bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor -1α in hepatocellular carcinoma
Authors: Zhang Lin , Huang Gang , Li Xiaowu , Zhang Yujun , Jiang Yan , Shen Junjie , Liu Jia , Wang Qingliang , Zhu Jin , Feng Xiaobin , Dong Jiahong , Qian Cheng 
Published: March 2013

Abstract

Background
High invasion and metastasis are the primary factors causing poor prognosis of patients with hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying these biological behaviors have not been completely elucidated. In this study, we investigate the molecular mechanism by which hypoxia promotes HCC invasion and metastasis through inducing epithelial-mesenchymal transition (EMT).

Methods
The expression of EMT markers was analyzed by immunohistochemistry. Effect of hypoxia on induction of EMT and ability of cell migration and invasion were performed. Luciferase reporter system was used for evaluation of Snail regulation by hypoxia-inducible factor -1α (HIF-1α).

Results
We found that overexpression of HIF-1α was observed in HCC liver tissues and was related to poor prognosis of HCC patients. HIF-1α expression profile was correlated with the expression levels of SNAI1, E-cadherin, N-cadherin and Vimentin. Hypoxia was able to induce EMT and enhance ability of invasion and migration in HCC cells. The same phenomena were also observed in CoCl2-treated cells. The shRNA-mediated HIF-1α suppression abrogated CoCl2-induced EMT and reduced ability of migration and invasion in HCC cells. Luciferase assay showed that HIF-1α transcriptional regulated the expression of SNAI1 based on two hypoxia response elements (HREs) in SNAI1 promoter.

Conclusions
We demonstrated that hypoxia-stabilized HIF1α promoted EMT through increasing SNAI1 transcription in HCC cells. This data provided a potential therapeutic target for HCC treatment.
A new chronobiological approach to discriminate between acute and chronic depression using peripheral temperature, rest-activity, and light exposure parameters
Authors: Moraes Cláudia Ávila , Cambras Trinitat , Diez-Noguera Antoni , Schimitt Regina , Dantas Giovana , Levandovski Rosa , Hidalgo Maria Paz 
Published: March 2013

Abstract

Background
Circadian theories for major depressive disorder have suggested that the rhythm of the circadian pacemaker is misaligned. Stable phase relationships between internal rhythms, such as temperature and rest/activity, and the external day-night cycle, are considered to be crucial for adapting to life in the external environmental. Therefore, the relationship and possible alterations among (i) light exposure, (ii) activity rhythm, and (iii) temperature rhythm could be important factors in clinical depression. This study aimed to investigate the rhythmic alterations in depression and evaluate the ability of chronobiological parameters to discriminate between healthy subjects and depressed patients.

Methods
Thirty female subjects, including healthy subjects, depressed patients in the first episode, and major recurrent depression patients. Symptoms were assessed using Hamilton Depression Scale, Beck Depression Inventory and Montgomery-Äsberg Scale. Motor activity, temperature, and light values were determined for 7 days by actigraph, and circadian rhythms were calculated.

Results
Depressed groups showed a lower amplitude in the circadian rhythm of activity and light exposure, but a higher amplitude in the rhythm of peripheral temperature. The correlation between temperature and activity values was different in the day and night among the control and depressed groups. For the same level of activity, depressed patients had lowest temperature values during the day. The amplitudes of temperature and activity were the highest discriminant parameters.

Conclusions
These results indicate that the study of rhythms is useful for diagnosis and therapy for depressive mood disorders.
Two series of new semisynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action
Authors: da Silva Gloria NS , Maria Nicole RG , Schuck Desirée C , Cruz Laura N , de Moraes Miriam S , Nakabashi Myna , Graebin Cedric , Gosmann Grace , Garcia Célia RS , Gnoatto Simone CB 
Published: March 2013

Abstract

Background
The discovery and development of anti-malarial compounds of plant origin and semisynthetic derivatives thereof, such as quinine (QN) and chloroquine (CQ), has highlighted the importance of these compounds in the treatment of malaria. Ursolic acid analogues bearing an acetyl group at C-3 have demonstrated significant anti-malarial activity. With this in mind, two new series of betulinic acid (BA) and ursolic acid (UA) derivatives with ester groups at C-3 were synthesized in an attempt to improve anti-malarial activity, reduce cytotoxicity, and search for new targets. In vitro activity against CQ-sensitive Plasmodium falciparum 3D7 and an evaluation of cytotoxicity in a mammalian cell line (HEK293T) are reported. Furthermore, two possible mechanisms of action of anti-malarial compounds have been evaluated: effects on mitochondrial membrane potential (ΔΨm) and inhibition of β-haematin formation.

Results
Among the 18 derivatives synthesized, those having shorter side chains were most effective against CQ-sensitive P. falciparum 3D7, and were non-cytotoxic. These derivatives were three to five times more active than BA and UA. A DiOC6(3) ΔΨm assay showed that mitochondria are not involved in their mechanism of action. Inhibition of β-haematin formation by the active derivatives was weaker than with CQ. Compounds of the BA series were generally more active against P. falciparum 3D7 than those of the UA series.

Conclusions
Three new anti-malarial prototypes were obtained from natural sources through an easy and relatively inexpensive synthesis. They represent an alternative for new lead compounds for anti-malarial chemotherapy.
Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study
Authors: Amr Mostafa , El-Mogy Ahmed , Shams Tarek , Vieira Karen , Lakhan Shaheen E 
Published: March 2013

AbstractBackgroundCurrent antidepressants used to treat pediatric patients have the disadvantage of limited efficacy and potentially serious side effects. The purpose of this study was to assess the efficacy of vitamin C as an adjuvant agent in the treatment of pediatric major depressive disorder in a six-month, double-blind, placebo-controlled pilot trial.MethodsThe study group (n=12) was given fluoxetine (10–20 mg/day) plus vitamin C (1000 mg/day) and control group (n=12) administered fluoxetine (10–20 mg/day) plus placebo. The data were analyzed by ANOVA andt-test for independent samples.ResultsBoth groups demonstrated significantly improved scores on the Children’s Depression Rating Scale (CDRS), the Children’s Depression Inventory (CDI), and the Clinical Global Impression (CGI). ANOVA was significantly different on all clinical measurements (group effect, time effect, and interaction), with the exception of group effect and interaction for CGI. Patients treated for six months with fluoxetine and vitamin C showed a significant decrease in depressive symptoms in comparison to the fluoxetine plus placebo group as measured by the CDRS (t=11.36,P<0.0001) and CDI (t=12.27,P<0.0001), but not CGI (t=0.13,P=0.90). No serious adverse effects were observed.ConclusionsThese preliminary results suggest that vitamin C may be an effective adjuvant agent in the treatment of MDD in pediatric patients.
Primary tracheobronchial mucoepidermoid carcinoma - a retrospective study of 32 patients
Authors: Song Zhengbo , Liu Zhuo , Wang Jiwen , Zhu Huineng , Zhang Yiping 
Published: March 2013

Abstract

Background
This retrospective study was designed to investigate the clinical characteristics, diagnosis, treatment and prognosis of primary tracheobronchial mucoepidermoid carcinoma (MEC).

Methods
Clinical data were retrospectively analyzed from 32 patients with pathologically confirmed primary tracheobronchial MEC between January 1990 and December 2010 at Zhejiang Cancer Hospital. The Kaplan-Meier methods were used to estimate and compare survival rates.

Results
There were 19 males and 13 females ranging in age from 7 to 73 years, with a median age of 28 years. Twenty-six of the 32 patients were treated with surgery alone. The other six patients were treated with surgery plus postoperative radiotherapy or chemotherapy. Six patients died during the follow-up time. The overall five-year survival rates were 81.25%, whereas the five-year survival rate of seven patients with high-grade tumors was only 28.6%. Stage I and II patients experienced better survival than Stage III and IV patients (the five-year survival rate was 100% and 43.6% respectively, P<0.001).

Conclusions
Primary tracheobronchial MEC is a rare disease. Histologic grading and TNM (tumor-node-metastasis)staging are independent prognostic factors. Surgical resection is the primary treatment.
Extranodal Rosai–Dorfman disease: a rare soft tissue neoplasm masquerading as a sarcoma
Authors: Komaragiri Mahathi , Sparber Lauren S , Santos-Zabala Maria Laureana , Dardik Michael , Chamberlain Ronald S 
Published: March 2013

Abstract

Introduction
Rosai–Dorfman disease (RDD) is a rare proliferative histiocytic disorder of unknown etiology. RDD typically presents with generalized lymphadenopathy and polymorphic histiocytic infiltration of the lymph node sinuses; however, occurrences of extranodal soft tissue RDD may rarely occur when masquerading as a soft tissue sarcoma.

Materials and methods
A comprehensive search of all published cases of soft tissue RDD without associated lymphadenopathy was conducted using PubMed and Google Scholar for the years 1988 to 2011. Ophthalmic RDD was excluded.

Results
Thirty-six cases of extranodal soft tissue RDD, including the current one, have been reported since 1988. Anatomical distribution varied among patients. Four (11.1%) patients presented with bilateral lesions in the same anatomic region. Pain was the most common symptom in six (16.8%) patients. Sixteen (41.6%) patients were managed surgically, of which one (2.8%) case experienced recurrence of disease.

Conclusion
RDD is a rare inflammatory non-neoplastic process that should be considered in the differential diagnosis of a soft tissue tumor. Thus, differentiation of extranodal RDD from more common soft tissue tumors such as soft tissue sarcoma or inflammatory myofibroblastic tumor is often difficult and typically requires definitive surgical excision with histopathological examination. While the optimal treatment for extranodal RDD remains ill-defined and controversial, surgical excision is typically curative.
Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases
Authors: Di Giorgio Angelo , Cardi Maurizio , Biacchi Daniele , Sibio Simone , Accarpio Fabio , Ciardi Antonio , Cornali Tommaso , Framarino Marialuisa , Sammartino Paolo 
Published: March 2013

Abstract

Background
More information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer.

Methods
From a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome.

Results
In the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion.

Conclusions
Our findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread.
Radar detection with the Neyman–Pearson criterion using supervised-learning-machines trained with the cross-entropy error
Authors: Jarabo-Amores María-Pilar , la Mata-Moya David de , Gil-Pita Roberto , Rosa-Zurera Manuel 
Published: March 2013

AbstractThe application of supervised learning machines trained to minimize the Cross-Entropy error to radar detection is explored in this article. The detector is implemented with a learning machine that implements a discriminant function, which output is compared to a threshold selected to fix a desired probability of false alarm. The study is based on the calculation of the function the learning machine approximates to during training, and the application of a sufficient condition for a discriminant function to be used to approximate the optimum Neyman–Pearson (NP) detector. In this article, the function a supervised learning machine approximates to after being trained to minimize the Cross-Entropy error is obtained. This discriminant function can be used to implement the NP detector, which maximizes the probability of detection, maintaining the probability of false alarm below or equal to a predefined value. Some experiments about signal detection using neural networks are also presented to test the validity of the study.
Amelioration of autoimmune neuroinflammation by the fusion molecule Fn14·TRAIL
Authors: Prinz-Hadad Hodaya , Mizrachi Tehila , Irony-Tur-Sinai Michal , Prigozhina Tatyana B , Aronin Alexandra , Brenner Talma , Dranitzki-Elhalel Michal 
Published: March 2013

Abstract

Background
Multiple sclerosis (MS) is a, T cell-mediated autoimmune disease, the management of which remains challenging. The recently described fusion protein, Fn14·TRAIL, combining the extracellular domain of Fn14 (capable of blocking the pro-inflammatory TWEAK ligand) fused to the extracellular domain of the TRAIL ligand (capable of sending apoptotic signals through its receptors on activated inflammatory cells) was designed to modulate the immune system as an anti-inflammatory agent. The present study explores the efficacy of this purified protein as an anti-inflammatory agent, using the animal model of MS - experimental autoimmune encephalomyelitis (EAE).

Methods
EAE was induced by myelin oligodendrocyte glycoprotein (MOG). Fn14·TRAIL or vehicle were injected daily for 4 to 16 days, at different time points after disease induction. Animals were examined daily and evaluated for EAE clinical signs. Lymphocytes were analyzed for ex vivo re-stimulation, cytokine secretion, transcription factor expression and subtype cell analysis. Spinal cords were checked for inflammatory foci. The Mann- Whitney rank sum test, Student’s t-test or ANOVA were used for statistical analysis.

Results
Significant improvement of EAE in the group treated with Fn14·TRAIL was noted from day 6 of disease onset and lasted until the end of follow-up (day 40 from disease induction), even in animals treated for 4 days only. Clinical improvement was linked to decreased lymphocyte infiltrates in the central nervous system (CNS) and to decreased Th1 and Th17 responses and to increased number of T- regulatory in the treated mice. No liver or kidney toxicity was evident. In vitro assays established the ability of Fn14·TRAIL to induce apoptosis of T cell lines expressing TRAIL receptors and TWEAK.

Conclusions
In this study we established the potency of Fn14·TRAIL, a unique fusion protein combining two potentially functional domains, in inhibiting the clinical course of EAE, even when given for a short time, without apparent toxicity. These findings make Fn14·TRAIL a highly promising agent to be used for targeted amelioration of neuro-inflammatory processes, as well as other autoimmune pathologies.
Modeling the obesity epidemic: social contagion and its implications for control
Authors: Ejima Keisuke , Aihara Kazuyuki , Nishiura Hiroshi 
Published: March 2013

AbstractBackgroundAs an obesity epidemic has grown worldwide, a variety of intervention programs have been considered, but a scientific approach to comparatively assessing the control programs has still to be considered. The present study aims to describe an obesity epidemic by employing a simple mathematical model that accounts for both social contagion and non-contagious hazards of obesity, thereby comparing the effectiveness of different types of interventions.MethodsAn epidemiological model is devised to describe the time- and age-dependent risk of obesity, the hazard of which is dealt with as both dependent on and independent of obesity prevalence, and parameterizing the model using empirically observed data. The equilibrium prevalence is investigated as our epidemiological outcome, assessing its sensitivity to different parameters that regulate the impact of intervention programs and qualitatively comparing the effectiveness. We compare the effectiveness of different types of interventions, including those directed to never-obese individuals (i.e. primary prevention) and toward obese and ex-obese individuals (i.e. secondary prevention).ResultsThe optimal choice of intervention programs considerably varies with the transmission coefficient of obesity, and a limited transmissibility led us to favour preventing weight gain among never-obese individuals. An abrupt decline in the prevalence is expected when the hazards of obesity through contagious and non-contagious routes fall into a particular parameter space, with a high sensitivity to the transmission potential of obesity from person to person. When a combination of two control strategies can be selected, primary and secondary preventions yielded similar population impacts and the superiority of the effectiveness depends on the strength of the interventions at an individual level.ConclusionsThe optimality of intervention programs depends on the contagiousness of obesity. Filling associated data gaps of obesity transmission would help systematically understand the epidemiological dynamics and consider required control programs.
Climate change and mosquito-borne diseases in China: a review
Authors: Bai Li , Morton Lindsay Carol , Liu Qiyong 
Published: March 2013

AbstractChina has experienced noticeable changes in climate over the past 100 years and the potential impact climate change has on transmission of mosquito-borne infectious diseases poses a risk to Chinese populations. The aims of this paper are to summarize what is known about the impact of climate change on the incidence and prevalence of malaria, dengue fever and Japanese encephalitis in China and to provide important information and direction for adaptation policy making. Fifty-five papers met the inclusion criteria for this study. Examination of these studies indicates that variability in temperature, precipitation, wind, and extreme weather events is linked to transmission of mosquito-borne diseases in some regions of China. However, study findings are inconsistent across geographical locations and this requires strengthening current evidence for timely development of adaptive options. After synthesis of available information we make several key adaptation recommendations including: improving current surveillance and monitoring systems; concentrating adaptation strategies and policies on vulnerable communities; strengthening adaptive capacity of public health systems; developing multidisciplinary approaches sustained by an new mechanism of inter-sectional coordination; and increasing awareness and mobilization of the general public.
Task-oriented training with computer gaming in people with rheumatoid arthritis or osteoarthritis of the hand: study protocol of a randomized controlled pilot trial
Authors: Srikesavan Cynthiav Swarnalatha , Shay Barbara , Robinson David B , Szturm Tony 
Published: March 2013

Abstract

Background
Significant restriction in the ability to participate in home, work and community life results from pain, fatigue, joint damage, stiffness and reduced joint range of motion and muscle strength in people with rheumatoid arthritis or osteoarthritis of the hand. With modest evidence on the therapeutic effectiveness of conventional hand exercises, a task-oriented training program via real life object manipulations has been developed for people with arthritis. An innovative, computer-based gaming platform that allows a broad range of common objects to be seamlessly transformed into therapeutic input devices through instrumentation with a motion-sense mouse has also been designed. Personalized objects are selected to target specific training goals such as graded finger mobility, strength, endurance or fine/gross dexterous functions. The movements and object manipulation tasks that replicate common situations in everyday living will then be used to control and play any computer game, making practice challenging and engaging.

Methods/Design
The ongoing study is a 6-week, single-center, parallel-group, equally allocated and assessor-blinded pilot randomized controlled trial. Thirty people with rheumatoid arthritis or osteoarthritis affecting the hand will be randomized to receive either conventional hand exercises or the task-oriented training. The purpose is to determine a preliminary estimation of therapeutic effectiveness and feasibility of the task-oriented training program. Performance based and self-reported hand function, and exercise compliance are the study outcomes. Changes in outcomes (pre to post intervention) within each group will be assessed by paired Student t test or Wilcoxon signed-rank test and between groups (control versus experimental) post intervention using unpaired Student t test or Mann–Whitney U test.

Discussion
The study findings will inform decisions on the feasibility, safety and completion rate and will also provide preliminary data on the treatment effects of the task-oriented training compared with conventional hand exercises in people with rheumatoid arthritis or osteoarthritis of the hand.

Trial registration
ClinicalTrials.gov: NCT01635582