bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondhand smoke in combination with ambient air pollution exposure is associated with increasedx CpG methylation and decreased expression of IFN-γ in T effector cells and Foxp3 in T regulatory cells in children
Authors: Kohli Arunima , Garcia Marco A , Miller Rachel L , Maher Christina , Humblet Olivier , Hammond S Katharine , Nadeau Kari 
Published: September 2012

Abstract

Background
Secondhand smoke (SHS) and ambient air pollution (AAP) exposures have been associated with increased prevalence and severity of asthma and DNA modifications of immune cells. In the current study, we examined the association between SHS and AAP with DNA methylation and expression of interferon-gamma (IFN-γ) and forkhead box protein 3 (Foxp3) in T cell populations.

Methods
Subjects 7–18 years old were recruited from Fresno (high AAP; n = 62) and Stanford, CA (low AAP; n = 40) and divided into SHS-exposed (Fresno: n = 31, Stanford: n = 6) and non-SHS-exposed (nSHS; Fresno: n = 31, Stanford: n = 34) groups. T cells purified from peripheral blood were assessed for levels of DNA methylation and expression of IFN-γ (in effector T cells) or Foxp3 (in regulatory T cells).

Results
Analysis showed a significant increase in mean % CpG methylation of IFN-γ and Foxp3 associated with SHS exposure (IFN-γ: FSHS 62.10%, FnSHS 41.29%, p < 0.05; SSHS 46.67%, SnSHS 24.85%, p < 0.05; Foxp3: FSHS 74.60%, FnSHS 54.44%, p < 0.05; SSHS 62.40%, SnSHS 18.41%, p < 0.05) and a significant decrease in mean transcription levels of both genes (IFN-γ: FSHS 0.75, FnSHS 1.52, p < 0.05; SHS 2.25, nSHS 3.53, p < 0.05; Foxp3: FSHS 0.75, FnSHS 3.29, p < 0.05; SSHS 4.8, SnSHS 7.2, p < 0.05). AAP was also associated with hypermethylation (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05) and decreased transcription of both genes (IFN-γ: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05; Foxp3: FSHS vs. SSHS, p < 0.05; FnSHS vs. SnSHS, p < 0.05). Average methylation between AAP- and SHS-only exposures was not significantly different (IFN-γ: p = 0.15; Foxp3: p = 0.27), nor was Foxp3 expression (p = 0.08); IFN-γ expression was significantly decreased in AAP-only subjects (p < 0.05).

Conclusions
Exposures to SHS and AAP are associated with significant hypermethylation and decreased expression of IFN-γ in Teffs and Foxp3 in Tregs. Relative contributions of each exposure to DNA modification and asthma pathogenesis warrant further investigation.
68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors
Authors: Li Xiang , Samnick Samuel , Lapa Constantin , Israel Ina , Buck Andreas K , Kreissl Michael C , Bauer Wolfgang 
Published: September 2012

Abstract

Background
Ga-[1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″- tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors.

Methods
Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed.

Results
The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation.

Conclusions
In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.
Association Between Circulating Tumor Cells and Prognosis in Patients With Stage III Melanoma With Sentinel Lymph Node Metastasis in a Phase III International Multicenter Trial
Authors: Hoshimoto Sojun , Shingai Tatsushi , Morton Donald L. , Kuo Christine , Faries Mark B. , Chong Kelly , Elashoff David , Wang He-Jing , Elashoff Robert M. , Hoon Dave S.B. 
Published: September 2012

Purpose The outcomes of patients with melanoma who have sentinel lymph node (SLN) metastases can be highly variable, which has precluded establishment of consensus regarding treatment of the group. The detection of high-risk patients from this clinical setting may be helpful for determination of both prognosis and management. We report the utility of multimarker reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) detection of circulating tumor cells (CTCs) in patients with melanoma diagnosed with SLN metastases in a phase III, international, multicenter clinical trial. Patients and Methods Blood specimens were collected from patients with melanoma (n = 331) who were clinically disease-free after complete lymphadenectomy (CLND) before entering onto a randomized adjuvant melanoma vaccine plus bacillus Calmette-Guérin (BCG) versus BCG placebo trial from 30 melanoma centers (United States and international). Blood was assessed using a verified multimarker RT-qPCR assay (MART-1, MAGE-A3, and GalNAc-T) of melanoma-associated proteins. Cox regression analyses were used to evaluate the prognostic significance of CTC status for disease recurrence and melanoma-specific survival (MSS). Results Individual CTC biomarker detection ranged from 13.4% to 17.5%. There was no association of CTC status (zero to one positive biomarkers v two or more positive biomarkers) with known clinical or pathologic prognostic variables. However, two or more positive biomarkers was significantly associated with worse distant metastasis disease-free survival (hazard ratio [HR] = 2.13, P = .009) and reduced recurrence-free survival (HR = 1.70, P = .046) and MSS (HR = 1.88, P = .043) in a multivariable analysis. Conclusion CTC biomarker status is a prognostic factor for recurrence-free survival, distant metastasis disease-free survival, and MSS after CLND in patients with SLN metastasis. This multimarker RT-qPCR analysis may therefore be useful in discriminating patients who may benefit from aggressive adjuvant therapy or stratifying patients for adjuvant clinical trials.
Parenthood in Survivors of Hodgkin Lymphoma: An EORTC-GELA General Population Case-Control Study
Authors: van der Kaaij Marleen A.E. , Heutte Natacha , Meijnders Paul , Abeilard-Lemoisson Edwige , Spina Michele , Moser Lotte C. , Allgeier Anouk , Meulemans Bart , Dubois Brice , Simons Arnold H.M. , Lugtenburg Pieternella J. , Aleman Berthe M.P. , Noordijk Evert M. , Fermé Christophe , Thomas José , Stamatoullas Aspasia , Fruchart Christophe , Brice Pauline , Gaillard Isabelle , Doorduijn Jeanette K. , Sebban Catherine , Smit Wilma G.J.M. , Bologna Serge , Roesink Judith M. , Ong Francisca , André Marc P.E. , Raemaekers John M.M. , Henry-Amar Michel , Kluin-Nelemans Hanneke C. 
Published: September 2012

PurposeWe investigated the impact of Hodgkin lymphoma (HL) on parenthood, including factors influencing parenthood probability, by comparing long-term HL survivors with matched general population controls.Patients and MethodsA Life Situation Questionnaire was sent to 3,604 survivors treated from 1964 to 2004 in successive clinical trials. Responders were matched with controls (1:3 or 4) for sex, country, education, and year of birth (10-year groups). Controls were given an artificial date of start of treatment equal to that of their matched case. The main end point was presence of biologic children after treatment, which was evaluated by using conditional logistic regression analysis. Logistic regression analysis was used to analyze factors influencing spontaneous post-treatment parenthood.ResultsIn all, 1,654 French and Dutch survivors were matched with 6,414 controls. Median follow-up was 14 years (range, 5 to 44 years). After treatment, the odds ratio (OR) for having children was 0.77 (95% CI, 0.68 to 0.87; P < .001) for survivors compared with controls. Of 898 survivors who were childless before treatment, 46.7% achieved post-treatment parenthood compared with 49.3% of 3,196 childless controls (OR, 0.87; P = .08). Among 756 survivors with children before treatment, 12.4% became parents after HL treatment compared with 22.2% of 3,218 controls with children before treatment (OR, 0.49; P < .001). Treatment with alkylating agents, second-line therapy, and age older than 35 years at treatment appeared to reduce the chances of spontaneous post-treatment parenthood.ConclusionSurvivors of HL had slightly but significantly fewer children after treatment than matched general population controls. The difference concerned only survivors who had children before treatment and appears to have more personal than biologic reasons. The chance of successful post-treatment parenthood was 76%.
Noninitiation of Adjuvant Chemotherapy in Women With Localized Breast Cancer: The Breast Cancer Quality of Care Study
Authors: Neugut Alfred I. , Hillyer Grace Clarke , Kushi Lawrence H. , Lamerato Lois , Leoce Nicole , Nathanson S. David , Ambrosone Christine B. , Bovbjerg Dana H. , Mandelblatt Jeanne S. , Magai Carol , Tsai Wei Yann , Jacobson Judith S. , Hershman Dawn L. 
Published: September 2012

Purpose For some women, adjuvant chemotherapy for nonmetastatic breast cancer decreases recurrences and increases survival; however, patient-physician decisions regarding chemotherapy receipt can be influenced by medical and nonmedical factors. Patients and Methods We used a prospective cohort design and multivariate modeling to investigate factors related to noninitiation of chemotherapy among women with newly diagnosed breast cancer recruited from three US sites. We interviewed patients at baseline and during treatment on sociodemographic, tumor, and treatment decision-making factors. Patients were categorized according to National Comprehensive Cancer Network guidelines as those for whom chemotherapy was definitely indicated, clinically discretionary, or discretionary based on age greater than 70 years. Results Of 1,145 patients recruited, chemotherapy was clinically indicated for 392 patients, clinically discretionary for 459 patients, discretionary because of age for 169 patients, and not indicated for 93 patients; data were insufficient for 32 patients. Chemotherapy rates were 90% for those in whom chemotherapy was clinically indicated, 36% for those in whom it was discretionary because of clinical factors, and 19% for those in whom it was discretionary based on age greater than 70 years. Nonreceipt of chemotherapy was associated with older age, more negative beliefs about treatment efficacy, less positive beliefs about chemotherapy, and more concern about adverse effects. In the two discretionary groups, clinical predictors of worse outcome (greater tumor size, positive nodes, worse grade, and estrogen receptor– and progesterone receptor–negative status) were associated with increased chemotherapy initiation. Conclusion Utilization of adjuvant chemotherapy was most common among patients who, based on clinical criteria, would most likely benefit from it, patients with more positive than negative beliefs regarding treatment efficacy, and patients with few concerns about adverse effects.
Overexpression of Cyclin D3 Improves Decidualization Defects in Hoxa-10−/− Mice
Authors: Sroga Julie M. , Gao Fei , Ma Xinghong , Das Sanjoy K. 
Published: September 2012

AbstractUterine decidualization, a crucial process for implantation, is a tightly regulated process encompassing proliferation, differentiation, and polyploidization of uterine stromal cells. Hoxa (Homeobox A)-10, a homeobox transcription factor, is highly expressed in decidualizing stromal cells. Targeted gene deletion experiments have demonstrated marked infertility resulting from severely compromised decidualization in Hoxa-10−/− mice. However, the underlying mechanism by which Hoxa-10 regulates stromal cell differentiation remains poorly understood. Cyclin D3, a G1 phase cell-cycle regulatory protein involved in stromal cell proliferation and decidualization, is significantly reduced in Hoxa-10−/− mice. The expression of cyclin D3 in the pregnant mouse uterus parallels stromal cell decidualization. Here, we show that adenovirus-driven cyclin D3 replacement in Hoxa-10−/− mice improves stromal cell decidualization. To address our question of whether cyclin D3 replacement in Hoxa-10−/− mice can improve decidualization, both in vitro and in vivo studies were completed after the addition of cyclin D3 or empty (control) viral vectors. Immunostaining demonstrated increased proliferation and decidualization in both in vitro and in vivo studies, and in situ hybridization confirmed increased expression of decidualization markers in vivo. Placentation was demonstrated as well in vivo in the cyclin D3-replaced animals. However, fertility was not restored in Hoxa-10−/− mice after d 10 of pregnancy. Finally, we identified several downstream targets of cyclin D3 during decidualization in vitro via proteomics experiments, and these were confirmed using in situ hybridization in vivo. Collectively, these results demonstrate that cyclin D3 expression influences a host of genes involved in decidualization and can improve decidualization in Hoxa-10−/− mice.
Effect of okadaic acid on cultured clam heart cells: involvement of MAPkinase pathways
Authors: Hanana Houda , Talarmin Hélène , Pennec Jean-Pierre , Droguet Mickael , Morel Julie , Dorange Germaine 
Published: September 2012

Summary
Okadaic acid (OA) is one of the main diarrhetic shellfish poisoning toxins and a potent inhibitor of protein phosphatases 1 and 2A. The downstream signal transduction pathways following the protein phosphatase inhibition are still unknown and the results of most of the previous studies are often conflicting. The aim of the present study was to evaluate the effects of OA on heart clam cells and to analyse its possible mechanisms of action by investigating the signal transduction pathways involved in OA cytotoxicity. We showed that OA at 1 µM after 24 h of treatment induces disorganization of the actin cytoskeleton, rounding and detachment of fibroblastic cells. Moreover, treatment of heart cells revealed a sequential activation of MAPK proteins depending on the OA concentration. We suggest that the duration of p38 and JNK activation is a critical factor in determining cell apoptosis in clam cardiomyocytes. In the opposite, ERK activation could be involved in cell survival. The cell death induced by OA is a MAPK modulated pathway, mediated by caspase 3-dependent mechanism. OA was found to induce no significant effect on spontaneous beating rate or inward L-type calcium current in clam cardiomyocytes, suggesting that PP1 was not inhibited even by the highest dose of OA.
The anti-motility signaling mechanism of TGFβ3 that controls cell traffic during skin wound healing
Authors: Han Arum , Bandyopadhyay Balaji , Jayaprakash Priyamvada , Lua Ingrid , Sahu Divya , Chen Mei , Woodley David T. , Li Wei 
Published: September 2012

Summary
When skin is wounded, migration of epidermal keratinocytes at the wound edge initiates within hours, whereas migration of dermal fibroblasts toward the wounded area remains undetectable until several days later. This “cell type traffic” regulation ensures proper healing of the wound, as disruptions of the regulation could either cause delay of wound healing or result in hypertrophic scars. TGFβ3 is the critical traffic controller that selectively halts migration of the dermal, but not epidermal, cells to ensure completion of wound re-epithelialization prior to wound remodeling. However, the mechanism of TGFβ3's anti-motility signaling has never been investigated. We report here that activated TβRII transmits the anti-motility signal of TGFβ3 in full to TβRI, since expression of the constitutively activated TβRI-TD mutant was sufficient to replace TGFβ3 to block PDGF-bb-induced dermal fibroblast migration. Second, the three components of R-Smad complex are all required. Individual downregulation of Smad2, Smad3 or Smad4 prevented TGFβ3 from inhibiting dermal fibroblast migration. Third, Protein Kinase Array allowed us to identify the protein kinase A (PKA) as a specific downstream effector of R-Smads in dermal fibroblasts. Activation of PKA alone blocked PDGF-bb-induced dermal fibroblast migration, just like TGFβ3. Downregulation of PKA's catalytic subunit nullified the anti-motility signaling of TGFβ3. This is the first report on anti-motility signaling mechanism by TGFβ family cytokines. Significance of this finding is not only limited to wound healing but also to other human disorders, such as heart attack and cancer, where the diseased cells have often managed to avoid the anti-motility effect of TGFβ.
A Nestin-cre transgenic mouse is insufficient for recombination in early embryonic neural progenitors
Authors: Liang Huixuan , Hippenmeyer Simon , Ghashghaei H. Troy 
Published: September 2012

Summary
Nestin-cre transgenic mice have been widely used to direct recombination to neural stem cells (NSCs) and intermediate neural progenitor cells (NPCs). Here we report that a readily utilized, and the only commercially available, Nestin-cre line is insufficient for directing recombination in early embryonic NSCs and NPCs. Analysis of recombination efficiency in multiple cre-dependent reporters and a genetic mosaic line revealed consistent temporal and spatial patterns of recombination in NSCs and NPCs. For comparison we utilized a knock-in Emx1cre line and found robust recombination in NSCs and NPCs in ventricular and subventricular zones of the cerebral cortices as early as embryonic day 12.5. In addition we found that the rate of Nestin-cre driven recombination only reaches sufficiently high levels in NSCs and NPCs during late embryonic and early postnatal periods. These findings are important when commercially available cre lines are considered for directing recombination to embryonic NSCs and NPCs.
Aerobic power, huddling and the efficiency of torpor in the South American marsupial, Dromiciops gliroides
Authors: Franco Marcela , Contreras Carolina , Cortés Pablo , Chappell Mark A. , Soto-Gamboa Mauricio , Nespolo Roberto F. 
Published: September 2012

Summary
During periods of cold, small endotherms depend on a continuous supply of food and energy to maintain euthermic body temperature (Tb), which can be challenging if food is limited. In these conditions, energy-saving strategies are critical to reduce the energetic requirements for survival. Mammals from temperate regions show a wide arrange of such strategies, including torpor and huddling. Here we provide a quantitative description of thermoregulatory capacities and energy-saving strategies in Dromiciops gliroides, a Microbiotherid marsupial inhabiting temperate rain forests. Unlike many mammals from temperate regions, preliminary studies have suggested that this species has low capacity for control and regulation of body temperature, but there is still an incomplete picture of its bioenergetics. In order to more fully understand the physiological capacities of this “living fossil”, we measured its scope of aerobic power and the interaction between huddling and torpor. Specifically, we evaluated: (1) the relation between basal (BMR) and maximum metabolic rate (MMR), and (2) the role of huddling on the characteristics of torpor at different temperatures. We found that BMR and MMR were above the expected values for marsupials and the factorial aerobic scope (from CO2) was 6.0±0.45 (using CO2) and 6.2±0.23 (using O2), an unusually low value for mammals. Also, repeatability of physiological variables was non-significant, as in previous studies, suggesting poor time-consistency of energy metabolism. Comparisons of energy expenditure and body temperature (using attached data-loggers) between grouped and isolated individuals showed that at 20°C both average resting metabolic rate and body temperature were higher in groups, essentially because animals remained non-torpid. At 10°C, however, all individuals became torpid and no differences were observed between grouped and isolated individuals. In summary, our study suggests that the main response of Dromiciops gliroides to low ambient temperature is reduced body temperature and torpor, irrespective of huddling. Low aerobic power and low time-consistency of most thermoregulatory traits of Dromiciops gliroides support the idea of poor thermoregulatory abilities in this species.
Systematic review on the association between F2-isoprostanes and cardiovascular disease
Authors: Zhang Zhi-Jiang 
Published: September 2012

Background Oxidative stress may play an aetiological role in the development and progression of cardiovascular disease (CVD). However, evidence on its biochemical markers has been controversial. This article aimed to assess the role of F2-isoprostanes, a marker for measuring in vivo lipid oxidation, as a biomarker for CVD, including coronary artery disease, stroke and peripheral artery disease. Methods A literature search was performed using PubMed and EMBASE (from 1966 to February 2012). Studies that investigated the association between F2-isoprostanes and CVD were eligible. Results Of the 22 eligible studies retrieved, 20 studies showed a significant association between F2-isoprostanes and CVD. However, to date, there have been only four population-based studies, with one study reporting null association. Although data from prospective studies are ideal to examine a role of such biomarkers in predicting future CVD events, only two studies were prospective. In addition, differences in population characteristics, sample handling/storage and assays, coupled with a lack of confounding adjustment, may all contribute to the enormous variation in previous studies. Conclusions High levels of F2-isoprostanes in urine or blood may be a non-specific indicator of CVD. However, further population-based studies are needed. In addition, multivariable analyses are required for future studies to control confounding and improve classification accuracy.