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Find video protocols related to scientific articles indexed in Pubmed.
Spatial and Temporal Emergence Pattern of Lyme Disease in Virginia.
Am. J. Trop. Med. Hyg.
PUBLISHED: 10-22-2014
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The emergence of infectious diseases over the past several decades has highlighted the need to better understand epidemics and prepare for the spread of diseases into new areas. As these diseases expand their geographic range, cases are recorded at different geographic locations over time, making the analysis and prediction of this expansion complicated. In this study, we analyze spatial patterns of the disease using a statistical smoothing analysis based on areal (census tract level) count data of Lyme disease cases in Virginia from 1998 to 2011. We also use space and space-time scan statistics to reveal the presence of clusters in the spatial and spatiotemporal distribution of Lyme disease. Our results confirm and quantify the continued emergence of Lyme disease to the south and west in states along the eastern coast of the United States. The results also highlight areas where education and surveillance needs are highest.
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Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial.
Lancet Infect Dis
PUBLISHED: 10-11-2014
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Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP.
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Derivation and external validation of a case mix model for the standardized reporting of 30-day stroke mortality rates.
Stroke
PUBLISHED: 10-07-2014
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Case mix adjustment is required to allow valid comparison of outcomes across care providers. However, there is a lack of externally validated models suitable for use in unselected stroke admissions. We therefore aimed to develop and externally validate prediction models to enable comparison of 30-day post-stroke mortality outcomes using routine clinical data.
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ICD-11 and SNOMED CT Common Ontology: circulatory system.
Stud Health Technol Inform
PUBLISHED: 08-28-2014
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The improvement of semantic interoperability between data in electronic health records and aggregated data for health statistics requires efforts to carefully align the two domain terminologies ICD and SNOMED CT. Both represent a new generation of ontology-based terminologies and classifications. The proposed alignment of these two systems and, in consequence, the validity of their cross-utilisation, requires a specific resource, named Common Ontology. We present the ICD-11 SNOMED CT Common Ontology building process including: a) the principles proposed for aligning the two systems with the help of a common model of meaning, b) the design of this common ontology, and c) preliminary results of the application to the diseases of the circulatory system.
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What's in a class? Lessons learnt from the ICD - SNOMED CT harmonisation.
Stud Health Technol Inform
PUBLISHED: 08-28-2014
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The upcoming ICD-11 will be harmonized with SNOMED CT via a common ontological layer (CO). We provide evidence for our hypothesis that this cannot be appropriately done by simple ontology alignment, due to diverging ontological commitment between the two terminology systems. Whereas the common ontology describes clinical situations, ICD-11 linearization codes are best to be interpreted as diagnostic statements. For the binding between ICD codes and classes from the ontological layer, a query-based approach is favoured.
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Associations between stroke mortality and weekend working by stroke specialist physicians and registered nurses: prospective multicentre cohort study.
PLoS Med.
PUBLISHED: 08-19-2014
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Observational studies have reported higher mortality for patients admitted on weekends. It is not known whether this "weekend effect" is modified by clinical staffing levels on weekends. We aimed to test the hypotheses that rounds by stroke specialist physicians 7 d per week and the ratio of registered nurses to beds on weekends are associated with mortality after stroke.
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Two cases of bacteriemia caused by nontoxigenic, non-O1, non-O139 Vibrio cholerae isolates in Ho Chi Minh City, Vietnam.
J. Clin. Microbiol.
PUBLISHED: 08-13-2014
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The toxigenic bacterium Vibrio cholerae belonging to the O1 and O139 serogroups is commonly associated with epidemic diarrhea in tropical settings; other diseases caused by this environmental pathogen are seldom identified. Here we report two unassociated cases of nonfatal, nontoxigenic V. cholerae non-O1, non-O139 bacteremia in patients with comorbidities in Ho Chi Minh City, Vietnam, that occurred within a 4-week period.
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Unbiased analysis of potential targets of breast cancer susceptibility loci by Capture Hi-C.
Genome Res.
PUBLISHED: 08-13-2014
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Genome-wide association studies have identified more than 70 common variants that are associated with breast cancer risk. Most of these variants map to non-protein-coding regions and several map to gene deserts, regions of several hundred kilobases lacking protein-coding genes. We hypothesized that gene deserts harbor long-range regulatory elements that can physically interact with target genes to influence their expression. To test this, we developed Capture Hi-C (CHi-C), which, by incorporating a sequence capture step into a Hi-C protocol, allows high-resolution analysis of targeted regions of the genome. We used CHi-C to investigate long-range interactions at three breast cancer gene deserts mapping to 2q35, 8q24.21, and 9q31.2. We identified interaction peaks between putative regulatory elements ("bait fragments") within the captured regions and "targets" that included both protein-coding genes and long noncoding (lnc) RNAs over distances of 6.6 kb to 2.6 Mb. Target protein-coding genes were IGFBP5, KLF4, NSMCE2, and MYC; and target lncRNAs included DIRC3, PVT1, and CCDC26. For one gene desert, we were able to define two SNPs (rs12613955 and rs4442975) that were highly correlated with the published risk variant and that mapped within the bait end of an interaction peak. In vivo ChIP-qPCR data show that one of these, rs4442975, affects the binding of FOXA1 and implicate this SNP as a putative functional variant.
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Emergence of carbapenem-resistant Acinetobacter baumannii as the major cause of ventilator-associated pneumonia in intensive care unit patients at an infectious disease hospital in southern Vietnam.
J. Med. Microbiol.
PUBLISHED: 07-18-2014
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Ventilator-associated pneumonia (VAP) is a serious healthcare-associated infection that affects up to 30?% of intubated and mechanically ventilated patients in intensive care units (ICUs) worldwide. The bacterial aetiology and corresponding antimicrobial susceptibility of VAP is highly variable, and can differ between countries, national provinces and even between different wards in the same hospital. We aimed to understand and document changes in the causative agents of VAP and their antimicrobial susceptibility profiles retrospectively over an 11 year period in a major infectious disease hospital in southern Vietnam. Our analysis outlined a significant shift from Pseudomonas aeruginosa to Acinetobacter spp. as the most prevalent bacteria isolated from quantitative tracheal aspirates in patients with VAP in this setting. Antimicrobial resistance was common across all bacterial species and we found a marked proportional annual increase in carbapenem-resistant Acinetobacter spp. over a 3 year period from 2008 (annual trend; odds ratio 1.656, P?=?0.010). We further investigated the possible emergence of a carbapenem-resistant Acinetobacter baumannii clone by multiple-locus variable number tandem repeat analysis, finding a blaOXA-23-positive strain that was associated with an upsurge in the isolation of this pathogen. We additionally identified a single blaNDM-1-positive A. baumannii isolate. This work highlights the emergence of a carbapenem-resistant clone of A. baumannii and a worrying trend of antimicrobial resistance in the ICU of the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam.
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Efficacy of aerosol applications of methoprene and synergized pyrethrin against Tribolium castaneum adults and eggs.
J. Econ. Entomol.
PUBLISHED: 07-17-2014
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Experiments were performed to determine the efficacy of a single aerosol application of the insecticides methoprene and piperonyl butoxide-synergized pyrethrin, alone or in combination, and the insecticide carrier, Isopar M, against Tribolium castaneum (Herbst), the red flour beetle. The initial test exposed adults to insecticide treatments and placed male/female pairs in flour. All adults exposed to synergized pyrethrin were knocked down for at least 24 h after exposure but they recovered. High adult survival and similar average numbers of living F1 progeny were produced regardless of treatment exposure. In a separate test, insecticide treatments were directly applied to newly laid eggs, which resulted in the suppression of egg hatch. Synergized pyrethrin was the most effective insecticide (P < or = 0.001) for suppressing egg hatch. The effect of flour on insecticide activity to eggs and consequent insect development was also evaluated. An amount of 0.01 g of flour in the exposure arena, 62-cm2 area, was not sufficient for individuals to develop beyond the early larval stages, regardless of the treatment. As the flour amount in the arena increased from 1 to 5 g, the number of eggs that could develop to the adult stage increased, but this number was significantly lower in the insecticide treatments than in the control or carrier treatments. The results of the later tests indicate a high efficacy of the insecticides alone or in combination on T. castaneum egg hatch and development to the adult stage.
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High-risk motorcycle taxi drivers in the HIV/AIDS era: a respondent-driven sampling survey in Kampala, Uganda.
Int J STD AIDS
PUBLISHED: 06-28-2014
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We evaluated motorcycle taxi ('boda-boda') drivers in Kampala for the prevalence of HIV/sexually transmitted infections.
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Country experience with strengthening of health systems and deployment of midwives in countries with high maternal mortality.
Lancet
PUBLISHED: 06-22-2014
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This paper complements the other papers in the Lancet Series on midwifery by documenting the experience of low-income and middle-income countries that deployed midwives as one of the core constituents of their strategy to improve maternal and newborn health. It examines the constellation of various diverse health-system strengthening interventions deployed by Burkina Faso, Cambodia, Indonesia, and Morocco, among which the scaling up of the pre-service education of midwives was only one element. Efforts in health system strengthening in these countries have been characterised by: expansion of the network of health facilities with increased uptake of facility birthing, scaling up of the production of midwives, reduction of financial barriers, and late attention for improving the quality of care. Overmedicalisation and respectful woman-centred care have received little or no attention.
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Improvement of maternal and newborn health through midwifery.
Lancet
PUBLISHED: 06-22-2014
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In the concluding paper of this Series about midwifery, we look at the policy implications from the framework for quality maternal and newborn care, the potential effect of life-saving interventions that fall within the scope of practice of midwives, and the historic sequence of health system changes that made a reduction in maternal mortality possible in countries that have expanded their midwifery workforce. Achievement of better health outcomes for women and newborn infants is possible, but needs improvements in the quality of reproductive, maternal, and newborn care, alongside necessary increases in universal coverage. In this report, we propose three priority research areas and outline how national investment in midwives and in their work environment, education, regulation, and management can improve quality of care. Midwifery and midwives are crucial to the achievement of national and international goals and targets in reproductive, maternal, newborn, and child health; now and beyond 2015.
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Midwifery and quality care: findings from a new evidence-informed framework for maternal and newborn care.
Lancet
PUBLISHED: 06-22-2014
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In this first paper in a series of four papers on midwifery, we aimed to examine, comprehensively and systematically, the contribution midwifery can make to the quality of care of women and infants globally, and the role of midwives and others in providing midwifery care. Drawing on international definitions and current practice, we mapped the scope of midwifery. We then developed a framework for quality maternal and newborn care using a mixed-methods approach including synthesis of findings from systematic reviews of women's views and experiences, effective practices, and maternal and newborn care providers. The framework differentiates between what care is provided and how and by whom it is provided, and describes the care and services that childbearing women and newborn infants need in all settings. We identified more than 50 short-term, medium-term, and long-term outcomes that could be improved by care within the scope of midwifery; reduced maternal and neonatal mortality and morbidity, reduced stillbirth and preterm birth, decreased number of unnecessary interventions, and improved psychosocial and public health outcomes. Midwifery was associated with more efficient use of resources and improved outcomes when provided by midwives who were educated, trained, licensed, and regulated. Our findings support a system-level shift from maternal and newborn care focused on identification and treatment of pathology for the minority to skilled care for all. This change includes preventive and supportive care that works to strengthen women's capabilities in the context of respectful relationships, is tailored to their needs, focuses on promotion of normal reproductive processes, and in which first-line management of complications and accessible emergency treatment are provided when needed. Midwifery is pivotal to this approach, which requires effective interdisciplinary teamwork and integration across facility and community settings. Future planning for maternal and newborn care systems can benefit from using the quality framework in planning workforce development and resource allocation.
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Mycobacterium fortuitum skin infections after subcutaneous injections with Vietnamese traditional medicine: a case report.
BMC Infect. Dis.
PUBLISHED: 06-09-2014
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BackgroundIatrogenic skin and soft tissue infections by rapidly growing mycobacteria are described with increasing frequency, especially among immunocompromised patients.Case presentationHere, we present an immunocompetent patient with extensive Mycobacterium fortuitum skin and soft tissue infections after subcutaneous injections to relieve joint pains by a Vietnamese traditional medicine practitioner. Moreover, we present dilemmas faced in less resourceful settings, influencing patient management.ConclusionThis case illustrates the pathogenic potential of rapid growing mycobacteria in medical or non-medical skin penetrating procedures, their world-wide distribution and demonstrates the dilemmas faced in settings with fewer resources.
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Identification of possible virulence marker from Campylobacter jejuni isolates.
Emerging Infect. Dis.
PUBLISHED: 05-27-2014
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A novel protein translocation system, the type-6 secretion system (T6SS), may play a role in virulence of Campylobacter jejuni. We investigated 181 C. jejuni isolates from humans, chickens, and environmental sources in Vietnam, Thailand, Pakistan, and the United Kingdom for T6SS. The marker was most prevalent in human and chicken isolates from Vietnam.
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An intervention to support HIV preexposure prophylaxis adherence in HIV-serodiscordant couples in Uganda.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-24-2014
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Daily preexposure prophylaxis (PrEP) is an effective HIV prevention strategy, but adherence is required for maximum benefit. To date, there are no empirically supported PrEP adherence interventions. This article describes the process of developing a PrEP adherence intervention and presents results on its impact on adherence.
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Successful discontinuation of the placebo arm and provision of an effective HIV prevention product after a positive interim efficacy result: the partners PrEP study experience.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-16-2014
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Dissemination of research results to study participants and stakeholders and provision of proven effective products in the immediate post-trial period are core elements of the conduct of biomedical HIV prevention clinical trials. Few biomedical HIV prevention trials have demonstrated HIV protection with novel interventions, and thus, communication of positive trial results and provision of an effective product have not been tested in many situations.
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Semantic analysis of SNOMED CT for a post-coordinated database of histopathology findings.
J Am Med Inform Assoc
PUBLISHED: 05-15-2014
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This research investigated the use of SNOMED CT to represent diagnostic tissue morphologies and notable tissue architectures typically found within a pathologist's microscopic examination report to identify gaps in expressivity of SNOMED CT for use in anatomic pathology.
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Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress.
Nucleic Acids Res.
PUBLISHED: 05-13-2014
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In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome-wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53-dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveal that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair.
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Evaluation of potential attractants for Liposcelis bostrychophila (Psocoptera: Liposcelididae).
J. Econ. Entomol.
PUBLISHED: 04-30-2014
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The psocid, Liposcelis bostrychophila Badonnel (Psocoptera: Liposcelididae), can cause significant damage to stored commodities, and its pest status in the United States has been increasing over the last decade. Because L. bostrychophila is difficult to control with conventional methods, it is critical to explore alternative approaches such as the use of attractants that can be incorporated into integrated pest management programs for monitoring psocids. The orientation response of several L. bostrychophila life stages (first and second instars, third and fourth instars, 0- to 7-d-old adults, 21- to 28-d-old adults, and adults of mixed ages) to a range of potential attractants (including whole and cracked grains, grain-based oils, wheat germ, brewer's yeast, and commercially available kairomone lures) was studied using a two-choice pitfall test to identify candidates for further development as lures in traps. Among the potential attractants evaluated, the strongest response by all stages of L. bostrychophila was to brewer's yeast. Other materials for which there was consistently a strong response were psocid diet, wheat germ, and wheat germ oil. These results show the potential for developing monitoring tools for integrated pest management programs for L. bostrychophila and other psocid species.
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The Greater Plains Collaborative: a PCORnet Clinical Research Data Network.
J Am Med Inform Assoc
PUBLISHED: 04-28-2014
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The Greater Plains Collaborative (GPC) is composed of 10 leading medical centers repurposing the research programs and informatics infrastructures developed through Clinical and Translational Science Award initiatives. Partners are the University of Kansas Medical Center, Children's Mercy Hospital, University of Iowa Healthcare, the University of Wisconsin-Madison, the Medical College of Wisconsin and Marshfield Clinic, the University of Minnesota Academic Health Center, the University of Nebraska Medical Center, the University of Texas Health Sciences Center at San Antonio, and the University of Texas Southwestern Medical Center. The GPC network brings together a diverse population of 10 million people across 1300 miles covering seven states with a combined area of 679?159 square miles. Using input from community members, breast cancer was selected as a focus for cohort building activities. In addition to a high-prevalence disorder, we also selected a rare disease, amyotrophic lateral sclerosis.
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Effect of abiotic factors on initiation of red flour beetle (Coleoptera: Tenebrionidae) flight.
J. Econ. Entomol.
PUBLISHED: 03-27-2014
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Traps baited with pheromones are used to monitor the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera-Tenebrionidae), populations in flour mills to aid in making pest management decisions, but the factors that influence T. castaneum movement are not fully understood. We investigated the impact of photoperiod, light intensity, temperature, and relative humidity on flight initiation. The percentage of adults initiating flight reached a maximum at 30 -35 degrees C, and then fell to zero at 22.5 and 45 degrees C. Only 2% of beetles flew in complete darkness, and the number of beetles initiating flight increased to 41% under 18 h of light and then decreased slightly to 37% under 24 h of light. Rates of flight initiation did not vary with light intensities from 1,784 to 4,356 lux or relative humidities from 25 to 85%. Thus, temperature and photoperiod are the main abiotic factors tested that impact flight initiation in T castaneum, which have broad ranges of temperatures and photoperiods over which they can fly. The current results should be useful in helping to interpret trap catches based on abiotic conditions during the trapping period, and the results should be useful in helping to understand T. castaneum movement outside grain storages and processing facilities and their potential to infest structures.
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Evaluation of synergized pyrethrin aerosol for control of Tribolium castaneum and Tribolium confusum (Coleoptera: Tenebrionidae).
J. Econ. Entomol.
PUBLISHED: 03-27-2014
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Aerosol insecticides are being used in flour mill pest management programs, but there is limited information on their efficacy on different insect life stages. In this study, we evaluated the efficacy of synergized pyrethrin applied as an aerosol against eggs, larvae, pupae, and adults of the red flour beetle, Tribolium castaneum (Herbst), and the confused flour beetle, Tribolium confusum Jacquelin du Val. Effects of direct and indirect exposure were evaluated by exposing each life stage to the aerosol and then transferring to untreated flour, transferring untreated insects to treated flour, or exposing both the insects and the flour to the aerosol. The aerosol produced >88% mortality of both species and all life stages when insects were directly treated and transferred to either treated or untreated flour. Mortality was significantly reduced when insects were either treated together with flour or untreated insects were transferred to treated flour (indirect exposure to the aerosol). Larvae and adults of both species were more tolerant compared with eggs and pupae. Recovery of moribund adults in the indirect exposure treatments was greater compared with recovery of moribund insects in the direct exposure treatments. Good sanitation before aerosol application could facilitate direct exposure of insects and thus increase aerosol efficacy inside flour mills.
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Spatial pattern in aerosol insecticide deposition inside a flour mill.
J. Econ. Entomol.
PUBLISHED: 03-27-2014
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Aerosol insecticides are commonly used for management of stored-product pests inside food facilities, but the physical complexity of the interior of most food facilities may influence the dispersal and deposition of droplets and create spatial variation in dosage. The spatial pattern in aerosol deposition was evaluated inside a flour mill using a high density grid of bioassay insects. Three insecticides, Aerotech with NyGuard and Pyrocide 100 + Diacon II, both pyrethrin and insect growth regulator combinations, and Vap20, an organophosphate, were evaluated at normal (27 degrees C) and high (40 degrees C) target temperatures. Using a newly developed efficacy index, there was spatial pattern to aerosol deposition detected for the pyrethrin insecticides and the pattern differed between aerosols and temperatures. Walls and corners, especially behind the direction of application, were especially vulnerable to zones of lower efficacy, and open areas in center of the room tended to have the highest efficacy. The organophosphate insecticide provided complete efficacy at all bioassay dish locations, probably due in part to its vapor toxicity. Using boxes 1 m in depth and 5, 10, or 20 cm in height and open on only one end, it was shown that aerosol dispersal under horizontal surfaces could be impacted by gap height, aerosol, and temperature. These results show the potential for spatial variation in aerosol efficacy within a food facility and identify locations with the potential to receive a lower insecticide dosage. To increase overall efficacy, these locations may be targeted for additional interventions to provide more uniform pest population suppression.
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Qualitative identification of dibenzoylmethane in licorice root (Glycyrrhiza glabra) using gas chromatography-triple quadrupole mass spectrometry.
Nat Prod Commun
PUBLISHED: 03-26-2014
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Licorice root (Glycyrrhiza glabra), an herbal Chinese medicine, has shown medicinal uses in therapeutics and cancer prevention. Dibenzoylmethane (DBM; 1, 3-diphenyl-1, 3-propadinedione), a small beta-diketone, has been reported to be a minor constituent of licorice and a known deregulator of the human prostate cancer cell cycle. Characterization of the phytochemical profiles of licorice root forms including commercially available DBM will advance our search in identifying novel reagents for prostate cancer therapeutics. Gas chromatography- triple quadrupole-mass spectrometric analysis was used for detecting DBM in licorice root extracts. DBM and all licorice forms exhibited a component with a retention time of 14.5 minutes. The major fragment ions detected were at m/z 77, 105, 147, 223 and 224 at the identified retention time by selected reaction monitoring/SRM. These data confirm the presence of DBM from its natural source (G. glabra), and the GC-MS/SRM method helps in the identification of this minor component in a complex biological matrix.
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Increased platelet expression of glycoprotein IIIa following aspirin treatment in aspirin-resistant but not aspirin-sensitive subjects.
Br J Clin Pharmacol
PUBLISHED: 01-18-2014
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Aspirin is widely used as an anti-platelet agent for cardiovascular prophylaxis. Despite aspirin treatment, many patients experience recurrent thrombotic events, and aspirin resistance may contribute to this. We examined the prevalence of aspirin resistance in a healthy population, and investigated whether the platelet proteome differed in aspirin-resistant subjects.
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C-reactive protein and brain natriuretic peptide as predictors of adverse events after lower extremity endovascular revascularization.
J. Vasc. Surg.
PUBLISHED: 01-17-2014
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High-sensitivity C-reactive protein (hsCRP) and brain natriuretic peptide (BNP) have been shown to be independent predictors of adverse cardiovascular outcomes and increased risk of secondary interventions or limb loss in patients with peripheral arterial disease (PAD). To assist clinicians in decision-making about treatment approaches and predicting postprocedure mortality and morbidity, we retrospectively examined patients with preprocedure hsCRP and BNP levels who underwent elective angioplasty or stent placement for lower extremity PAD.
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Mapping for maternal and newborn health: the distributions of women of childbearing age, pregnancies and births.
Int J Health Geogr
PUBLISHED: 01-04-2014
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The health and survival of women and their new-born babies in low income countries has been a key priority in public health since the 1990s. However, basic planning data, such as numbers of pregnancies and births, remain difficult to obtain and information is also lacking on geographic access to key services, such as facilities with skilled health workers. For maternal and newborn health and survival, planning for safer births and healthier newborns could be improved by more accurate estimations of the distributions of women of childbearing age. Moreover, subnational estimates of projected future numbers of pregnancies are needed for more effective strategies on human resources and infrastructure, while there is a need to link information on pregnancies to better information on health facilities in districts and regions so that coverage of services can be assessed.
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Molecular characterization and expression analysis of chloroplast protein import components in tomato (Solanum lycopersicum).
PLoS ONE
PUBLISHED: 01-01-2014
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The translocon at the outer envelope membrane of chloroplasts (Toc) mediates the recognition and initial import into the organelle of thousands of nucleus-encoded proteins. These proteins are translated in the cytosol as precursor proteins with cleavable amino-terminal targeting sequences called transit peptides. The majority of the known Toc components that mediate chloroplast protein import were originally identified in pea, and more recently have been studied most extensively in Arabidopsis. With the completion of the tomato genome sequencing project, it is now possible to identify putative homologues of the chloroplast import components in tomato. In the work reported here, the Toc GTPase cDNAs from tomato were identified, cloned and analyzed. The analysis revealed that there are four Toc159 homologues (slToc159-1, -2, -3 and -4) and two Toc34 homologues (slToc34-1 and -2) in tomato, and it was shown that tomato Toc159 and Toc34 homologues share high sequence similarity with the comparable import apparatus components from Arabidopsis and pea. Thus, tomato is a valid model for further study of this system. The expression level of Toc complex components was also investigated in different tissues during tomato development. The two tomato Toc34 homologues are expressed at higher levels in non-photosynthetic tissues, whereas, the expression of two tomato Toc159 homologues, slToc159-1 and slToc159-4, were higher in photosynthetic tissues, and the expression patterns of slToc159-2 was not significantly different in photosynthetic and non-photosynthetic tissues, and slToc159-3 expression was limited to a few select tissues.
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CD11b+ migratory dendritic cells mediate CD8 T cell cross-priming and cutaneous imprinting after topical immunization.
PLoS ONE
PUBLISHED: 01-01-2014
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Topical antigen application is a focus of current vaccine research. This immunization route mimics natural antigen exposure across a barrier tissue and generates T cells imprinted for skin-selective homing. Soluble antigens introduced through this route require cross-presentation by DC to generate CD8 T cell responses. Here we have explored the relative contribution of various skin-derived DC subsets to cross-priming and skin-selective imprinting. In our model, DC acquire soluble Ag in vivo from immunized murine skin for cross-presentation to naïve CD8 T cells ex vivo. We find CD11b(+) migratory DC to be the relevant cross-priming DC in this model. Both Langerin(+) and Langerin(-) CD11b(+) migratory DC can cross-present antigen in our system, but only the Langerin+ subset can induce expression of the skin-selective addressin E-selectin ligand. Thus, the CD11b(+) Langerin(+) migratory DC population, comprised primarily of Langerhans cells, both cross-primes naïve CD8 T cells and imprints them with skin-homing capabilities.
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The characterization of ESBL genes in Escherichia coli and Klebsiella pneumoniae causing nosocomial infections in Vietnam.
J Infect Dev Ctries
PUBLISHED: 12-17-2013
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Extended-spectrum ?-lactamases (ESBLs) are enzymes capable of hydrolyzing oxyimino-?-lactams and inducing resistance to third generation cephalosporins. The genes encoding ESBLs are widespread and generally located on highly transmissible resistance plasmids. We aimed to investigate the complement of ESBL genes in E. coli and Klebsiella pneumoniae causing nosocomial infections in hospitals in Ho Chi Minh City, Vietnam.
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Prevalence, genetic diversity and recombination of species G enteroviruses infecting pigs in Vietnam.
J. Gen. Virol.
PUBLISHED: 12-09-2013
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Picornaviruses infecting pigs, described for many years as "porcine enteroviruses", have recently been recognised as containing viruses within three distinct genera (Teschovirus, Sapelovirus and Enterovirus). To better characterise the epidemiology and genetic diversity of members of the Enterovirus genus, faecal samples from pigs from four provinces in Vietnam were screened by polymerase chain reaction using conserved enterovirus-specific primers from the 5 untranslated region. High rates of infection were recorded in pigs on all farms, with detection frequencies of approximately 90% in recently weaned pigs but declining to 40% in those aged over one year. No differences in EV detection rates were observed between pigs with and without diarrhoea (74% [n=70] compared with 72% [n=128]). Genetic analysis of consensus VP4/VP2 and VP1 sequences amplified from a subset of EV-infected pigs identified species G EVs in all samples. Among these, VP1 sequence comparisons identified six type 1 and seven type 6 variants while four further VP1 sequences failed to group with any previously identified EV-G types. These have now been formally assigned as EV-G types 8-11 by the Picornavirus Study Group. Comparison of VP1, VP4/VP2, 3Dpol and 5untranslated regions of study samples and those available on public databases showed frequent, bootstrap supported differences in their phylogenies indicative of extensive within-species recombination between genome regions. In summary, we have identified extremely high frequencies of infection with EV-G in pigs in Vietnam, substantial genetic diversity and recombination within the species and evidence for a much large number of circulating EV-G types than currently described.
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The genomic landscape of oesophagogastric junctional adenocarcinoma.
J. Pathol.
PUBLISHED: 12-06-2013
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The incidence of oesophagogastric junctional (OGJ) adenocarcinoma is rising rapidly in western countries, in contrast to the declining frequency of distal gastric carcinoma. Treatment options for adenocarcinomas involving the oesophagogastric junction are limited and the overall prognosis is extremely poor. To determine the genomic landscape of OGJ adenocarcinoma, exomes of eight tumours and matched germline DNA were subjected to massively parallel DNA sequencing. Microsatellite instability was observed in three tumours which coincided with an elevated number of somatic mutations. In total, 117 genes were identified that had predicted coding alterations in more than one tumour. Potentially actionable coding mutations were identified in 67 of these genes, including those in CR2, HGF , FGFR4, and ESRRB. Twenty-nine genes harbouring somatic coding mutations and copy number changes in the MSS OGJ dataset are also known to be altered with similar predicted functional consequence in other tumour types. Compared with the published mutational profile of gastric cancers, 49% (57/117) of recurrently mutated genes were unique to OGJ tumours. TP53, SYNE1, and ARID1A were amongst the most frequently mutated genes in a larger OGJ cohort. Our study provides an insight into the mutational landscape of OGJ adenocarcinomas and confirms that this is a highly mutated and heterogeneous disease. Furthermore, we have uncovered somatic mutations in therapeutically relevant genes which may represent candidate drug targets.
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Genome-wide Profiling of Genetic Synthetic Lethality Identifies CDK12 as a Novel Determinant of PARP1/2 Inhibitor Sensitivity.
Cancer Res.
PUBLISHED: 11-15-2013
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Small-molecule inhibitors of PARP1/2, such as olaparib, have been proposed to serve as a synthetic lethal therapy for cancers that harbor BRCA1 or BRCA2 mutations. Indeed, in clinical trials, PARP1/2 inhibitors elicit sustained antitumor responses in patients with germline BRCA gene mutations. In hypothesizing that additional genetic determinants might direct use of these drugs, we conducted a genome-wide synthetic lethal screen for candidate olaparib sensitivity genes. In support of this hypothesis, the set of identified genes included known determinants of olaparib sensitivity, such as BRCA1, RAD51, and Fanconis anemia susceptibility genes. In addition, the set included genes implicated in established networks of DNA repair, DNA cohesion, and chromatin remodeling, none of which were known previously to confer sensitivity to PARP1/2 inhibition. Notably, integration of the list of candidate sensitivity genes with data from tumor DNA sequencing studies identified CDK12 deficiency as a clinically relevant biomarker of PARP1/2 inhibitor sensitivity. In models of high-grade serous ovarian cancer (HGS-OVCa), CDK12 attenuation was sufficient to confer sensitivity to PARP1/2 inhibition, suppression of DNA repair via homologous recombination, and reduced expression of BRCA1. As one of only nine genes known to be significantly mutated in HGS-OVCa, CDK12 has properties that should confirm interest in its use as a biomarker, particularly in ongoing clinical trials of PARP1/2 inhibitors and other agents that trigger replication fork arrest. Cancer Res; 1-11. ©2013 AACR.
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Efficacy of preexposure prophylaxis for HIV-1 prevention among high-risk heterosexuals: subgroup analyses from a randomized trial.
AIDS
PUBLISHED: 11-11-2013
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Daily oral antiretroviral preexposure prophylaxis (PrEP) is a promising strategy for prevention of HIV-1 acquisition. Three clinical trials demonstrated PrEP efficacy; however, two PrEP trials among women did not find protection against HIV-1. One hypothesis proposed for these divergent results is that PrEP efficacy may be reduced in populations with higher HIV-1 incidence.
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Impaired decision making on the Balloon Analogue Risk Task as a result of long-term alcohol use.
J Clin Exp Neuropsychol
PUBLISHED: 11-11-2013
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The Balloon Analogue Risk Task (BART) is an experimental measure of risk taking that has commonly been employed to measure the risk taking behavior of nonclinical populations. Previous research has indicated that the task measures a unique aspect of behavioral disinhibition, but there has not as yet been focus upon the possible impact of other aspects of cognitive processing on performance. The current study investigated the cognitive factors related to performance of the BART in an alcohol-using sample. Seventeen individuals with long-term alcohol use were matched for age and education to a group of 17 nonusing participants. The results indicated that the alcohol-using group pumped the balloons on the BART to a lesser extent than did the nonusing group across all trials on the task. The results indicate that the alcohol-using group made less "optimal" decisions on the BART most notably due to neuropsychological impairment in the domains of immediate memory and executive functioning.
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Estimating surface visibility at Hong Kong from ground-based LIDAR, sun photometer and operational MODIS products.
J Air Waste Manag Assoc
PUBLISHED: 10-25-2013
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Hong Kongs surface visibility has decreased in recent years due to air pollution from rapid social and economic development in the region. In addition to deteriorating health standards, reduced visibility disrupts routine civil and public operations, most notably transportation and aviation. Regional estimates of visibility solved operationally using available ground and satellite-based estimates of aerosol optical properties and vertical distribution may prove more effective than standard reliance on a few existing surface visibility monitoring stations. Previous studies have demonstrated that such satellite measurements correlate well with near-surface optical properties, despite these sensors do not consider range-resolved information and indirect parameterizations necessary to solve relevant parameters. By expanding such analysis to include vertically resolved aerosol profile information from an autonomous ground-based lidar instrument, this work develops six models for automated assessment of surface visibility. Regional visibility is estimated using co-incident ground-based lidar, sun photometer visibility meter and MODerate-resolution maging Spectroradiometer (MODIS) aerosol optical depth data sets. Using a 355 nm extinction coefficient profile solved from the lidar MODIS AOD (aerosol optical depth) is scaled down to the surface to generate a regional composite depiction of surface visibility. These results demonstrate the potential for applying passive satellite depictions of broad-scale aerosol optical properties together with a ground-based surface lidar and zenith-viewing sun photometer for improving quantitative assessments of visibility in a city such as Hong Kong.
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Biased agonism as a mechanism for differential signaling by chemokine receptors.
J. Biol. Chem.
PUBLISHED: 10-21-2013
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Chemokines display considerable promiscuity with multiple ligands and receptors shared in common, a phenomenon that is thought to underlie their biochemical "redundancy." Their receptors are part of a larger seven-transmembrane receptor superfamily, commonly referred to as G protein-coupled receptors, which have been demonstrated to be able to signal with different efficacies to their multiple downstream signaling pathways, a phenomenon referred to as biased agonism. Biased agonism has been primarily reported as a phenomenon of synthetic ligands, and the biologic prevalence and importance of such signaling are unclear. Here, to assess the presence of biased agonism that may underlie differential signaling by chemokines targeting the same receptor, we performed a detailed pharmacologic analysis of a set of chemokine receptors with multiple endogenous ligands using assays for G protein signaling, ?-arrestin recruitment, and receptor internalization. We found that chemokines targeting the same receptor can display marked differences in their efficacies for G protein- or ?-arrestin-mediated signaling or receptor internalization. This ligand bias correlates with changes in leukocyte migration, consistent with different mechanisms underlying the signaling downstream of these receptors induced by their ligands. These findings demonstrate that biased agonism is a common and likely evolutionarily conserved biological mechanism for generating qualitatively distinct patterns of signaling via the same receptor in response to different endogenous ligands.
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Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial.
PLoS Negl Trop Dis
PUBLISHED: 10-01-2013
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Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A.
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Tracking the establishment of local endemic populations of an emergent enteric pathogen.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-30-2013
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Shigella sonnei is a human-adapted pathogen that is emerging globally as the dominant agent of bacterial dysentery. To investigate local establishment, we sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data show that S. sonnei was introduced into Vietnam in the 1980s and has undergone localized clonal expansion, punctuated by genomic fixation events through periodic selective sweeps. We uncover geographical spread, spatially restricted frontier populations, and convergent evolution through local gene pool sampling. This work provides a unique, high-resolution insight into the microevolution of a pioneering human pathogen during its establishment in a new host population.
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Bigger, faster? Associations between hospital thrombolysis volume and speed of thrombolysis administration in acute ischemic stroke.
Stroke
PUBLISHED: 09-19-2013
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There is evidence that high-volume hospitals may produce better patient outcomes. We aimed to identify whether there were any associations between hospital thrombolysis volume and speed of thrombolysis (tissue-type plasminogen activator [tPA]) administration in patients with ischemic stroke.
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Individual Variation in Sleep Quality and Duration Is Related to Cerebral Mu Opioid Receptor Binding Potential during Tonic Laboratory Pain in Healthy Subjects.
Pain Med
PUBLISHED: 09-18-2013
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Although poor sleep is a consequence of pain, sleep disturbance reciprocally induces hyperalgesia and exacerbates clinical pain. Conceptual models of chronic pain implicate dysfunctional supraspinal pain processing mechanisms, mediated in part by endogenous opioid peptides. Our preliminary work indicates that sleep disruption impairs psychophysical measures of descending pain modulation, but few studies have investigated whether insufficient sleep may be associated with alterations in endogenous opioid systems. This preliminary, exploratory investigation sought to examine the relationship between sleep and functioning of the cerebral mu opioid system during the experience of pain in healthy participants.
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Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.
PLoS Med.
PUBLISHED: 09-01-2013
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Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.
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CCR7 plays no appreciable role in trafficking of central memory CD4 T cells to lymph nodes.
J. Immunol.
PUBLISHED: 08-09-2013
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CCR7?/? mice exhibit profound anomalies in lymph node and spleen architecture, which complicates the study of CCR7-mediated T cell trafficking in vivo. To circumvent this problem, we established in vivo models in which wild-type and CCR7?/? populations coexist within mice possessing normal lymphoid organs and must compete for developmental niches within the tissues of these mice. Under the conditions we have created in vivo, we find the entry of memory CD4 T cells into lymph nodes from the blood to be independent of CCR7. Thus, the central memory CD4 T cells that traffic though lymph nodes, which are often defined by their expression of CCR7, do not appear to gain any competitive homing advantage by expressing this receptor. Furthermore, in contrast to cutaneous dendritic cell populations, we found that CCR7 deficiency had no appreciable effect on the exit of CD4 T cells from inflamed skin. Finally, we found that wild-type and CCR7?/? precursors were equally represented within the major thymic subpopulations, despite previous findings that CCR7 plays a role in seeding the thymus from bone marrow-derived T cell precursors.
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Semantic interoperation and electronic health records: context sensitive mapping from SNOMED CT to ICD-10.
Stud Health Technol Inform
PUBLISHED: 08-08-2013
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An important case for successful deployment of a lifetime electronic health record is reuse of clinical data from the electronic health record (EHR) for epidemiology, reimbursement, and research. We report a collaboration between the IHTSDO and the WHO to develop knowledge-based tools supporting translation of data from SNOMED CT to the ICD-10 classification. These tools have been vetted by an international community and are available for system vendors to enhance the interoperability of their products. The maps we created are also informing the development of the next generation of classifications which will employ a common ontology base between SNOMED CT and ICD-11 to promote interoperability.
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Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study.
Clin. Cancer Res.
PUBLISHED: 08-06-2013
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Preclinical data suggest that exposure to PARP inhibitors (PARPi) may compromise benefit to subsequent chemotherapy, particularly platinum-based regimens, in patients with BRCA1/2 mutation carrier ovarian cancer (PBMCOC), possibly through the acquisition of secondary BRCA1/2 mutations. The efficacy of chemotherapy in the PARPi-resistant setting was therefore investigated.
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Identification of Salmonella enterica serovar Typhi genotypes by use of rapid multiplex ligation-dependent probe amplification.
J. Clin. Microbiol.
PUBLISHED: 07-03-2013
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Salmonella enterica serovar Typhi, the causative agent of typhoid fever, is highly clonal and genetically conserved, making isolate subtyping difficult. We describe a standardized multiplex ligation-dependent probe amplification (MLPA) genotyping scheme targeting 11 key phylogenetic markers of the S. Typhi genome. The MLPA method demonstrated 90% concordance with single nucleotide polymorphism (SNP) typing, the gold standard for S. Typhi genotyping, and had the ability to identify isolates of the H58 haplotype, which is associated with resistance to multiple antimicrobials. Additionally, the assay permitted the detection of fluoroquinolone resistance-associated mutations in the DNA gyrase-encoding gene gyrA and the topoisomerase gene parC with a sensitivity of 100%. The MLPA methodology is simple and reliable, providing phylogenetically and phenotypically relevant genotyping information. This MLPA scheme offers a more-sensitive and interpretable alternative to the nonphylogenetic subgrouping methodologies that are currently used in reference and research laboratories in areas where typhoid is endemic.
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Parallel RNA interference screens identify EGFR activation as an escape mechanism in FGFR3-mutant cancer.
Cancer Discov
PUBLISHED: 06-06-2013
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Activation of fibroblast growth factor receptors (FGFR) is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference (RNAi) genetic screens, we show that the EGF receptor (EGFR) limits sensitivity to FGFR inhibition in FGFR3-mutant and -translocated cell lines, but not in other FGFR-driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3-dependent lines, inhibition of FGFR3 results in transient downregulation of mitogen-activated protein kinase signaling that is rescued by rapid upregulation of EGFR signaling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signaling via repression of FGFR3, with EGFR inhibition rescued by delayed upregulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNAi screens in identifying common resistance mechanisms to targeted therapies.
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Endemic norovirus infections in children, Ho Chi Minh City, Vietnam, 2009-2010.
Emerging Infect. Dis.
PUBLISHED: 06-06-2013
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We performed a case-control investigation to identify risk factors for norovirus infections among children in Vietnam. Of samples from 1,419 children who had diarrhea and 609 who were asymptomatic, 20.6% and 2.8%, respectively, were norovirus positive. Risk factors included residential crowding and symptomatic contacts, indicating person-to-person transmission of norovirus.
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Associations between the organisation of stroke services, process of care, and mortality in England: prospective cohort study.
BMJ
PUBLISHED: 05-14-2013
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To estimate the relations between the organisation of stroke services, process measures of care quality, and 30 day mortality in patients admitted with acute ischaemic stroke.
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The dynamics of GII.4 Norovirus in Ho Chi Minh City, Vietnam.
Infect. Genet. Evol.
PUBLISHED: 04-05-2013
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Norovirus (NoV) is a major cause of epidemic gastroenteritis in industrialized countries, yet the epidemiological significance of NoV in industrializing countries remains poorly understood. The spatiotemporal distribution of NoV genotypes identified in 2054 enrolled children was investigated between May 2009 and December 2010, in Ho Chi Minh City (HCMC), Vietnam. A total of 315 NoV extracted from stool samples were genotyped and GPS mapped to their source. Genogroup II NoV, particularly GII.4, were predominant, and the GII.4 strains could be subgrouped into GII.4-2006b (Minerva) and GII.4-2010 (New Orleans) variants. There was no spatiotemporal structure among the endemic GII strains; yet a significant spatiotemporal signal corresponding with the novel introduction of GII.4-2010 variant was detected. These data show that NoV GII.4 variants are highly endemic in HCMC and describe a scenario of rapid NoV strain replacement occurring in HCMC in early 2010.
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Combination antifungal therapy for cryptococcal meningitis.
N. Engl. J. Med.
PUBLISHED: 04-05-2013
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Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.
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Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor.
J. Pathol.
PUBLISHED: 03-21-2013
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PARP inhibitors (PARPi) for the treatment of BRCA1 or BRCA2 deficient tumours are currently the focus of seminal clinical trials exploiting the concept of synthetic lethality. Although clinical resistance to PARPi has been described, the mechanism underlying this has not been elucidated. Here, we investigate tumour material from patients who had developed resistance to the PARPi olaparib, subsequent to showing an initial clinical response. Massively parallel DNA sequencing of treatment-naive and post-olaparib treatment biopsies identified tumour-specific BRCA2 secondary mutations in olaparib-resistant metastases. These secondary mutations restored full-length BRCA2 protein, and most likely cause olaparib resistance by re-establishing BRCA2 function in the tumour cells.
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UGA is an additional glycine codon in uncultured SR1 bacteria from the human microbiota.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-18-2013
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The composition of the human microbiota is recognized as an important factor in human health and disease. Many of our cohabitating microbes belong to phylum-level divisions for which there are no cultivated representatives and are only represented by small subunit rRNA sequences. For one such taxon (SR1), which includes bacteria with elevated abundance in periodontitis, we provide a single-cell genome sequence from a healthy oral sample. SR1 bacteria use a unique genetic code. In-frame TGA (opal) codons are found in most genes (85%), often at loci normally encoding conserved glycine residues. UGA appears not to function as a stop codon and is in equilibrium with the canonical GGN glycine codons, displaying strain-specific variation across the human population. SR1 encodes a divergent tRNA(Gly)UCA with an opal-decoding anticodon. SR1 glycyl-tRNA synthetase acylates tRNA(Gly)UCA with glycine in vitro with similar activity compared with normal tRNA(Gly)UCC. Coexpression of SR1 glycyl-tRNA synthetase and tRNA(Gly)UCA in Escherichia coli yields significant ?-galactosidase activity in vivo from a lacZ gene containing an in-frame TGA codon. Comparative genomic analysis with Human Microbiome Project data revealed that the human body harbors a striking diversity of SR1 bacteria. This is a surprising finding because SR1 is most closely related to bacteria that live in anoxic and thermal environments. Some of these bacteria share common genetic and metabolic features with SR1, including UGA to glycine reassignment and an archaeal-type ribulose-1,5-bisphosphate carboxylase (RubisCO) involved in AMP recycling. UGA codon reassignment renders SR1 genes untranslatable by other bacteria, which impacts horizontal gene transfer within the human microbiota.
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Human resources for health and universal health coverage: fostering equity and effective coverage.
Bull. World Health Organ.
PUBLISHED: 03-12-2013
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Achieving universal health coverage (UHC) involves distributing resources, especially human resources for health (HRH), to match population needs. This paper explores the policy lessons on HRH from four countries that have achieved sustained improvements in UHC: Brazil, Ghana, Mexico and Thailand. Its purpose is to inform global policy and financial commitments on HRH in support of UHC. The paper reports on country experiences using an analytical framework that examines effective coverage in relation to the availability, accessibility, acceptability and quality (AAAQ) of HRH. The AAAQ dimensions make it possible to perform tracing analysis on HRH policy actions since 1990 in the four countries of interest in relation to national trends in workforce numbers and population mortality rates. The findings inform key principles for evidence-based decision-making on HRH in support of UHC. First, HRH are critical to the expansion of health service coverage and the package of benefits; second, HRH strategies in each of the AAAQ dimensions collectively support achievements in effective coverage; and third, success is achieved through partnerships involving health and non-health actors. Facing the unprecedented health and development challenges that affect all countries and transforming HRH evidence into policy and practice must be at the heart of UHC and the post-2015 development agenda. It is a political imperative requiring national commitment and leadership to maximize the impact of available financial and human resources, and improve healthy life expectancy, with the recognition that improvements in health care are enabled by a health workforce that is fit for purpose.
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Tribolium castaneum (Coleoptera: Tenebrionidae) associated with rice mills: fumigation efficacy and population rebound.
J. Econ. Entomol.
PUBLISHED: 03-02-2013
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The red flourbeetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae), is the most important stored-product insect pest infesting rice (Oryza sativa L.) mills in the United States. Due to the phasing out of methyl bromide in accordance with the 1987 Montreal Protocol, the efficacy of alternative fumigants in controlling flour beetles in mill structures must be evaluated. Long-term trapping data sets (2-6 yr) of T. castaneum in and around seven rice mills were analyzed to assess the efficacy of sulfuryl fluoride fumigation (n = 25). Fumigation efficacy was evaluated as the percentage reduction in mean trap captures of adults and proportion of traps capturing at least one adult beetle. Beetle trap captures fluctuated seasonally, with increased captures during the warmer months, June-September, that dropped off during the cooler months, October-March. Fumigations resulted in a 66 +/- 6% (mean +/- SE) reduction in mean trap captures within mills and a 52 +/- 6% reduction in the proportion of traps capturing at least one adult beetle. Lengths of time for captures to reach prefumigation levels, or rebound rates, were variable, and adult capture levels inside were most influenced by seasonal temperature changes. Temperatures inside mills followed those outside the mill closely, and a significant positive relationship between outside temperatures and trap captures was observed. Inside and outside trap captures exhibited a significant, positive relationship, but fumigations consistently led to reductions in beetle captures outside of mills, highlighting the interconnectedness of populations located inside and outside mill structures.
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Multiple single-cell genomes provide insight into functions of uncultured Deltaproteobacteria in the human oral cavity.
PLoS ONE
PUBLISHED: 02-13-2013
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Despite a long history of investigation, many bacteria associated with the human oral cavity have yet to be cultured. Studies that correlate the presence or abundance of uncultured species with oral health or disease highlight the importance of these community members. Thus, we sequenced several single-cell genomic amplicons from Desulfobulbus and Desulfovibrio (class Deltaproteobacteria) to better understand their function within the human oral community and their association with periodontitis, as well as other systemic diseases. Genomic data from oral Desulfobulbus and Desulfovibrio species were compared to other available deltaproteobacterial genomes, including from a subset of host-associated species. While both groups share a large number of genes with other environmental Deltaproteobacteria genomes, they encode a wide array of unique genes that appear to function in survival in a host environment. Many of these genes are similar to virulence and host adaptation factors of known human pathogens, suggesting that the oral Deltaproteobacteria have the potential to play a role in the etiology of periodontal disease.
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An oral preparation of Lactobacillus acidophilus for the treatment of uncomplicated acute watery diarrhoea in Vietnamese children: study protocol for a multicentre, randomised, placebo-controlled trial.
Trials
PUBLISHED: 01-28-2013
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Diarrhoeal disease is a major global health problem, particularly affecting children under the age of 5 years. Besides oral rehydration solution, probiotics are also commonly prescribed to children with acute watery diarrhoea in some settings. Results from randomised clinical trials (RCTs) in which investigators studied the effect of probiotics on diarrhoeal symptoms have largely shown a positive effect; yet, the overall quality of the data is limited. In Vietnam, probiotics are the most frequently prescribed treatment for children hospitalised with acute watery diarrhoea, but there is little justification for this treatment in this location. We have designed a RCT to test the hypothesis that an oral preparation of Lactobacillus acidophilus is superior to placebo in the treatment of acute watery diarrhoea in Vietnamese children.
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The effect of opportunistic illness on HIV RNA viral load and CD4+ T cell count among HIV-positive adults taking antiretroviral therapy.
J Int AIDS Soc
PUBLISHED: 01-25-2013
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HIV RNA viral load (VL) has been shown to increase during opportunistic illnesses (OIs), suggesting active HIV replication in response to infection among patients not taking antiretroviral therapy (ART). We assessed the effects of OIs on HIV RNA VL and CD4+ T cell counts among patients on ART with initially suppressed VL.
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Effects of infection control measures on acquisition of five antimicrobial drug-resistant microorganisms in a tetanus intensive care unit in Vietnam.
Intensive Care Med
PUBLISHED: 01-10-2013
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To quantify the effects of barrier precautions and antibiotic mixing on prevalence and acquisition of five drug-resistant microorganisms within a single tetanus intensive care unit at a tertiary referral hospital in Ho Chi Minh City, Vietnam.
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Comparative metagenomic and rRNA microbial diversity characterization using archaeal and bacterial synthetic communities.
Environ. Microbiol.
PUBLISHED: 01-05-2013
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Next-generation sequencing has dramatically changed the landscape of microbial ecology, large-scale and in-depth diversity studies being now widely accessible. However, determining the accuracy of taxonomic and quantitative inferences and comparing results obtained with different approaches are complicated by incongruence of experimental and computational data types and also by lack of knowledge of the true ecological diversity. Here we used highly diverse bacterial and archaeal synthetic communities assembled from pure genomic DNAs to compare inferences from metagenomic and SSU rRNA amplicon sequencing. Both Illumina and 454 metagenomic data outperformed amplicon sequencing in quantifying the community composition, but the outcome was dependent on analysis parameters and platform. New approaches in processing and classifying amplicons can reconstruct the taxonomic composition of the community with high reproducibility within primer sets, but all tested primers sets lead to significant taxon-specific biases. Controlled synthetic communities assembled to broadly mimic the phylogenetic richness in target environments can provide important validation for fine-tuning experimental and computational parameters used to characterize natural communities.
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Antiretroviral prophylaxis for sexual and injection drug use acquisition of HIV.
Am J Prev Med
PUBLISHED: 01-04-2013
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During the past few years, much has been learned about pre-exposure prophylaxis (PrEP) of HIV from studies conducted in the U.S. and elsewhere. A review and summary was conducted of articles and reports published through August 2012 on the safety and efficacy of PrEP in humans; U.S.-based studies assessing PrEP knowledge, attitudes, and use among at-risk populations and healthcare providers; and models of the cost effectiveness of PrEP. PrEP is generally safe and effective and may be cost effective in a targeted population. Awareness and interest in PrEP are increasing. PrEP is an important new addition to HIV prevention services, but continued study is warranted.
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A successful antimicrobial regime for Chromobacterium violaceum induced bacteremia.
BMC Infect. Dis.
PUBLISHED: 01-03-2013
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Chromobacterium violaceum is a proteobacterium found in soil and water in tropical regions. The organism rarely causes infection in humans, yet can cause a severe systemic infection by entering the bloodstream via an open wound.
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A genetic screen using the PiggyBac transposon in haploid cells identifies Parp1 as a mediator of olaparib toxicity.
PLoS ONE
PUBLISHED: 01-01-2013
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Genetic perturbation screens have the potential to dissect a wide range of cellular phenotypes. Such screens have historically been difficult in diploid mammalian cells. The recent derivation of haploid embryonic stem cells provides an opportunity to cause loss of function mutants with a random mutagen in a mammalian cell with a normal genetic background. We describe an approach to genetic screens that exploits the highly active piggyBac transposon in haploid mammalian cells. As an example of haploid transposon (HTP) screening, we apply this approach to identifying determinants of cancer drug toxicity and resistance. In a screen for 6-thioguanine resistance we recovered components of the DNA mismatch repair pathway, a known requirement for toxicity. In a further screen for resistance to the clinical poly(ADP-ribose) polymerase (PARP) inhibitor olaparib we recovered multiple Parp1 mutants. Our results show that olaparib toxicity to normal cells is mediated predominantly via Parp1, and suggest that the clinical side effects of olaparib may be on target. The transposon mutant libraries are stable and can be readily reused to screen other drugs. The screening protocol described has several advantages over other methods such as RNA interference: it is rapid and low cost, and mutations can be easily reverted to establish causality.
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Distinct and complex bacterial profiles in human periodontitis and health revealed by 16S pyrosequencing.
ISME J
PUBLISHED: 12-15-2011
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Periodontitis has a polymicrobial etiology within the framework of a complex microbial ecosystem. With advances in sequencing technologies, comprehensive studies to elucidate bacterial community differences have recently become possible. We used 454 sequencing of 16S rRNA genes to compare subgingival bacterial communities from 29 periodontally healthy controls and 29 subjects with chronic periodontitis. Amplicons from both the V1-2 and V4 regions of the 16S gene were sequenced, yielding 1,393,579 sequences. They were identified by BLAST against a curated oral 16S database, and mapped to 16 phyla, 106 genera, and 596 species. 81% of sequences could be mapped to cultivated species. Differences between health- and periodontitis-associated bacterial communities were observed at all phylogenetic levels, and UniFrac and principal coordinates analysis showed distinct community profiles in health and disease. Community diversity was higher in disease, and 123 species were identified that were significantly more abundant in disease, and 53 in health. Spirochaetes, Synergistetes and Bacteroidetes were more abundant in disease, whereas the Proteobacteria were found at higher levels in healthy controls. Within the phylum Firmicutes, the class Bacilli was health-associated, whereas the Clostridia, Negativicutes and Erysipelotrichia were associated with disease. These results implicate a number of taxa that will be targets for future research. Some, such as Filifactor alocis and many Spirochetes were represented by a large fraction of sequences as compared with previously identified targets. Elucidation of these differences in community composition provides a basis for further understanding the pathogenesis of periodontitis.
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The cutaneous trunci muscle reflex: a predictor of recovery in dogs with acute thoracolumbar myelopathies caused by intervertebral disc extrusions.
Vet Surg
PUBLISHED: 12-08-2011
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To determine whether changes in the cutaneous trunci muscle (CTM) reflex are an early predictor of outcome in dogs with severe acute thoracolumbar intervertebral disc extrusion (IVDE).
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Endometrial carcinoma diagnosed by scapular biopsy: A case report.
Gynecol Oncol Case Rep
PUBLISHED: 12-01-2011
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? Endometrial cancer diagnosed by scapular biopsy. ? Advanced cancer may present with metastatic disease to the bone.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.