bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome 10, Frequently Lost in Human Melanoma, Encodes Multiple Tumor-Suppressive Functions
Authors: Kwong Lawrence N. , Chin Lynda 
Published: January 2014

Abstract
Although many DNA aberrations in melanoma have been well characterized, including focal amplification and deletions of oncogenes and tumor suppressors, broad regions of chromosomal gain and loss are less well understood. One possibility is that these broad events are a consequence of collateral damage from targeting single loci. Another possibility is that the loss of large regions permits the simultaneous repression of multiple tumor suppressors by broadly decreasing the resident gene dosage and expression. Here, we test this hypothesis in a targeted fashion using RNA interference to suppress multiple candidate residents in broad regions of loss. We find that loss of chromosome regions 6q, 10, and 11q21-ter is correlated with broadly decreased expression of most resident genes and that multiple resident genes impacted by broad regional loss of chromosome 10 are tumor suppressors capable of affecting tumor growth and/or invasion. We also provide additional functional support for Ablim1 as a novel tumor suppressor. Our results support the hypothesis that multiple cancer genes are targeted by regional chromosome copy number aberrations. Cancer Res; 74(6); 1814–21. ©2014 AACR.
Genetic and Phenotypic Diversity in Breast Tumor Metastases
Authors: Almendro Vanessa , Kim Hee Jung , Cheng Yu-Kang , Gönen Mithat , Itzkovitz Shalev , Argani Pedram , van Oudenaarden Alexander , Sukumar Saraswati , Michor Franziska , Polyak Kornelia 
Published: January 2014

Abstract
Metastatic disease is the main cause of cancer-related mortality due to almost universal therapeutic resistance. Despite its high clinical relevance, our knowledge of how cancer cell populations change during metastatic progression is limited. Here, we investigated intratumor genetic and phenotypic heterogeneity during metastatic progression of breast cancer. We analyzed cellular genotypes and phenotypes at the single cell level by performing immunoFISH in intact tissue sections of distant metastatic tumors from rapid autopsy cases and from primary tumors and matched lymph node metastases collected before systemic therapy. We calculated the Shannon index of intratumor diversity in all cancer cells and within phenotypically distinct cell populations. We found that the extent of intratumor genetic diversity was similar regardless of the chromosomal region analyzed, implying that it may reflect an inherent property of the tumors. We observed that genetic diversity was highest in distant metastases and was generally concordant across lesions within the same patient, whereas treatment-naïve primary tumors and matched lymph node metastases were frequently genetically more divergent. In contrast, cellular phenotypes were more discordant between distant metastases than primary tumors and matched lymph node metastases. Diversity for 8q24 was consistently higher in HER2+ tumors compared with other subtypes and in metastases of triple-negative tumors relative to primary sites. We conclude that our integrative method that couples ecologic models with experimental data in human tissue samples could be used for the improved prognostication of patients with cancer and for the design of more effective therapies for progressive disease.Cancer Res; 74(5); 1338–48. ©2014 AACR.
Effect of Microstimulation of the Superior Colliculus on Visual Space Attention
Authors: Gattass Ricardo , Desimone Robert 
Published: January 2014

Abstract
We investigated the effect of microstimulation of the superficial layers of the superior colliculus (SC) on the performance of animals in a peripheral detection paradigm while maintaining fixation. In a matching-to-sample paradigm, a sample stimulus was presented at one location followed by a brief test stimulus at that (relevant) location and a distractor at another (irrelevant) location. While maintaining fixation, the monkey indicated whether the sample and the test stimulus matched, ignoring the distractor. The relevant and irrelevant locations were switched from trial to trial. Cells in the superficial layers of SC gave enhanced responses when the attended test stimulus was inside the receptive field compared with when the (physically identical) distractor was inside the field. These effects were found only in an “automatic” attentional cueing paradigm, in which a peripheral stimulus explicitly cued the animal as to the relevant location in the receptive field. No attentional effects were found with block of trials. The transient enhancement to the attended stimulus was observed at the onset and not at the offset of the stimulus. Electrical stimulation at the site corresponding to the irrelevant distractor location in the SC causes it to gain control over attention, causing impaired performance of the task at the relevant location. Stimulation at unattended sites without the presence of a distractor stimulus causes little or no impairment in performance. The effect of stimulation decays with successive stimulations. The animals learn to ignore the stimulation unless the parameters of the task are varied.
A new genus with six new species of Typhlopolycystidinae Evdonin, 1977 (Platyhelminthes, Kalyptorhynchia, Polycystididae)
Authors: SCHOCKAERT ERNEST R. , MARTENS PAUL M. , REVIS NATHALIE , JANSSEN TOON , WILLEMS WIM , ARTOIS TOM J. 
Published: January 2014

Five new species of the new taxon Brunetorhynchus n. gen. are described: B. deconincki n. sp., B. microstylis n. sp. and B. complicatus n. sp. are from the Mediterranean, B. canariensis n. sp. is from the Canary Island Lanzarote, B. cannoni n. sp. is from the Australian East coast and one species from the Galapagos, formerly described as Limipolycystis spec., is transferred to the new genus as B. dubius n. sp.. As in Limipolycystis, these species have a single stylet, (accessory stylet type II), an accessory secretion vesicle (type II) and a prostate vesicle (type III) in the male atrium, although the latter vesicle is absent in some species. Unlike the species of Limipolycystis, where the seminal receptacle is a sclerotized tubule, the species of the new taxon have a pear-shaped seminal receptacle on the oviduct.
Medial Opening Wedge High Tibial Osteotomy for Medial Compartment Overload/Arthritis in the Varus Knee
Authors: Bonasia Davide Edoardo , Dettoni Federico , Sito Gabriele , Blonna Davide , Marmotti Antongiulio , Bruzzone Matteo , Castoldi Filippo , Rossi Roberto 
Published: January 2014

Background: Medial opening wedge high tibial osteotomy (OWHTO) is a widely accepted procedure for the treatment of medial compartment arthritis of the knee. Compared with closing wedge HTO, however, the outcomes of OWHTO reported in the literature are incomplete. Purpose: To identify the positive and negative prognostic factors related to the outcomes of OWHTO through an evaluation of midterm study results and survivorship analysis. Study Design: Case series; Level of evidence, 4. Methods: From January 2001 to December 2009, a total of 141 consecutive OWHTOs were performed in 123 patients. Only patients with symptomatic medial knee overload/arthritis were included. The patients were evaluated preoperatively and at every follow-up visit with (1) the Knee Society score, (2) the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, (3) another self-evaluation scale, (4) long-leg radiographs, and (5) plain radiographs. Preoperative, intraoperative, and postoperative variables were investigated to find an association with the outcomes. Results: Of the 123 patients, 15 were lost to follow-up, and 24 were excluded from the study, leaving 84 patients (99 OWHTOs) for the present study. The mean age of the patients at the time of surgery was 54.5 ± 9.2 years. The mean follow-up was 51.5 ± 23.8 months. The Knee Society and WOMAC scores significantly improved after surgery ( P < .001). The variables significantly related to a poor outcome were (1) age >56 years ( P = .008) and (2) postoperative knee flexion <120° ( P < .001); the variables significantly related to a good outcome were (1) Ahlbäck grade 0 arthritis of the medial compartment ( P < .001) and (2) excellent preoperative Knee Society score ( P < .001). The Kaplan-Meier analysis showed a survival rate of 98.7% at 5 years and 75.9% at 7.5 years. Conclusion: With correct indications, OWHTO is a reliable procedure for medial knee arthritis/overload. The outcomes reported are similar to those from other studies, although the variables related to outcomes are slightly different.
Survey Regarding Provisions of a 3-Day Supply of an Antihypertensive
Authors: Seal David W. , Walton Je'Laune , Williams Sherifa , Wilson Robert , Smith-Benson Joshua 
Published: January 2014

Objective: To evaluate the provisions made by pharmacists when dispensing an emergency supply of an antihypertensive medication to patients in a community setting. Participants: Pharmacists and nonpharmacists (pharmacy technicians or interns) who were employed with community pharmacies and have witnessed or dispensed an emergency supply of an antihypertensive medication. Those who agreed to participate in this study via informed consent. Intervention: A short questionnaire was used to assess the provisions made by community pharmacists from the perspectives of both the pharmacists and the nonpharmacists. Main outcome measures: Availability of blood pressure machines, evaluation of blood pressure readings, and patient counseling sessions or assessments prior to dispensing the emergency supply of an antihypertensive were the major outcome measures. Results Among the participants, 92% of the pharmacists and 79% of the nonpharmacists reported they have witnessed or dispensed an emergency supply of an antihypertensive medication. Of those, 82% of the pharmacists and 78% of the nonpharmacists recognized there were blood pressure machines available. However, 78% of the pharmacists and 72% of the nonpharmacists acknowledged the patient’s blood pressure was not checked. Conclusion/Implication: This observational study demonstrates that provisions when dispensing an emergency supply of an antihypertensive medication are inconsistent. Further evaluation is warranted.
A Research Elective Course on Dietary Supplements to Engage Doctor of Pharmacy Students in Primary Literature Evaluation and Scholarly Activity
Authors: Islam Mohammed A. , Gunaseelan Simi , Khan Seher A. 
Published: January 2014

Purpose: To develop and implement a research elective course to enhance skills of pharmacy students on primary literature evaluation and evidence-based practice on dietary supplements and generate scholarly publications. Methods: A 2 credit hour independent research elective course was designed and implemented in the third-year doctor of pharmacy curriculum. The course involved student-led research activities that included formulating research project, reviewing of primary literature, collection and evaluation of data, and writing of review articles for publication in peer-reviewed journals. An online survey was administered to evaluate students’ perceptions of the course. Results: Students successfully completed the course. The course resulted in peer-reviewed publications through student–faculty collaboration. Pharmacy students enrolled in the elective course perceived that the course helped them enhance their analytical reasoning, critical thinking and drug-literature evaluation skills, gain evidence-based knowledge, and apply the knowledge into practice during their advanced pharmacy practice experiences community pharmacy rotations. Conclusions: The course provided opportunity to the pharmacy students to not only critically search and evaluate the literature but also publish in peer-reviewed journals. Other pharmacy schools/colleges can adopt this course model to create opportunities for student–faculty collaborations toward scholarly accomplishments.
Smoking is not associated with autoantibody production in systemic lupus erythematosus patients, unaffected first-degree relatives, nor healthy controls
Authors: Young KA , Terrell DR , Guthridge JM , Kamen DL , Gilkeson GS , Karp DR , Ishimori ML , Weisman MH , Holers VM , Harley JB , Norris JM , James JA 
Published: January 2014

Objective The objective of this paper is to examine whether smoking is associated with autoantibody production in systemic lupus erythematosus (SLE) patients, unaffected first-degree relatives (FDR) of individuals with SLE—a group at increased risk of developing SLE—or unaffected, unrelated controls. Methods Detailed demographic, environmental, clinical, and therapeutic information was collected by questionnaire on 1242 SLE patients, 981 FDRs, and 946 controls in the Lupus Family Registry and Repository; a blood sample was obtained. All sera were tested for multiple lupus autoantibodies by immunofluorescence and luminex bead-based assays. Generalized estimating equations, adjusting for age, gender, and ethnicity and accounting for correlation within families, were used to assess smoking status with the dichotomous outcome variables of positivity for SLE status, positivity of ANA by immunofluorescence (≥1:120), positivity for ≥1 autoantibody by the luminex assay, and positivity for each of the 11 autoantibodies. Results Current smoking was associated with being positive for ≥1 autoantibody (excluding ANA) (adjusted OR = 1.53, 95% CI 1.04-2.24) in our subjects with SLE. No association was observed in unaffected FDRs or healthy controls. Former smoking was associated with anti-Ro/SS-A60 in our unaffected FDRs. There was an increased association with anti-nRNP A seropositivity, as well as a decreased association with anti-nRNP 68 positivity, in current smokers in SLE subjects. Conclusions No clear association between smoking status and individual autoantibodies was detected in SLE patients, unaffected FDRs, nor healthy controls within this collection. The association of smoking with SLE may therefore manifest its risk through mechanisms outside of autoantibody production, at least for the specificities tested.
The Sydney Mental Health Client Mortality Audit: what does it tell us and what are we to do?
Authors: O’Connor Nick , Hunt Glenn E , O’Hara-Aarons Maureen , Hall Allan , Snars Jeff , Storm Victor , Lambert Tim 
Published: January 2014

Objectives: To examine the characteristics of those mental health clients of an Australian metropolitan health service who died during a 6 year period, 2005 – 2010. Methods: The medical records, and where available, coronial post-mortem examinations were audited for 109 people with schizophrenia who died while they were clients of the mental health service. Results: The mean age of death for men was 45 years and for women, 47 years, compared to the general population’s male and female life expectancy of 79 and 84 years, respectively. About one-half of the deaths were due to suicide ( n = 55), followed by natural causes ( n = 42; 39%), undetermined causes ( n = 7), and accidents or acts of violence ( n = 5). Smoking rates, diagnosed diabetes and hypertension were higher in the group that died from natural causes. Morbid obesity (body mass index (BMI) > 35 kg/m2) rates were higher in the group that died of natural causes (38%), compared with the suicide group (5%). Conclusions: While suicide accounts for the majority of those dying prematurely in this study cohort, it appears that for those who survive the risk of suicide in the earlier period of a chronic psychotic illness, there is yet another threat to life expectancy: death from preventable cardiorespiratory disorders, due to a poor lifestyle and social deprivation.
Tuberculosis–Diagnostic Expert System: An architecture for translating patients information from the web for use in tuberculosis diagnosis
Authors: Osamor Victor C , Azeta Ambrose A , Ajulo Oluseyi O 
Published: January 2014

Background: Over 1.5–2 million tuberculosis deaths occur annually. Medical professionals are faced with a lot of challenges in delivering good health-care with unassisted automation in hospitals where there are several patients who need the doctor’s attention. Objective: To automate the pre-laboratory screening process against tuberculosis infection to aid diagnosis and make it fast and accessible to the public via the Internet. The expert system we have built is designed to also take care of people who do not have access to medical experts, but would want to check their medical status. Methods: A rule-based approach has been used, and unified modeling language and the client–server architecture technique were applied to model the system and to develop it as a web-based expert system for tuberculosis diagnosis. Algorithmic rules in the Tuberculosis–Diagnosis Expert System necessitate decision coverage where tuberculosis is either suspected or not suspected. The architecture consists of a rule base, knowledge base, and patient database. These units interact with the inference engine, which receives patient’ data through the Internet via a user interface. Results: We present the architecture of the Tuberculosis–Diagnosis Expert System and its implementation. We evaluated it for usability to determine the level of effectiveness, efficiency and user satisfaction. The result of the usability evaluation reveals that the system has a usability of 4.08 out of a scale of 5. This is an indication of a more-than-average system performance. Conclusion: Several existing expert systems have been developed for the purpose of supporting different medical diagnoses, but none is designed to translate tuberculosis patients’ symptomatic data for online pre-laboratory screening. Our Tuberculosis–Diagnosis Expert System is an effective solution for the implementation of the needed web-based expert system diagnosis.
Helicobacter pylori-driven modulation of NK cell expansion, intracellular cytokine expression and cytotoxic activity
Authors: Rudnicka Karolina , Miszczyk Eliza , Matusiak Agnieszka , Walencka Maria , Moran Anthony P , Rudnicka Wiesława , Chmiela Magdalena 
Published: January 2014

During Helicobacter pylori (Hp) infections , innate immune cells may be positively or negatively modulated by Hp compounds or by Hp-induced cytokines. We have shown previously that the natural cytotoxic activity of PBMC was lower in Hp-infected [Hp(+)] than Hp-uninfected individuals [Hp(−)]. Here, we asked whether the Hp-modulated cytotoxic amplitude is associated with changes in the number of NK cells, their activation or intracellular cytokine expression. Flow cytometry immunophenotyping of PBMC was performed with regard to the surface receptors CD3, CD56 and CD25, and intracellular cytokine expression of IL-2, IFN-γ and IL-10 after in vitro stimulation with Hp glycine acid extract (GE), Hp LPS or standard Escherichia coli LPS . Hp GE-driven enhancement of lymphocyte cytotoxic activity was associated with the expansion of CD3−CD56+CD25+ NK cells and the up-regulation of IFN-γ and/or IL-2 synthesis, up to the higher level in Hp(−) than in Hp(+), while Hp LPS-mediated decrease in lymphocyte cytotoxicity was accompanied by the lack of CD3−CD56+CD25+ NK propagation, the inhibition of pro-inflammatory cytokine expression and intense expansion of IL-10–producing NK cells. Thus, the cytotoxic and cytokine activities of NK cells were dependent on the type of antigenic challenge and the Hp status, that is, NK cells could be modulated positively by Hp GE Ags and negatively by Hp LPS.
Inherited genetic susceptibility to monoclonal gammopathy of unknown significance
Authors: Weinhold Niels , Johnson David C. , Rawstron Andrew C. , Försti Asta , Doughty Chi , Vijayakrishnan Jayaram , Broderick Peter , Dahir Nasrin B. , Begum Dil B. , Hosking Fay J. , Yong Kwee , Walker Brian A. , Hoffmann Per , Mühleisen Thomas W. , Langer Christian , Dörner Elisabeth , Jöckel Karl-Heinz , Eisele Lewin , Nöthen Markus M. , Hose Dirk , Davies Faith E. , Goldschmidt Hartmut , Morgan Gareth J. , Hemminki Kari , Houlston Richard S. 
Published: January 2014

Key Points
Inherited genetic variation increases risk to developing multiple myeloma through predisposition to MGUS. Loci identified that increase risk of developing MGUS include 2p23.3, 3p22.1, 3q26.2, 6p21.33, 7p15.3, 17p11.2, and 22q13.1.
Gene expression profiling of mesenteric lymph nodes from sheep with natural scrapie
Authors: Filali Hicham , Martín-Burriel Inmaculada , Harders Frank , Varona Luis , Hedman Carlos , Mediano Diego R , Monzón Marta , Bossers Alex , Badiola Juan J , Bolea Rosa 
Published: January 2014

Abstract

Background
Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease.

Results
In the clinical stage of the disease, we detected 105 genes that were differentially expressed (≥2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR.

Conclusions
The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease.
Performance research on time-triggered Ethernet based on network calculus
Authors: Xiang Yu , Wang Wei , Zhang Xiang , Li Zhenwei 
Published: January 2014

Abstract
In the paper, we research on the performance of time-triggered Ethernet based on network calculus. Three kinds of data with different priority are imported to research on time-triggered Ethernet. Firstly, we adopt network calculus to obtain the theory-bound value of the network performance parameters. Then, we design and implement the time-triggered Ethernet clock synchronization, redundancy fault-tolerant, multi-data communication, service-performance model, node model, and network model successfully in two different topologies. Lastly, we compare the simulation value with the network calculus value and obtain the comparison result. The result shows that the performance parameters of time-triggered Ethernet well meet the theory value, and time-triggered Ethernet specification is feasible.