bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCL3L1 copy number, HIV load, and immune reconstitution in sub-Saharan Africans
Authors: Aklillu Eleni , Odenthal-Hesse Linda , Bowdrey Jennifer , Habtewold Abiy , Ngaimisi Eliford , Yimer Getnet , Amogne Wondwossen , Mugusi Sabina , Minzi Omary , Makonnen Eyasu , Janabi Mohammed , Mugusi Ferdinand , Aderaye Getachew , Hardwick Robert , Fu Beiyuan , Viskaduraki Maria , Yang Fengtang , Hollox Edward J 
Published: November 2013

Abstract

Background
The role of copy number variation of the CCL3L1 gene, encoding MIP1α, in contributing to the host variation in susceptibility and response to HIV infection is controversial. Here we analyse a sub-Saharan African cohort from Tanzania and Ethiopia, two countries with a high prevalence of HIV-1 and a high co-morbidity of HIV with tuberculosis.

Methods
We use a form of quantitative PCR called the paralogue ratio test to determine CCL3L1 gene copy number in 1134 individuals and validate our copy number typing using array comparative genomic hybridisation and fiber-FISH.

Results
We find no significant association of CCL3L1 gene copy number with HIV load in antiretroviral-naïve patients prior to initiation of combination highly active anti-retroviral therapy. However, we find a significant association of low CCL3L1 gene copy number with improved immune reconstitution following initiation of highly active anti-retroviral therapy (p = 0.012), replicating a previous study.

Conclusions
Our work supports a role for CCL3L1 copy number in immune reconstitution following antiretroviral therapy in HIV, and suggests that the MIP1α -CCR5 axis might be targeted to aid immune reconstitution.
Preoperative serum CA 72.4 as prognostic factor of recurrence and death, especially at TNM stage II, for colorectal cancer
Authors: Ayude Daniel , Rodríguez-Berrocal Francisco Javier , Ayude José , Blanco-Prieto Sonia , Vázquez-Iglesias Lorena , Vázquez-Cedeira Marta , Páez de la Cadena María 
Published: November 2013

Abstract

Background
Nowadays, evaluation of colorectal cancer prognosis and decision-making for treatment continues to be based primarily on TNM tumour stage. Administration of adjuvant chemotherapy is especially challenging for stage II patients that can have very different disease-related outcomes. Therefore, more reliable prognostic markers need to be developed to improve the selection of stage II patients at high risk for recurrence. Our purpose is to assess the prognostic value of preoperative serum CA 72.4 to improve the risk stratification of CRC patients.

Methods
Preoperative sera collected from 71 unselected patients between January 1994 and February 1997 was assayed for CA 72.4 and CEA levels. Patients were followed-up for at least 30 months or until relapse. Survival curves were estimated by the Kaplan-Meier method and the prognostic value was determined using Log-Rank test and Cox regression analysis.

Results
Preoperative CA 72.4 levels above 7 U/mL correlate with a worse prognosis, with associated recurrence and death percentages exceeding the displayed by CEA. In a multivariate analysis, its combination with CEA proved the most important independent factor predicting survival. Remarkably, at stage II CA 72.4 also discriminates better than CEA those patients that will relapse or die from those with a favourable prognosis; however, CEA has not a negligible effect on survival.

Conclusions
The most outstanding finding of the present work is the correct classification of nearly every patient with bad prognosis (relapse or death) at TNM stage II when CEA and CA 72.4 are used altogether. This could improve the decision-making involved in the treatment of stage II colon cancer. Certainly further large-scale studies must be performed to determine whether CA 72.4 can be effectively used in the clinical setting.
Ten-year changes in the prevalence of overweight, obesity and central obesity among the Chinese adults in urban Shanghai, 1998–2007 — comparison of two cross-sectional surveys
Authors: Hou Xuhong , Liu Yu , Lu Huijuan , Ma Xiaojing , Hu Cheng , Bao Yuqian , Jia Weiping 
Published: November 2013

Abstract

Background
In China, obesity is expected to increase rapidly in both urban and rural areas. However, there have been no comprehensive reports on secular trends in obesity prevalence among Chinese adults in urban Shanghai, which is the largest city in southern China.

Methods
In 1998–2001 and again in 2007–2008, two independent population-based cross-sectional surveys were conducted in Shanghai to investigate the prevalence of metabolic disorders. These surveys obtained height, waist circumference (WC), and weight measurements for Chinese adults aged between 20 and 74 years who lived in urban communities. From the 1998–2001 survey, 4,894 participants (2,081 men and 2,813 women, mean age: 48.9 years) were recruited, and 4,395 participants (1,599 men and 2,796 women, mean age: 49.8 years) were recruited from the 2007–2008 survey. Using the World Health Organization criteria, overweight was defined as 25 kg/m2 ≤ BMI < 30 kg/m2 and obesity as BMI ≥ 30 kg/m2. Central obesity was defined as WC ≥ 90 cm in men or ≥85 cm in women. The differences in prevalence of obesity, central obesity and overweight between the two surveys were tested using multivariable logistic regression analyses.

Results
Compared to the 1998–2001 survey, in the 2007–2008 survey the BMI distribution for men and the WC distribution for both genders is shifted significantly to the right along the x-axis (all p < 0.001). Over the ten years, the prevalence of combined overweight and obesity increased 24% (from 31.5% to 39.1%, p < 0.001) in men, but decreased 8% (from 27.3% to 25.0%; p < 0.01) in women. The prevalence of central obesity increased 40% in men (from 19.5% to 27.3%; p < 0.01), but the increase was not significant in women (15.0% to 17.1%; p = 0.051). In the total population, only central obesity showed a significant change between the populations in the two surveys, increasing 29% (from 17.3% to 22.4%; p < 0.001).

Conclusions
Over this 10 year period, central obesity increased significantly in the Shanghai adult population. However, the prevalence of combined overweight and obesity was significantly increased in men but not in women.
The endotoxin/toll-like receptor-4 axis mediates gut microvascular dysfunction associated with post-prandial lipidemia
Authors: Yi Ping , Pang Jia , Alexander Jonathan Steven , Rivera Chantal 
Published: November 2013

Abstract

Background
Postprandial lipidemia is important in the development of coronary artery disease (CAD). Consumption of a meal high in monounsaturated fat was correlated with acute impairment of endothelial function. However, the mechanisms underlying impaired endothelial function in the postprandial state have not yet been elucidated. The effects of polyunsaturated fat (corn oil) and monounsaturated fat (olive oil) on vascular dysfunction in intestinal postcapillary venules and arterioles were examined in wild-type (WT) mice, mice genetically deficient in TLR4 (TLR4-/-) and mice pre-treated with antibiotics by intravital microscopy which was performed 1.0, 1.5, 2.0, 2.5 hours after oil administration. After intravital microscopy, samples of jejunum were therefore collected to test TLR4, pNF-kB p65 and SIRT1 protein expression by western blotting.

Results
Our findings showed that feeding mono-unsaturated olive oil or polyunsaturated corn oil promoted leukocyte and platelet trafficking in the gut microvasculature, and impaired endothelium-dependent arteriolar vasodilator responses during postprandial lipidemia. The expression of TLR4, pNF-kB p65 was significantly increased in mice gavaged with olive oil at 2 h and was significantly reduced in mice gavaged for 7 days with antibiotics and in TLR4 knockout (TLR4-/-) mice. At the same time, SIRT1 protein expression is diminished by feeding olive oil for 2 h, a phenomenon that is attenuated in mice pre-treated with antibiotics and in TLR4-/- mice. Corn oil treated mice exhibited a pattern of response similar to olive oil.

Conclusions
Dietary oils may be negative regulators of SIRT1 which activate the innate immune response through the endotoxin/TLR4 axis. Our findings establish a link between innate immunity (i.e. the endotoxin/TLR4 axis) and epigenetic controls mediated by SIRT1 in the genesis of diet associated vascular stress.
Contribution of oligomerization to the anti-HIV-1 properties of SAMHD1
Authors: Brandariz-Nuñez Alberto , Valle-Casuso Jose Carlos , White Tommy E , Nguyen Laura , Bhattacharya Akash , Wang Zhonghua , Demeler Borries , Amie Sarah , Knowlton Caitlin , Kim Baek , Ivanov Dmitri N , Diaz-Griffero Felipe 
Published: November 2013

Abstract

Background
SAMHD1 is a restriction factor that potently blocks infection by HIV-1 and other retroviruses. We have previously demonstrated that SAMHD1 oligomerizes in mammalian cells by immunoprecipitation. Here we investigated the contribution of SAMHD1 oligomerization to retroviral restriction.

Results
Structural analysis of SAMHD1 and homologous HD domain proteins revealed that key hydrophobic residues Y146, Y154, L428 and Y432 stabilize the extensive dimer interface observed in the SAMHD1 crystal structure. Full-length SAMHD1 variants Y146S/Y154S and L428S/Y432S lost their ability to oligomerize tested by immunoprecipitation in mammalian cells. In agreement with these observations, the Y146S/Y154S variant of a bacterial construct expressing the HD domain of human SAMHD1 (residues 109–626) disrupted the dGTP-dependent tetramerization of SAMHD1 in vitro. Tetramerization-defective variants of the full-length SAMHD1 immunoprecipitated from mammalian cells and of the bacterially-expressed HD domain construct lost their dNTPase activity. The nuclease activity of the HD domain construct was not perturbed by the Y146S/Y154S mutations. Remarkably, oligomerization-deficient SAMHD1 variants potently restricted HIV-1 infection.

Conclusions
These results suggested that SAMHD1 oligomerization is not required for the ability of the protein to block HIV-1 infection.
Histopathological changes in the liver of tree shrew (Tupaia belangeri chinensis) persistently infected with hepatitis B virus
Authors: Ruan Ping , Yang Chun , Su Jianjia , Cao Ji , Ou Chao , Luo Chengpiao , Tang Yanping , Wang Qi , Yang Fang , Shi Junlin , Lu Xiaoxu , Zhu Linqun , Qin Hong , Sun Wen , Lao Yuanzhi , Li Yuan 
Published: November 2013

Abstract

Background
An animal model for HBV that more closely approximates the disease in humans is needed. The tree shrew (Tupaia belangeri) is closely related to primates and susceptible to HBV. We previously established that neonatal tree shrews can be persistently infected with HBV in vivo, and here present a six year follow-up histopathological study of these animals.

Methods
Group A consists of six tree shrews with persistent HBV infection, group B consists of three tree shrews with suspected persistent HBV infection, while group C consists of four tree shrews free of HBV infection. Serum and liver tissues samples were collected periodically from all animals. HBV antigen and HBV antibodies were detected by ELISA and/or TRFIA. HBV DNA in serum and in liver biopsies was measured by FQ-PCR. Liver biopsies were applied for general histopathologic observation and scoring, immunohistochemical detections of HBsAg and HBcAg, and ultrastructural observation with electron microscope technique.

Results
Hydropic, fatty and eosinophilic degeneration of hepatocytes, lymphocytic infiltration and hyperplasia of small bile ducts in the portal area were observed in group A. One animal infected with HBV for over six years showed multiple necrotic areas which had fused to form bridging necrosis and fibrosis, and megalocytosis. The hepatic histopathological scores of group A were higher than those of group B and C. The histopathological score correlated positively with the duration of infection.

Conclusions
Hepatic histopathological changes observed in chronically HBV-infected tree shrews are similar to those observed in HBV-infected humans. The tree shrew may represent a novel animal model for HBV infection.
Co-expression network analysis and genetic algorithms for gene prioritization in preeclampsia
Authors: Tejera Eduardo , Bernardes João , Rebelo Irene 
Published: November 2013

Abstract

Background
In this study, we explored the gene prioritization in preeclampsia, combining co-expression network analysis and genetic algorithms optimization approaches. We analysed five public projects obtaining 1,146 significant genes after cross-platform and processing of 81 and 149 microarrays in preeclamptic and normal conditions, respectively.

Methods
After co-expression network construction, modular and node analysis were performed using several approaches. Moreover, genetic algorithms were also applied in combination with the nearest neighbour and discriminant analysis classification methods.

Results
Significant differences were found in the genes connectivity distribution, both in normal and preeclampsia conditions pointing to the need and importance of examining connectivity alongside expression for prioritization. We discuss the global as well as intra-modular connectivity for hubs detection and also the utility of genetic algorithms in combination with the network information. FLT1, LEP, INHA and ENG genes were identified according to the literature, however, we also found other genes as FLNB, INHBA, NDRG1 and LYN highly significant but underexplored during normal pregnancy or preeclampsia.

Conclusions
Weighted genes co-expression network analysis reveals a similar distribution along the modules detected both in normal and preeclampsia conditions. However, major differences were obtained by analysing the nodes connectivity. All models obtained by genetic algorithm procedures were consistent with a correct classification, higher than 90%, restricting to 30 variables in both classification methods applied.
Combining the two methods we identified well known genes related to preeclampsia, but also lead us to propose new candidates poorly explored or completely unknown in the pathogenesis of preeclampsia, which may have to be validated experimentally.
Two simple, brief, naturalistic activities and their impact on positive affect: feeling grateful and eating ice cream
Authors: Linley Peter Alex , Dovey Helen , de Bruin Eveline , Transler Catherine , Wilkinson Joy , Maltby John , Hurling Robert 
Published: November 2013

Abstract

Background
Positive psychology interventions have been shown to increase happiness and well-being, and researchers are beginning to speculate on the mechanisms through which these interventions may be effective. People are also naturally attuned to the things that will make them happier in their daily lives, and there is a case for considering how more naturalistic, everyday activities may also increase positive affect, happiness and well-being.

Methods
Study 1 involved 89 participants who completed a gratefulness activity while eating an ice cream for two days, following baseline measurement for two days. Participants completed the PANAS (Positive and Negative Affect Scale) twice per day, in the afternoon and in the evening, with the activity between these two times on the activity days. Study 2 involved 280 participants who formed four groups (gratefulness activity; ice cream consumption; gratefulness activity and ice cream consumption; control group), which undertook the relevant activity for two days. Participants completed baseline and follow-up measures, including the PANAS and the GQ-6 (Gratitude Questionnaire-6) on the day before and day following the two activity days. On the activity days themselves, participants completed the PANAS before and after their activity.

Results
In Study 1, we found that the combination of the gratefulness activity and eating ice cream led to increased positive affect. In Study 2, we explored this finding further, and found that any combination of the gratefulness activity and eating ice cream (together or alone) led to increased positive affect. The same pattern of results was observed for affect balance and the ratio of positive to negative emotions. The gratefulness activity only also led to increased gratitude as measured by the GQ-6. Results showed that even simple, naturalistic everyday activities can lead to increases in positive affect. This experience of positive affect may be one mediating pathway through which positive psychology interventions, and indeed everyday activities, are effective in enhancing happiness and well-being.

Conclusions
Researchers should consider the role of everyday activities in enhancing happiness and well-being, in addition to investigating the operational mechanisms of more formal positive psychology interventions.
Lapatinib–induced NF-kappaB activation sensitizes triple-negative breast cancer cells to proteasome inhibitors
Authors: Chen Yun-Ju , Yeh Ming-Hsin , Yu Meng-Chieh , Wei Ya-Ling , Chen Wen-Shu , Chen Jhen-Yu , Shih Chih-Yu , Tu Chih-Yen , Chen Chia-Hung , Hsia Te-Chun , Chien Pei-Hsuan , Liu Shu-Hui , Yu Yung-Luen , Huang Wei-Chien 
Published: November 2013

Abstract
Introduction
Triple-negative breast cancer (TNBC), a subtype of breast cancer with negative expressions of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), is frequently diagnosed in younger women and has poor prognosis for disease-free and overall survival. Due to the lack of known oncogenic drivers for TNBC proliferation, clinical benefit from currently available targeted therapies is limited, and new therapeutic strategies are urgently needed.

Methods
Triple-negative breast cancer cell lines were treated with proteasome inhibitors in combination with lapatinib (a dual epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor). Their in vitro and in vivo viability was examined by MTT assay, clonogenic analysis, and orthotopic xenograft mice model. Luciferase reporter gene, immunoblot, and RT-qPCR, immunoprecipitation assays were used to investigate the molecular mechanisms of action.

Results
Our data showed that nuclear factor (NF)-κB activation was elicited by lapatinib, independent of EGFR/HER2 inhibition, in TNBCs. Lapatinib-induced constitutive activation of NF-κB involved Src family kinase (SFK)-dependent p65 and IκBα phosphorylations, and rendered these cells more vulnerable to NF-κB inhibition by p65 small hairpin RNA. Lapatinib but not other EGFR inhibitors synergized the anti-tumor activity of proteasome inhibitors both in vitro and in vivo. Our results suggest that treatment of TNBCs with lapatinib may enhance their oncogene addiction to NF-κB, and thus augment the anti-tumor activity of proteasome inhibitors.

Conclusions
These findings suggest that combination therapy of a proteasome inhibitor with lapatinib may benefit TNBC patients.
Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts
Authors: Pfefferle Adam D , Herschkowitz Jason I , Usary Jerry , Harrell Joshua Chuck , Spike Benjamin T , Adams Jessica R , Torres-Arzayus Maria I , Brown Myles , Egan Sean E , Wahl Geoffrey M , Rosen Jeffrey M , Perou Charles M 
Published: November 2013

Abstract
Background
Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models are a useful resource for studying mammary cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and should improve preclinical drug testing.

Results
Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes. Cross-species analyses using three independent human breast cancer datasets identified eight murine classes that resemble specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1)-Tag, TgWAP-Myc and Trp53-/-. Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathway signatures between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis.

Conclusions
This study of murine models of breast carcinoma encompasses the largest comprehensive genomic dataset to date to identify human-to-mouse disease subtype counterparts. Our approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple genetically engineered mouse models are needed to represent the diversity of human breast cancers. The reported trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of human disease subtypes are used.
Coexistence of Malignant Struma Ovarii and Cervical Papillary Thyroid Carcinoma
Authors: Leong Aaron , Roche Philip J. R. , Paliouras Miltiadis , Rochon Louise , Trifiro Mark , Tamilia Michael 
Published: November 2013

Context:
Struma ovarii is an uncommon monodermal teratoma in which thyroid tissue is the predominant element. Malignant transformation of struma ovarii is an even rarer occurrence.

Case Presentation:
We describe a 42-year-old woman who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a symptomatic left pelvic mass. Histology revealed malignant struma ovarii with classical papillary thyroid carcinoma expression. Ultrasonography of the cervical neck showed thyroid micronodules and a dominant 1-cm nodule in the left thyroid lobe. As the ovarian tumor was large, the patient underwent a total thyroidectomy with the intention of administering 131I therapy in an adjuvant setting. Histology of the cervical thyroid gland revealed bilateral multifocal papillary thyroid carcinoma with extrathyroidal extension and perithyroidal lymph node metastasis.

Methods:
Morphological (microscopy), immunohistochemical (Hector Battifora mesothelial cell 1, cytokeratin-19, galectin-3), and molecular (BRAF V600E, RAS, RET-PTC) characteristics and clonality analysis of the cervical thyroid and ovarian tumors were explored to distinguish them as separate malignancies.

Results:
The thyroid-type tumors from the cervical gland and ovary were discordant in terms of tissue histology and level of cytokeratin-19 expression. The clinical features and tumor profile results supported the independent existence of these two embryologically related, although topographically distinct, malignancies.

Conclusion:
Our findings provided support for synchronous, albeit distinct, primary tumors in the ovary and cervical thyroid. “Field cancerization” and early genomic instability may explain multifocality in all thyroid-type tissue. In this regard, patients with malignant struma ovarii should undergo imaging of their thyroid gland for coexisting disease and thyroidectomy recommended for suspected malignancy or in preparation for radioiodine therapy.