bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘Clinically definite benign multiple sclerosis’, an unwarranted conceptual hodgepodge: evidence from a 30-year observational study
Authors: Leray E , Coustans M , Le Page E , Yaouanq J , Oger J , Edan G 
Published: August 2012

Background: Benign multiple sclerosis (BMS) is a controversial concept which is still debated. However identification of this kind of patients is crucial to prevent them from unnecessary exposure to aggressive and/or long term medical treatments. Objectives: To assess two definitions of ‘clinically definite benign multiple sclerosis’ (CDBMS) using long-term follow-up data, and to look for prognostic factors of CDBMS. Methods: In 874 patients with definite relapsing–remitting MS, followed up for at least 10 years, disability was assessed using the Disability Status Scale (DSS). CDBMS was defined by either DSS score≤2 (CDBMS1 group) or DSS score≤ 3 (CDBMS2 group) at 10 years. We estimated the proportion of patients who were still benign at 20 and 30 years after clinical onset. Results: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1 and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252) of cases were still benign 10 years later, and 41.1% (23/56) after an additional decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the CDBMS2 group. Conclusions: This 30-year observational study, which is one of the largest published series, indicates that favourable 10-year disability scores of DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After every decade almost half of the CDBMS were no longer benign. CDBMS, as currently defined, is an unwarranted conceptual hodgepodge. Other criteria using new biomarkers (genetic, biologic or MRI) should be found to detect benign cases of MS.
Locative journalism: Designing a location-dependent news medium for smartphones
Authors: Nyre Lars , Bjørnestad Solveig , Tessem Bjørnar , Øie Kjetil Vaage 
Published: August 2012

This article provides an account of the tensions between locative context-awareness and the act of writing journalistic copy for a mobile application. Based on the field trials of the interdisciplinary LocaNews project, the article discusses locative media’s potential for spatially sensitive news journalism. In 2009 researchers in Norway made a medium design called LocaNews, and tested it out with pre-planned procedures for the two fundamental activities: production and reception. Of those who participated, 12 people worked as journalists, editors, technicians, and they generated 93 journalistic stories that were read and watched by 32 test-users who were interviewed. The present article deals with findings regarding the production of news content, and presents the strategies used to reinterpret the traditional news criteria of journalism to be fit for a GPS-equipped smartphone. First, the article discusses the connection between journalism and cartography, and then introduces the experimental method used for this research. The bulk of the article consists of an evaluation of the experimental attempt at practising location-dependent journalism. It deals with four issues: putting stories on the map, the characteristics of ‘zoom in stories’, the construction of an implied position for the readers, and finally the formulation of news criteria that focus on spatial proximity instead of temporal actuality.
Polyfunctional CD4+ T cells are essential for eradicating advanced B-cell lymphoma after chemotherapy
Authors: Ding Zhi-Chun , Huang Lei , Blazar Bruce R. , Yagita Hideo , Mellor Andrew L. , Munn David H. , Zhou Gang 
Published: August 2012

AbstractThe finding that many chemotherapeutic agents have immunostimulatory effects has provided the impetus to combine chemotherapy and immunotherapy for synergistic antitumor effects. However, the critical determinants of effective antitumor immunity after chemotherapy have not been defined. Here we report that adoptive transfer of tumor-specific CD4+ T cells after chemotherapy with cyclophosphamide gave rise to polyfunctional CD4+ effector cells, which in turn intensified the inflammatory milieu and enhanced the activation of CD8+ T cells in the tumor microenvironment. Although this combined chemoimmunotherapy initially resulted in progressive regression of advanced B-cell lymphoma, its therapeutic efficacy was not durable and most mice succumbed to late relapse. Notably, relapse was associated with acquisition of a tolerized phenotype in tumor-specific CD4+ T cells, characterized by overexpression of program death-1 (PD-1). Remarkably, effective antitumor immunity was maintained and cure became prevalent when polyfunctional CD4+ effector cells were prevented from undergoing PD-1–mediated tolerization, either by antibody blockade of the PD-1–PD-L1 pathway, or targeted ablation of PD-1 in tumor-specific CD4+ T cells. Our study suggests that tumor-reactive CD4+ T cells act as the “gatekeepers” of the host antitumor immunity in the postchemotherapy setting, thereby their functional status governs the choice between eradication versus regrowth of residual tumors.
Regulation of PUMA induced by mechanical stress in rat cardiomyocytes
Authors: Cheng Wen-Pin , Wu Gong-Jhe , Wang Bao-Wei , Shyu Kou-Gi 
Published: August 2012

Abstract

Background
PUMA (p53-up-regulated modulator of apoptosis), an apoptosis regulated gene, increased during endoplasmic reticulum stress. However, the expression of PUMA in cardiomyocytes under mechanical stress is little known. We aimed to investigate the regulation mechanism of PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes.

Methods
Aorta-caval (AV) shunt was performed in adult Wistar rats to induce volume overload. Rat neonatal cardiomyocytes were stretched by vacuum to 20% of maximum elongation at 60 cycles/min.

Results
PUMA protein and mRNA were up-regulated in the shunt group as compared with sham group. The increased PUMA protein expression and apoptosis induced by shunt was reversed by treatment with atorvastatin at 30 mg/kg/ day orally for 7 days. TUNEL assay showed that treatment with atorvastatin inhibited the apoptosis induced by volume overload. Cyclic stretch significantly enhanced PUMA protein and gene expression. Addition of c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and interferon-γ (INF-γ) antibody 30 min before stretch reduced the induction of PUMA protein. Gel shift assay demonstrated that stretch increased the DNA binding activity of interferon regulatory factor-1. Stretch increased, while PUMA-Mut plasmid, SP600125 and INF-γ antibody abolished the PUMA promoter activity induced by stretch. PUMA mediated apoptosis induced by stretch was reversed by PUMA siRNA and atorvastatin.

Conclusions
Mechanical stress enhanced apoptosis and PUMA expression in cardiomyocytes. Treatment with atorvastatin reversed both PUMA expression and apoptosis induced by mechanical stress in cardiomyocytes.
Exploring metazoan evolution through dynamic and holistic changes in protein families and domains
Authors: Wang Zhengyuan , Zarlenga Dante , Martin John , Abubucker Sahar , Mitreva Makedonka 
Published: August 2012

Abstract

Background
Proteins convey the majority of biochemical and cellular activities in organisms. Over the course of evolution, proteins undergo normal sequence mutations as well as large scale mutations involving domain duplication and/or domain shuffling. These events result in the generation of new proteins and protein families. Processes that affect proteome evolution drive species diversity and adaptation. Herein, change over the course of metazoan evolution, as defined by birth/death and duplication/deletion events within protein families and domains, was examined using the proteomes of 9 metazoan and two outgroup species.

Results
In studying members of the three major metazoan groups, the vertebrates, arthropods, and nematodes, we found that the number of protein families increased at the majority of lineages over the course of metazoan evolution where the magnitude of these increases was greatest at the lineages leading to mammals. In contrast, the number of protein domains decreased at most lineages and at all terminal lineages. This resulted in a weak correlation between protein family birth and domain birth; however, the correlation between domain birth and domain member duplication was quite strong. These data suggest that domain birth and protein family birth occur via different mechanisms, and that domain shuffling plays a role in the formation of protein families. The ratio of protein family birth to protein domain birth (domain shuffling index) suggests that shuffling had a more demonstrable effect on protein families in nematodes and arthropods than in vertebrates. Through the contrast of high and low domain shuffling indices at the lineages of Trichinella spiralis and Gallus gallus, we propose a link between protein redundancy and evolutionary changes controlled by domain shuffling; however, the speed of adaptation among the different lineages was relatively invariant. Evaluating the functions of protein families that appeared or disappeared at the last common ancestors (LCAs) of the three metazoan clades supports a correlation with organism adaptation. Furthermore, bursts of new protein families and domains in the LCAs of metazoans and vertebrates are consistent with whole genome duplications.

Conclusion
Metazoan speciation and adaptation were explored by birth/death and duplication/deletion events among protein families and domains. Our results provide insights into protein evolution and its bearing on metazoan evolution.
Predicting waist circumference from body mass index
Authors: Bozeman Samuel R , Hoaglin David C , Burton Tanya M , Pashos Chris L , Ben-Joseph Rami H , Hollenbeak Christopher S 
Published: August 2012

Abstract

Background
Being overweight or obese increases risk for cardiometabolic disorders. Although both body mass index (BMI) and waist circumference (WC) measure the level of overweight and obesity, WC may be more important because of its closer relationship to total body fat. Because WC is typically not assessed in clinical practice, this study sought to develop and verify a model to predict WC from BMI and demographic data, and to use the predicted WC to assess cardiometabolic risk.

Methods
Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES) and the Atherosclerosis Risk in Communities Study (ARIC). We developed linear regression models for men and women using NHANES data, fitting waist circumference as a function of BMI. For validation, those regressions were applied to ARIC data, assigning a predicted WC to each individual. We used the predicted WC to assess abdominal obesity and cardiometabolic risk.

Results
The model correctly classified 88.4% of NHANES subjects with respect to abdominal obesity. Median differences between actual and predicted WC were − 0.07 cm for men and 0.11 cm for women. In ARIC, the model closely estimated the observed WC (median difference: − 0.34 cm for men, +3.94 cm for women), correctly classifying 86.1% of ARIC subjects with respect to abdominal obesity and 91.5% to 99.5% as to cardiometabolic risk.
The model is generalizable to Caucasian and African-American adult populations because it was constructed from data on a large, population-based sample of men and women in the United States, and then validated in a population with a larger representation of African-Americans.

Conclusions
The model accurately estimates WC and identifies cardiometabolic risk. It should be useful for health care practitioners and public health officials who wish to identify individuals and populations at risk for cardiometabolic disease when WC data are unavailable.
An exploratory study of the variables impacting preterm birth rates in New Mexico
Authors: Gwin Kara M , Schrader Ronald , Peters Kimberley , Moreno Armida , Thiel Kristina W , Leslie Kimberly K 
Published: August 2012

Abstract

Background
Preterm birth (PTB) is a substantial health problem that accounts for significant infant morbidity and mortality and poses an economic burden to both individuals and the state of residence. The goal of this study was to identify maternal risk factors for PTB in New Mexico, a poor state with a unique ethnic background, in order to identify populations at increased risk that would benefit from intervention.

Methods
This was a cross-sectional retrospective exploratory analysis of 377,770 singleton live births in the state of New Mexico from 1991-2005. Gestational age of less than 37 weeks was defined as PTB. The Kotelchuck Index was used as a measure for level of prenatal care described as inadequate, intermediate, adequate, and intensive.

Results
Of the live births analyzed, 28,036 of these were preterm (7.4%). Overall the PTB rate rose at a rate of 0.18% per year from 1991-2005. Among patients with medical risk factors, the absence of prenatal care was associated with higher odds for PTB as compared to adequate prenatal care. Other risk factors were unmarried status, education less than high school, tobacco/alcohol use, black, Asian, and white Hispanic ethnicity, and the presence of one or more medical risk factors. Statistically significant protective factors for PTB were age 25-29, education surpassing high school, and Native American race.

Conclusions
This study identified several factors that correlate with increased PTB in New Mexico, in particular ethnicity and level of prenatal care. The finding that Native American patients have a lower PTB rate compared to other groups, even though this group is traditionally one of low socioeconomic status in New Mexico, signifies that other factors yet to be identified affect PTB.
Generation of a new bioluminescent model for visualisation of mammary tumour development in transgenic mice
Authors: Zagozdzon Agnieszka M , O’Leary Patrick , Callanan John J , Crown John , Gallagher William M , Zagozdzon Radoslaw 
Published: August 2012

Abstract

Background
Numerous transgenic models have been generated to study breast cancer. However, despite many advantages, traditional transgenic models for breast cancer are also burdened with difficulties in early detection and longitudinal observation of transgene-induced tumours, which in most cases are randomly located and occur at various time points. Methods such as palpation followed by mechanical measurement of the tumours are of limited value in transgenic models. There is a crucial need for making these previously generated models suitable for modern methods of tumour visualisation and monitoring, e.g. by bioluminescence-based techniques. This approach was successfully used in the current study.

Results
A new mouse strain (MMTV-Luc2 mice) expressing Luc2 luciferase primarily in mammary tissue in females, with low-level background expression in internal organs, was generated and bred to homozygosity. After these mice were intercrossed with MMTV-PyVT mice, all double transgenic females developed mammary tumours by the age of 10 weeks, the localisation and progression of which could be effectively monitored using the luminescence-based
in vivo
imaging. Luminescence-based readout allowed for early visualisation of the locally overgrown mammary tissue and for longitudinal evaluation of local progression of the tumours. When sampled
ex vivo
at the age of 10 weeks, all tumours derived from MMTV-Luc2PyVT females displayed robust bioluminescent signal.

Conclusions
We have created a novel transgenic strain for visualisation and longitudinal monitoring of mammary tumour development in transgenic mice as an addition and/or a new and more advanced alternative to manual methods. Generation of this mouse strain is vital for making many of the existing mammary tumour transgenic models applicable for
in vivo
imaging techniques.
Ultra high risk of psychosis on committal to a young offender prison: an unrecognised opportunity for early intervention
Authors: Flynn Darran , Smith Damian , Quirke Luke , Monks Stephen , Kennedy Harry G 
Published: August 2012

Abstract

Background
The ultra high risk state for psychosis has not been studied in young offender populations. Prison populations have higher rates of psychiatric morbidity and substance use disorders. Due to the age profile of young offenders one would expect to find a high prevalence of individuals with pre-psychotic or ultra-high risk mental states for psychosis (UHR). Accordingly young offender institutions offer an opportunity for early interventions which could result in improved long term mental health, social and legal outcomes. In the course of establishing a mental health in-reach service into Ireland’s only young offender prison, we sought to estimate unmet mental health needs.

Methods
Every third new committal to a young offenders prison was interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to identify the Ultra High Risk (UHR) state and a structured interview for assessing drug and alcohol misuse according to DSM-IV-TR criteria, the Developmental Understanding of Drug Misuse and Dependence - Short Form (DUNDRUM-S).

Results
Over a twelve month period 171 young male offenders aged 16 to 20 were assessed. Of these 39 (23%, 95% confidence interval 18% to 30%) met UHR criteria. UHR states peaked at 18 years, were associated with lower SOFAS scores for social and occupational function and were also associated with multiple substance misuse. The relationship with lower SOFAS scores persisted even when co-varying for multiple substance misuse.

Conclusions
Although psychotic symptoms are common in community samples of children and adolescents, the prevalence of the UHR state in young offenders was higher than reported for community samples. The association with impaired function also suggests that this may be part of a developing disorder. Much more attention should be paid to the relationship of UHR states to substance misuse and to the health needs of young offenders.
Development of an efficient, non-viral transfection method for studying gene function and bone growth in human primary cranial suture mesenchymal cells reveals that the cells respond to BMP2 and BMP3
Authors: Dwivedi Prem P , Anderson Peter J , Powell Barry C 
Published: August 2012

Abstract

Background
Achieving efficient introduction of plasmid DNA into primary cultures of mammalian cells is a common problem in biomedical research. Human primary cranial suture cells are derived from the connective mesenchymal tissue between the bone forming regions at the edges of the calvarial plates of the skull. Typically they are referred to as suture mesenchymal cells and are a heterogeneous population responsible for driving the rapid skull growth that occurs in utero and postnatally. To better understand the molecular mechanisms involved in skull growth, and in abnormal growth conditions, such as craniosynostosis, caused by premature bony fusion, it is essential to be able to easily introduce genes into primary bone forming cells to study their function.

Results
A comparison of several lipid-based techniques with two electroporation-based techniques demonstrated that the electroporation method known as nucleofection produced the best transfection efficiency. The parameters of nucleofection, including cell number, amount of DNA and nucleofection program, were optimized for transfection efficiency and cell survival. Two different genes and two promoter reporter vectors were used to validate the nucleofection method and the responses of human primary suture mesenchymal cells by fluorescence microscopy, RT-PCR and the dual luciferase assay. Quantification of bone morphogenetic protein (BMP) signalling using luciferase reporters demonstrated robust responses of the cells to both osteogenic BMP2 and to the anti-osteogenic BMP3.

Conclusions
A nucleofection protocol has been developed that provides a simple and efficient, non-viral alternative method for in vitro studies of gene and protein function in human skull growth. Human primary suture mesenchymal cells exhibit robust responses to BMP2 and BMP3, and thus nucleofection can be a valuable method for studying the potential competing action of these two bone growth factors in a model system of cranial bone growth.
Primary synovial sarcoma of the parapharyngeal space: a clinicopathologic study of five cases
Authors: Zhu Ming , Li Jun , Wang Ke-Jing , Shang Jin-Biao 
Published: August 2012

Abstract
We report five cases of primary synovial sarcomas arising in the parapharyngeal space. The patients were all men with a median age of 35 years (range 22 to 41 years). The tumors were non-encapsulated solid masses ranging from 2.0 to 6.6 cm in size. Histologically, three cases were biphasic subtype, and the other two cases were monophasic subtype. Immunohistochemically, the tumor cells were strongly positive for bcl-2 and CD99, partly positive for CK and EMA, and negative for CD117, CD34, SMA and desmin in all five cases. S-100 protein was detected in one case. The presence of an SYT–SSX1 and/or SYT-SSX2 gene fusion resulting from t(X;18) was demonstrated from paraffin blocks by reverse transcriptase polymerase chain reaction in five cases. All five patients received tumor radical excision and postoperative radiotherapy, and two patients with pulmonary metastasis received additional chemotherapy. Follow-up data revealed that two patients with tumor size <5 cm were alive without disease for 54 and 57 months, one patient with tumor size <5 cm was alive with pulmonary metastasis for 78 months, and two patients with tumor size >5 cm died of disease 26 and 37 months after the diagnosis, respectively. Primary parapharyngeal synovial sarcoma is a rare variant that occurs more frequently in males than females. Accurate diagnosis depends on morphologic and immunohistochemical examination and proper molecular analysis. The prognosis is relatively good in those patients whose tumor size is less than 5 cm.