bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular carcinoma (HCC)
Authors: Hashiguchi Motoyuki , Ueno Shinichi , Sakoda Masahiko , Iino Satoshi , Hiwatashi Kiyokazu , Minami Koji , Ando Kei , Mataki Yuko , Maemura Kosei , Shinchi Hiroyuki , Ishigami Sumiya , Natsugoe Shoji 
Published: December 2013

Abstract

Background
While recent research has shown that expression of ZEB-1 in a variety of tumors has a crucial impact on patient survival, there is little information regarding ZEB-1 expression in hepatocellular carcinoma (HCC). This study investigated the co-expression of ZEB-1 and E-cadherin in HCC by immunohistochemistry and evaluated its association with clinical factors, including patient prognosis.

Methods
A total of 108 patients with primary HCC treated by curative hepatectomy were enrolled. ZEB-1 expression was immunohistochemically categorized as positive if at least 1% cancer cells exhibited nuclear staining. E-cadherin expression was divided into preserved and reduced expression groups and correlations between ZEB-1 and E-cadherin expression and clinical factors were then evaluated.

Results
With respect to ZEB-1 expression, 23 patients were classified into the positive group and 85 into the negative group. Reduced E-cadherin expression was seen in 44 patients and preserved expression in the remaining 64 patients. ZEB-1 positivity was significantly associated with reduced expression of E-cadherin (p = 0.027). Moreover, significant associations were found between ZEB-1 expression and venous invasion and TNM stage. ZEB-1 positivity was associated with poorer prognosis (p = 0.025). Reduced E-cadherin expression was significantly associated with intrahepatic metastasis and poorer prognosis (p = 0.047). In particular, patients with both ZEB-1 positivity and reduced E-cadherin expression had a poorer prognosis (p = 0.005). Regardless of E-cadherin status, ZEB-1 was not a significant prognostic factor by multivariate analysis. There was no statistical difference in overall survival when E-cadherin expression was reduced in the ZEB-1 positive group (p = 0.24).

Conclusions
Positive ZEB-1 expression and loss of E-cadherin expression are correlated with poor prognosis in HCC patients and malignancy of ZEB-1 positive tumors involves EMT.
Trends and determinants of mortality in women of reproductive age in rural Guinea-Bissau, West Africa – a cohort study
Authors: Mane Maram , Fisker Ane B , Ravn Henrik , Aaby Peter , Rodrigues Amabelia 
Published: December 2013

Abstract

Background
There are few studies reporting mortality of women of reproductive age (WRA) in developing countries. The trend and patterns of their mortality may be important for documenting the health status of the population in general.

Methods
We used a prospective open cohort of women aged 12 to 49 years living in the Bandim Health Project’s rural Health and Demographic Surveillance System (HDSS) in 5 regions of Guinea-Bissau from 1996 to 2007. Information on in- and out-migration and deaths were collected through the HDSS routine procedures. We assessed the trends in mortality and the associated determinants using Cox regression models.

Results
We followed 27,185 WRA for 141,693 person-years-at-risk (PYO) among whom 9,093 moved out and 1,006 died. Overall standardized mortality rate was 759 per 100,000 PYO. WRA mortality did not decline, but three periods could be distinguished: a stable mortality between 1996–2000 followed by 14% increase in mortality [Hazard rate ratio (HRR) = 1.14; 95% confidence interval (CI): 0.98-1.32; p = 0.08] between 2001–2003, and then in the last period from 2004–2007 a 25% decline (HRR = 0.75; 95% CI: 0.64-0.87; p < 0.001) in relation to the first period. Compared with the years 1990–1996 mortality increased in the first two periods until 2003; only in the last period did mortality reach the same level as in 1990–1996 (HRR = 0.96; 95% CI: 0.82-1.13; p = 0.62). The level of mortality differed between regions. In the adjusted analysis the eastern regions Bafata (HRR = 1.79; 95% CI: 1.38-2.32; p < 0.001) and Gabu (HRR = 1.70; 95% CI: 1.28-2.26; p < 0.001) had significantly higher mortality, but the hazard rate did not differ by ethnic group. As expected the rate increased with increasing age.

Conclusions
Over the twelve-year period mortality of WRA did not decline. A stable mortality in the beginning was followed by an increase and then a return to the previous levels. Further monitoring of mortality is needed to identify the risk factors for the striking regional differences. Advantage should be taken of the HDSS to monitor progress towards the MDGs and beyond.
Household catastrophic medical expenses in eastern China: determinants and policy implications
Authors: Li Xiaohong , Shen Jay J , Lu Jun , Wang Ying , Sun Mei , Li Chengyue , Chang Fengshui , Hao Mo 
Published: December 2013

Abstract

Background
Much of research on household catastrophic medical expenses in China has focused on less developed areas and little is known about this problem in more developed areas. This study aimed to analyse the incidence and determinants of catastrophic medical expenses in eastern China.

Methods
Data were obtained from a health care utilization and expense survey of 11,577 households conducted in eastern China in 2008. The incidence of household catastrophic medical expenses was calculated using the method introduced by the World Health Organization. A multi-level logistic regression model was used to identify the determinants.

Results
The incidence of household catastrophic medical expenses in eastern China ranged from 9.24% to 24.79%. Incidence of household catastrophic medical expenses was lower if the head of household had a higher level of education, labor insurance coverage, while the incidence was higher if they lived in rural areas, had a family member with chronic diseases, had a child younger than 5 years old, had a person at home who was at least 65 years old, and had a household member who was hospitalized. Moreover, the impact of the economic level on catastrophic medical expenses was non-linear. The poorest group had a lower incidence than that of the second lowest income group and the group with the highest income had a higher incidence than that of the second highest income group. In addition, region was a significant determinant.

Conclusions
Reducing the incidence of household catastrophic medical expenses should be one of the priorities of health policy. It can be achieved by improving residents’ health status to reduce avoidable health services such as hospitalization. It is also important to design more targeted health insurance in order to increase financial support for such vulnerable groups as the poor, chronically ill, children, and senior populations.
Health examination utilization in the visually disabled population in Taiwan: a nationwide population-based study
Authors: Hsu Yueh-Han , Tsai Wen-Chen , Kung Pei-Tseng 
Published: December 2013

AbstractBackgroundPeople with visual disabilities have increased health needs but face worse inequity to preventive health examinations. To date, only a few nationwide studies have analyzed the utilization of preventive adult health examinations by the visually disabled population. The aim of this study was to investigate the utilization of health examinations by the visually disabled population, and analyze the factors associated with the utilization.MethodsVisual disability was certified by ophthalmologists and authenticated by the Ministry of the Interior (MOI), Taiwan. We linked data from three different nationwide datasets (from the MOI, Bureau of Health Promotion, and National Health Research Institutes) between 2006 and 2008 as the data sources. Independent variables included demographic characteristics, income status, health status, and severity of disability; health examination utilization status was the dependent variable. The chi-square test was used to check statistical differences between variables, and a multivariate logistic regression model was used to examine the associated factors with health examination utilization.ResultsIn total, 47,812 visually disabled subjects aged 40 years and over were included in this study, only 16.6% of whom received a health examination. Lower utilization was more likely in male subjects, in those aged 65 years and above, insured dependents and those with a top-ranked premium-based salary, catastrophic illness/injury, chronic diseases of the genitourinary system, and severe or very severe disabilities.ConclusionThe overall health examination utilization in the visually disabled population was very low. Lower utilization occurred mainly in males, the elderly, and those with severe disabilities.
Combination of SLC administration and Tregs depletion is an attractive strategy for targeting hepatocellular carcinoma
Authors: Chen Long , Zhou Shuang , Qin Jie , Hu Heng , Ma Huiying , Liu Binbin , Wang Xuan , Ma Jiaqi , Ye Shenglong , Zhong Cuiping , Zhou Guomin , Liang Chunmin 
Published: December 2013

Abstract

Background
Secondary lymphoid tissue chemokine (SLC) is a key CC chemokine for chemotaxis of immune cells and has been an attractive candidate for anti-tumor treatments. However, among the immune cells recruited by SLC to tumors, the CD25+ Foxp3+ regulatory T cells (Tregs) compromise the anti-tumor effects. In this study, we proposed the combination therapy of intratumoral co-administration of SLC and anti-CD25 monoclonal antibodies (mAbs). We hypothesized that the intratumoral injections of SLC and depletion of Tregs would have stronger inhibition effects on the progression of hepatocellular carcinoma (HCC) in mice.

Methods
C57BL/6 mice were inoculated subcutaneously with the murine HCC cell line, and mice with visible tumors were treated intratumorally with SLC, SLC plus anti-CD25 mAbs or the control antibodies. The percentages of Tregs, effector CD8+ T cells and CD4+ T cells were checked in the tumors, lymph nodes, spleen and liver at regular intervals. The levels of intratumoral IL-12, IFN-γ, IL-10 and TGF-β1 were evaluated. The final anti-tumor effects were measured by the tumor volume and weight as well as the intratumoral activity of MMP2 and MMP9. Bone-marrow-derived dendritic cells were used to explore the mechanisms of maturation induced by SLC in vitro.

Results
Our experiments showed the combination therapy significantly decreased the frequency of Tregs, and increased CD8+ T cells and CD4+ T cells at tumor sites. These alterations were accompanied by an increased level of IL-12 and IFN-γ, and decreased level of IL-10 and TGF-β1. Unexpectedly, we observed a significantly decreased percentage of Tregs, and increased CD8+ T cells and CD4+ T cells in the lymph nodes, spleen and liver after the combination therapy. The growth and invasiveness of HCC was also maximally inhibited in the combination therapy compared with the SLC alone. Furthermore, we confirmed SLC induced the maturation of DCs via NF-κB p65 and this maturation would benefit the combination therapy.

Conclusions
Our data demonstrated that intratumoral co-administration of SLC and anti-CD25 mAbs was an effective treatment for HCC, which was correlated with the altered tumor microenvironment and systemically optimized percentages of Tregs, CD8+ T cells and CD4+ T cells in peripheral immune organs.
Efficient piezoelectric ZnO nanogenerators based on Au-coated silica sphere array electrode
Authors: Ko Yeong Hwan , Nagaraju Goli , Yu Jae Su 
Published: December 2013

Abstract
We reported ZnO nanorod-based piezoelectric nanogenerators (NGs) with Au-coated silica sphere array as an efficient top electrode. This electrode can readily bend the ZnO nanorods due to its enhanced surface roughness, thus resulting in more increased and regular piezoelectric charge output. Under a low external pushing force of 0.3 kgf, the output current and voltage were increased by approximately 2.01 and 1.51 times, respectively, in comparison with a conventional Au top electrode without silica spheres. Also, the effect of Au-coated silica spheres on the bending radius of ZnO nanorods was theoretically investigated.
One-step colloidal synthesis of biocompatible water-soluble ZnS quantum dot/chitosan nanoconjugates
Authors: Ramanery Fábio P , Mansur Alexandra AP , Mansur Herman S 
Published: December 2013

Abstract
Quantum dots (QDs) are luminescent semiconductor nanocrystals with great prospective for use in biomedical and environmental applications. Nonetheless, eliminating the potential cytotoxicity of the QDs made with heavy metals is still a challenge facing the research community. Thus, the aim of this work was to develop a novel facile route for synthesising biocompatible QDs employing carbohydrate ligands in aqueous colloidal chemistry with optical properties tuned by pH. The synthesis of ZnS QDs capped by chitosan was performed using a single-step aqueous colloidal process at room temperature. The nanobioconjugates were extensively characterised by several techniques, and the results demonstrated that the average size of ZnS nanocrystals and their fluorescent properties were influenced by the pH during the synthesis. Hence, novel 'cadmium-free’ biofunctionalised systems based on ZnS QDs capped by chitosan were successfully developed exhibiting luminescent activity that may be used in a large number of possible applications, such as probes in biology, medicine and pharmacy.
Allosteric induction of the CD4-bound conformation of HIV-1 Gp120
Authors: Roitburd-Berman Anna , Dela Gal , Kaplan Gilad , Lewis George K , Gershoni Jonathan M 
Published: December 2013

Abstract

Background
HIV-1 infection of target cells is mediated via the binding of the viral envelope protein, gp120, to the cell surface receptor CD4. This interaction leads to conformational rearrangements in gp120 forming or revealing CD4 induced (CD4i) epitopes which are critical for the subsequent recognition of the co-receptor required for viral entry. The CD4-bound state of gp120 has been considered a potential immunogen for HIV-1 vaccine development. Here we report on an alternative means to induce gp120 into the CD4i conformation.

Results
Combinatorial phage display peptide libraries were screened against HIV-1 gp120 and short (14aa) peptides were selected that bind the viral envelope and allosterically induce the CD4i conformation. The lead peptide was subsequently systematically optimized for higher affinity as well as more efficient inductive activity. The peptide:gp120 complex was scrutinized with a panel of neutralizing anti-gp120 monoclonal antibodies and CD4 itself, illustrating that peptide binding does not interfere with or obscure the CD4 binding site.

Conclusions
Two surfaces of gp120 are considered targets for the development of cross neutralizing antibodies against HIV-1; the CD4 binding site and CD4i epitopes. By implementing novel peptides that allosterically induce the CD4i epitopes we have generated a viral envelope that presents both of these surfaces simultaneously.
Analgesic Tolerance of Opioid Agonists in Mutant Mu-Opioid Receptors Expressed in Sensory Neurons following Intrathecal Plasmid Gene Delivery
Authors: Li Guangwen , Ma Fei , Gu Yanping , Huang Li-Yen Mae 
Published: December 2013

Background Phosphorylation sites in the C-terminus of mu-opioid receptors (MORs) are known to play critical roles in the receptor functions. Our understanding of their participation in opioid analgesia is mostly based on studies of opioid effects on mutant receptors expressed in in vitro preparations, including cell lines, isolated neurons and brain slices. The behavioral consequences of the mutation have not been fully explored due to the complexity in studies of mutant receptors in vivo. To facilitate the determination of the contribution of phosphorylation sites in MOR to opioid-induced analgesic behaviors, we expressed mutant and wild-type human MORs (hMORs) in sensory dorsal root ganglion (DRG) neurons, a major site for nociceptive (pain) signaling and determined morphine- and the full MOR agonist, DAMGO,-induced effects on heat-induced hyperalgesic behaviors and potassium current (IK) desensitization in these rats. Findings A mutant hMOR DNA with the putative phosphorylation threonine site at position 394 replaced by an alanine (T394A), i.e., hMOR-T, or a plasmid containing wild type hMOR (as a positive control) was intrathecally delivered. The plasmid containing GFP or saline was used as the negative control. To limit the expression of exogenous DNA to neurons of DRGs, a neuron-specific promoter was included in the plasmid. Following a plasmid injection, hMOR-T or hMOR receptors were expressed in small and medium DRG neurons. Compared with saline or GFP rats, the analgesic potency of morphine was increased to a similar extent in hMOR-T and hMOR rats. Morphine induced minimum IK desensitization in both rat groups. In contrast, DAMGO increased analgesic potency and elicited IK desensitization to a significantly less extent in hMOR-T than in hMOR rats. The development and extent of acute and chronic tolerance induced by repeated morphine or DAMGO applications were not altered by the T394A mutation. Conclusions These results indicate that phosphorylation of T394 plays a critical role in determining the potency of DAMGO-induced analgesia and IK desensitization, but has limited effect on morphine-induced responses. On the other hand, the mutation contributes minimally to both DAMGO- and morphine-induced behavioral tolerance. Furthermore, the study shows that plasmid gene delivery of mutant receptors to DRG neurons is a useful strategy to explore nociceptive behavioral consequences of the mutation.
Synthesis and biological evaluation of Combretastatin A-4 derivatives containing a 3’-O-substituted carbonic ether moiety as potential antitumor agents
Authors: Ma Mingyi , Sun Longru , Lou Hongxiang , Ji Mei 
Published: December 2013

Abstract

Background
Combretastatin A-4 (CA-4), which is an excellent antineoplastic agent, was isolated from Combretum caffrum. To date, structural modification studies of CA-4 have focused predominantly on the construction of new therapeutic agents for drug discovery. As a part of our ongoing work towards the modification of natural products, we have focused on the 3’-O-substituent groups in the B-ring of CA-4 under the hypothesis that these novel derivatives will possess good bioactivities and behave as effective antiproliferative pro-drugs.

Results
A series of novel CA-4 derivatives, which contained a 3’-O-substituted carbonic ether moiety, were synthesized and evaluated for their antitumor activities against four tumor cell lines, including MDA-MB-231, MCF-7, K562 and A549 cells. These derivatives exhibited clear antitumor activities, and CA-4E, in particular, showed the highest bioactivity of all of the derivatives tested against all four tumor cell lines, with IC50 values in the range of 1 to 180 nM. Based on its high bioactivity, CA-4E was subsequently selected to investigate the antitumor mechanism of these synthetic compounds. The cell cycle results demonstrated that CA-4E induced time- and dose-dependent G2/M arrest in a similar manner to CA-4, although its effect was more powerful than that of CA-4, and the apoptosis data showed that CA-4E induced cellular apoptosis in a dose-dependent manner.

Conclusions
The newly synthesized CA-4 derivatives exhibited good antitumor activities in vitro, with CA-4E, in particular, showing the highest bioactivity of all of the compounds tested. Furthermore, CA-4E induced time- and dose-dependent G2/M arrest and cellular apoptosis in a dose-dependent manner. Taken together, these results suggest that CA-4E should be subjected to further investigation as a potential anticancer drug candidate.
Chemical characterisation of museum-curated ethnographic resins from Australia and New Guinea used as adhesives, medicines and narcotics
Authors: Bradshaw Fiona 
Published: December 2013

Abstract

Background
Six ethnographic museum resins with documented adhesive, medicinal and narcotic uses have been analysed by gas chromatography–mass spectrometry (GC-MS) as a step towards understanding the role of specific resins in 20th century Australia and New Guinea. Curated in the Pitt Rivers Museum for over a hundred years, these specimens are examples of resin used for three different purposes, some accompanied by ethnographic accounts from the collectors themselves.

Results
The six ethnographic resins have been chemically characterised and identified to species where possible: an adhesive resin from New South Wales is identified as Xanthorrhoea resinosa Pers.; adhesives from New Guinea are tentatively identified as Canarium luzonicum Miq. and beeswax mixed with Canarium spp.; a narcotic resin from New Guinea is identified as Canarium salomonense B.L.Burtt; and the characterisation of spinifex resin from West Australian ‘medicine shells’ hypothesised to be Triodia irritans R.Br is presented.

Conclusions
This study concludes that molecular differentiation between resins from different species is still possible after a hundred years of aging in a museum environment and demonstrates the potential of resin analysis on such aged museum items. These data alongside re-visited ethnographic accounts can confirm, correct, or provide new information to museum records. Furthermore, they can shed new light on the study of the role of these particular resins and mixtures that were used in Indigenous Sahul and contribute towards a framework of analysis and understanding of archaeological resins from this region.
Inhibition of synovitis and joint destruction by a new single domain antibody specific for cyclophilin A in two different mouse models of rheumatoid arthritis
Authors: Wang Li , Jia Junfeng , Wang Conghua , Ma Xiaokui , Liao Chenggong , Fu Zhiguang , Wang Bin , Yang Xiangmin , Zhu Ping , Li Yu , Chen Zhinan 
Published: December 2013

Abstract
Introduction
Cyclophilin A (CypA) is implicated in rheumatoid arthritis (RA) pathogenesis. We studied whether a novel anti-CypA single domain antibody (sdAb) treatment would modulate the severity of the disease in two different animal models of RA.

Methods
A novel sdAb, named sdAbA1, was screened from an immunized camel sdAb library and found to have a high binding affinity (KD = 6.9 × 10-9 M) for CypA. The SCID-HuRAg model and the collagen-induced arthritis (CIA) in mice were used to evaluate the effects of sdAbA1 treatment on inflammation and joint destruction. For in vitro analysis, monocytes/macrophages were purified from synovial fluid and peripheral blood of patients with RA and were tested for the effect of anti-CypA sdAb on metalloproteinase (MMP) production. Human monocyte cell line THP-1 cells were selected and western blot analyses were performed to examine the potential signaling pathways.

Results
In the CIA model of RA, the sdAbA1 treatment resulted in a significant decrease in clinical symptoms as well as of joint damage (P <0.05). In the SCID-HuRAg model, treatment with anti-CypA antibody sdAbA1 significantly reduced cartilage erosion, inflammatory cell numbers and MMP-9 production in the implanted tissues (P <0.05). It also significantly reduced the levels of human inflammatory cytokines IL-6 and IL-8 in mouse serum (P <0.05). No toxic effects were observed in the two animal models. In vitro results showed that sdAbA1 could counteract CypA-dependent MMP-9 secretion and IL-8 production by interfering with the ERK-NF-κB pathway.

Conclusions
Blockade of CypA significantly inhibited synovitis and cartilage/bone erosion in the two tested animal models of RA. Our findings provide evidence that sdAbA1 may be a potential therapeutic agent for RA.