bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of in vivo chemoresistant human hepatocellular carcinoma cells with transendothelial differentiation capacities
Authors: Marfels Christian , Hoehn Miriam , Wagner Ernst , Günther Michael
Published: April 2013

Background

Chemotherapeutic treatment of hepatocellular carcinoma often leads to chemoresistance during therapy or upon relapse of tumors. For the development of better treatments a better understanding of biochemical changes in the resistant tumors is needed. In this study, we focus on the characterization of in vivo chemoresistant human hepatocellular carcinoma HUH-REISO established from a metronomically cyclophosphamide (CPA) treated HUH7 xenograft model.

Methods

SCID mice bearing subcutaneous HUH7 tumors were treated i.p. with 75 mg/kg CPA every six days. Tumors were evaluated by immunohistochemistry, a functional blood-flow Hoechst dye assay, and qRT-PCR for ALDH-1, Notch-1, Notch-3, HES-1, Thy-1, Oct-4, Sox-2 and Nanog mRNA levels. Cell lines of these tumors were analyzed by qRT-PCR and in endothelial transdifferentiation studies on matrigel.

Results

HUH-REISO cells, although slightly more sensitive against activated CPA in vitro than parental HUH-7 cells, fully retained their in vivo CPA chemoresistance upon xenografting into SCID mice. Histochemical analysis of HUH-REISO tumors in comparison to parental HUH-7 cells and passaged HUH-PAS cells (in vivo passaged without chemotherapeutic pressure) revealed significant changes in host vascularization of tumors and especially in expression of the tumor-derived human endothelial marker gene PECAM-1/CD31 in HUH-REISO. In transdifferentiation studies with limited oxygen and metabolite diffusion, followed by a matrigel assay, only the chemoresistant HUH-REISO cells exhibited tube formation potential and expression of human endothelial markers ICAM-2 and PECAM-1/CD31. A comparative study on stemness and plasticity markers revealed upregulation of Thy-1, Oct-4, Sox-2 and Nanog in resistant xenografts. Under therapeutic pressure by CPA, tumors of HUH-PAS and HUH-REISO displayed regulations in Notch-1 and Notch-3 expression.

Conclusions

Chemoresistance of HUH-REISO was not manifested under standard in vitro but under in vivo conditions. HUH-REISO cells showed increased pluripotent capacities and the ability of transdifferentiation to endothelial like cells in vitro and in vivo. These cells expressed typical endothelial surface marker and functionality. Although the mechanism behind chemoresistance of HUH-REISO and involvement of plasticity remains to be clarified, we hypothesize that the observed Notch regulations and upregulation of stemness genes in resistant xenografts are involved in the observed cell plasticity.
Can the 12-item general health questionnaire be used to identify medical students who might ‘struggle’ on the medical course? A prospective study on two cohorts
Authors: James David , Yates Janet , Ferguson Eamonn
Published: April 2013

Background

Students who fail to thrive on the Nottingham undergraduate medical course frequently suffer from anxiety, depression or other mental health problems. These difficulties may be the cause, or the result of, academic struggling. Early detection of vulnerable students might direct pastoral care and remedial support to where it is needed. We investigated the use of the short-form General Health Questionnaire (GHQ-12) as a possible screening tool.

Methods

Two consecutive cohorts (2006 and 2007) were invited to complete the GHQ-12. The questionnaire was administered online, during the second semester (after semester 1 exams) for the 2006 cohort and during the first semester for the 2007 cohort. All data were held securely and confidentially. At the end of the course, GHQ scores were examined in relation to course progress.

Results

251 students entered the course in 2006 and 254 in 2007; 164 (65%) and 160 (63%), respectively, completed the GHQ-12. In both cohorts, the study and non-study groups were very similar in terms of pre-admission socio-demographic characteristics and overall course marks. In the 2006 study group, the GHQ Likert score obtained part-way through the first year was negatively correlated with exam marks during Years 1 and 2, but the average exam mark in semester 1 was the sole independent predictor of marks in semester 2 and Year 2. No correlations were found for the 2007 study group but the GHQ score was a weak positive predictor of marks in semester 2, with semester 1 average exam mark again being the strongest predictor. A post-hoc moderated-mediation analysis suggested that significant negative associations of GHQ scores with semester 1 and 2 exams applied only to those who completed the GHQ after their semester 1 exams. Students who were identified as GHQ ‘cases’ in the 2006 group were statistically less likely to complete the course on time (OR = 4.74, p 0.002). There was a non-significant trend in the same direction in the 2007 group.

Conclusions

Results from two cohorts provide insufficient evidence to recommend the routine use of the GHQ-12 as a screening tool. The timing of administration could have a critical influence on the results, and the theoretical and practical implications of this finding are discussed. Low marks in semester 1 examinations seem be the best single indicator of students at risk for subsequent poor performance.
Clinical utility of measuring expression levels of KAP1, TIMP1 and STC2 in peripheral blood of patients with gastric cancer
Authors: Wang Yuan-Yu , Li Li , Zhao Zhong-Sheng , Wang Hui-Ju
Published: April 2013

Background

We examined preoperative kinesin II-associated protein (KAP1), TIMP metallopeptidase inhibitor 1 (TIMP1) and stanniocalcin 2 (STC2) expression levels in patients with gastric cancers to assess their clinical application for diagnosing and monitoring diseases.

Methods

Real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of KAP1, TIMP1, STC2, talin 2 (TLN2), sushi-repeat-containing protein, X-linked 2 (SRPX2) and secreted protein, acidic, cysteine-rich (SPARC) in the patients’ peripheral blood karyocytes. The data were analyzed with receiver operating characteristics (ROC) curves.

Results

A total of 112 patients with gastric cancer, 42 patients with recurrence and 107 healthy volunteers were recruited. There were significant correlations between KAP1, TIMP1 and STC2 levels, and TNM tumor stages and distant metastases. The area under the ROC curves (AUC) of KAP1 was 0.803 ± 0.040 (P = 0.0001), the AUC of TIMP1 was 0.767 ± 0.043 (P = 0.0001) and the AUC of STC2 was 0.769 ± 0.045 (P = 0.0001), thus differentiating preoperative gastric cancer patients from healthy volunteers by ROC curve analysis. The AUC of STC2 was 0.739 ± 0.070 (P = 0.004) and the AUC of KAP1 was 0.418 ± 0.088 (P = 0.319), thus differentiating recurrence of gastric cancer from healthy volunteers by ROC curve analysis. High TIMP1 and STC2 expression levels were suspected to be poor prognostic factors of disease recurrence in patients with gastric cancer.

Conclusions

KAP1, TIMP1 and STC2 expression levels may be potential biomarkers for the screening, diagnosis, prognosis and surveillance of gastric cancer.
Metal-assisted chemical etching of Ge(100) surfaces in water toward nanoscale patterning
Authors: Kawase Tatsuya , Mura Atsushi , Dei Katsuya , Nishitani Keisuke , Kawai Kentaro , Uchikoshi Junichi , Morita Mizuho , Arima Kenta
Published: April 2013

We propose the metal-assisted chemical etching of Ge surfaces in water mediated by dissolved oxygen molecules (O2). First, we demonstrate that Ge surfaces around deposited metallic particles (Ag and Pt) are preferentially etched in water. When a Ge(100) surface is used, most etch pits are in the shape of inverted pyramids. The mechanism of this anisotropic etching is proposed to be the enhanced formation of soluble oxide (GeO2) around metals by the catalytic activity of metallic particles, reducing dissolved O2 in water to H2O molecules. Secondly, we apply this metal-assisted chemical etching to the nanoscale patterning of Ge in water using a cantilever probe in an atomic force microscopy setup. We investigate the dependences of probe material, dissolved oxygen concentration, and pressing force in water on the etched depth of Ge(100) surfaces. We find that the enhanced etching of Ge surfaces occurs only when both a metal-coated probe and saturated-dissolved-oxygen water are used. In this study, we present the possibility of a novel lithography method for Ge in which neither chemical solutions nor resist resins are needed.
Optimized maximum noise fraction for dimensionality reduction of Chinese HJ-1A hyperspectral data
Authors: Gao Lianru , Zhang Bing , Sun Xu , Li Shanshan , Du Qian , Wu Changshan
Published: April 2013

The important techniques in processing hyperspectral data acquired by interference imaging spectrometer onboard Small Satellite Constellation for Environment and Disaster mitigation (HJ-1A) are studied in this article. First, a new noise estimation method, named residual-scaled local standard deviations, is used to analyze the noise condition of HJ-1A hyperspectral images. Then, an optimized maximum noise fraction (OMNF) transform is proposed for dimensionality reduction of HJ-1A images, which adopts an accurately estimated noise covariance matrix for noise whitening. The proposed OMNF method is less sensitive to noise distribution and interference existence, thus it can more efficiently compact useful data information in a low-dimensional space. The proposed OMNF is evaluated through two applications, i.e., spectral unmixing and classification, using the HJ-1A image acquired at the Bohai Sea area in China. It demonstrates that the proposed OMNF provides better performance in comparison with other traditional dimensionality reduction methods.
Rhesus macaques vaccinated with consensus envelopes elicit partially protective immune responses against SHIV SF162p4 challenge
Authors: Eugene Hermancia S , Pierce-Paul Brooke R , Craigo Jodi K , Ross Ted M
Published: April 2013

The development of a preventative HIV/AIDS vaccine is challenging due to the diversity of viral genome sequences, especially in the viral envelope (Env160). Since it is not possible to directly match the vaccine strain to the vast number of circulating HIV-1 strains, it is necessary to develop an HIV-1 vaccine that can protect against a heterologous viral challenge. Previous studies from our group demonstrated that a mixture of wild type clade B Envgp160swere able to protect against a heterologous clade B challenge more effectively than a consensus clade B Envgp160vaccine. In order to broaden the immune response to other clades of HIV, in this study rhesus macaques were vaccinated with a polyvalent mixture of purified HIV-1 trimerized consensus Envgp140proteins representing clades A, B, C, and E. The elicited immune responses were compared to a single consensus Envgp140representing all isolates in group M (Con M). Both vaccines elicited anti- Envgp140IgG antibodies that bound an equal number of HIV-1 Envgp160proteins representing clades A, B and C. In addition, both vaccines elicited antibodies that neutralized the HIV-1SF162isolate. However, the vaccinated monkeys were not protected against SHIVSF162p4challenge. These results indicate that consensus Envgp160vaccines, administered as purified Envgp140trimers, elicit antibodies that bind to Envgp160sfrom strains representing multiple clades of HIV-1, but these vaccines did not protect against heterologous SHIV challenge.
Evaluation of inter-fraction and intra-fraction errors during volumetric modulated arc therapy in nasopharyngeal carcinoma patients
Authors: Yin Wen-Jing , Sun Ying , Chi Feng , Fang Jian-Lan , Guo Rui , Yu Xiao-Li , Mao Yan-Ping , Qi Zhen-Yu , Guo Ying , Liu Meng-Zhong , Ma Jun
Published: April 2013

Background

This prospective study was conducted to evaluate inter- and intra-fraction errors in nasopharyngeal carcinoma (NPC) patients undergoing volumetric modulated arc therapy (VMAT) using cone-beam computed tomography (CBCT) and to thus obtain planning target volume (PTV) margins to effectively guide treatment in the future.

Methods

Fifteen NPC patients scheduled to undergo VMAT were prospectively enrolled in the study. For each patient, three CBCT scans were obtained; one after daily conventional positioning, one after online correction with 2 mm tolerance and one after 1 week of VMAT delivery. The scans were registered to the planning CT to determine the inter- and intra-fraction errors. Patient positioning errors were analyzed for time trends over the course of radiotherapy. PTV margins were calculated from the systematic (Σ) and random (σ) errors.

Results

The average absolute values of the pre-correction, post-correction and intra-fraction errors (in order) were 1.1, 0.6 and 0.4 mm in the medial–lateral (ML) direction, 1.2, 0.7 and 0.5 mm in the superior–inferior (SI) direction and 1.1, 0.7 and 0.5 mm in the anterior–posterior (AP) direction. The corresponding Σ were 1.0–1.4 mm, 0.4–0.5 mm and 0.2–0.4 mm, while the corresponding σ were 0.7–0.8 mm, 0.6–0.7 mm and 0.5–0.6 mm. With time, gradual increases in both the inter- and intra-fraction three-dimensional displacements were observed (P = 0.019 and P = 0.044, respectively). The total PTV margins accounting for pre-correction and intra-fraction errors were 3.4–4.1 mm and those accounting for post-correction and intra-fraction errors were 1.7–2.2 mm.

Conclusions

CBCT is an effective modality to evaluate and improve the accuracy of VMAT in NPC patients. Inter- and intra-fraction three-dimensional displacements increased as a function of time during the course of radiotherapy. In our institution, we recommend a PTV margin of 5 mm for NPC patients undergoing VMAT without CBCT and 3 mm for those treated with rigorous daily CBCT scans.
Multi-analyte approach for determining the extraction of tobacco constituents from pouched snus by consumers during use
Authors: Digard Helena , Gale Nathan , Errington Graham , Peters Nicola , McAdam Kevin
Published: April 2013

Background

Snus is a smokeless oral tobacco product with a significant history of use in Sweden, where it is regulated under food legislation. Users place a small porous sachet or a pinch of loose snus between the upper jaw and cheek for approximately one hour, leading to partial intake of tobacco constituents. To understand user exposure to tobacco, a multi-analyte approach based on the extraction of pouches by methanol, ethanol and water was validated and applied to the measurement of various constituents, including nicotine, four tobacco-specific nitrosamines (TSNAs), propylene glycol, water, ammonium, nitrate, sodium, chloride, linalool, citronellol, linalyl acetate and geraniol, extracted from snus pouches during use by human consumers.

Results

After validation against established single-analyte methods, the multi-analyte approach was used to determine constituent levels in snus pouches before and after one hour of use. Although the concentrations in the snus pouches varied from nanogram (e.g. TSNAs) to milligram (e.g. nicotine, sodium and propylene glycol) quantities (25.1 ng to 35.3 mg per 1 g pouch), the mean percentage extracted varied only from 19.2% for linalyl acetate to 37.8% for the TSNA 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) among all constituents analyzed. The TSNAs, some of which are known carcinogens, showed the highest percentage extraction (range 34.6%–37.8%). Measurement variability was low for all analytes, ranging from 2.4% (total TSNAs, NAT) to 9.5% (geraniol). By contrast, inter-subject variability ranged from 6.7% (NAB) to 52.2% (linalyl acetate), and was greater than 20% for eight of the constituents analyzed. Intra-subject variability ranged from 3.4% (citronellol) to 29.7% (geraniol).

Conclusions

Generally, less than a third of each constituent tested was extracted during one hour of snus use, independent of constituent concentration. The variable nature of in-use extraction was shown to be driven by inter-subject variability. The results provide insight into possible mechanisms controlling constituent extraction in the mouth during snus use, and provide reference data for the development of in-vitro laboratory systems for estimating extraction of tobacco constituents from snus.
Contrast mimicking a subarachnoid hemorrhage after lumbar percutaneous epidural neuroplasty: a case report
Authors: Oh Chang Hyun , An Seong Dae , Choi Seung Hyun , Ji Gyu Yeul
Published: April 2013

Introduction

Subarachnoid hemorrhage is one of the most feared acute neurologic events. Accurate diagnosis of subarachnoid hemorrhage is essential, and computed tomography of the brain is the first diagnostic imaging study. However, in rare circumstances, a similar appearance may occur in the absence of blood in the subarachnoid space. The contrast enhancement of subarachnoid space is a rare complication after lumbar percutaneous epidural neuroplasty, with, to the best of our knowledge, no previous report in the literature.

Case presentation

A 42-year-old Korean male patient, who underwent a spinal operation five years previously at the level of L4 to S1, visited our clinic with persistent and aggravating low back pain. An imaging study revealed the focal and diffuse disc protrusion at the level of L4/5 and L5/S1. The clinician decided to perform a lumbar percutaneous epidural neuroplasty. During the procedure, dural adhesion was suspected at the previously operated level, and the neuroplasty catheter was malpositioned into the intradural space on the first attempt. After the catheter was repositioned, the scheduled epidural neuroplasty was completed. Our patient had no definite abnormal neurological signs. But, after a day, our patient complained of severe headache with sustained high blood pressure without neurological disorientation. Computed tomography of his brain showed a subarachnoid hemorrhage-like appearance with intracranial air. Sequential angiography, subtractional magnetic resonance imaging and examination of the cerebrospinal fluid revealed no abnormalities. Follow-up computed tomography after one day revealed no definite intracranial hemorrhage, and our patient was discharged with improved low back pain without neurological deficit.

Conclusion

We report a rare case of contrast mimicking a subarachnoid hemorrhage after lumbar percutaneous epidural neuroplasty. The physician should keep in mind a rare case like this, and the supine position with head elevation is necessary to avoid a similar complication after lumbar percutaneous epidural neuroplasty.
Multiple ileal perforations due to regular diclofenac sodium injections: a case report
Authors: Park Won Seok , Kim Sang Wook , Lee Seok , Lee Soo Teik , Park Ho Sung
Published: April 2013

Background

Although the adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the upper gastrointestinal tract have been well characterized, those specific to the lower gastrointestinal tract are less clear, as only a limited number of articles and case reports exist in the literature.

Case presentation

We describe a case of a 69-year-old woman who presented to the emergency department due to sudden onset abdominal distension and pain. Notably, she reported using intramuscular diclofenac sodium twice daily for 14 days after knee joint replacement surgery. The patient denied any other coexisting diseases. As a subsequent X-ray and computed tomography (CT) scan showed free air in the abdomen, an exploratory laparotomy was performed, revealing four free perforations in the terminal ileum. Findings on microscopic analysis were non-specific.

Conclusion

We report a unique case of multiple ileal perforations due to regular diclofenac sodium injections and contend that ileal perforation can be considered as a source for pneumoperitoneum with concomitant peritonitis in patients with a history of NSAID use if other possibilities are excluded.
A quantitative homogeneous assay for fragile X mental retardation 1 protein
Authors: Schutzius Gabi , Bleckmann Dorothee , Kapps-Fouthier Sandra , di Giorgio Francesco , Gerhartz Bernd , Weiss Andreas
Published: April 2013

Background

Hypermethylation of the fragile X mental retardation 1 gene FMR1 results in decreased expression of FMR1 protein FMRP, which is the underlying cause of Fragile X syndrome – an incurable neurological disorder characterized by mental retardation, anxiety, epileptic episodes and autism. Disease-modifying therapies for Fragile X syndrome are thus aimed at treatments that increase the FMRP expression levels in the brain. We describe the development and characterization of two assays for simple and quantitative detection of FMRP protein.

Method

Antibodies coupled to fluorophores that can be employed for time-resolved Förster’s resonance energy transfer were used for the development of homogeneous, one-step immunodetection. Purified recombinant human FMRP and patient cells were used as control samples for assay development.

Results

The assays require small sample amounts, display high stability and reproducibility and can be used to quantify endogenous FMRP in human fibroblasts and peripheral blood mononuclear cells. Application of the assays to FXS patient cells showed that the methods can be used both for the characterization of clinical FXS patient samples as well as primary readouts in drug-discovery screens aimed at increasing endogenous FMRP levels in human cells.

Conclusion

This study provides novel quantitative detection methods for FMRP in FXS patient cells. Importantly, due to the simplicity of the assay protocol, the method is suited to be used in screening applications to identify compounds or genetic interventions that result in increased FMRP levels in human cells.
From the Editor's desk
Authors: Tyrer Peter
Published: April 2013

Icing in the cake

I write this as I am putting the finishing touches to a Simnel cake, one of the most tasty of old recipes. Those of my readers who are familiar with cake-making will realise that a Simnel cake is unusual in having icing in the middle of the cake, not just on top. This reminded me in a curious way of the British Journal of Psychiatry a journal with shiny yellow icing on the outside but quite a helping of icing in the middle as well. The making of a Simnel cake is a staging process, just as Scott et al (pp. 243-245) describe, with the marzipan icing, preferably golden like our journal, making the second and fourth layers, and with a delicate balance of currants and sultanas - no they are not the same but share many features, just like hospital and community psychiatry (Thornicroft & Tansella, pp. 246-248) - as a rich component of the cake mixture. But a Simnel cake needs spices too, so a touch of allspice, just like Warner (pp. 284-285) & Fearon's (pp. 249-250) feisty exchange of opinions about early intervention in psychosis, adds that extra touch of flavour, with just a lemon soupçcon of Amsterdam et al (pp. 301-306) and Thase (pp. 251-252) to tickle the palate's outer senses. But as every reader knows, there are extras in the cake, and in the Journal too, and they add to the flavour. It is absolutely clear that Zaara's 'speed limits' described by Shabbir Amanullah (p. 285) have to refer to the eating of Simnel cake, as with such a marvellous combination of flavours you have to eat slowly to take them all in.
Can early intervention services modify pathways into care?
Authors: Fearon Paul
Published: April 2013

Pathways into care have not changed significantly since the introduction of early intervention services for psychosis in London. Some groups have different pathways into care and those whose pathway originates in primary care have a longer route to services. This editorial explores the nature of these challenges, for both early intervention services and referring agencies.
Allogeneic Hematopoietic Cell Transplantation for Fanconi Anemia in Patients With Pretransplantation Cytogenetic Abnormalities, Myelodysplastic Syndrome, or Acute Leukemia
Authors: Ayas Mouhab , Saber Wael , Davies Stella M. , Harris Richard E. , Hale Gregory A. , Socie Gerard , LeRademacher Jennifer , Thakar Monica , Deeg H. Joachim J. , Al-Seraihy Amal , Battiwalla Minoo , Camitta Bruce M. , Olsson Richard , Bajwa Rajinder S. , Bonfim Carmem M. , Pasquini Ricardo , MacMillan Margaret L. , George Biju , Copelan Edward A. , Wirk Baldeep , Al Jefri Abdullah , Fasth Anders L. , Guinan Eva C. , Horn Biljana N. , Lewis Victor A. , Slavin Shimon , Stepensky Polina , Bierings Marc , Gale Robert Peter
Published: April 2013

Purpose

Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi anemia (FA). Data on outcomes in patients with pretransplantation cytogenetic abnormalities, myelodysplastic syndrome (MDS), or acute leukemia have not been separately analyzed.

Patients and Methods

We analyzed data on 113 patients with FA with cytogenetic abnormalities (n = 54), MDS (n = 45), or acute leukemia (n = 14) who were reported to the Center for International Blood and Marrow Transplant Research from 1985 to 2007.

Results

Neutrophil recovery occurred in 78% and 85% of patients at days 28 and 100, respectively. Day 100 cumulative incidences of acute graft-versus-host disease grades B to D and C to D were 26% (95% CI, 19% to 35%) and 12% (95% CI, 7% to 19%), respectively. Survival probabilities at 1, 3, and 5 years were 64% (95% CI, 55% to 73%), 58% (95% CI, 48% to 67%), and 55% (95% CI, 45% to 64%), respectively. In univariate analysis, younger age was associated with superior 5-year survival (≤ v > 14 years: 69% [95% CI, 57% to 80%] v 39% [95% CI, 26% to 53%], respectively; P = .001). In transplantations from HLA-matched related donors (n = 82), younger patients (≤ v > 14 years: 78% [95% CI, 64% to 90%] v 34% [95% CI, 20% to 50%], respectively; P < .001) and patients with cytogenetic abnormalities only versus MDS/acute leukemia (67% [95% CI, 52% to 81%] v 43% [95% CI, 27% to 59%], respectively; P = .03) had superior 5-year survival.

Conclusion

Our analysis indicates that long-term survival for patients with FA with cytogenetic abnormalities, MDS, or acute leukemia is achievable. Younger patients and recipients of HLA-matched related donor transplantations who have cytogenetic abnormalities only have the best survival.
Associations Between Cigarette Smoking Status and Colon Cancer Prognosis Among Participants in North Central Cancer Treatment Group Phase III Trial N0147
Authors: Phipps Amanda I. , Shi Qian , Newcomb Polly A. , Nelson Garth D. , Sargent Daniel J. , Alberts Steven R. , Limburg Paul J.
Published: April 2013

Purpose

By using data from North Central Cancer Treatment Group Phase III Trial N0147, a randomized adjuvant trial of patients with stage III colon cancer, we assessed the relationship between smoking and cancer outcomes, disease-free survival (DFS), and time to recurrence (TTR), accounting for heterogeneity by patient and tumor characteristics.

Patients and Methods

Before random assignment to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or FOLFOX plus cetuximab, 1,968 participants completed a questionnaire on smoking history and other risk factors. Cox models assessed the association between smoking history and the primary trial outcome of DFS (ie, time to recurrence or death), as well as TTR, adjusting for other clinical and patient factors. The median follow-up was 3.5 years among patients who did not experience events.

Results

Compared with never-smokers, ever smokers experienced significantly shorter DFS (3-year DFS proportion: 70% v 74%; hazard ratio [HR], 1.21; 95% CI, 1.02 to 1.42). This association persisted after multivariate adjustment (HR, 1.23; 95% CI, 1.02 to 1.49). There was significant interaction in this association by BRAF mutation status (P = .03): smoking was associated with shorter DFS in patients with BRAF wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95% CI, 0.50 to 1.29) colon cancer. Smoking was more strongly associated with poorer DFS in those with KRAS mutated versus KRAS wild-type colon cancer (HR, 1.50 [95% CI, 1.12 to 2.00] v HR, 1.09 [95% CI, 0.85 to 1.39]), although interaction by KRAS mutation status was not statistically significant (P = .07). Associations were comparable in analyses of TTR.

Conclusion

Overall, smoking was significantly associated with shorter DFS and TTR in patients with colon cancer. These adverse relationships were most evident in patients with BRAF wild-type or KRAS mutated colon cancer.
Ovarian Expression of Insulin-Like Peptide 3 (INSL3) and Its Receptor (RXFP2) During Development of Bovine Antral Follicles and Corpora Lutea and Measurement of Circulating INSL3 Levels During Synchronized Estrous Cycles
Authors: Satchell Leanne , Glister Claire , Bleach Emma C. , Glencross Richard G. , Bicknell Andrew B. , Dai Yanzhenzi , Anand-Ivell Ravinder , Ivell Richard , Knight Philip G.
Published: April 2013

Insulin-like peptide 3 (INSL3), a major product of testicular Leydig cells, is also expressed by the ovary, but its functional role remains poorly understood. Here, we quantified expression of INSL3 and its receptor RXFP2 in theca interna cell (TIC) and granulosa cell compartments of developing bovine antral follicles and in corpora lutea (CL). INSL3 and RXFP2 mRNA levels were much higher in TIC than granulosa cell and increased progressively during follicle maturation with INSL3 peaking in large (11-18 mm) estrogen-active follicles and RXFP2 peaking in 9- to 10-mm follicles before declining in larger (11-18 mm) follicles. Expression of both INSL3 and RXFP2 in CL was much lower than in TIC. In situ hybridization and immunohistochemistry confirmed abundant expression of INSL3 mRNA and protein in TIC. These observations indicate follicular TIC rather than CL as the primary site of both INSL3 production and action, implying a predominantly autocrine/paracrine role in TIC. To corroborate the above findings, we showed that in vitro exposure of TIC to a luteinizing concentration of LH greatly attenuated expression of both INSL3 and its receptor while increasing progesterone secretion and expression of STAR and CYP11A1. Moreover, in vivo, a significant cyclic variation in plasma INSL3 was observed during synchronized estrous cycles. INSL3 and estradiol-17β followed a similar pattern, both increasing after luteolysis, before falling sharply after the LH surge. Thus, theca-derived INSL3, likely from the dominant preovulatory follicle, is detectable in peripheral blood of cattle, and expression is down-regulated during luteinization induced by the preovulatory LH surge. Collectively, these findings underscore the likely role of INSL3 as an important intrafollicular modulator of TIC function/steroidogenesis, while raising doubts about its potential contribution to CL function.
Palladin Is a Regulator of Actin Filament Bundles at the Ectoplasmic Specialization in Adult Rat Testes
Authors: Qian Xiaojing , Mruk Dolores D. , Wong Elissa W. P. , Lie Pearl P. Y. , Cheng C. Yan
Published: April 2013

In rat testes, the ectoplasmic specialization (ES) at the Sertoli-Sertoli and Sertoli-spermatid interface known as the basal ES at the blood-testis barrier and the apical ES in the adluminal compartment, respectively, is a testis-specific adherens junction. The remarkable ultrastructural feature of the ES is the actin filament bundles that sandwiched in between the cisternae of endoplasmic reticulum and apposing plasma membranes. Although these actin filament bundles undergo extensive reorganization to switch between their bundled and debundled state to facilitate blood-testis barrier restructuring and spermatid adhesion/transport, the regulatory molecules underlying these events remain unknown. Herein we report findings of an actin filament cross-linking/bundling protein palladin, which displayed restrictive spatiotemporal expression at the apical and the basal ES during the epithelial cycle. Palladin structurally interacted and colocalized with Eps8 (epidermal growth factor receptor pathway substrate 8, an actin barbed end capping and bundling protein) and Arp3 (actin related protein 3, which together with Arp2 form the Arp2/3 complex to induce branched actin nucleation, converting bundled actin filaments to an unbundled/branched network), illustrating its role in regulating actin filament bundle dynamics at the ES. A knockdown of palladin in Sertoli cells in vitro with an established tight junction (TJ)-permeability barrier was found to disrupt the TJ function, which was associated with a disorganization of actin filaments that affected protein distribution at the TJ. Its knockdown in vivo also perturbed F-actin organization that led to a loss of spermatid polarity and adhesion, causing defects in spermatid transport and spermiation. In summary, palladin is an actin filament regulator at the ES.
Energy efficiency as a unifying principle for human, environmental, and global health
Authors: Fontana Luigi , Atella Vincenzo , Kammen Daniel M
Published: April 2013

A strong analogy exists between over/under consumption of energy at the level of the human body and of the industrial metabolism of humanity. Both forms of energy consumption have profound implications for human, environmental, and global health. Globally, excessive fossil-fuel consumption, and individually, excessive food energy consumption are both responsible for a series of interrelated detrimental effects, including global warming, extreme weather conditions, damage to ecosystems, loss of biodiversity, widespread pollution, obesity, cancer, chronic respiratory disease, and other lethal chronic diseases. In contrast, data show that the efficient use of energy—in the form of food as well as fossil fuels and other resources—is vital for promoting human, environmental, and planetary health and sustainable economic development. While it is not new to highlight how efficient use of energy and food can address some of the key problems our world is facing, little research and no unifying framework exists to harmonize these concepts of sustainable system management across diverse scientific fields into a single theoretical body. Insights beyond reductionist views of efficiency are needed to encourage integrated changes in the use of the world’s natural resources, with the aim of achieving a wiser use of energy, better farming systems, and healthier dietary habits. This perspective highlights a range of scientific-based opportunities for cost-effective pro-growth and pro-health policies while using less energy and natural resources.
Safety as Absolute Priority of Nuclear Power
Authors: Пристер  , Prister B.
Published: April 2013

Nuclear power safety problems are considered. Need of continuous safety culture increasing and readiness of response to nuclear power plants failures which fast development leads to accident is shown. Analysis of severe accidents on nuclear power plants over last 50 years is presented. Necessity of development of systems for preventive readiness to failures, emergency reaction and ensuring the execution mechanism of international rules of nuclear power plants safe operation is proved.
Problems of Russian Black Sea Coast Landscape Technogenic Transformation
Authors: Дьяченко  , Dyachenko Vladimir , Роговский  , Rogovskiy Viktor , Матасова  , Matasova I.
Published: April 2013

Analysis of major factors and consequences of Russian Black Sea coast technogenic transformation has been performed. Pollution features of all landscape components and concatenation of disease incidence of cities inhabitants with this pollution are revealed.
Workplace Assessment for Working Conditions: New Order, New Problems
Authors: Федорец  , Fedorets Aleksandr , Мишутинская  , Mishutinskaya E.
Published: April 2013

The most significant innovations of workplace assessment procedure according to working conditions, characteristic mistakes and contradictions as well as some positive moments are noted in this article. It is the authors’ opinion that a new Order has provisions which practically exclude possibilities for legitimate carrying out of workplace assessment procedure by any certifying organizations and don’t allow the organizations to prove undoubtedly the need of compensations connected with working conditions.
Technical Regulation Reforms in Power Industry Through a Prism of CJSC ENSERTIKO History
Authors: Медведев  , Medvedev V.
Published: April 2013

CJSC ENSERTIKA main activities in Russian power reorganization period as well as in modern conditions are considered. The

assessment of enactment results of a number of standard documents regulating conditions and rules of production and services

certification is presented. Certification problems caused by development of interstate or supranational technical regulations are shown. The fear has being expressed that three-level model of Russian normative and technical regulation accepted in the Law No. 184-FZ for providing communication between legal norms and technical norms becomes inadequate for technical regulation targets.
All That is Users Might Not be Gold: How Labeling Products as User Designed Backfires in the Context of Luxury Fashion Brands
Authors: Fuchs Christoph , Prandelli Emanuela , Schreier Martin , Dahl Darren W.
Published: April 2013

An emerging literature stream posits that drawing on users rather than internal designers in new product creation may benefit firms because the resulting products effectively satisfy consumer needs. Four studies conducted in the context of the luxury fashion industry uncover an important conceptual boundary condition of this positive user-design effect. Contrary to extant research, the results show that being “close” to users does not help but rather harms luxury fashion brands. Specifically, the authors find that user design backfires because consumer demand for a given luxury fashion brand collection is reduced if the collection is labeled as user (vs. company) designed. The results further reveal the underlying rationale for this reversal: user-designed luxury products are perceived to be lower in quality and fail to signal high status, which results in a loss of agentic feelings for the consumer. The authors explore several strategies luxury brands can pursue to overcome this negative user-design effect. Finally, they find that negative outcomes of user design are attenuated for luxury fashion products that are not used for status signaling—that is, product categories of a luxury brand that are characterized by lower status relevance for the consumer.
Laboratory Evaluation of Reclaimed Asphalt Pavement–Quarry Waste Blends as Unbound Highway Pavement Material
Authors: Edeh Joseph Ejelikwu , Joel Manasseh , Okpe Samuel Adakole
Published: April 2013

Large quantities of quarry waste (QW) are generated in the blasting of rocks and are stockpiled on production sites. Also, pavement rehabilitation and reconstruction generate a large volume of reclaimed asphalt pavement (RAP) waste that is disposed of along road alignments. All of these wastes are environmental hazards. This paper presents the results of a laboratory evaluation of the characteristics of RAP–QW blends with a view to determine their suitability for use as flexible pavement material. The mixtures were subjected to British Standard light (standard Proctor) compactive efforts to determine their compaction characteristics and California bearing ratios. The test results show that the properties of RAP waste improved with QW treatment. The maximum dry density increased as the optimum moisture content decreased with higher QW contents in the blends. Optimum California bearing ratio values of 52 % (unsoaked) and 66 % (soaked for 24 h) were recorded for 80 % RAP + 20 % QW and 60 % RAP + 40 % QW blends, respectively. With the potential for time-dependent increases in strength in view, the optimum blends satisfied durability requirements with insignificant water absorption and can be used as sub-base material in flexible pavement construction. This research provides results of the evaluation of RAP–QW blends as highway construction material, as based on the determination of the California bearing ratio. Further work may be encouraged to assess the resilient modulus of this material under cyclic load.
Extremely Low Birth Weight and Infant Mortality Rates in the United States
Authors: Lau Carissa , Ambalavanan Namasivayam , Chakraborty Hrishikesh , Wingate Martha S. , Carlo Waldemar A.
Published: April 2013

OBJECTIVE:

Infant mortality rates (IMR) and neonatal mortality rates (NMR) in the United States have not decreased recently. The purpose of this study was to determine the contributions of birth weight and gestational age subgroups to the IMR and NMR in the United States.

METHODS:

We used the most recent (1983–2005) US linked birth and infant death data and simple regression analysis to determine the contributions of specific birth weight and gestational age subgroups to trends in IMR and NMR.

RESULTS:

IMR and NMR decreased between 1983 and 2005 for all birth weight and gestational age subgroups. There was an increase in births of very low birth weight infants from 1.2% to 1.5% (P < .001) over this period. The proportion of very low birth weight–infant deaths increased from 42.9% to 54.8%, resulting in recent nonsignificant declines in IMR and NMR. The proportion of live-birth infants <500 g increased from 0.12% to 0.18% (P < .001). The adjusted IMR and NMR over time (excluding infants <500 g) have steeper declining trends than the ones including infants <500 g. The changes in overall IMR and NMR in recent years (2000–2005) are not statistically significant. However, the adjusted IMR and NMR trends during this time are highly significant.

CONCLUSIONS:

The increased proportions of infants <500 g and other low birth weight infants contribute greatly to the lack of a decrease in IMR and NMR from 2000 to 2005, although birth weight– and gestational age–specific IMR and NMR continue to decrease.
Sexual Initiation, Contraceptive Use, and Pregnancy Among Young Adolescents
Authors: Finer Lawrence B. , Philbin Jesse M.
Published: April 2013

OBJECTIVE:

To present new data on sexual initiation, contraceptive use, and pregnancy among US adolescents aged 10 to 19, and to compare the youngest adolescents’ behaviors with those of older adolescents.

METHODS:

Using nationally representative data from several rounds of the National Survey of Family Growth, we performed event history (ie, survival) analyses to examine timing of sexual initiation and contraceptive use. We calculated adolescent pregnancy rates by single year of age using data from the National Center for Health Statistics, the Guttmacher Institute, and the US Census Bureau.

RESULTS:

Sexual activity is and has long been rare among those 12 and younger; most is nonconsensual. By contrast, most older teens (aged 17–19) are sexually active. Approximately 30% of those aged 15 to 16 have had sex. Pregnancy rates among the youngest teens are exceedingly low, for example, ∼1 per 10 000 girls aged 12. Contraceptive uptake among girls as young as 15 is similar to that of their older counterparts, whereas girls who start having sex at 14 or younger are less likely to have used a method at first sex and take longer to begin using contraception.

CONCLUSIONS:

Sexual activity and pregnancy are rare among the youngest adolescents, whose behavior represents a different public health concern than the broader issue of pregnancies to older teens. Health professionals can improve outcomes for teenagers by recognizing the higher likelihood of nonconsensual sex among younger teens and by teaching and making contraceptive methods available to teen patients before they become sexually active.
Carcinoid heart disease
Authors: Bencze Ágnes , Szücs Nikolette , Igaz Péter , Leiszter Katalin , Nagy Zsolt , Patócs Attila , Rácz Károly
Published: April 2013

Carcinoids are rare tumors originating from neuroendocrine cells. A large proportion of these tumors produce serotonin and other biologically active hormones which may produce carcinoid syndrome characterized by flushing, diarrhoea and bronchospasm. Carcinoid heart disease, a rare complication of carcinoid syndrome, may itself have a great impact on life expectancy of patients with carcinoid syndrome. The authors present a case history of a patients with carcinoid heart disease and they review the symptoms, diagnosis and therapeutic options of this rare complication of carcinoid syndrome. Orv. Hetil., 2013, 154, 546–550.
Fabrication and Basic Investigation of Flat Lignocellulosic Carbon Material for Self-Supporting Electrodes in Electric Double-Layer Capacitors
Authors: Funabashi Tsubasa , Sato Masamichi , Kitajima Masao , Shoji Shuichi , Mizuno Jun
Published: April 2013

A novel flat, wood-based carbon material with heterogeneous pores, referred to as flat lignocellulosic carbon material (FLCM), was successfully fabricated by carbonizing samples of the softwood Picea jezoensis (Ezomatsu or Jezo spruce, a Japanese conifer). Simultaneous improvements of the specific surface area of the FLCM and the affinity of electric double-layer capacitor (EDLC) for electrolyte solvents were achieved by vacuum ultraviolet/ozone (VUV/O3) treatment. The specific surface area of the VUV/O3-treated FLCM showed a 50% increase over that of the original FLCM. The spectra measured by X-ray photoelectron spectroscopy (XPS) indicated that the number of O-C=O (carboxyl or ester) bonds increased, whereas the number of C-C bonds decreased. Additionally, the feasibility of using the FLCM as a self-supporting electrode in EDLCs was examined by measuring the electrochemical properties in a three-electrode system. The FLCM was confirmed as an appropriate self-supporting EDLC electrode material without warps and cracks. In addition, the FLCM can be used without any binder. Realization of FLCM-based EDLC electrodes with bendability, an area of several tens of square centimeters, and no risk of warp or crack formation, were indicated. Thus, FLCMs present a fascinating class of self-supporting carbon electrode materials for EDLCs.
Tuning Hierarchical Cluster Assembly in Pulsed Laser Deposition of Al-doped ZnO
Authors: Gondoni Paolo , Russo Valeria , Bottani Carlo E. , Bassi Andrea Li , Casari Carlo S.
Published: April 2013

The synthesis of hierarchically assembled Al-doped ZnO layers by Pulsed Laser Deposition (PLD) at room temperature was investigated. PLD was performed in a background pressure of 100 Pa O2 to deposit clusters in a low energy regime and obtain nano- and mesostructures resulting from a hierarchical assembly of nanoclusters. We here analyzed the effects of varying the gas flow rate on mesoscale morphology, mass density and optical properties. The variation of the target-to-substrate distance was also investigated, identifying its effects on mass density and film morphology. The optimization of optical properties in terms of transparency and light scattering capability is of potential interest for photovoltaic applications.