bluuebunny/crossref_metadata_2025 huggingface dataset:
Tumor Hypoxia Does Not Drive Differentiation of Tumor-Associated Macrophages but Rather Fine-Tunes the M2-like Macrophage Population
Authors: Laoui Damya , Van Overmeire Eva , Di Conza Giusy , Aldeni Chiara , Keirsse Jiri , Morias Yannick , Movahedi Kiavash , Houbracken Isabelle , Schouppe Elio , Elkrim Yvon , Karroum Oussama , Jordan Bénédicte , Carmeliet Peter , Gysemans Conny , De Baetselier Patrick , Mazzone Massimiliano , Van Ginderachter Jo A.
Published: November 2013

Tumor-associated macrophages (TAM) are exposed to multiple microenvironmental cues in tumors, which collaborate to endow these cells with protumoral activities. Hypoxia, caused by an imbalance in oxygen supply and demand because of a poorly organized vasculature, is often a prominent feature in solid tumors. However, to what extent tumor hypoxia regulates the TAM phenotype in vivo is unknown. Here, we show that the myeloid infiltrate in mouse lung carcinoma tumors encompasses two morphologically distinct CD11bhiF4/80hiLy6Clo TAM subsets, designated as MHC-IIlo and MHC-IIhi TAM, both of which were derived from tumor-infiltrating Ly6Chi monocytes. MHC-IIlo TAM express higher levels of prototypical M2 markers and reside in more hypoxic regions. Consequently, MHC-IIlo TAM contain higher mRNA levels for hypoxia-regulated genes than their MHC-IIhi counterparts. To assess the in vivo role of hypoxia on these TAM features, cancer cells were inoculated in prolyl hydroxylase domain 2 (PHD2)-haplodeficient mice, resulting in better-oxygenated tumors. Interestingly, reduced tumor hypoxia did not alter the relative abundance of TAM subsets nor their M2 marker expression, but specifically lowered hypoxia-sensitive gene expression and angiogenic activity in the MHC-IIlo TAM subset. The same observation in PHD2+/+→ PHD2+/− bone marrow chimeras also suggests organization of a better-oxygenized microenvironment. Together, our results show that hypoxia is not a major driver of TAM subset differentiation, but rather specifically fine-tunes the phenotype of M2-like MHC-IIlo TAM. Cancer Res; 74(1); 24–30. ©2013 AACR.
Personal History of Diabetes, Genetic Susceptibility to Diabetes, and Risk of Brain Glioma: A Pooled Analysis of Observational Studies
Authors: Kitahara Cari M. , Linet Martha S. , Brenner Alina V. , Wang Sophia S. , Melin Beatrice S. , Wang Zhaoming , Inskip Peter D. , Freeman Laura E. Beane , Braganza Melissa Z. , Carreón Tania , Feychting Maria , Gaziano J. Michael , Peters Ulrike , Purdue Mark P. , Ruder Avima M. , Sesso Howard D. , Shu Xiao-Ou , Waters Martha A. , White Emily , Zheng Wei , Hoover Robert N. , Fraumeni Joseph F. , Chatterjee Nilanjan , Yeager Meredith , Chanock Stephen J. , Hartge Patricia , Rajaraman Preetha
Published: November 2013

Background: Brain glioma is a relatively rare and fatal malignancy in adulthood with few known risk factors. Some observational studies have reported inverse associations between diabetes and subsequent glioma risk, but possible mechanisms are unclear.

Methods: We conducted a pooled analysis of original data from five nested case–control studies and two case–control studies from the United States and China that included 962 glioma cases and 2,195 controls. We examined self-reported diabetes history in relation to glioma risk, as well as effect modification by seven glioma risk-associated single-nucleotide polymorphisms (SNP). We also examined the associations between 13 diabetes risk-associated SNPs, identified from genome-wide association studies, and glioma risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable-adjusted logistic regression models.

Results: We observed a 42% reduced risk of glioma for individuals with a history of diabetes (OR = 0.58; 95% CI, 0.40–0.84). The association did not differ by sex, study design, or after restricting to glioblastoma, the most common histological subtype. We did not observe any significant per-allele trends among the 13 diabetes-related SNPs examined in relation to glioma risk.

Conclusion: These results support an inverse association between diabetes history and glioma risk. The role of genetic susceptibility to diabetes cannot be excluded, and should be pursued in future studies together with other factors that might be responsible for the diabetes–glioma association.

Impact: These data suggest the need for studies that can evaluate, separately, the association between type 1 and type 2 diabetes and subsequent risk of adult glioma. Cancer Epidemiol Biomarkers Prev; 23(1); 47–54. ©2013 AACR.
Low Levels of Circulating Estrogen Sensitize PTEN-Null Endometrial Tumors to PARP Inhibition In Vivo
Authors: Janzen Deanna M. , Paik Daniel Y. , Rosales Miguel A. , Yep Brian , Cheng Donghui , Witte Owen N. , Kayadibi Huseyin , Ryan Christopher M. , Jung Michael E. , Faull Kym , Memarzadeh Sanaz
Published: November 2013

Earlier in vitro work demonstrated that PARP inhibition induces cell death in PTEN-null endometrial cancer cell lines, but the in vivo therapeutic efficacy of these agents against endometrial cancer remains unknown. Here, we test the efficacy of AZD2281 (olaparib), an oral PARP inhibitor, in the therapy of PTEN-null endometrial tumors in a preclinical endometrial cancer mouse model. Primary endometrial tumors were generated by epithelial loss of PTEN using an in vivo model. This model recapitulates epithelial-specific loss of PTEN seen in human tumors, and histologically resembles endometrioid carcinomas, the predominant subtype of human endometrial cancers. Olaparib was administered orally to tumor-bearing mice in two hormonal extremes: high or low estrogen. Olaparib treatment achieved a significant reduction in tumor size in a low estrogenic milieu. In striking contrast, no response to olaparib was seen in tumors exposed to high levels of estrogen. Two key observations were made when estrogen levels were dropped: (i) the serum concentration of olaparib was significantly increased, resulting in sustained PARP inhibition at the tumor bed; and (ii) the homologous recombination pathway was compromised, as evidenced by decreased Rad51 protein expression and function. These two mechanisms may account for the sensitization of PTEN-null tumors to olaparib with estrogen deprivation. Results of this preclinical trial suggest that orally administered PARP inhibitors in a low estrogenic hormonal milieu can effectively target PTEN-null endometrial tumors. Extension of this work to clinical trials could personalize the therapy of women afflicted with advanced endometrial cancer using well-tolerated orally administered therapeutic agents. Mol Cancer Ther; 12(12); 2917–28. ©2013 AACR.
Comparison of the Outcome of Conventional in vitro Fertilization and Intracytoplasmic Sperm Injection in Moderate Male Infertility from Ejaculate
Authors: Xie Bao-Guo , Huang Yuan-Hua , Zhu Wei-Jie , Jin Song
Published: November 2013

Objective: To evaluate whether couples with moderate male infertility should be treated with conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Patients and Methods: A total of 249 couples with moderate male infertility undergoing their first IVF/ICSI cycle were enrolled in the study. The couples were divided into two groups according to the results of semen analysis: moderate oligozoospermia (O group) and moderate oligoasthenozoospermia (OA group). Sibling oocytes were randomized into groups to be inseminated either by conventional IVF or ICSI. Fertilization rate, embryo quality, implantation rate, and clinical pregnancy rate were examined. Results: There was no difference in the fertilization, implantation, and pregnancy rates between conventional IVF and ICSI in either the O group or OA group (p > 0.05). Additionally, in the OA group, the good quality embryo rate was similar after IVF or ICSI (p > 0.05). However, in the O group, the good quality embryo rate was significantly higher after ICSI than after IVF (p < 0.05). Conclusions: Couples with moderate oligozoospermia or moderate oligoasthenozoospermia did not influence the major indices of IVF. Because of the uncertainties concerning the safety of ICSI, couples with moderate oligozoospermia or moderate oligoasthenozoospermia need not be subjected to this procedure.
Nonmydriatic Ultra-Wide-Field Scanning Laser Ophthalmoscopy (Optomap) versus Two-Field Fundus Photography in Diabetic Retinopathy
Authors: Liegl Raffael , Liegl Kristine , Ceklic Lala , Haritoglou Christos , Kampik Anselm , Ulbig Michael W. , Kernt Marcus , Neubauer Aljoscha S.
Published: November 2013

The purpose of this study was to investigate the diagnostic properties of a 2-laser wavelength nonmydriatic 200° ultra-wide-field scanning laser ophthalmoscope (SLO) versus mydriatic 2-field 45° color fundus photography (EURODIAB standard) for assessing diabetic retinopathy (DR). A total of 143 consecutive eyes of patients with different levels of DR were graded regarding DR level and macular edema based on 2-field color photographs or 1 Optomap Panoramic 200 SLO image. All SLO images were nonmydriatic and all photographs mydriatic. Grading was performed masked to patient and clinical data. Based on photography, 20 eyes had no DR, 44 had mild, 18 moderate and 42 severe nonproliferative DR, and 19 eyes had proliferative DR. Overall correlation for grading DR level compared to Optomap SLO was moderate with kappa 0.54 (p < 0.001), fair-to-moderate in macular edema grading with kappa 0.39 (p < 0.001), and substantial for grading clinically significant macular edema (kappa 0.77). The wide-field SLO offers a wider field of view and can potentially better differentiate lesions by applying the 2 laser wavelengths. However, these advantages over 2-field fundus photography need to be confirmed in further studies.
Two new species of Hemielimaea Brunner von Wattenwyl from China
Authors: WANG YE-YING , MA JIAN-ZHANG , LIU CHUN-XIANG
Published: November 2013

Two new species Hemielimaea (Hemielimaea) paracari sp. nov. and H. (H.) parva sp. nov. from southwestern China are described. Characteristics of the stridulatory file on underside of male left tegmen, male stridulatory area on left and right tegmen, and abdominal apex of male are provided. Important and necessary illustrations of the new species are presented. Materials come from the following two depositories: Institute of Zoology, Chinese Academy of Sciences, Beijing, China (IZCAS), and China Agricultural University, Beijing, China (CAU).
An Investigation of the Connections among Convection, Clouds, and Climate Sensitivity in a Global Climate Model
Authors: Zhao Ming
Published: November 2013

This study explores connections between process-level modeling of convection and global climate model (GCM) simulated clouds and cloud feedback to global warming through a set of perturbed-physics and perturbed sea surface temperature experiments. A bulk diagnostic approach is constructed, and a set of variables is derived and demonstrated to be useful in understanding the simulated relationship. In particular, a novel bulk quantity, the convective precipitation efficiency or equivalently the convective detrainment efficiency, is proposed as a simple measure of the aggregated properties of parameterized convection important to the GCM simulated clouds. As the convective precipitation efficiency increases in the perturbed-physics experiments, both liquid and ice water path decrease, with low and middle cloud fractions diminishing at a faster rate than high cloud fractions. This asymmetry results in a large sensitivity of top-of-atmosphere net cloud radiative forcing to changes in convective precipitation efficiency in this limited set of models.

For global warming experiments, intermodel variations in the response of cloud condensate, low cloud fraction, and total cloud radiative forcing are well explained by model variations in response to total precipitation (or detrainment) efficiency. Despite significant variability, all of the perturbed-physics models produce a sizable increase in precipitation efficiency to warming. A substantial fraction of the increase is due to its convective component, which depends on the parameterization of cumulus mixing and convective microphysical processes. The increase in convective precipitation efficiency and associated change in convective cloud height distribution owing to warming explains the increased cloud feedback and climate sensitivity in recently developed Geophysical Fluid Dynamics Laboratory GCMs. The results imply that a cumulus scheme using fractional removal of condensate for precipitation and inverse calculation of the entrainment rate tends to produce a lower climate sensitivity than a scheme using threshold removal for precipitation and the entrainment rate formulated inversely dependent on convective depth.
Comparing profiles of mental disorder across birth cohorts: Results from the 2007 Australian National Survey of Mental Health and Wellbeing
Authors: Sunderland Matthew , Carragher Natacha , Buchan Heather , Batterham Philip J , Slade Tim
Published: November 2013

Objective:

To describe and compare individuals with any DSM-IV mental disorder from three different birth cohorts – young (16–34 years), middle age (35–59 years) and older age (60–85 years) – on a range of clinically relevant factors.

Method:

Data were derived from the 2007 Australian National Survey of Mental Health and Wellbeing. Individuals from three birth cohorts with a range of mental health and substance use disorders were identified using DSM-IV criteria and compared using regression analysis. The specific factors that were compared include: (1) type of disorder/disorders present; (2) suicidality; (3) number of co-occurring disorders; (4) levels of distress and impairment; (5) self-assessed physical and mental health; (6) presence of physical conditions; (7) size and quality of social support/network; and (8) treatment-seeking behaviour.

Results:

The birth cohorts differed dramatically in terms of the specific disorders that were present. The older cohort were significantly more likely to experience internalising disorders and significantly less likely to experience externalising disorders in comparison to the young cohort. The older cohort were significantly more likely to experience co-morbid physical conditions as well as lower life satisfaction, poorer self-rated physical health, increased functional impairment, and more days out of role. The younger cohort had a significantly larger peer group that they could confide in and rely on in comparison to the older cohort.

Conclusions:

Clinicians and researchers need to be cognisant that mental disorders manifest as highly heterogeneous constructs. The presentation of a disorder in a younger individual could be vastly different from the presentation of the same disorder in an older individual. The additional burden associated with these factors and how they apply to different birth cohorts must be taken into consideration when planning mental health services and effective treatment for the general population.
Identifying the Institutional Effects of Mixed Systems in New Democracies: The Case of Lesotho
Authors: Rich Timothy S , Banerjee Vasabjit , Recker Sterling
Published: November 2013

This paper addresses the effects of the mixed system used for the last three elections in Lesotho (2002, 2007 and 2012), a small African country with a turbulent history regarding opposition acceptance of elections. The decision to implement a mixed system was in part to encourage democratic stability, yet whether the electoral system has become more conducive to democratic competition is unclear. Through an analysis of national and district-level results, this paper addresses the following questions. First, at the district level, is competition consistent with Duverger’s law or the contamination thesis and is a progression over time evident? Second, does the population size of a district influence the number of candidates and the concentration of votes? Finally, following recent research on detecting electoral fraud, this paper tackles whether the reports of district results suggest extra-institutional manipulation.
Model Comparison in Group Decision Making
Authors: Kim Jung-Hyun , Kim Jinhee , Park Hee Sun
Published: November 2013

In some studies based on social identity perspectives, identification with others and conformity to a majority opinion have been indisputable outcomes when individuals involved all look alike. In contrast, another group of studies suggests individuals in a visually deindividuated condition are reluctant to agree with a majority opinion. To investigate such inconsistency, we set up and tested a hypothesized model that compares two processes that provide competing predictions about the effect of uniform visual cue on conformity: the social identification process derived from the social identity model of deindividuation effects (SIDE) and the compensatory nonconformity process derived from optimal distinctiveness theory (ODT). We also investigate how changes in the visual cue conditions affect those two processes. Implications are discussed regarding the comparison of two models and the investigation of conditions under which either process is more or less operant during group interaction.
Moral Intuition
Authors: Weaver Gary R. , Reynolds Scott J. , Brown Michael E.
Published: November 2013

In contrast to older, conventional accounts that treat ethical decision making and behavior as the result of deliberative and intendedly rational processes, a rapidly growing body of social science research has framed ethical thought and behavior as driven by intuition. We review this important new body of knowledge in terms of both the process and content of moral intuition. Then, to demonstrate its value to organizational scholars, we consider the potential impact of moral intuition research in four areas of organizational studies especially suited to insights from this research: leadership, organizational corruption, ethics training and education, and divestiture socialization. Our review and discussion suggest that the literature on moral intuition is incredibly rich, fruitful, and meaningful to a wide range of audiences.
Caregiving Choice and Emotional Stress Among Cancer Caregivers
Authors: Longacre Margaret L. , Ross Eric A. , Fang Carolyn Y.
Published: November 2013

Caring for a relative or friend with cancer may be highly demanding and emotionally burdensome. Theory suggests that personal characteristics of a caregiver may contribute directly to a caregiver’s emotional health. An underexplored variable is a caregiver’s perception of choice in providing care to a relative or friend. Thus, this study sought to characterize perceived choice in providing care among family cancer caregivers and examine its association with emotional stress. This study is a secondary analysis of cross-sectional telephone interviews of 1,247 family caregivers, which included 104 cancer caregivers. The findings indicated that a high majority of cancer caregivers expressed elevated emotional stress. Most caregivers perceived themselves to have had a choice in providing care; however, a perceived lack of choice in providing care was significantly associated with greater emotional stress. Assessing clinical and policy-related strategies for alleviating concerns related to choice may be of value in the cancer context.
Management of a rare gastrobronchial fistula following recurrent pancreatitis
Authors: Nawaz Muhammad Asghar , Dickson Euan , Colquhoun Ian W
Published: November 2013

A 41-year-old male smoker presented with choking and coughing up food associated with repeated vomiting. Four years previously, following recurrent episodes of pancreatitis, he required percutaneous necrosectomy. He subsequently had a cholecystectomy and mesh repair of the abdominal wall, and later developed multiple problems including a gastrobronchial fistula. Computed tomography revealed a fistulous connection for which he had a combined procedure. Through a thoracolaparotomy approach, the left lower lobe and fistulous connection were removed along with the surrounding diaphragm and the associated fundus of the stomach. The diaphragm defect was repaired without mesh.
Workplace Violence Experiences of Homeless Women and Women Residing in Battered Women Shelters
Authors: Anderson Debra Gay , Fallin Amanda , Al-Modallal Hanan
Published: November 2013

Intimate partner violence (IPV) is a pervasive problem that follows victims from the home into the workplace. Many women who experience violence in their homes are also harassed at work and are abused in the workplace. For the current study, 30 women who reported a history of workplace violence were recruited from a homeless women’s shelter. Of the participants, 13 experienced domestic violence in the workplace; this article focuses on the results obtained from those 13 respondents. This article also discusses the link between homelessness, IPV, and workplace violence.
Who Is The Help? Use of Film to Explore Diversity
Authors: Lee Eun-Kyoung Othelia , Priester Mary Ann
Published: November 2013

Helping learners understand the intersectionality of gender, race, and class can be challenging. This study describes the use of the film The Help to stimulate discussion about racism and intersectionality. As evidenced by posttest survey data, the film enabled learners to identify the importance of gender, race/ethnicity, and social class. Qualitative analysis revealed that viewing The Help with a diverse audience can provide a forum to explore multiple concepts associated with intersectionality. This study shows that carefully selected films help remove some barriers to learning cultural competence by creating an environment in which individuals feel safe discussing personal biases.
Human Infants’ Learning of Social Structures
Authors: Mascaro Olivier , Csibra Gergely
Published: November 2013

We tested 15-month-olds’ capacity to represent social-dominance hierarchies with more than two agents. Our results showed that infants found it harder to memorize dominance relations that were presented in an order that hindered the incremental formation of a single structure (Study 1). These results suggest that infants attempt to build structures incrementally, relation by relation, thereby simplifying the complex problem of recognizing a social structure. Infants also found circular dominance structures harder to process than linear dominance structures (Study 2). These expectations about the shape of structures may facilitate learning. Our results suggest that infants attempt to represent social structures composed of social relations. They indicate that human infants go beyond learning about individual social partners and their respective relations and form hypotheses about how social groups are organized.
MBA Students’ Workplace Writing
Authors: Lentz Paula
Published: November 2013

Employers frequently complain about the state of their employees’ writing skills. Much of the current research on this subject explores workplace writing skills from the employer’s perspective. However, this article examines workplace writing from the employees’ perspective. Specifically, it analyzes MBA students’ responses to a course assignment in which they assessed their writing strengths and weaknesses and reflected on opportunities and threats to demonstrating good writing skills in the workplace. Results indicate employers must show that they value good writing and that writing skills must become the employee’s habit. Implications for business communication pedagogy are discussed.
Visual Kei: Hybridity and Gender in Japanese Popular Culture
Authors: McLeod Ken
Published: November 2013

This article examines the Japanese pop music genre of visual kei, a genre marked by emphasis on elaborate visual display often involving cross-dressing of male band members. The genre, in addition, employs a variety of musical styles and influences that speaks to an underlying concept of hybridity in the construction of the visual and sonic image of both practitioners and consumers of the genre. In particular this article analyzes the practice of visual kei from the perspective of the bands and their music, fans of the genre and the relationship of visual kei to other forms of Japanese popular culture that involve androgyny and gender slippage. As such this article theorizes the importance of the concept of ‘hybridity’, as developed in postcolonial studies, to illuminate the liminality of recent Japanese cultural identity formation that is promulgated through visual kei.
Body Talk—Group Specific Talk? A Focus Group Study of Variations in Body Ideals and Body Talk among Norwegian Youth1
Authors: Lundin Kvalem Ingela , Strandbu Åse
Published: November 2013

The study investigates how body ideals are discussed and conceptualized among groups of Norwegian youth. Altogether 48 girls and 15 boys, most aged 17 years, took part in nine focus groups, in order to study subcultural body ideals. Major differences were found between east-end and west-end boys (representing socioeconomic differences), where the former were more concerned about being big. Even though the ideals were more or less the same across the groups, the ways of addressing, conceptualizing and discussing body ideals clearly differed between the groups. The analyses reveal that body talk within peer groups seems to contribute to define adequate levels of effort that should be put into reaching the dominating body ideal.
Stacking wood and staying warm: Time, temporality and housework around domestic heating systems
Authors: Jalas Mikko , Rinkinen Jenny
Published: November 2013

This paper presents a study of the socio-technical ordering of time around wood-fuelled heating systems of detached houses. It analyses the sequences and rhythms that organize the work of domestic heating, its synchronization with other daily activities, and tempo as the subjective experience of time in these activities. The study is based on a large, pre-existing Finnish free-form diary collection. We suggest that domestic energy technologies become useable and useful through the gradual embedding that involves the temporal organization of everyday life. As a result, technologies that organize time are not only convenient in an invisible way but also act as taken-for-granted coordinates and rhythms of human pursuits in everyday life. In many countries, wood-fuelled heating systems remain a common renewable energy technology in detached houses and stand as one option to lower related carbon emissions. However, the broader use of wood is compromised by time and convenience.
Collective memory and autobiographical memory: Similar but not the same
Authors: Schuman Howard , Corning Amy
Published: November 2013

Sociologists and psychologists have independently identified the same general period in individual development for the formation of many memories. Yet the cross-disciplinary similarity is rarely recognized, because most psychologists study autobiographical memories of personal events, while sociologists focus on collective memories of national and world events. We examine autobiographical and collective memories together within a large national cross-section survey of Americans. Both types of memory are located primarily in the same broad period, identified here as ages 5–30 years. However, within that period, autobiographical personal memories as measured by cue-word associations typically refer to earlier ages, while collective memories assessed with a standard open-ended question typically refer to somewhat later ages. Other types of questions yield still other memory content and ages. Reconceptualizing the reminiscence bump or critical period reconciles these diverse results.
Self-Reported Sleep Difficulties and Self-Care Strategies Among Rural Older Adults
Authors: Sandberg Joanne C. , Suerken Cynthia K. , Quandt Sara A. , Altizer Kathryn P. , Bell Ronny A. , Lang Wei , Nguyen Ha T. , Grzywacz Joseph G. , Arcury Thomas A.
Published: November 2013

This study examined the use of self-care strategies to address difficulty sleeping among community-dwelling older adults. Data were collected from a series of 18 questionnaires administered to 195 rural African American and white older adults in North Carolina. Participants reported whether they had experienced difficulty sleeping and strategies used to respond to the symptom. The most widely used strategies included ignoring the symptom, staying in bed or resting, and praying. Herb and supplement use were not reported. Ethnicity, income, and education were associated with use of specific self-care strategies for sleep. This variation suggests that older adults may draw on cultural understandings to interpret the significance of difficulty sleeping and influence their use of self-care strategies, including complementary and alternative medicine use. This information may enable health care providers to communicate with the older patients about sleep difficulty strategies to minimize sleep problems.
Acute lymphoblastic leukemia in children with Down syndrome: a retrospective analysis from the Ponte di Legno study group
Authors: Buitenkamp Trudy D. , Izraeli Shai , Zimmermann Martin , Forestier Erik , Heerema Nyla A. , van den Heuvel-Eibrink Marry M. , Pieters Rob , Korbijn Carin M. , Silverman Lewis B. , Schmiegelow Kjeld , Liang Der-Cheng , Horibe Keizo , Arico Maurizio , Biondi Andrea , Basso Giuseppe , Rabin Karin R. , Schrappe Martin , Cario Gunnar , Mann Georg , Morak Maria , Panzer-Grümayer Renate , Mondelaers Veerle , Lammens Tim , Cavé Hélène , Stark Batia , Ganmore Ithamar , Moorman Anthony V. , Vora Ajay , Hunger Stephen P. , Pui Ching-Hon , Mullighan Charles G. , Manabe Atsushi , Escherich Gabriele , Kowalczyk Jerzy R. , Whitlock James A. , Zwaan C. Michel
Published: November 2013

Key Points

Although the risk of ALL relapse is significantly higher in children with DS, good-prognosis subgroups have been identified. Patients with DS-ALL have higher treatment-related mortality throughout the treatment period independent of the therapeutic regimen.
Replication characteristics of swine influenza viruses in precision-cut lung slices reflect the virulence properties of the viruses
Authors: Meng Fandan , Punyadarsaniya Darsaniya , Uhlenbruck Sabine , Hennig-Pauka Isabel , Schwegmann-Wessels Christel , Ren Xiaofeng , Dürrwald Ralf , Herrler Georg
Published: November 2013

Precision-cut lung slices of pigs were infected with five swine influenza A viruses of different subtypes (A/sw/Potsdam/15/1981 H1N1, A/sw/Bad Griesbach/IDT5604/2006 H1N1, A/sw/Bakum/1832/2000 H1N2, A/sw/Damme/IDT5673/2006 H3N2, A/sw/Herford/IDT5932/2007 H3N2). The viruses were able to infect ciliated and mucus-producing cells. The infection of well-differentiated respiratory epithelial cells by swine influenza A viruses was analyzed with respect to the kinetics of virus release into the supernatant. The highest titres were determined for H3N2/2006 and H3N2/2007 viruses. H1N1/1981 and H1N2/2000 viruses replicated somewhat slower than the H3N2 viruses whereas a H1N1 strain from 2006 multiplied at significantly lower titres than the other strains. Regarding their ability to induce a ciliostatic effect, the two H3N2 strains were found to be most virulent. H1N1/1981 and H1N2/2000 were somewhat less virulent with respect to their effect on ciliary activity. The lowest ciliostatic effect was observed with H1N1/2006. In order to investigate whether this finding is associated with a corresponding virulence in the host, pigs were infected experimentally with H3N2/2006, H1N2/2000, H1N1/1981 and H1N1/2006 viruses. The H1N1/2006 virus was significantly less virulent than the other viruses in pigs which was in agreement with the results obtained by the in vitro-studies. These findings offer the possibility to develop an ex vivo-system that is able to assess virulence of swine influenza A viruses.
Evidence that a tax on sugar sweetened beverages reduces the obesity rate: a meta-analysis
Authors: Cabrera Escobar Maria A , Veerman J Lennert , Tollman Stephen M , Bertram Melanie Y , Hofman Karen J
Published: November 2013

Background

Excess intake of sugar sweetened beverages (SSBs) has been shown to result in weight gain. To address the growing epidemic of obesity, one option is to combine programmes that target individual behaviour change with a fiscal policy such as excise tax on SSBs. This study evaluates the literature on SSB taxes or price increases, and their potential impact on consumption levels, obesity, overweight and body mass index (BMI). The possibility of switching to alternative drinks is also considered.

Methods

The following databases were used: Pubmed/Medline, The Cochrane Database of Systematic Reviews, Google Scholar, Econlit, National Bureau of Economics Research (NBER), Research Papers in Economics (RePEc). Articles published between January 2000 and January 2013, which reported changes in diet or BMI, overweight and/or obesity due to a tax on, or price change of, SSBs were included.

Results

Nine articles met the criteria for the meta-analysis. Six were from the USA and one each from Mexico, Brazil and France. All showed negative own-price elasticity, which means that higher prices are associated with a lower demand for SSBs. Pooled own price-elasticity was -1.299 (95% CI: -1.089 - -1.509). Four articles reported cross-price elasticities, three from the USA and one from Mexico; higher prices for SSBs were associated with an increased demand for alternative beverages such as fruit juice (0.388, 95% CI: 0.009 – 0.767) and milk (0.129, 95% CI: -0.085 – 0.342), and a reduced demand for diet drinks (-0.423, 95% CI: -0.628 - -1.219). Six articles from the USA showed that a higher price could also lead to a decrease in BMI, and decrease the prevalence of overweight and obesity.

Conclusions

Taxing SSBs may reduce obesity. Future research should estimate price elasticities in low- and middle-income countries and identify potential health gains and the wider impact on jobs, monetary savings to the health sector, implementation costs and government revenue. Context-specific cost-effectiveness studies would allow policy makers to weigh these factors.
Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition
Authors: Gelsomino Giada , Corsetto Paola A , Campia Ivana , Montorfano Gigliola , Kopecka Joanna , Castella Barbara , Gazzano Elena , Ghigo Dario , Rizzo Angela M , Riganti Chiara
Published: November 2013

Background

The activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the response to chemotherapy in multidrug resistant (MDR) tumors.

Methods

We studied the effect of omega 3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in human chemosensitive colon cancer HT29 cells and in their MDR counterpart, HT29-dx cells.

Results

MDR cells, which overexpressed Pgp and MRP1, had a dysregulated cholesterol metabolism, due to the lower expression of ubiquitin E3 ligase Trc8: this produced lower ubiquitination rate of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoAR), higher cholesterol synthesis, higher cholesterol content in MDR cells. We found that DHA and EPA re-activated Trc8 E3 ligase in MDR cells, restored the ubiquitination rate of HMGCoAR to levels comparable with chemosensitive cells, reduced the cholesterol synthesis and incorporation in DRMs. Omega 3 PUFAs were incorporated in whole lipids as well as in DRMs of MDR cells, and altered the lipid composition of these compartments. They reduced the amount of Pgp and MRP1 contained in DRMs, decreased the transporters activity, restored the antitumor effects of different chemotherapeutic drugs, restored a proper tumor-immune system recognition in response to chemotherapy in MDR cells.

Conclusions

Our work describes a new biochemical effect of omega 3 PUFAs, which can be useful to overcome chemoresistance in MDR colon cancer cells.
Human immunodeficiency virus type 1 viral protein R (Vpr) induces CCL5 expression in astrocytes via PI3K and MAPK signaling pathways
Authors: Gangwani Mohitkumar R , Noel Richard J , Shah Ankit , Rivera-Amill Vanessa , Kumar Anil
Published: November 2013

Background

Neurocognitive impairments remain prevalent in HIV-1 infected individuals despite current antiretroviral therapies. It is increasingly becoming evident that astrocytes play a critical role in HIV-1 neuropathogenesis through the production of proinflammatory cytokines/chemokines. HIV-1 viral protein R (Vpr) plays an important role in neuronal dysfunction; however, its role in neuroinflammation is not well characterized. The major objective of this study was to determine the effect of Vpr in induction of proinflammatory chemokine CCL5 in astrocytes and to define the underlying mechanism(s).

Methods

SVGA astrocytes were either mock transfected or were transfected with a plasmid encoding HIV-1 Vpr, and the cells were harvested at different time intervals. The mRNA level of CCL5 expression was quantified using real-time RT-PCR, and cell culture supernatants were assayed for CCL5 protein concentration. Immunocytochemistry was performed on HIV-1 Vpr transfected astrocytes to check CCL5 expression. Various signaling mechanisms such as p38 MAPK, PI3K/Akt, NF-κB and AP-1 were explored using specific chemical inhibitors and siRNAs.

Results

HIV-1 Vpr transfected astrocytes exhibited time-dependent induction of CCL5 as compared to mock-transfected astrocytes at both the mRNA and protein level. Immunostained images of astrocytes transfected with HIV-1 Vpr also showed much higher accumulation of CCL5 in comparison to untransfected and mock-transfected astrocytes. Pre-treatment with NF-κB (SC514) and PI3K/Akt (LY294002) inhibitor partially abrogated CCL5 mRNA and protein expression levels as opposed to untreated controls after HIV-1 Vpr transfection. Specific siRNAs against p50 and p65 subunits of NF-κB, p38δ MAPK, Akt-2 and Akt-3, and AP-1 transcription factor substantially inhibited the production of CCL5 in HIV-1 Vpr transfected astrocytes.

Conclusion

These results demonstrate the ability of HIV-1 Vpr to induce CCL5 in astrocytes in a time-dependent manner. Furthermore, this effect was observed to be mediated by transcription factors NF-κB and AP-1 and involved the p38-MAPK and PI3K/Akt pathway.
Phenotypic expression of the p.Leu1077Pro CFTR mutation in Sicilian cystic fibrosis patients
Authors: Parisi Giuseppe Fabio , Cutello Silvia , Di Dio Giovanna , Rotolo Novella , La Rosa Mario , Leonardi Salvatore
Published: November 2013

Background

The p.Leu1077Pro CFTR mutation was firstly described in 1992 as a mild allele that confers a pancreatic sufficiency phenotype but the information collected in database CFTR2 lead to consider p.Leu1077Pro as a severe CF mutation. Although it is typical of Southern Italy, p.Leu1077Pro is not included in the mutation panel firstly tested in individuals originated from this area. The aim of our study was to describe prevalence and clinical features in patients bearing this mutation followed in our Cystic Fibrosis Centre to demonstrate that this mutation should be included in the mutation panel firstly tested in patients originated from Southern Italy.

Findings

We reviewed data from a cohort of 111 cystic fibrosis patients. 4 patients who were heterozygous for the p.Leu1077Pro mutation were included in the study.

In our Cystic Fibrosis Centre, the prevalence of p.Leu1077Pro is 3.6% among all mutations. All patients had positive sweat test values, pancreatic insufficiency and pulmonary exacerbations. One out of four patients even showed both FEV1 and FVC values significantly below the normal range, the presence of bronchiectasis and chronic Pseudomonas aeruginosa colonization.

Conclusions

We found that the p.Leu1077Pro CFTR mutation is associated with a classic CF phenotype confirming what is reported in CFTR2 database. The relatively high prevalence of p.Leu1077Pro associated with the severe clinical course of the disease in patients bearing this mutation is of interest for genetic counselling purposes, as it should be part of mutation panel to be tested in individuals originated from Southern Italy.
Epstein-Barr Virus encoded LMP1 regulates cyclin D1 promoter activity by nuclear EGFR and STAT3 in CNE1 cells
Authors: Xu Yang , Shi Ying , Yuan Qi , Liu Xuli , Yan Bin , Chen Ling , Tao Yongguang , Cao Ya
Published: November 2013

The principal Epstein–Barr virus (EBV) oncoprotein, latent membrane protein 1 (LMP1) is strongly associated with nasopharyngeal carcinoma (NPC), a prevalent cancer in China. The epidermal growth factor receptor (EGFR) is important in carcinogenesis, as it is a ubiquitously expressed receptor tyrosine kinase. Signal transducer and activator of transcription 3 (STAT3) is a master transcriptional regulator in proliferation and apoptosis. Our previous study demonstrated that the nuclear EGFR could bind to the cyclin D1 promoter directly in the presence of LMP1, and the correlation between EGFR and STAT3 in NPC remains to be further explored. Here, we have shown that the interaction of EGFR and STAT3 increased in the nucleus in the presence of LMP1. LMP1 promoted both EGFR and STAT3 binding to the promoter region of cyclin D1, in turn, enhancing the promoter activity of cyclin D1. Furthermore, we demonstrated that both transcriptional activity and mRNA levels of cyclin D1 were decreased by small molecule interference of EGFR and STAT3 activity. These findings may provide a novel linkage between the EGFR and STAT3 signaling pathways and the activation of cyclin D1 by LMP1 in the carcinogenesis of NPC.
Hand hygiene monitoring technology: protocol for a systematic review
Authors: Srigley Jocelyn A , Lightfoot David , Fernie Geoff , Gardam Michael , Muller Matthew P
Published: November 2013

Background

Healthcare worker hand hygiene is thought to be one of the most important strategies to prevent healthcare-associated infections, but compliance is generally poor. Hand hygiene improvement interventions must include audits of compliance (almost always with feedback), which are most often done by direct observation - a method that is expensive, subjective, and prone to bias. New technologies, including electronic and video hand hygiene monitoring systems, have the potential to provide continuous and objective monitoring of hand hygiene, regular feedback, and for some systems, real-time reminders. We propose a systematic review of the evidence supporting the effectiveness of these systems. The primary objective is to determine whether hand hygiene monitoring systems yield sustainable improvements in hand hygiene compliance when compared to usual care.

Methods/Design

MEDLINE, EMBASE, CINAHL, and other relevant databases will be searched for randomized control studies and quasi-experimental studies evaluating a video or electronic hand hygiene monitoring system. A standard data collection form will be used to abstract relevant information from included studies. Bias will be assessed using the Cochrane Effective Practice and Organization of Care Group Risk of Bias Assessment Tool. Studies will be reviewed independently by two reviewers, with disputes resolved by a third reviewer. The primary outcome is directly observed hand hygiene compliance. Secondary outcomes include healthcare-associated infection incidence and improvements in hand hygiene compliance as measured by alternative metrics. Results will be qualitatively summarized with comparisons made between study quality, the measured outcome, and study-specific factors that may be expected to affect outcome (for example, study duration, frequency of feedback, use of real-time reminders). Meta-analysis will be performed if there is more than one study of similar systems with comparable outcome definitions.

Discussion

Electronic and video monitoring systems have the potential to improve hand hygiene compliance and prevent healthcare-associated infection, but are expensive, difficult to install and maintain, and may not be accepted by all healthcare workers. This review will assess the current evidence of effectiveness of these systems before their widespread adoption.

Study registration

PROSPERO registration number: CRD42013004519
The Importance of Compressed Straw Fuel in Rural China: Taking Henan Province as an Example
Authors: Jun-Hong Liu , Jun-He Zhang , Fu-Mei Wang , Rui-Fang Liu
Published: November 2013

By questionnaire survey, the writers investigated the application of compressed straw fuel in Shuangmiao Village, Nan yang City in Henan Province. From the information obtained, effects of compressed straw fuel on farmers were analyzed. It was concluded that compressed straw fuel took the place of straw as well as coal. Switching to compressed straw fuel not only contributed to farmers' health and quality of life, but also benefited rural energy structure and the environment. We expect that the use of compressed straw fuel will play a more important role in the further improvement of life in China's rural areas.
How Should Developing Countries Cope with Pollution-Migration? An Extended Model of North-South Trade and its Numerical Simulation
Authors: Song Malin , Wang Shuhong
Published: November 2013

In recent years, with rapidly growing world trade and increasingly stricter environmental controls in developed countries, some enterprises have transferred heavily polluting plants to developing countries where environmental controls are more relaxed. This kind of pollution-“migration” is therefore threatening the environment of some developing or rather “emerging” countries. How to achieve a balance between economic development and environmental protection has already become an important issue that needs to be handled appropriately by developing countries when actively engaging in industrial migration. This paper extends the North-South trade model by introducing environmental pollution taxation to make an in-depth analysis. The calculation of the model leads to the conclusion that motivation of polluting companies in developed countries decreases when transferring to developing countries with a rising environmental pollution tax. Through numerical simulation, this paper finds the minimum environmental pollution tax rate that is likely to prevent industrial migration. When the tax is lower than this, pollution migration would not be stop; and if the tax is too high, it will hurt the economic development of developing countries. Hence, the minimum environmental pollution tax is the optimal tax rate for balanced development.
3D Impulse Response Measurements of Spaces Using an Inexpensive Microphone Array
Authors: Protheroe Daniel , Guillemin Bernard
Published: November 2013

The acoustical characteristics of a room are traditionally determined using omnidirectional impulse response measurements, yielding information about sound reflections in terms of magnitude and time, but not direction. However, the direction of reflections is often important, and thus the need for a practical, low cost measurement system for determining this. In this paper we present the performance of a low cost measurement system utilising an inexpensive microphone array, namely the Core Sound TetraMic, for the determination of 3D room impulse responses. These can then be visualised, for example, as a “hedgehog pattern”. Experiments undertaken in an anechoic chamber indicate that the accuracy of directional estimation of this system is in the region of ±7.5°.