bluuebunny/crossref_metadata_2025 huggingface dataset:
How we treat Richter syndrome
Authors: Parikh Sameer A. , Kay Neil E. , Shanafelt Tait D.
Published: January 2014

Richter syndrome (RS) is defined as the transformation of chronic lymphocytic leukemia (CLL) into an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). RS occurs in approximately 2% to 10% of CLL patients during the course of their disease, with a transformation rate of 0.5% to 1% per year. A combination of germline genetic characteristics, clinical features (eg, advanced Rai stage), biologic (ζ-associated protein-70+, CD38+, CD49d+) and somatic genetic (del17p13.1 or del11q23.1) characteristics of CLL B cells, and certain CLL therapies are associated with higher risk of RS. Recent studies have also identified the crucial role of CDKN2A loss, TP53 disruption, C-MYC activation, and NOTCH1 mutations in the transformation from CLL to RS. An excisional lymph node biopsy is considered the gold standard for diagnosis of RS; a 18F-fluorodeoxyglucose positron emission tomography scan can help inform the optimal site for biopsy. Approximately 80% of DLBCL cases in patients with CLL are clonally related to the underlying CLL, and the median survival for these patients is approximately 1 year. In contrast, the remaining 20% of patients have a clonally unrelated DLBCL and have a prognosis similar to that of de novo DLBCL. For patients with clonally related DLBCL, induction therapy with either an anthracycline- or platinum-based regimen is the standard approach. Postremission stem cell transplantation should be considered for appropriate patients. This article summarizes our approach to the clinical management of CLL patients who develop RS.
gsGator: an integrated web platform for cross-species gene set analysis
Authors: Kang Hyunjung , Choi Ikjung , Cho Sooyoung , Ryu Daeun , Lee Sanghyuk , Kim Wankyu
Published: January 2014

Background

Gene set analysis (GSA) is useful in deducing biological significance of gene lists using a priori defined gene sets such as gene ontology (GO) or pathways. Phenotypic annotation is sparse for human genes, but is far more abundant for other model organisms such as mouse, fly, and worm. Often, GSA needs to be done highly interactively by combining or modifying gene lists or inspecting gene-gene interactions in a molecular network.

Description

We developed gsGator, a web-based platform for functional interpretation of gene sets with useful features such as cross-species GSA, simultaneous analysis of multiple gene sets, and a fully integrated network viewer for visualizing both GSA results and molecular networks. An extensive set of gene annotation information is amassed including GO & pathways, genomic annotations, protein-protein interaction, transcription factor-target (TF-target), miRNA targeting, and phenotype information for various model organisms. By combining the functionalities of Set Creator, Set Operator and Network Navigator, user can perform highly flexible and interactive GSA by creating a new gene list by any combination of existing gene sets (intersection, union and difference) or expanding genes interactively along the molecular networks such as protein-protein interaction and TF-target. We also demonstrate the utility of our interactive and cross-species GSA implemented in gsGator by several usage examples for interpreting genome-wide association study (GWAS) results. gsGator is freely available at http://gsGator.ewha.ac.kr.

Conclusions

Interactive and cross-species GSA in gsGator greatly extends the scope and utility of GSA, leading to novel insights via conserved functional gene modules across different species.
Ectopic expression of the phosphomimic mutant version of Arabidopsis response regulator 1 promotes a constitutive cytokinin response phenotype
Authors: Kurepa Jasmina , Li Yan , Perry Sharyn E , Smalle Jan A
Published: January 2014

Background

Cytokinins control numerous plant developmental processes, including meristem formation and activity, nutrient distribution, senescence timing and responses to both the abiotic and biotic environments. Cytokinin signaling leads to the activation of type-B response regulators (RRBs), Myb-like transcription factors that are activated by the phosphorylation of a conserved aspartate residue in their response receiver domain. Consistent with this, overexpression of RRBs does not substantially alter plant development, but instead leads to cytokinin hypersensitivity.

Results

Here we present comparative analysis of plants overexpressing Arabidopsis RRB 1 (ARR1) or a phosphomimic ARR1D94E mutant in which the conserved aspartate-94 (D94) is replaced by the phosphomimic residue glutamate (E). The D94E substitution causes a 100-fold increase in response activation and instigates developmental and physiological changes that characterize wild-type plants treated with cytokinins or transgenic plants with increased cytokinin content.

Conclusion

The current model of cytokinin signaling emphasizes the essential role of conserved aspartate residue phosphorylation of RRBs in promoting cytokinin responses. Our comparative analyses of developmental and physiological traits of ARR1 and ARR1D94E overexpressing plants revealed that the ARR1D94E protein is indeed a constitutive and wide-spectrum cytokinin response activator.
Cognitive and neuropsychiatric impairment in cerebral radionecrosis patients after radiotherapy of nasopharyngeal carcinoma
Authors: Wu Xiaohong , Gu Mofa , Zhou Guijuan , Xu Xue , Wu Mengmeng , Huang Haiwei
Published: January 2014

Background

We sought to characterize the cognitive function and neuropsychiatric symptoms in cerebral radionecrosis (CRN) patients who have received conformal radiation for nasopharyngeal carcinoma.

Methods

A total of 40 patients treated with radiotherapy (RT) that developed CRN (RT + CRN), 40 patients treated with radiotherapy that did not have CRN (RT-No-CRN), and 36 newly diagnosed untreated nasopharyngeal carcinoma patients (No-RT) were recruited. The cognitive function and neuropsychiatric symptoms were evaluated with Montreal cognitive assessment (MoCA), the mini-mental state examination (MMSE), activity of daily living scale (ADL), neuropsychiatric inventory (NPI), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA).

Results

The RT + CRN group had the lowest mean MMSE, MoCA and ADL scores, while highest mean NPI, HAMD and HAMA scores among the three patient groups (P < 0.05). Thirty (75%) of the RT + CRN patients were deemed cognitively impaired by the MoCA compared with 9 (22.5%) by the MMSE (χ

2
 = 22.064; P < 0.001). Eighty-two percents of subject in RT + CRN group experienced neuropsychiatric symptoms within the past 4 weeks. Irritability, anxiety, depression and agitation in the RT + CRN group were of the most significantly frequent among the 3 groups.

Conclusions

The CRN patients generally have manifestations in cognitive and psychological impairment, which have their typical characteristics, and should be considered in CRN treatment and rehabilitation. The MoCA classifies more CRN patients as cognitively impaired than the MMSE, justifying further studies of the MoCA as an appropriate screen for CRN.
Head-Eye movement control tests in patients with chronic neck pain; Inter-observer reliability and discriminative validity
Authors: Della Casa Eveline , Affolter Helbling Jutta , Meichtry André , Luomajoki Hannu , Kool Jan
Published: January 2014

Background

Head-eye movement control deficit is an identified problem in patients with chronic neck pain, particularly in cases of whiplash associated disorders (WAD). To date, there is no evidence concerning the reliability and validity of visually assessed active head-eye movement control tests. Therefore, the objectives of the present cross-sectional study were, a) to develop a test battery; and b) to investigate inter-observer reliability and discriminative validity in patients with chronic neck pain compared to healthy controls.

Methods

The study was conducted at two physiotherapy clinics in Switzerland. Ethics Committee approval was obtained. Ten active head-eye coordination tests, on 23 patients with chronic neck pain and associated symptoms and 19 healthy controls, were videotaped. The tests included eye movements in the neutral head position and 45° relative neck rotation, gaze stability and sequential head-eye movements. All tests were performed in the sitting and standing positions. Two blinded physiotherapists independently rated the randomized videos. Performance was rated as "negative", "moderately positive" or "clearly positive". Weighted kappa (wK) and 95% confidence intervals (CI) were calculated to investigate inter-observer reliability. Good reliability was defined as wK >0.5 with a lower boundary of 95% CI >0.2. Odds ratios (to define cut-off points) and the distribution of the classificator, numbers of positive tests, were calculated.

Results

Three out of ten tests showed "excellent" (wK 0.82 to 0.86), five out of ten tests showed "substantial" (wK 0.69 to 0.79) and two out of ten tests showed "moderate" (wK 0.54 to 0.59) reliability. Results were comparable in the sitting and standing positions. On average, three out of five tests were rated positive in patients and one out of five tests was rated positive in healthy controls. An odds ratio of 13.3 to 18.6 was obtained using ≥2/5 tests as a cut-off point.

Conclusion

Visual assessment by physiotherapists of head-eye movement control tests is reliable. The test battery is able to discriminate between patients with chronic neck pain and healthy controls. There were no differences in performance between the sitting and standing positions. The test battery can therefore be reduced to five tests. Further research is needed to identify the test-retest stability and responsiveness.
Immigrant-native differences in caries-related knowledge, attitude, and oral health behaviors: a cross-sectional study in Taiwan
Authors: Chen Chih-Chang , Chiou Shang-Jyh , Ting Chun-Chan , Lin Ying-Chun , Hsu Chih-Cheng , Chen Fu-Li , Lee Chien-Hung , Chen Ted , Chang Chin-Shun , Lin Ya-Ying , Huang Hsiao-Ling
Published: January 2014

Background

With the growing number of transnational marriages in Taiwan, oral health disparities have become a public health issue. This study assessed immigrant-native differences in oral health behaviors of urban mothers and their children.

Methods

We used the baseline data of an oral health promotion program to examine the immigrant-native differences in caries-related knowledge, attitude, and oral health behaviors. A cross-sectional study was conducted to collect data from mothers in urban area, Taiwan. A total of 150 immigrant and 440 native mothers completed the self-report questionnaires. Logistic regression models analyzed the racial differences in oral health behaviors.

Results

Approximately 37% of immigrant mothers used dental floss, 25% used fluoride toothpaste, and only 13.5% of them regularly visited a dentist. Less that 40% of immigrant mothers brush their children’s teeth before aged one year, 45% replaced child’s toothbrush within 3 months, and only half of the mothers regularly took their child to the dentist. Immigrant mothers had lower level of caries-related knowledge and attitudes than native mothers (p < .001). Compared to native group, the immigrant mothers were less likely to use of dental floss ([Adjusted odds ratio (aOR) =0.35], fluoride toothpaste (aOR = 0.29), visit a dentist in the past 2 years (aOR = 0.26), and take their children to regular dental check-up (aOR = 0.38); whereas, they were more likely to not consume sweeten beverages (aOR = 3.13).

Conclusions

The level of caries-related knowledge, attitudes and oral health behaviors were found lower in immigrant mothers than native ones. The findings suggested cross-cultural caries prevention programs aimed at reducing immigrant-native disparities in child oral health care must be developed for these immigrant minorities.
Ethylenediaminetetraacetic acid as capping ligands for highly water-dispersible iron oxide particles
Authors: Yi Yunfeng , Zhang Ying , Wang Yixiao , Shen Lihua , Jia Mengmeng , Huang Yu , Hou Zhenqing , Zhuang Guohong
Published: January 2014

Monodispersed magnetite (Fe3O4) particles were synthesized using a high-temperature hydrolysis reaction with the assistance of ethylenediaminetetraacetic acid (EDTA) as capping ligands. These particles were composed of small primary nanocrystals and their sizes could be tuned from about 400 to about 800 nm by simply changing the EDTA or precursor concentration. Surface-tethered EDTA made the particles highly water-dispersible. The as-prepared magnetite particles also showed superparamagnetic behavior at room temperature, and their magnetic properties were size dependent. In addition, the particles had a strong response to external magnetic field due to their high magnetization saturation values. These properties were very important for some potential biomedical applications, such as magnetic separation and magnetic-targeted substrate delivery.
Tunable nonlinear optical properties in nanocrystalline Si/SiO2 multilayers under femtosecond excitation
Authors: Zhang Pei , Zhang Xiaowei , Xu Jie , Mu Weiwei , Xu Jun , Li Wei , Chen Kunji
Published: January 2014

The nonlinear optical properties of nanocrystalline-Si/SiO2 (nc-Si/SiO2) multilayers have been investigated through Z-scan technique by using a Ti-sapphire laser with 50-fs pulse duration at 800 nm as a pump laser. It is interesting to note that with increasing the annealing temperature to make the sample change from amorphous phase to nanocrystalline state, the nonlinear absorption turns the reverse saturation absorption into saturation absorption while the nonlinear optical refraction is also changed simultaneously from self-defocusing to self-focusing. We propose that the localized states at the nc-Si/SiO2 interfaces play the key role in the observed switching behaviors. Our results demonstrate that the tunable optical nonlinearities can be achieved by controlling the microstructures of nc-Si, which can be used as engineering different nonlinear optical devices.
Breastfeeding in Saudi Arabia: a review
Authors: Al Juaid Daifellah AM , Binns Colin W , Giglia Roslyn C
Published: January 2014

Background

Breastfeeding is viewed as the optimal method of infant feeding that provides many benefits to both the infant and the mother. The monitoring and reporting of breastfeeding indicators are essential for any country to plan and implement effective promotion programs for sustainable breastfeeding. The aim of this review is to examine the available studies and data on breastfeeding in Saudi Arabia, and determine the potential factors that affect breastfeeding practices and duration in this country.

Methods

The databases of Web of Knowledge, Science Direct and PubMed were searched using the relevant key words. Only studies that reported breastfeeding practices, rates and indicators in Saudi Arabia were included. Standard WHO definitions for breastfeeding categories were used in this review.

Results

Seventeen cross-sectional studies were identified and reviewed and five stated they used standard definitions. The self-administered questionnaire as a measurement tool was the predominant method of data collection. Infants' ages range from less than six months up to five years. Initiation rates were high (mostly above 90%), but a few studies reported low rates of timely initiation (within the first hour). The exclusive breastfeeding rate could not be accurately determined as rates range from 0.8% to 43.9% among studies due to the lack of clear definitions and the nature of study design. The partial (mixed) feeding method was common and the category of 'any breastfeeding' has generally high rates. The mean duration of breastfeeding has showed a progressive decline over time from 13.4 months in 1987 to 8.5 months in 2010. Factors associated with a high prevalence of breastfeeding and longer duration include increased maternal age, low educational levels, rural residence, low income, multiparity and avoiding contraceptives. The most common reason for breastfeeding cessation was insufficient breast milk. Other reasons include sickness, new pregnancy and breastfeeding problems.

Conclusions

Breastfeeding indicators in Saudi Arabia could not be monitored or compared relying on the available data because no longitudinal studies have been conducted in this country. A cohort study design would be the most appropriate procedure to rigorously assess and report valid results on breastfeeding practices and patterns in the Saudi society.
Polymorphisms within the Telomerase Reverse Transcriptase gene (TERT) in four breeds of dogs selected for difference in lifespan and cancer susceptibility
Authors: McAloney Camille A , Silverstein Kevin A T , Modiano Jaime F , Bagchi Anindya
Published: January 2014

Background

Enzymatic activity of Telomerase Reverse Transcriptase (TERT) is important in maintaining the telomere length and has been implicated in cancer and aging related pathology. Since cancer susceptibility as well as longevity of dogs vary between breeds, this study involved sequencing the entire TERT gene of Canis familiaris from DNA samples obtained from forty dogs, with ten dogs each of four breeds: Shih Tzu, Dachshund, Irish Wolfhound, and Newfoundland, each with different life expectancies and susceptibility to cancer.

Results

We compared the sequences of all forty individuals amongst one another and with the published sequence of canine TERT, and analyzed relationships between members of the same or different breeds. Two separate phylogenetic trees were generated and analyzed from these individuals. Polymorphisms were found most frequently in intronic regions of the gene, although exonic polymorphisms also were observed. In many locations genotypes were observed that were either homozygous for the reference sequence or heterozygous, but the variant homozygous genotype was not observed.

Conclusions

We propose that these homozygous variants are likely to have adverse effects in dogs. It was also found that the polymorphisms did not segregate by breed. Because the four breeds chosen come from geographically and physiologically distinct backgrounds, it can be inferred that the polymorphic diversification of TERT preceded breed derivation.
Personalized peer-comparison feedback and its effect on emergency medicine resident ultrasound scan numbers
Authors: Hempel Dorothea , Pivetta Emanuele , Kimberly Heidi H
Published: January 2014

Background

Clinician-performed ultrasound has become a widely utilized tool in emergency medicine and is a mandatory component of the residency curricula. We aimed to assess the effect of personalized peer-comparison feedback on the number of ultrasound scans performed by emergency medicine residents.

Findings

A personalized peer-comparison feedback was performed by sending 44 emergency medicine residents a document including personally identified scan numbers and class averages. The number of ultrasound scans per clinical shift for a 3-month period before and after the feedback intervention was calculated. The average number of ultrasound exams per shift improved from 0.39 scans/shift before to 0.61 scans/shift after feedback (p = 0.04). Among the second year residents, the scans/shift ratio improved from 0.35 to 0.87 (p = 0.07); for third year residents, from 0.51 to 0.58 (p = 0.46); and from 0.33 to 0.41 (p = 0.21) for the fourth year residents before and after the intervention, respectively.

Conclusions

A personalized peer-comparison feedback provided to emergency medicine residents resulted in increased ultrasound scan numbers per clinical shift. Incorporating this method of feedback may help encourage residents to scan more frequently.
Toward a typology of incubators based on HRM
Authors: Bakkali Chaffik , Messeghem Karim , Sammut Sylvie
Published: January 2014

The fact that there are major differences between one incubator and another has resulted in many authors working on multiple typologies. Although these typologies are relatively common in the literature, they all tend to use the same classification criteria (objectives of the structures, funding, etc.). In this article, we hope to broaden the viewpoint to human resource management (HRM) within incubators. We defend the theory that the differences between incubators are not only found at the level of their objectives or their funding, but also at the level of their HRM policies. Through conceptual reflection, we thus propose HR management that is specific to each type of structure, based on Pichault and Nizet's configurational approach (2000), as well as on Mahé de Boislandelle's social mix (1993).
Quantitative proteomic analysis of sphere-forming stem-like oral cancer cells
Authors: Misuno Kaori , Liu Xiaojun , Feng Sizhe , Hu Shen
Published: January 2014

Introduction

The purpose of this study is to identify target proteins that may play important functional roles in oral cancer stem-like cells (CSCs) using mass spectrometry-based quantitative proteomics.

Methods

Sphere-formation assays were performed on highly invasive UM1 and lowly invasive UM2 oral cancer cell lines, which were derived from the same tongue squamous cell carcinoma, to enrich CSCs. Quantitative proteomic analysis of CSC-like and non-CSC UM1 cells was carried out using tandem mass tagging and two-dimensional liquid chromatography with Orbitrap mass spectrometry.

Results

CSC-like cancer cells were found to be present in the highly invasive UM1 cell line but absent in the lowly invasive UM2 cell line. Stem cell markers SOX2, OCT4, SOX9 and CD44 were up-regulated, whereas HIF-1 alpha and PGK-1 were down-regulated in CSC-like UM1 cells versus non-CSC UM1 cells. Quantitative proteomic analysis indicated that many proteins in cell cycle, metabolism, G protein signal transduction, translational elongation, development, and RNA splicing pathways were differentially expressed between the two cell phenotypes. Both CREB-1-binding protein (CBP) and phosphorylated CREB-1 were found to be significantly over-expressed in CSC-like UM1 cells.

Conclusions

CSC-like cells can be enriched from the highly invasive UM1 oral cancer cell line but not from the lowly invasive UM2 oral cancer cell line. There are significant proteomic alterations between CSC-like and non-CSC UM1 cells. In particular, CBP and phosphorylated CREB-1 were significantly up-regulated in CSC-like UM1 cells versus non-CSC UM1 cells, suggesting that the CREB pathway is activated in the CSC-like cells.
Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy
Authors: Zhou Yu , Yang Jixin , Watkins Daniel J , Boomer Laura A , Matthews Mika A , Su Yanwei , Besner Gail E
Published: January 2014

Introduction

Intestinal dysmotility following human necrotizing enterocolitis suggests that the enteric nervous system is injured during the disease. We examined human intestinal specimens to characterize the enteric nervous system injury that occurs in necrotizing enterocolitis, and then used an animal model of experimental necrotizing enterocolitis to determine whether transplantation of neural stem cells can protect the enteric nervous system from injury.

Methods

Human intestinal specimens resected from patients with necrotizing enterocolitis (n = 18), from control patients with bowel atresia (n = 8), and from necrotizing enterocolitis and control patients undergoing stoma closure several months later (n = 14 and n = 6 respectively) were subjected to histologic examination, immunohistochemistry, and real-time reverse-transcription polymerase chain reaction to examine the myenteric plexus structure and neurotransmitter expression. In addition, experimental necrotizing enterocolitis was induced in newborn rat pups and neurotransplantation was performed by administration of fluorescently labeled neural stem cells, with subsequent visualization of transplanted cells and determination of intestinal integrity and intestinal motility.

Results

There was significant enteric nervous system damage with increased enteric nervous system apoptosis, and decreased neuronal nitric oxide synthase expression in myenteric ganglia from human intestine resected for necrotizing enterocolitis compared with control intestine. Structural and functional abnormalities persisted months later at the time of stoma closure. Similar abnormalities were identified in rat pups exposed to experimental necrotizing enterocolitis. Pups receiving neural stem cell transplantation had improved enteric nervous system and intestinal integrity, differentiation of transplanted neural stem cells into functional neurons, significantly improved intestinal transit, and significantly decreased mortality compared with control pups.

Conclusions

Significant injury to the enteric nervous system occurs in both human and experimental necrotizing enterocolitis. Neural stem cell transplantation may represent a novel future therapy for patients with necrotizing enterocolitis.
Decellularized silk fibroin scaffold primed with adipose mesenchymal stromal cells improves wound healing in diabetic mice
Authors: Navone Stefania Elena , Pascucci Luisa , Dossena Marta , Ferri Anna , Invernici Gloria , Acerbi Francesco , Cristini Silvia , Bedini Gloria , Tosetti Valentina , Ceserani Valentina , Bonomi Arianna , Pessina Augusto , Freddi Giuliano , Alessandrino Antonio , Ceccarelli Piero , Campanella Rolando , Marfia Giovanni , Alessandri Giulio , Parati Eugenio Agostino
Published: January 2014

Introduction

Silk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice.

Methods

The conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse’s back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors.

Results

We found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15–17 days of controls. RT2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs’ migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay.

Conclusions

Our results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans.
Second-Hand Smoke As a Predictor of Smoking Cessation Among Lung Cancer Survivors
Authors: Eng Lawson , Su Jie , Qiu Xin , Palepu Prakruthi R. , Hon Henrique , Fadhel Ehab , Harland Luke , La Delfa Anthony , Habbous Steven , Kashigar Aidin , Cuffe Sinead , Shepherd Frances A. , Leighl Natasha B. , Pierre Andrew F. , Selby Peter , Goldstein David P. , Xu Wei , Liu Geoffrey
Published: January 2014

Purpose

Second-hand smoke (SHS; ie, exposure to smoking of friends and spouses in the household) reduces the likelihood of smoking cessation in noncancer populations. We assessed whether SHS is associated with cessation rates in lung cancer survivors.

Patients and Methods

Patients with lung cancer were recruited from Princess Margaret Cancer Centre, Toronto, ON, Canada. Multivariable logistic regression and Cox proportional hazard models evaluated the association of sociodemographics, clinicopathologic variables, and SHS with either smoking cessation or time to quitting.

Results

In all, 721 patients completed baseline and follow-up questionnaires with a mean follow-up time of 54 months. Of the 242 current smokers at diagnosis, 136 (56%) had quit 1 year after diagnosis. Exposure to smoking at home (adjusted odds ratio [aOR], 6.18; 95% CI, 2.83 to 13.5; P < .001), spousal smoking (aOR, 6.01; 95% CI, 2.63 to 13.8; P < .001), and peer smoking (aOR, 2.49; 95% CI, 1.33 to 4.66; P = .0043) were each associated with decreased rates of cessation. Individuals exposed to smoking in all three settings had the lowest chances of quitting (aOR, 9.57; 95% CI, 2.50 to 36.64; P < .001). Results were similar in time-to-quitting analysis, in which 68% of patients who eventually quit did so within 6 months after cancer diagnosis. Subgroup analysis revealed similar associations across early- and late-stage patients and between sexes.

Conclusion

SHS is an important factor associated with smoking cessation in lung cancer survivors of all stages and should be a key consideration when developing smoking cessation programs for patients with lung cancer.
Longitudinal Serum Testosterone, Luteinizing Hormone, and Follicle-Stimulating Hormone Levels in a Population-Based Sample of Long-Term Testicular Cancer Survivors
Authors: Sprauten Mette , Brydøy Marianne , Haugnes Hege S. , Cvancarova Milada , Bjøro Trine , Bjerner Johan , Fosså Sophie D. , Oldenburg Jan
Published: January 2014

Purpose

To assess longitudinal long-term alterations of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in testicular cancer survivors (TCSs).

Patients and Methods

In all, 307 TCSs treated from 1980 to 1994 provided blood samples after orchiectomy but before further treatment, at Survey I (SI; 1998-2002), and Survey II (SII; 2007-2008). Levels of sex hormones were categorized according to quartiles and reference range (2.5 and 97.5 percentiles) of 599 controls for each decadal age group. TCSs were categorized according to treatment: surgery, radiotherapy (RT), or chemotherapy (CT). The risk of higher (LH) or lower (testosterone) levels was assessed with χ2 test (FSH) or ordinal logistic regression analysis and expressed as odds ratios (ORs) with 95% CIs.

Results

Risk of lower testosterone and higher LH and FSH levels was significantly increased for TCSs at all time points after RT or CT. At SII, ORs were 3.3 (95% CI, 2.3 to 4.7) for lower testosterone categories and 5.2 (95% CI, 3.5 to 7.9) for RT and CT. ORs for increased LH and FSH were 4.4 (95% CI, 3.1 to 6.5) and 18.9 (95% CI, 11.0 to 32.6) for RT, respectively, and 3.6 (95% CI, 2.4 to 5.3) and 14.2 (95% CI, 8.3 to 24.4) for CT, respectively. The cumulative platinum dose was significantly associated with risk of higher LH levels at both surveys and higher FSH at SI. In total, half the TCSs had at least one of three sex hormone levels outside the reference range at SII.

Conclusion

Long-term TCSs are at risk of premature hormonal aging. Our findings may pertain to cancer survivors in general, underlining the importance of extended follow-up.
Neoadjuvant Chemotherapy Without Routine Use of Radiation Therapy for Patients With Locally Advanced Rectal Cancer: A Pilot Trial
Authors: Schrag Deborah , Weiser Martin R. , Goodman Karyn A. , Gon̈en Mithat , Hollywood Ellen , Cercek Andrea , Reidy-Lagunes Diane L. , Gollub Marc J. , Shia Jinru , Guillem Jose G. , Temple Larissa K.F. , Paty Philip B. , Saltz Leonard B.
Published: January 2014

Purpose

Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in clinical stages II to III rectal cancer, it delays administration of optimal chemotherapy. We evaluated preoperative infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy.

Patients and Methods

Thirty-two patients with clinical stages II to III rectal cancer participated in this single-center phase II trial. All were candidates for low anterior resection with total mesorectal excision (TME). Patients were to receive six cycles of FOLFOX, with bevacizumab included for cycles 1 to 4. Patients with stable/progressive disease were to have radiation before TME, whereas responders were to have immediate TME. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX × 6 was recommended, but adjuvant regimens were left to clinician discretion. The primary outcome was R0 resection rate.

Results

Between April 2007 and December 2008, 32 (100%) of 32 study participants had R0 resections. Two did not complete preoperative chemotherapy secondary to cardiovascular toxicity. Both had preoperative chemoradiotherapy and then R0 resections. Of 30 patients completing preoperative chemotherapy, all had tumor regression and TME without preoperative chemoradiotherapy. The pathologic complete response rate to chemotherapy alone was 8 of 32 (25%; 95% CI, 11% to 43%). The 4-year local recurrence rate was 0% (95% CI, 0% to 11%); the 4-year disease-free survival was 84% (95% CI, 67% to 94%).

Conclusion

For selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes. Preoperative Radiation or Selective Preoperative Radiation and Evaluation Before Chemotherapy and TME (PROSPECT), a randomized phase III trial to validate this experience, is now open in the US cooperative group network.
Identification of Potentially Avoidable Hospitalizations in Patients With GI Cancer
Authors: Brooks Gabriel A. , Abrams Thomas A. , Meyerhardt Jeffrey A. , Enzinger Peter C. , Sommer Karen , Dalby Carole K. , Uno Hajime , Jacobson Joseph O. , Fuchs Charles S. , Schrag Deborah
Published: January 2014

Purpose

To identify and characterize potentially avoidable hospitalizations in patients with GI malignancies.

Patients and Methods

We compiled a retrospective series of sequential hospital admissions in patients with GI cancer. Patients were admitted to an inpatient medical oncology or palliative care service between December 2011 and July 2012. Practicing oncology clinicians used a consensus-driven medical record review process to categorize each hospitalization as “potentially avoidable” or “not avoidable.” Patient demographic and clinical data were abstracted, and quantitative and qualitative analyses were performed to identify patient characteristics and outcomes associated with potentially avoidable hospitalizations.

Results

We evaluated 201 hospitalizations in 154 unique patients. The median age was 62 years, and colorectal cancer was the most common diagnosis (32%). The majority of hospitalized patients had metastatic cancer (81%). In all, 53% of hospitalizations were attributable to cancer symptoms, and 28% were attributable to complications of cancer treatment. Medical oncologists identified 39 hospitalizations (19%) as potentially avoidable. Hospitalizations were more likely to be categorized as potentially avoidable for patients with the following characteristics: age ≥ 70 years (odds ratio [OR], 2.63; 95% CI, 1.15 to 6.02), receipt of an oncologist's advice to consider hospice (OR, 6.09; 95% CI, 2.54 to 14.58), or receipt of three or more lines of chemotherapy (OR, 2.68; 95% CI, 1.01 to 7.08). Ninety-day mortality was higher after avoidable hospitalizations compared with hospitalizations that were not avoidable (OR, 6.4; 95% CI, 1.8 to 22.3).

Conclusion

Potentially avoidable hospitalizations are common in patients with advanced GI cancer. The majority of potentially avoidable hospitalizations occurred in patients with advanced treatment-refractory cancers near the end of life.
Growth Hormone, Insulin-Like Growth Factor-1, and the Kidney: Pathophysiological and Clinical Implications
Authors: Kamenický Peter , Mazziotti Gherardo , Lombès Marc , Giustina Andrea , Chanson Philippe
Published: January 2014

Besides their growth-promoting properties, GH and IGF-1 regulate a broad spectrum of biological functions in several organs, including the kidney. This review focuses on the renal actions of GH and IGF-1, taking into account major advances in renal physiology and hormone biology made over the last 20 years, allowing us to move our understanding of GH/IGF-1 regulation of renal functions from a cellular to a molecular level. The main purpose of this review was to analyze how GH and IGF-1 regulate renal development, glomerular functions, and tubular handling of sodium, calcium, phosphate, and glucose. Whenever possible, the relative contributions, the nephronic topology, and the underlying molecular mechanisms of GH and IGF-1 actions were addressed. Beyond the physiological aspects of GH/IGF-1 action on the kidney, the review describes the impact of GH excess and deficiency on renal architecture and functions. It reports in particular new insights into the pathophysiological mechanism of body fluid retention and of changes in phospho-calcium metabolism in acromegaly as well as of the reciprocal changes in sodium, calcium, and phosphate homeostasis observed in GH deficiency. The second aim of this review was to analyze how the GH/IGF-1 axis contributes to major renal diseases such as diabetic nephropathy, renal failure, renal carcinoma, and polycystic renal disease. It summarizes the consequences of chronic renal failure and glucocorticoid therapy after renal transplantation on GH secretion and action and questions the interest of GH therapy in these conditions.
CLM3, a Multitarget Tyrosine Kinase Inhibitor With Antiangiogenic Properties, Is Active Against Primary Anaplastic Thyroid Cancer In Vitro and In Vivo
Authors: Antonelli Alessandro , Bocci Guido , Fallahi Poupak , La Motta Concettina , Ferrari Silvia Martina , Mancusi Caterina , Fioravanti Anna , Di Desidero Teresa , Sartini Stefania , Corti Alessandro , Piaggi Simona , Materazzi Gabriele , Spinelli Claudio , Fontanini Gabriella , Danesi Romano , Da Settimo Federico , Miccoli Paolo
Published: January 2014

Context and Objective:

We have studied the antitumor activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) proposed for a multiple signal transduction inhibition [including the RET tyrosine kinase, epidermal growth factor receptor, and vascular endothelial growth factor (VEGF) receptor and with antiangiogenic activity] in primary anaplastic thyroid cancer (ATC) cells, in the human cell line 8305C (undifferentiated thyroid cancer), and in an ATC-cell line (AF).

Design and Main Outcome Measures:

CLM3 was tested in primary ATC cells at the concentrations of 5, 10, 30, and 50 μM; in 8305C cells, in AF cells, at 1, 5, 10, 30, 50, or 100 μM; and in AF cells in CD nu/nu mice.

Results:

CLM3 significantly inhibited the proliferation of 8305C and AF cells, also inducing apoptosis. A significant reduction of proliferation with CLM3 in ATC cells (P < .01, ANOVA) was shown. CLM3 increased the percentage of apoptotic ATC cells dose dependently (P < .001, ANOVA) and inhibited migration (P < .01) and invasion (P < .001). The AF cell line was injected sc in CD nu/nu mice, and tumor masses became detectable 15 days later. CLM3 (50 mg/kg per die) significantly inhibited tumor growth (starting 16 d after the beginning of treatment). CLM3 significantly decreased the VEGF-A expression and microvessel density in AF tumor tissues. Furthermore, CLM3 inhibited epidermal growth factor receptor, AKT, and ERK1/2 phosphorylation and down-regulated cyclin D1 in 8305C and AF cells.

Conclusions:

The antitumor and antiangiogenic activity of a pyrazolo[3,4-d]pyrimidine compound (CLM3) is very promising in anaplastic thyroid cancer, opening the way to a future clinical evaluation.
Current and Evolving Approaches to Individualizing Estrogen Receptor-Based Therapy for Menopausal Women
Authors: Santen Richard J. , Kagan Risa , Altomare Corrado J. , Komm Barry , Mirkin Sebastian , Taylor Hugh S.
Published: January 2014

Context:

Adding progestogens to estrogens changes the risk profile of hormonal therapy for menopausal women, and recent data support the need for progestogen-free options. Several current and evolving approaches to managing estrogen deficiency allow for progestogen omission. We review the mechanisms of estrogen activity and provide an overview of emerging and available estrogen receptor (ER)–based therapies.

Evidence Acquisition:

PubMed was searched for relevant English-language articles using keywords pertaining to estrogen deficiency, menopause, hormone therapy, and estrogen-only therapy. Pivotal or recent randomized controlled trials, large observational studies, comprehensive meta-analyses, and established therapeutic guidelines were compiled.

Evidence Synthesis:

Advances in our understanding of ER pharmacology have led to therapies designed to optimize ER activity, including selective ER modulators (SERMs) and tissue-selective estrogen complexes (TSECs). Each estrogen, SERM, and TSEC exhibits a unique profile of tissue-specific activity, spanning the spectrum from ER agonism to antagonism. Systemic estrogens unopposed by progestogens effectively manage menopausal symptoms in hysterectomized postmenopausal women but require progestogen use in postmenopausal women with a uterus. SERMs are effective for managing certain aspects of estrogen deficiency in postmenopausal women, but data suggest that pairing a SERM with estrogens to form a TSEC provides a more optimal therapeutic profile for women with a uterus.

Conclusions:

Treating signs and symptoms of estrogen deficiency requires an individualized approach based on a woman's goals and the purported risks of different therapies. New and emerging agents have demonstrated efficacy in postmenopausal women with a uterus, while allowing these women to avoid progestogens and their possible adverse effects.
Propagation of the Change in Membrane Potential Owing to the Circulating Current within a Membrane System in Analogy with Neurotransmission
Authors: Kushida Yuki , Shirai Osamu , Kitazumi Yuki , Kano Kenji
Published: January 2014

The propagation of the change in membrane potential between two aqueous phases across two parallel membranes from the sending site to the receiving site was elucidated. The potential differences at every interface are controlled by the ion transfers and the circulating current flowed to keep the electroneutrality of every phase.
Credibility Contests: The Elephant in the Room
Authors: Green Michael
Published: January 2014

The primary duty of a court is to do justice. Implicit in this process is the principle that the court should assess the evidence in accordance with current scientific knowledge. Trials by ordeal and combat have long since been abandoned as it was recognised that they did not produce reliable, just outcomes. The law moved with the times. In criminal cases juries are directed that they can only convict ‘if they are sure’. The jurors might be sure, but are they correct? There now exists a substantial body of scientific evidence, which indicates that humans are very poor lie detectors, in fact performing at around chance. Given this incongruity in the system, is it not time to re-evaluate how cases are put before the courts, and what weight is placed on oral testimony? This is particularly acute in ‘credibility contests' where, it is argued, it is usually unsafe to convict.
Reviews
Authors: Stimson Blake , Wikström Josefine , Paul Richard
Published: January 2014

Anywhere or Not at All: Philosophy of Contemporary Art, Peter Osborne (2013) London: Verso, 288 pages, ISBN 9781781680940, p/bk, £19.95.

On the performativization of action: Discussions around politics and aesthetics in non-governmental activism

Sensible Politics: The Visual Culture of Nongovernmental Activism, Meg McLagan and Yates McKee (eds) (2012) 1st ed., New York: Zone Books, 662 pp., ISBN 978-1935408246, h/bk, £25.95.

Ian Wallace: At the Intersection of Painting and Photography (2013) Vancouver Art Gallery/Black Dog Publishing, Vancouver & London, pp. 352, 1907317570, hb, £28.45.
Lyotard, art, seeing
Authors: Mapp Nigel
Published: January 2014

This araticle examines elements of Jean-François Lyotard’s paradoxical negotiations with aesthetic experiences in order to characterize his critical involvement with discursivized forms of knowing and explanation. These elements are offered as salient and salutary correctives to the symmetrical dogmas of disenchanting naturalisms and culturalisms currently programming typical misprisions of the aesthetic. Lyotard’s 1971 Discourse, Figure, as well as some of his later writings on visual art and artists, are not interpretatively integrated here but instead explored in terms of an anti-discursive logic that actually animates what appear to be their own anti-aesthetic commitments and conclusions. The article tracks the ambivalent, but persistent, role that perception, art-medium and sensate experience play in Lyotard’s efforts to see beyond them. This result impacts not only on the kinds of ‘demystification’ his work should be seen to espouse, but on that pervasive pseudo-category itself.
Simulation of CO Preferential Oxidation (COPrOx) Monolithic Reactors
Authors: Jeifetz Leandro G. , Giunta Pablo Daniel , Mariño Fernando J. , Amadeo Norma E. , Laborde Miguel Á.
Published: January 2014

In this work, a COPrOx monolithic reactor with a CuO/CeO2/Al2O3catalytic washcoat was modelled to purify a H2stream for a 2 kW PEM fuel cell. Preliminary simulations included isothermal monoliths operating between 423 and 463 K, and the optimization of linear axial temperature profiles. For a fixed total system size and a desired CO outlet molar fraction lower than 20 ppm, an isothermal temperature profile maximized the global selectivity towards CO oxidation. Then, different schemes of adiabatic monoliths with interstage cooling were modelled and evaluated. It was found that wide operating temperature ranges lower the necessary number of stages, but decrease the global selectivity and rise system sensitivity to inlet temperatures. A 1D heterogeneous model was used to simulate the monoliths.
The effect of whole-body, repetitive, inhomogeneous static magnetic field-exposure on the symptoms of experimental autoimmune encephalomyelitis in mice
Authors: László János F. , Solténszky Judit , Pórszász Róbert , Kónya Attila
Published: January 2014

Experimental autoimmune encephalomyelitis (EAE) is a model for human multiple sclerosis (MS) in rodents. Static magnetic field (SMF)-exposure was shown to be beneficial in specific cases of inflammatory background, where it suppresses symptoms. The null-hypothesis was that animals with induced EAE exposed to SMF would show different seriousness of symptoms, than those in the sham-exposed control group. Three replicated series of repetitive, 30 min/day whole-body exposure to SMF with 477 mT peak-to-peak magnetic induction and 48 T/m lateral induction gradient was tested on female CSJLF1 mice with a mild, mouse spinal cord homogenate emulsion-induced EAE. Conventional scores of the animal response to EAE were compared between sham- and SMF-exposed groups of animals. Following pilot test we used 18 animals per group. Primary outcome measure was the daily group average of standard EAE scores. Results show that SMF-exposure has a strong, reproducible, and significantly beneficial effect up to 51.82% (p<0.001) over sham-exposure on the symptoms of EAE in the course of the 25 days of the experiment. This study aimed to build experimental research foundation for a later therapy option by applying SMF-exposure in the clinical management of MS.