB-1B EGFP22 reached its two major target cells, but had a growth defect in these two tissues. Therefore, the integrity of VP22 is critical for an efficient replication in vivo, for tumor formation and horizontal transmission. An examination of EGFP fluorescence in rRB-1B EGFP22-induced tumors showed that about 0.1% of the cells were in lytic phase. EGFP-positive tumor cells were selected by cytometry and analyzed for MDV morphogenesis by transmission electron microscopy. Only few particles were present per cell, and all types of virions (except mature enveloped virions) were detected unequivocally inside tumor lymphoid cells. These results indicate that MDV morphogenesis in tumor cells is more similar to the morphorgenesis in fibroblastic cells in culture, albeit poorly efficient, than in feather follicle epithelial cells.
Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury
Authors: Fletcher Lauren , Isgor Elif , Sprague Shane , Williams Lindsey H , Alajajian Betty B , Jimenez David F , Digicaylioglu Murat 
Published: December 2013

Abstract

Background
Insulin-like growth factor binding protein-2 (IGFBP-2) regulates the bioavailability, transportation, and localization of insulin-like growth factor-I (IGF-I), an effective neuroprotectant in animal stroke models especially when administered intranasally. Therefore, determining IGFBP-2′s endogenous distribution in the normal and ischemic brain is essential in maximizing the neuroprotective potential of the intranasal IGF-I treatment approach. However, current data on IGFBP-2 is limited to mRNA and in situ hybridization studies. The purpose of this study was to determine if there are any changes in IGFBP-2 protein levels and distribution in ischemic brain and also to determine if IGFBPs play a role in the transportation of intranasally administered IGF-I into the brain.

Results
Using an in vitro approach, we show that ischemia causes changes in the distribution of IGFBP-2 in primary cortical neurons and astrocytes. In addition, we show using the transient middle cerebral artery occlusion (MCAO) model in mice that there is a significant increase in IGFBP-2 levels in the stroke penumbra and core after 72 h. This correlated with an overall increase in IGF-I after stroke, with the highest levels of IGF-I in the stroke core after 72 h. Brain sections from stroke mice indicate that neurons and astrocytes located in the penumbra both have increased expression of IGFBP-2, however, IGFBP-2 was not detected in microglia. We used binding competition studies to show that intranasally administered exogenous IGF-I uptake into the brain is not receptor mediated and is likely facilitated by IGFBPs.

Conclusions
The change in protein levels indicates that IGFBP-2 plays an IGF-I-dependent and -independent role in the brain’s acute (neuroprotection) and chronic (tissue remodeling) response to hypoxic-ischemic injury. Competition studies indicate that IGFBPs may have a role in rapid transportation of exogenous IGF-I from the nasal tissue to the site of injury.
The mediating role of dietary factors and leisure time physical activity on socioeconomic inequalities in body mass index among Australian adults
Authors: Gearon Emma , Backholer Kathryn , Hodge Allison , Peeters Anna 
Published: December 2013

AbstractBackgroundThe relationship between socioeconomic position and obesity has been clearly established, however, the extent to which specific behavioural factors mediate this relationship is less clear. This study aimed to ascertain the contribution of specific dietary elements and leisure-time physical activity (LTPA) to variations in obesity with education in the baseline (1990–1994) Melbourne Collaborative Cohort Study (MCCS).Methods18, 489 women and 12, 141 men were included in this cross-sectional analysis. A series of linear regression models were used in accordance with the products of coefficients method to examine the mediating role of alcohol, soft drink (regular and diet), snacks (healthy and sweet), savoury items (healthy and unhealthy), meeting fruit and vegetable guidelines and LTPA on the relationship between education and body mass index (BMI).ResultsCompared to those with lowest educational attainment, those with the highest educational attainment had a 1 kg/m2lower BMI. Among men and women, 27% and 48%, respectively, of this disparity was attributable to differences in LTPA and diet. Unhealthy savoury item consumption and LTPA contributed most to the mediated effects for men and women. Alcohol and diet soft drink were additionally important mediators for women.ConclusionsDiet and LTPA are potentially modifiable behavioural risk factors for the development of obesity that contribute substantially to inequalities in BMI. Our findings highlight the importance of specific behaviours which may be useful to the implementation of effective, targeted public policy to reduce socioeconomic inequalities in obesity.
Getting vaccinated or not getting vaccinated? Different reasons for getting vaccinated against seasonal or pandemic influenza
Authors: Bonfiglioli Roberta , Vignoli Michela , Guglielmi Dina , Depolo Marco , Violante Francesco Saverio 
Published: December 2013

Abstract

Background
A large number of studies have investigated the motivation behind health care workers (HCWs) taking the influenza vaccine. But with the appearance of pandemic influenza, it became important to better analyse the reasons why workers get vaccinated against seasonal and/or pandemic influenza.

Methods
Three main categories of reasons were identified with an Exploratory Factor Analysis. An analysis of variance (ANOVA) was used to verify the existence of differences between three categories of choices (taking of seasonal and pandemic vaccine, only the seasonal vaccine or none). In addition, a multinomial logistic regression analysis was performed to analyse the association between stated intentions and update of seasonal and pandemic vaccine. Questionnaires were returned from 168 HCWs (67.3% women).

Results
The results showed that age and being well-informed about vaccination topics are the most important variables in determining the choice to take the vaccine.

Conclusions
The results highlight the importance of enhancing education programs to improve awareness among HCWs concerning the benefits of taking the influenza vaccination, with particular attention paid to younger workers.
Suppression of urinary bladder urothelial carcinoma cell by the ethanol extract of pomegranate fruit through cell cycle arrest and apoptosis
Authors: Lee Song-Tay , Lu Min-Hua , Chien Lan-Hsiang , Wu Ting-Feng , Huang Li-Chien , Liao Gwo-Ing 
Published: December 2013

Abstract

Background
Pomegranate possesses many medicinal properties such as antioxidant, anti-inflammation and antitumor. It has been extensively used as a folk medicine by many cultures. Pomegranate fruit has been shown to have the inhibitory efficacy against prostate cancer and lung cancer in vitro and in vivo. It can be exploited in chemoprevention and chemotherapy of prostate cancer. In this study we examined the anti-cancer efficacy of pomegranate fruit grown in Taiwan against urinary bladder urothelial carcinoma (UBUC) and its mechanism of action.

Methods
Edible portion of Taiwanese pomegranate was extracted using ethanol and the anti-cancer effectiveness of ethanol extract was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry and western immunoblotting were exploited to uncover the molecular pathways underlying anti-UBUC activity of Taiwanese pomegranate ethanol extract.

Results
This study demonstrated that Taiwanese pomegranate fruit ethanol extract (PEE) could effectively restrict the proliferation of UBUC T24 and J82 cells. Cell cycle analyses indicated that the S phase arrest induced by PEE treatment might be caused by an increase in cyclin A protein level and a decrease in the expression of cyclin-dependent kinase 1. The results of western immunoblotting demonstrated that PEE treatment could not only evoke the activation of pro-caspase-3, -8,-9 but also increase Bax/Bcl-2 ratio in T24 cells. The above observations implicated that PEE administration might trigger the apoptosis in T24 cells through death receptor signaling and mitochondrial damage pathway. Besides we found that PEE exposure to T24 cells could provoke intensive activation of procaspase-12 and enhance the expressions of CHOP and Bip, endoplasmic reticulum (ER) stress marker, suggesting that ER stress might be the cardinal apoptotic mechanism of PEE-induced inhibition of bladder cancer cell.

Conclusions
The analytical results of this study help to provide insight into the molecular mechanism of induced bladder cancer cell apoptosis by pomegranate and to develop novel mechanism-based chemopreventive strategy for bladder cancer.
Size-dependent mechanical behavior of nanoscale polymer particles through coarse-grained molecular dynamics simulation
Authors: Zhao Junhua , Nagao Shijo , Odegard Gregory M , Zhang Zhiliang , Kristiansen Helge , He Jianying 
Published: December 2013

Abstract
Anisotropic conductive adhesives (ACAs) are promising materials used for producing ultra-thin liquid-crystal displays. Because the mechanical response of polymer particles can have a significant impact in the performance of ACAs, understanding of this apparent size effect is of fundamental importance in the electronics industry. The objective of this research is to use a coarse-grained molecular dynamics model to verify and gain physical insight into the observed size dependence effect in polymer particles. In agreement with experimental studies, the results of this study clearly indicate that there is a strong size effect in spherical polymer particles with diameters approaching the nanometer length scale. The results of the simulations also clearly indicate that the source for the increases in modulus is the increase in relative surface energy for decreasing particle sizes. Finally, the actual contact conditions at the surface of the polymer nanoparticles are shown to be similar to those predicted using Hertz and perfectly plastic contact theory. As ACA thicknesses are reduced in response to reductions in polymer particle size, it is expected that the overall compressive stiffness of the ACA will increase, thus influencing the manufacturing process.
The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial
Authors: Feng Rui-zhi , Lv Jian-qin , Johnson Angela K , Montoya Juan D , Mao Bing 
Published: December 2013

Abstract

Background
Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets.

Methods/design
This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy.

Discussion
This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial.

Trial registration
This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197.
Does a placebo effect really occur in dogs afflicted by hip osteoarthritis as measured by force platform gait analysis?
Authors: Moreau Maxim , Lussier Bertrand , Pelletier Jean-Pierre , Troncy Eric 
Published: December 2013

AbstractA recent study investigated the therapeutic response of dogs afflicted by hip osteoarthritis when evaluating therapeutic modalities compared to a negative (placebo) control group. Authors suggested a placebo effect based on peak vertical force measurement. In addition, small effect size for each of the tested therapeutics as well as the extremely large sample size needed (>450) to discern therapeutic efficacy using force platform gait analysis were reported. We wish to express our concerns regarding the eligibility criteria used to select the studied cohort, the small effect size, and the placebo effect reported in force platform gait analysis.
Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for advanced-stage unresectable intrahepatic cholangiocarcinoma
Authors: Kim Young-Il , Park Joong-Won , Kim Bo Hyun , Woo Sang Myung , Kim Tae Hyun , Koh Young Hwan , Lee Woo Jin , Kim Chang-Min 
Published: December 2013

Abstract

Background
A standard treatment for unresectable advanced-stage intrahepatic cholangiocarcinoma (IHCC) has not yet been established. Although neoadjuvant concurrent chemoradiotherapy (CCRT) and liver transplantation are associated with long-term survival in select patients, the outcomes of CCRT for advanced-stage unresectable IHCC remain unclear. The aim of our study was to evaluate the outcomes of CCRT in patients with unresectable advanced-stage IHCC.

Methods
We retrospectively reviewed the records of all patients with unresectable advanced stage (stage IVa or IVb) IHCC who were pathologically diagnosed and treated at National Cancer Center, Korea, from June 2001 to March 2012. Of the total of 92 patients, 25 (27.1%) received capecitabine plus cisplatin (XP) chemotherapy with external radiotherapy (RT) (XP-CCRT group) and 67 (72.8%) received XP chemotherapy alone (XP group). The clinical characteristics and outcomes of the 2 groups were compared.

Results
The 92 patients comprised 72 male and 20 female patients, with a median age of 58 years (range 26–78 years). The baseline clinical characteristics of the 2 groups were similar. Patients in the XP-CCRT group received a mean 44.7 Gy of RT and a mean 5.6 cycles of XP chemotherapy, whereas patients in the XP group received a mean 4.0 cycles. The disease control rate was higher in the XP-CCRT group than in the XP group, but the difference was not statistically significant (56.0% vs. 41.5%, p = 0.217). Although neutropenia was significantly more frequent in the XP-CCRT than in the XP group (48% vs. 9%, p < 0.001), the rates of other toxicities and > grade 3 toxicities did not differ. At a median follow-up of 5.3 months, PFS (4.3 vs. 1.9 months, p = 0.001) and OS (9.3 vs. 6.2 months, p = 0.048) were significantly longer in the XP-CCRT than in the XP group.

Conclusions
XP-CCRT was well tolerated and was associated with longer PFS and OS than XP chemotherapy alone in patients with unresectable advanced IHCC. Controlled randomized trials are required to determine whether XP-CCRT is a primary treatment option for patients with unresectable advanced IHCC.
Safety and efficacy of thoracoscopic wedge resection for elderly high-risk patients with stage I peripheral non-small-cell lung cancer
Authors: Lin Ling , Hu Dingzhong , Zhong Chenxi , Zhao Heng 
Published: December 2013

Abstract

Background
Elderly patients with severe cardiopulmonary and other system dysfunctions are unable to tolerate pulmonary lobectomy. This study aimed to evaluate the risk and efficacy of wedge resection under video-assisted thoracoscopic surgery (VATS) on elderly high-risk patients with stage I peripheral non-small-cell lung cancer (PNSCLC).

Methods
Elderly patients (≥70 years) with suspected PNSCLC were divided into high-risk group and conventional risk group. The high-risk patients confirmed in stage I by the examination of positron emission tomography computed tomography (PET-CT) and the postoperative patients in stage I PNSCLC with negative incisal margin were treated with VATS wedge resection. The conventional risk patients were treated with VATS radical resection and systematic lymphadenectomy. The clinical and pathological data were recorded. The total survival, tumor-free survival, recurrence time and style of patients were followed up.

Results
The operative time and blood loss of the VATS wedge resection group (69.4 ± 15.5 min, 52.1 ± 11.2 ml) were significantly less than those of the VATS radical resection group (128 ± 35.5 min, 217.9 ± 87.1 ml). Neither groups had postoperative death. The overall and tumor-free survival rate of the VATS wedge resection group within three years were 66.7% and 60.0%, and those of the VATS radical resection group were 93.8% and 94.1%, without significant difference (P > 0.05). The recurrence rates of the VATS wedge resection group and VATS radical resection group were 14.3% and 3.0%, without significant difference (P > 0.05).

Conclusion
It is safe, minimally invasive and meaningful to perform VATS wedge resection on the elderly high-risk patients with stage I PNSCLC.
The placebo effect in allergen‐specific immunotherapy trials
Authors: Narkus Annemie , Lehnigk Ulrike , Haefner Dietrich , Klinger Regine , Pfaar Oliver , Worm Margitta 
Published: December 2013

AbstractBackgroundDouble‐blind, placebo‐controlled (DBPC) trials are the gold standard for demonstrating clinical efficacy and tolerability. The placebo effect, although an important feature in placebo‐controlled studies, has never been systematically investigated in allergen‐specific immunotherapy (SIT) studies. This study was performed to examine the placebo response in SIT trials that employed a baseline observational period and two treatment years using a symptom‐medication‐score (SMS) as the primary endpoint.MethodsThe placebo effect was evaluated in six DBPC SIT studies (five studies using subcutaneous SIT (SCIT) and one sublingual (SLIT)), two grass, two birch and two house dust mite (HDM) SIT, including a total of 472 adult patients treated with a placebo. The results were reported as changes from baseline of the SMS area under the curve after two years of perennial placebo therapy during the respective evaluation periods. Pollen counts and IgG4 levels were additionally analysed.ResultsSubcutaneously treated placebo patients displayed a marked decrease in the SMS. The mean placebo effect in the SCIT trials with comparable allergen exposure was up to 41% in the second treatment year and, in contrast, reached only 1% in the SLIT trial. Allergen exposure had an inverse influence on the placebo effect. No changes from baseline in allergen specific IgG4 antibodies were observed in the placebo‐treated patients.ConclusionsSIT studies display a significant placebo effect, mainly observed in subcutaneous immunotherapy, with high variability depending on the route of application and allergen exposure. Our findings indicate the differential role of the placebo effect in SIT efficacy depending on the route of administration and pollen exposure.