bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient relaxed search in hierarchically clustered sequence datasets
Authors: Bader Kai C. , Atallah Mikhail J. , Grothoff Christian 
Published: October 2012

This article presents a new algorithm for finding oligonucleotide signatures that are specific and sensitive for organisms or groups of organisms in large-scale sequence datasets. We assume that the organisms have been organized in a hierarchy, for example, a phylogenetic tree. The resulting signatures, binding sites for primers and probes, match the maximum possible number of organisms in the target group while having at most
k
matches outside of the target group.

The key step in the algorithm is the use of the lowest common ancestor (LCA) to search the organism hierarchy; this allows the combinatorial problem in almost linear time (empirically observed) to be solved. The presented algorithm improves performance by several orders of magnitude in terms of both memory consumption and runtime when compared to the best-known previous algorithms while giving identical, exact solutions.
This article gives a formal description of the algorithm, discusses details of our concrete, publicly available implementation, and presents the results from our performance evaluation.
A new paradigm for the development of future medical software systems
Authors: Meixner Gerrit , Zuehlke Detlef 
Published: October 2012

In many areas of human life, computer-based Information Technology (IT) has prevailed and become essential for the coordinated and efficient organization of workflows. Especially in the field of health care, interaction between human beings and IT is a sensitive subject. Inevitably, people working in the field of health care will have to make use of the potentials of IT in order to meet the enormous demands on e.g. patient management. When we look at the situation of current medical software systems, we can find major advances in the performance capacities of modern software systems, but must also note their rapid penetration into almost every facet of the daily hospital routine. Today medical software systems can be characterized as a vast number of (networked) software which each fulfills specific functions (e.g., hospital information system, Picture Archiving and Communication System) and which is used by different user groups (e.g., physicians, nurses, medical secretaries) with diverse user tasks [4]. Yet, for almost two decades, graphical user interfaces have dominated the interaction of medical software systems in most cases. In the future, a broader range of paradigms will emerge, allowing for multi-modal interaction. But also the growing number of heterogeneous platforms (operating systems, graphical libraries) and devices utilized complementarily (e.g., PC, Toughbook, Smartphone, PDA) demand for the development of congeneric user interfaces for a plethora of target platforms. Especially "mobile healthcare computing devices (MHCDs) are rapidly becoming an integral part of hospital information systems. Deployment of these devices is becoming an important IT strategy designed to assist in improving quality of care, enhancing patient services, increasing productivity, lowering costs, improving cash flow, as well as facilitating other critical delivery processes" [3]. For MHCDs aspects like getting the right information at the right time in the right place (context sensitivity) is important.
To be able to cope with requirements like interoperability, context-sensitivity and device-independent usage a model-based approach for the development of user interfaces (MBUID) appears to be favourable [2].
Distinctive Features of the Differentiated Phenotype and Infiltration of Tumor-Reactive Lymphocytes in Clear Cell Renal Cell Carcinoma
Authors: Wang Qiong J. , Hanada Ken-ichi , Robbins Paul F. , Li Yong F. , Yang James C. 
Published: October 2012

AbstractClear cell renal cell carcinoma (RCC) is considered an immunogenic tumor, but it has been difficult to identify tumor-infiltrating lymphocytes (TIL) that show in vitro tumor recognition. We compared the characteristics of fresh RCC TIL to peripheral blood lymphocytes (PBL) or melanoma TIL. Our results showed that RCC TIL contained fewer CD27+ T cells, and fewer naïve and central memory (CM) T cells, but more effector memory (EM) T cells than melanoma TIL or renal PBL. We hypothesized that factors in the RCC microenvironment were skewing TIL phenotype toward EM. One possibility was the expression of CD70 on nearly all human RCCs, but not melanomas. Differentiation of naïve T cells to EM cells only occurred from CD70 costimulation in concert with T-cell receptor (TCR) stimulation (signal one), suggesting that EM TIL responding to CD70 would be enriched for T cells reactive with local antigens, including those associated with RCC. Clonotypic analysis of TCRs in fresh RCCs showed that EM T cells were more clonally expanded than CM or naïve T cells, and the clonal expansion occurred at the tumor site as oligoclonal TCRs were distinct from PBL TCRs from the same patient. In addition, we found that 2 TCRs from the highly represented EM TIL clones, when reexpressed in fresh PBL, recognized an MHC-class II or MHC-class I–restricted antigens shared by multiple RCC lines. Our results suggest that RCC-reactive TIL do exist in situ, but may be difficult to recover and study because of proliferative exhaustion, driven by tumor-expressed CD70. Cancer Res; 72(23); 6119–29. ©2012 AACR.
Expression of Wnt3 Activates Wnt/β-Catenin Pathway and Promotes EMT-like Phenotype in Trastuzumab-Resistant HER2-Overexpressing Breast Cancer Cells
Authors: Wu Yanyuan , Ginther Charles , Kim Juri , Mosher Nicole , Chung Seyung , Slamon Dennis , Vadgama Jaydutt V. 
Published: October 2012

Abstract
To understand the mechanisms leading to trastuzumab resistance in HER2-overexpressing breast tumors, we created trastuzumab-insensitive cell lines (SKBR3/100-8 and BT474/100-2). The cell lines maintain HER2 receptor overexpression and show increase in EGF receptor (EGFR). Upon trastuzumab treatment, SKBR3/100-8 and BT474/100-2 cell lines displayed increased growth rate and invasiveness. The trastuzumab resistance in SKBR3/100-8 and BT474/100-2 was accompanied with activation of the Wnt/β-catenin signaling pathway. Further investigation found that Wnt3 overexpression played a key role toward the development of trastuzumab resistance. The expression of Wnt3 in trastuzumab-resistant cells increased nuclear expression of β-catenin and transactivated expression of EGFR. The increased Wnt3 in the trastuzumab-resistant cells also promoted a partial EMT-like transition (epithelial-to-mesenchymal transition); increased N-cadherin, Twist, Slug; and decreased E-cadherin. Knockdown of Wnt3 by siRNA restored cytoplasmic expression of β-catenin and decreased EGFR expression in trastuzumab-resistant cells. Furthermore, the EMT markers were decreased, E-cadherin was increased, and the cell invasiveness was inhibited in response to the Wnt3 downregulation. Conversely, SKBR3 cells which had been stably transfected with full-length Wnt3 exhibited EMT-like transition. The Wnt3 transfectants, SKBR3/Wnt3-7 and SKBR3/Wnt3-9, showed a significant decrease in E-cadherin and increase in N-cadherin, Twist, and Slug. The cells were less sensitive to trastuzumab than parental SKBR3 and vector-transfected cells. In summary, our data suggest that Wnt3 overexpression activates Wnt/β-catenin signaling pathway that leads to transactivation of EGFR and promotes EMT-like transition. This could be an important mechanism leading to trastuzumab resistance in HER2-overexpressing breast cancer cells. Mol Cancer Res; 10(12); 1597–606. ©2012 AACR.
Viewpoint: Reversible nature of platelet binding causing transfusion-related acute lung injury (TRALI) syndrome may explain dyspnea after ticagrelor and elinogrel
Authors: Serebruany Victor 
Published: October 2012

SummaryThere may be a universal mechanism explaining dyspnea after ticagrelor and elinogrel, namely, transfusion-related acute lung injury (TRALI). Indeed, recent clinical trials with ticagrelor (DISPERSE, DISPERSE-II, and PLATO), and elinogrel (INNOVATE PCI) revealed double-digit rates of dyspnea after novel reversible antiplatelet agents. In contrast, dyspnea is not associated with conventional non-reversible agents such as aspirin, or thienopyridines (ticlopidine, clopidogrel, or prasugrel) suggesting distinct mechanism of shortness of breath after ticagrelor and elinogrel. The adenosine hypothesis has been offered to explain such adverse association. However, despite obvious similarity between ticagrelor and adenosine molecules, the chemical structure of elinogrel is entirely different. In fact, ticagrelor is a cyclopentyl-triazolo-pyrimidine, while elinogrel is a quinazolinedione. Since both agents cause dyspnea, the adenosine hypothesis is no longer valid. In contrast, the reversible nature of platelet inhibition attributable to both ticagrelor and elinogrel causing premature cell ageing, apoptosis, impaired turnover due to sequestration of overloaded, exhausted platelets in the pulmonary circulation are among potential autoimmune mechanism(s) resulting in the development of a TRALI-like reaction, and frequent dyspnea. Despite expected benefit for better bleeding control, further development of reversible antithrombins is severely limited due to the existence of a potentially universal serious adverse event, such as TRALI-syndrome with dyspnea as a predominant clinical manifestation. Since TRALI is an established number one contributor to mortality after blood transfusions, ticagrelor death “benefit”in PLATO is challenged further.
Why does ticagrelor induce dyspnea?
Authors: Faioni Elena , Cattaneo Marco 
Published: October 2012

SummaryIn studies that compared the reversible P2Y12 inhibitor ticagrelor with the irreversible inhibitor clopidogrel, dyspnea was observed more frequently among ticagrelor-treated patients than among clopidogreltreated patients. Because dyspnea was not associated with acidosis, pulmonary or cardiac dysfunction, alterations in the mechanisms and pathways of the sensation of dyspnea may be involved in its pathogenesis. It has been hypothesised that the sensation of dyspnea in ticagrelor-treated patients is triggered by adenosine, because ticagrelor inhibits its clearance, thereby increasing its concentration in the circulation. However, dipyridamole, a much stronger inhibitor of adenosine clearance than ticagrelor, usually does not cause dyspnea. We hypothesise that inhibition of P2Y12 on sensory neurons increases the sensation of dyspnea, particularly when reversible inhibitors are used. We base our hypothesis on the following considerations: 1) cangrelor and elinogrel, which, like ticagrelor, are reversible P2Y12 inhibitors, also increase the incidence of dyspnea;2) it is biologically plausible that inhibition of P2Y12 on sensory neurons increases the sensation of dyspnea;3) inhibition of P2Y12 on platelets (which do not have a nucleus) by clopidogrel is permanent, despite the once daily administration and the short plasma half-life of the inhibitor;4) in contrast, inhibition of P2Y12 on neurons by clopidogrel may be temporary and transient, because neurons have a nucleus and can therefore rapidly replace the inhibited receptors with newly synthetised ones;5) inhibition of P2Y12 on neurons by reversible inhibitors is permanent, because the plasma drug concentration is maintained high by repeated dosing, in order to ensure permanent inhibition of platelet P2Y12.
Mental illness recognition and beliefs about adequate treatment of a patient with schizophrenia: Association with gender and perception of aggressiveness-dangerousness in a community sample of Mexico City
Authors: Robles-García Rebeca , Fresán Ana , Berlanga Carlos , Martínez Nicolás 
Published: October 2012

Backgound: In developing countries, little is known about public recognition and beliefs about treatment of severe mental disorders, both emergent key elements in reducing stigma and the gap of treatment of such patients. It has been proposed that they may be related to gender and perception of patient’s aggressiveness and/or dangerousness. Aims: To assess mental illness recognition and beliefs about treatment of schizophrenia, and to determine their relationship with perception of patient’s aggressiveness/dangerousness and gender of the perceiver in a community sample of Mexico City. Methods: A convenience sample of 1038 subjects responded to a questionnaire that assesses all variables after reading a vignette of a patient with paranoid schizophrenia. Results: Women were 1.88 times more likely to recognize the presence of mental illness and considered psychiatric interventions as the most adequate treatment of symptoms. In contrast, non-psychiatric interventions were more often considered by men (64.7%). Responders who recognize mental illness were more likely to perceive the patient as dangerous, which was related to the suggestion of more restrictive interventions. Conclusions: It is necessary to direct special efforts to increase mental health literacy among men. The general public needs objective information about aggression and dangerousness in anti-stigma campaigns among developing countries similar to Mexico.
Risk of new psychiatric episodes in the year following divorce in midlife: Cause or selection? A nationwide register-based study of 703,960 individuals
Authors: Björkenstam Emma , Hallqvist Johan , Dalman Christina , Ljung Rickard 
Published: October 2012

Aims: To examine if divorce is associated with an increased risk of psychiatric disorder. Methods: A register-based cohort study of all married or divorced individuals aged 45–54 in Sweden in 2006. After exclusion of 129,669 individuals with a history of psychiatric care in 1987–2005, we followed 703,960 persons for psychiatric disorder during 2007, measured as psychiatric inpatient care, outpatient care and use of psychotropic medication. Marital trajectories were taken into consideration. Data were analysed using Poisson regression. Results: Divorced women and men had a higher risk for psychiatric inpatient care compared to married (ORwomen = 3.2, 95%CI = 1.6–6.3, ORmen = 3.3, 95%CI = 2.0–5.4). The longer the marriage, the lower the risk for psychiatric disorders. Lower educational level increased the risk for psychiatric inpatient care. Conclusions: In conclusion, our study supports both the selection hypothesis, linking healthy individuals to long and stable marriages, and the social causation hypothesis, linking the stress of recent divorce to increased psychiatric disorder for both women and men.
Knowledge and attitudes towards mental illness among college students: Insights into the wider English-speaking Caribbean population
Authors: Youssef Farid F , Bachew Raecho , Bodie Dalecia , Leach Richanna , Morris Kevin , Sherma Glenderia 
Published: October 2012

Background: Mental illness is a significant contributor to global disease burden and this is expected to increase over the coming decades. Traditionally mental illness has not been well understood by the general public, resulting in poor attitudes towards persons with mental illness and stigmatization. Such conditions are common in the Caribbean where less than 5% of the health budget is allocated to mental illness. Aims: To assess knowledge and attitudes towards mental illness among college students within the English-speaking Caribbean. Methods: A self-report questionnaire was adapted from previous studies designed to measure knowledge and attitudes of mental illness. Students were sampled from the University of the West Indies campuses in Jamaica, Barbados and Trinidad & Tobago. Results: Responses were collected from 673 persons with a response rate of 84%. While participants were agreed that particular diseases were mental illnesses, overall knowledge scores were low. Knowledge was higher among those persons who knew someone with a mental illness. Attitude scores were suggestive of stigmatization, with drug abuse and schizophrenia seen in a particularly poor light. Conclusions: These results suggest that widespread educational campaigns need to be implemented across the region, designed to both increase knowledge about mental illness and reduce discrimination towards persons suffering with mental illness.
The limitations of simple gene set enrichment analysis assuming gene independence
Authors: Tamayo Pablo , Steinhardt George , Liberzon Arthur , Mesirov Jill P 
Published: October 2012

Since its first publication in 2003, the Gene Set Enrichment Analysis method, based on the Kolmogorov-Smirnov statistic, has been heavily used, modified, and also questioned. Recently a simplified approach using a one-sample t-test score to assess enrichment and ignoring gene-gene correlations was proposed by Irizarry et al. 2009 as a serious contender. The argument criticizes Gene Set Enrichment Analysis’s nonparametric nature and its use of an empirical null distribution as unnecessary and hard to compute. We refute these claims by careful consideration of the assumptions of the simplified method and its results, including a comparison with Gene Set Enrichment Analysis’s on a large benchmark set of 50 datasets. Our results provide strong empirical evidence that gene–gene correlations cannot be ignored due to the significant variance inflation they produced on the enrichment scores and should be taken into account when estimating gene set enrichment significance. In addition, we discuss the challenges that the complex correlation structure and multi-modality of gene sets pose more generally for gene set enrichment methods.
Mobile Gaming
Authors: Chaudhary Anju Grover 
Published: October 2012

With more than 811 million mobile subscribers as of March 2011 (Sohoni 2011), India not only ranks as the second largest mobile phone customer base in the world after China with 900 million mobile phone subscribers ( China Has Over 900 Mobile Users…, 2011) but is believed to have one of the highest penetration of cell phones since they are expected to reach more than 97 per cent of the country’s population of 1.26 billion by 2014 ( India’s Cellphone Users… 2011). Moreover, the Indian mobile entertainment industry itself is witnessing a tremendous growth according to the industry specialists who have predicted that the market will reach up to $4.9 billion by 2015 (Srikaparchi 2011). This is a substantial increase from $1.2 billion in 2009, which puts it at the compounded annual growth rate (CAGR) of 26 per cent in the period 2009–2015. This significant growth of the mobile entertainment industry can be attributed to a number of factors, including the booming economy as a result of the rising middle class, growth of the mobile handset market, localization of entertainment content, rise in the number of service providers and gaming companies as well as foreign collaborations. The rising middle class is one of the determining factors in the growth of the mobile gaming industry. According to a report of the National Council for Applied Economic Research’s (NCAER) Center for Macro Consumer Research, there will be 267 million middle class people in India by 2015–16, thus providing a great market opportunity for the mobile entertainment industry (Press Trust of India 2011). Moreover, having more than half the population below the age group of 25 is another reason why the gaming industry will flourish in the future as it is the younger generation who is technically savvy and more likely than adults to use mobiles for information and entertainment. With the booming economy, availability of low-priced devices and better network coverage, rural people are also in the market for using cellphones for edutainment purposes.
Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis
Authors: Augutis Kristin , Axelsson Markus , Portelius Erik , Brinkmalm Gunnar , Andreasson Ulf , Gustavsson Mikael K , Malmeström Clas , Lycke Jan , Blennow Kaj , Zetterberg Henrik , Mattsson Niklas 
Published: October 2012

Background: Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear. Objective: To characterize the CSF biomarkers of APP degradation in MS, including the effects of disease-modifying therapy. Methods: CSF samples from 87 MS patients (54 relapsing–remitting (RR) MS; 33 secondary progressive (SP) MS and 28 controls were analyzed for sAPP and Aβ peptides by immunoassays, plus a subset of samples was analyzed by immunoprecipitation and mass spectrometry (IP-MS). Patients treated with natalizumab or mitoxantrone were examined at baseline, and after 1–2 years of treatment. Results: CSF sAPP and Aβ peptide levels were reduced in MS patients; but they increased again towards normal, after natalizumab treatment. A multivariate model of IP-MS-measured Aβ species separated the SPMS patients from controls, with RRMS patients having intermediate levels. Conclusions: We confirmed and extended our previous observations of altered CSF sAPP and Aβ peptide levels in MS patients. We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF Aβ isoform distribution was found to be distinct in SPMS patients, as compared to the controls.
Treatment with 4-aminopyridine improves upper limb tremor of a patient with multiple sclerosis: a video case report
Authors: Schniepp Roman , Jakl Veronika , Wuehr Max , Havla Joachim , Kümpfel Tanja , Dieterich Marianne , Strupp Michael , Jahn Klaus 
Published: October 2012

The reversible potassium channel blocker 4-aminopyridine is effective in the treatment of numerous cerebellar dysfunctions, such as episodic ataxia type 2 and downbeat nystagmus syndrome. In 2011, its sustained release form, dalfampridine, was admitted in Europe for the treatment of walking difficulties in patients with multiple sclerosis (MS). Here we report the case of a 44-year old patient with a progressive MS whose upper limb tremor was markedly reduced under treatment with 4-aminopyridine, as documented in a Tremor Activities of Daily Living questionnaire and in the 9-Hole Peg test. Hand accelerations decreased in the left hand from 10.9 m/sec2 to 2.2 m/sec2 and in the right hand from 4.2 m/sec2 to 0.9 m/sec2. This case report indicates for the first time that 4-aminopyridine might be effective in the symptomatic treatment of tremor entities in patients with MS. The finding calls for further prospective studies to determine the usefulness of 4-aminopyridine or its sustained-release form dalfampridine in treating patients with tremor and MS.
On Benjamin’s Theses, or the utility of the concept of historical time
Authors: Renton David 
Published: October 2012

Abstract: Roger Griffin’s paper points towards the importance of historical time when discussing fascism. Walter Benjamin’s Theses, the discussion of which informs Griffin’s paper, engages with the topic of historical time at several points, especially in its discussion of the theory of progress that Benjamin found in German Social Democracy, to which the Theses was directly opposed. Revisiting sympathetically a theory of progress akin to that of Karl Kautsky and other Marxist writers enables us to add substance to the key Marxist concept of fascism as a reactionary movement. Combining this idea with an emphasis on the autonomous, mass character of fascism enables us to grasp the dynamics of fascism as a contradictory whole: a future-orientated and activist politics without revolutionary content.