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- Photon statistics and speckle visibility spectroscopy with partially coherent X-rays.Li L, Kwaśniewski P, Orsi D, Wiegart L, Cristofolini L, Caronna C, Fluerasu AJ Synchrotron Radiat
- High-throughput synchrotron X-ray diffraction for combinatorial phase mapping.Gregoire JM, Van Campen DG, Miller CE, Jones RJ, Suram SK, Mehta AJ Synchrotron Radiat
- Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.Han BY, Wu S, Foo CS, Horton RM, Jenne CN, Watson SR, Whittle B, Goodnow CC, Cyster JGElife
- Is local hypoperfusion the reason for transient neurological deficits after STA-MCA bypass for moyamoya disease?Mukerji N, Cook DJ, Steinberg GKJ Neurosurg
- Carbapenemase-producing Klebsiella pneumoniae.Robilotti E, Deresinski SF1000Prime Rep
- Computational modeling of hypertensive growth in the human carotid artery.Sáez P, Peña E, Martínez MA, Kuhl EComput Mech
- Association Between Insomnia Symptoms and Functional Status in U.S. Older Adults.Spira AP, Kaufmann CN, Kasper JD, Ohayon MM, Rebok GW, Skidmore E, Parisi JM, Reynolds CFJ Gerontol B Psychol Sci Soc Sci
- Battle of the Bulge: miR-195 Versus miR-29b in Aortic Aneurysm.Spin JM, Tsao PSCirc Res
- Conditional density-based analysis of T cell signaling in single-cell data.Krishnaswamy S, Spitzer MH, Mingueneau M, Bendall SC, Litvin O, Stone E, Pe'er D, Nolan GPScience
- The Role of Genome Sequencing in Personalized Breast Cancer Prevention.Sieh W, Rothstein JH, McGuire V, Whittemore ASCancer Epidemiol Biomarkers Prev
- Using the wisdom of the crowds to find critical errors in biomedical ontologies: a study of SNOMED CT.Mortensen JM, Minty EP, Januszyk M, Sweeney TE, Rector AL, Noy NF, Musen MAJ Am Med Inform Assoc
- Toward a science of learning systems: a research agenda for the high-functioning Learning Health System.Friedman C, Rubin J, Brown J, Buntin M, Corn M, Etheredge L, Gunter C, Musen M, Platt R, Stead W, Sullivan K, Van Houweling DJ Am Med Inform Assoc
- Does a medial retraction blade transmit direct pressure to pharynx/esophagus wall during anterior cervical surgery?Han IH, Lee SH, Lee JM, Kim HS, Nam KH, Duetzmann S, Park J, Choi BKSpine (Phila Pa 1976)
- T-Cell Profile in Adipose Tissue Is Associated With Insulin Resistance and Systemic Inflammation in Humans.McLaughlin T, Liu LF, Lamendola C, Shen L, Morton J, Rivas H, Winer D, Tolentino L, Choi O, Zhang H, Ch'ng M, Engleman EArterioscler Thromb Vasc Biol
- Waking sleeping algal cells.Li X, Umen JG, Jonikas MCProc Natl Acad Sci U S A
- Heparin Use in Hemodialysis Patients following Gastrointestinal Bleeding.Shen JI, Mitani AA, Winkelmayer WCAm J Nephrol
- Comparative analysis of regulatory information and circuits across distant species.Boyle AP, Araya CL, Brdlik C, Cayting P, Cheng C, Cheng Y, Gardner K, Hillier LW, Janette J, Jiang L, Kasper D, Kawli T, Kheradpour P, Kundaje A, Li JJ, Ma L, Niu W, Rehm EJ, Rozowsky J, Slattery M, Spokony R, Terrell R, Vafeados D, Wang D, Weisdepp P, Wu YC, Xie D, Yan KK, Feingold EA, Good PJ, Pazin MJ, Huang H, Bickel PJ, Brenner SE, Reinke V, Waterston RH, Gerstein M, White KP, Kellis M, Snyder MNature
- Comparative analysis of metazoan chromatin organization.Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A, Tolstorukov MY, Appert A, Parker SC, Gu T, Kundaje A, Riddle NC, Bishop E, Egelhofer TA, Hu SS, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RA, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM, Strome S, Elgin SC, Liu XS, Lieb JD, Ahringer J, Karpen GH, Park PJNature
- Neural constraints on learning.Sadtler PT, Quick KM, Golub MD, Chase SM, Ryu SI, Tyler-Kabara EC, Yu BM, Batista APNature
- Regulatory analysis of the C. elegans genome with spatiotemporal resolution.Araya CL, Kawli T, Kundaje A, Jiang L, Wu B, Vafeados D, Terrell R, Weissdepp P, Gevirtzman L, Mace D, Niu W, Boyle AP, Xie D, Ma L, Murray JI, Reinke V, Waterston RH, Snyder MNature
- Re: co-existence of intramuscular spindle cell lipoma with an intramuscular ordinary lipoma. Report of a case.Chernev I, Mctighe S, Stanley DPPol J Pathol
- Processing properties of ON and OFF pathways for Drosophila motion detection.Behnia R, Clark DA, Carter AG, Clandinin TR, Desplan CNature
- Hydrological controls on methylmercury distribution and flux in a tidal marsh.Zhang H, Moffett KB, Windham-Myers L, Gorelick SMEnviron Sci Technol
- Age-related macular degeneration and protective effect of HMG Co-A reductase inhibitors (statins): results from the National Health and Nutrition Examination Survey 2005-2008.Barbosa DT, Mendes TS, Cíntron-Colon HR, Wang SY, Bhisitkul RB, Singh K, Lin SCEye (Lond)
- The impact of change in pregnancy body mass index on the development of gestational hypertensive disorders.Swank ML, Caughey AB, Farinelli CK, Main EK, Melsop KA, Gilbert WM, Chung JHJ Perinatol
- Outcomes of extremely preterm infants following severe intracranial hemorrhage.Davis AS, Hintz SR, Goldstein RF, Ambalavanan N, Bann CM, Stoll BJ, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Das A, Higgins RD, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research NetworkJ Perinatol
- Genetically encoded voltage sensor goes live.Marshel JH, Deisseroth KNat Biotechnol
- A single-molecule long-read survey of the human transcriptome.Sharon D, Tilgner H, Grubert F, Snyder MNat Biotechnol
- Hypertension: Do calcium-channel blockers increase breast cancer risk?Wang A, Manson JENat Rev Cardiol
- Classic biphasic pulmonary blastoma demonstrated by 18F-FDG PET/CT.Keu KV, Berry GJ, Quon AClin Nucl Med
Photon statistics and speckle visibility spectroscopy with partially coherent X-rays.
J Synchrotron Radiat. 2014 Nov 1;21(Pt 6):1288-1295
Authors: Li L, Kwaśniewski P, Orsi D, Wiegart L, Cristofolini L, Caronna C, Fluerasu A
A new approach is proposed for measuring structural dynamics in materials from multi-speckle scattering patterns obtained with partially coherent X-rays. Coherent X-ray scattering is already widely used at high-brightness synchrotron lightsources to measure dynamics using X-ray photon correlation spectroscopy, but in many situations this experimental approach based on recording long series of images (i.e. movies) is either not adequate or not practical. Following the development of visible-light speckle visibility spectroscopy, the dynamic information is obtained instead by analyzing the photon statistics and calculating the speckle contrast in single scattering patterns. This quantity, also referred to as the speckle visibility, is determined by the properties of the partially coherent beam and other experimental parameters, as well as the internal motions in the sample (dynamics). As a case study, Brownian dynamics in a low-density colloidal suspension is measured and an excellent agreement is found between correlation functions measured by X-ray photon correlation spectroscopy and the decay in speckle visibility with integration time obtained from the analysis presented here.
PMID: 25343797 [PubMed - as supplied by publisher]
High-throughput synchrotron X-ray diffraction for combinatorial phase mapping.
J Synchrotron Radiat. 2014 Nov 1;21(Pt 6):1262-1268
Authors: Gregoire JM, Van Campen DG, Miller CE, Jones RJ, Suram SK, Mehta A
Discovery of new materials drives the deployment of new technologies. Complex technological requirements demand precisely tailored material functionalities, and materials scientists are driven to search for these new materials in compositionally complex and often non-equilibrium spaces containing three, four or more elements. The phase behavior of these high-order composition spaces is mostly unknown and unexplored. High-throughput methods can offer strategies for efficiently searching complex and multi-dimensional material genomes for these much needed new materials and can also suggest a processing pathway for synthesizing them. However, high-throughput structural characterization is still relatively under-developed for rapid material discovery. Here, a synchrotron X-ray diffraction and fluorescence experiment for rapid measurement of both X-ray powder patterns and compositions for an array of samples in a material library is presented. The experiment is capable of measuring more than 5000 samples per day, as demonstrated by the acquisition of high-quality powder patterns in a bismuth-vanadium-iron oxide composition library. A detailed discussion of the scattering geometry and its ability to be tailored for different material systems is provided, with specific attention given to the characterization of fiber textured thin films. The described prototype facility is capable of meeting the structural characterization needs for the first generation of high-throughput material genomic searches.
PMID: 25343793 [PubMed - as supplied by publisher]
Zinc finger protein Zfp335 is required for the formation of the naïve T cell compartment.
Authors: Han BY, Wu S, Foo CS, Horton RM, Jenne CN, Watson SR, Whittle B, Goodnow CC, Cyster JG
The generation of naïve T lymphocytes is critical for immune function yet the mechanisms governing their maturation remain incompletely understood. We have identified a mouse mutant, bloto, that harbors a hypomorphic mutation in the zinc finger protein Zfp335. Zfp335(bloto/bloto) mice exhibit a naïve T cell deficiency due to an intrinsic developmental defect that begins to manifest in the thymus and continues into the periphery, affecting T cells that have recently undergone thymic egress. The effects of Zfp335(bloto) are multigenic and cannot be attributed to altered thymic selection, proliferation or Bcl2-dependent survival. Zfp335 binds to promoter regions via a consensus motif, and its target genes are enriched in categories related to protein metabolism, mitochondrial function, and transcriptional regulation. Restoring the expression of one target, Ankle2, partially rescues T cell maturation. These findings identify Zfp335 as a transcription factor and essential regulator of late-stage intrathymic and post-thymic T cell maturation.
PMID: 25343476 [PubMed - as supplied by publisher]
Is local hypoperfusion the reason for transient neurological deficits after STA-MCA bypass for moyamoya disease?
J Neurosurg. 2014 Oct 24;:1-5
Authors: Mukerji N, Cook DJ, Steinberg GK
OBJECT Hyperperfusion is believed to be the cause of transient neurological events (TNEs) in patients with moyamoya disease (MMD) who have undergone an extracranial-to-intracranial (EC-IC) bypass between the superficial temporal artery (STA) and the middle cerebral artery (MCA). The objective of this study was to evaluate this possibility by analyzing cerebral blood flow (CBF) data obtained with thermal diffusion probes used at the authors' center. METHODS The authors examined postoperative cerebral perfusion in 31 patients with MMD who underwent a direct EC-IC STA-MCA bypass. A Hemedex Q500 flow probe was placed in the frontal lobe adjacent to the bypass and connected to a Bowman cerebral perfusion monitor, and CBF data were statistically analyzed using JMP 8.0.2 software. Seven patients experienced a TNE after surgery in the left hemisphere (that is, after left-sided surgery), manifesting as dysphasia approximately 24 hours postoperatively and which had improved by 48 hours. No TNEs were observed after right-sided surgeries. Operative and postoperative CBFs in the left side with the TNE were compared with those in the left side with no TNE and on the right side. RESULTS A detailed analysis of 64,980 minute-by-minute flow observations showed that the initial postbypass CBF was higher on the left side where the TNEs occurred. This CBF increase was followed by a widely fluctuating pattern and a statistically significant and sharp drop in perfusion (p < 0.001, mean difference of CBF between groups, paired t-test) associated with a TNE not observed in the other 2 groups. CONCLUSIONS On the basis of the authors' initial observations, an early-onset altered pattern of CBF was identified. These findings suggest local hypoperfusion as the cause of the TNEs. This hypoperfusion may originate from competing blood flows resulting from impaired cerebral autoregulation and a fluctuating flow in cerebral microcirculation.
PMID: 25343178 [PubMed - as supplied by publisher]
Carbapenemase-producing Klebsiella pneumoniae.
F1000Prime Rep. 2014;6:80
Authors: Robilotti E, Deresinski S
The continuing emergence of infections due to multidrug resistant bacteria is a serious public health problem. Klebsiella pneumoniae, which commonly acquires resistance encoded on mobile genetic elements, including ones that encode carbapenemases, is a prime example. K. pneumoniae carrying such genetic material, including both blaKPC and genes encoding metallo-β-lactamases, have spread globally. Many carbapenemase-producing K. pneumoniae are resistant to multiple antibiotic classes beyond β-lactams, including tetracyclines, aminoglycosides, and fluoroquinolones. The optimal treatment, if any, for infections due to these organisms is unclear but, paradoxically, appears to often require the inclusion of an optimally administered carbapenem.
PMID: 25343037 [PubMed]
Computational modeling of hypertensive growth in the human carotid artery.
Comput Mech. 2014 Jun;53(6):1183-1196
Authors: Sáez P, Peña E, Martínez MA, Kuhl E
Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively.
PMID: 25342868 [PubMed - as supplied by publisher]
Association Between Insomnia Symptoms and Functional Status in U.S. Older Adults.
J Gerontol B Psychol Sci Soc Sci. 2014 Nov;69(Suppl 1):S35-S41
Authors: Spira AP, Kaufmann CN, Kasper JD, Ohayon MM, Rebok GW, Skidmore E, Parisi JM, Reynolds CF
OBJECTIVES: We studied the association between insomnia symptoms and late-life functioning, including physical capacity, limitations in household activities, and participation in valued activities.
METHODS: Participants were 6,050 adults independent in self-care activities from a representative sample of older Medicare beneficiaries. They completed objective measures of physical capacity and self-report measures of insomnia symptoms, help and difficulty with household activities, and participation in valued activities.
RESULTS: After adjustment, insomnia symptoms were associated with a greater odds of receiving help or having difficulty with selected household activities (laundry, shopping), greater odds of help or difficulty with ≥1 household activity [1 symptom vs. 0, odds ratio (OR)=1.27, p < .05; 2 symptoms vs. 0, OR = 1.35, p < .01), and of restricted participation in specific valued activities (attending religious services, going out for enjoyment) and in ≥1 valued activity (1 symptom vs. 0, OR = 1.29, p < .05; 2 symptoms vs. 0, OR = 1.50, p < .01). There was no independent association between insomnia symptoms and physical capacity.
DISCUSSION: Among older adults, insomnia symptoms are associated with a greater odds of limitation in household activities and of restricted participation in valued activities. Insomnia interventions may improve functioning and quality of life among elders.
PMID: 25342821 [PubMed - as supplied by publisher]
Battle of the Bulge: miR-195 Versus miR-29b in Aortic Aneurysm.
Circ Res. 2014 Oct 24;115(10):812-3
Authors: Spin JM, Tsao PS
PMID: 25342766 [PubMed - in process]
Conditional density-based analysis of T cell signaling in single-cell data.
Science. 2014 Oct 23;
Authors: Krishnaswamy S, Spitzer MH, Mingueneau M, Bendall SC, Litvin O, Stone E, Pe'er D, Nolan GP
Cellular circuits sense the environment, process signals, and compute decisions using networks of interacting proteins. To model such a system, the abundance of each activated protein species can be described as a stochastic function of the abundance of other proteins. High-dimensional single-cell technologies, like mass cytometry, offer an opportunity to characterize signaling circuit-wide. However, the challenge of developing and applying computational approaches to interpret such complex data remains. Here, we developed computational methods, based on established statistical concepts, to characterize signaling network relationships by quantifying the strengths of network edges and deriving signaling response functions. In comparing signaling between naïve and antigen-exposed CD4+ T-lymphocytes, we find that although these two cell subtypes had similarly-wired networks, naïve cells transmitted more information along a key signaling cascade than did antigen-exposed cells. We validated our characterization on mice lacking the extracellular-regulated MAP kinase (ERK2), which showed stronger influence of pERK on pS6 (phosphorylated-ribosomal protein S6), in naïve cells compared to antigen-exposed cells, as predicted. We demonstrate that by using cell-to-cell variation inherent in single cell data, we can algorithmically derive response functions underlying molecular circuits and drive the understanding of how cells process signals.
PMID: 25342659 [PubMed - as supplied by publisher]
The Role of Genome Sequencing in Personalized Breast Cancer Prevention.
Cancer Epidemiol Biomarkers Prev. 2014 Oct 23;
Authors: Sieh W, Rothstein JH, McGuire V, Whittemore AS
BACKGROUND: There is uncertainty about the benefits of using genome-wide sequencing to implement personalized preventive strategies at the population level, with some projections suggesting little benefit. We used data for all currently known breast cancer susceptibility variants to assess the benefits and harms of targeting preventive efforts to a population subgroup at highest genomic risk of breast cancer.
METHODS: We used the allele frequencies and effect sizes of 86 known breast cancer variants to estimate the population distribution of breast cancer risks and evaluate the strategy of targeting preventive efforts to those at highest risk. We compared the efficacy of this strategy with that of a "best-case" strategy based on a risk distribution estimated from breast cancer concordance in monozygous twins, and with strategies based on previously estimated risk distributions.
RESULTS: Targeting those in the top 25% of the risk distribution would include approximately half of all future breast cancer cases, compared with 70% captured by the best-case strategy and 35% based on previously known variants. In addition, current evidence suggests that reducing exposure to modifiable nongenetic risk factors will have greatest benefit for those at highest genetic risk.
CONCLUSIONS: These estimates suggest that personalized breast cancer preventive strategies based on genome sequencing will bring greater gains in disease prevention than previously projected. Moreover, these gains will increase with increased understanding of the genetic etiology of breast cancer.
IMPACT: These results support the feasibility of using genome-wide sequencing to target the women who would benefit from mammography screening. Cancer Epidemiol Biomarkers Prev; 1-6. ©2014 AACR.
PMID: 25342391 [PubMed - as supplied by publisher]
Using the wisdom of the crowds to find critical errors in biomedical ontologies: a study of SNOMED CT.
J Am Med Inform Assoc. 2014 Oct 23;
Authors: Mortensen JM, Minty EP, Januszyk M, Sweeney TE, Rector AL, Noy NF, Musen MA
OBJECTIVES: The verification of biomedical ontologies is an arduous process that typically involves peer review by subject-matter experts. This work evaluated the ability of crowdsourcing methods to detect errors in SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) and to address the challenges of scalable ontology verification.
METHODS: We developed a methodology to crowdsource ontology verification that uses micro-tasking combined with a Bayesian classifier. We then conducted a prospective study in which both the crowd and domain experts verified a subset of SNOMED CT comprising 200 taxonomic relationships.
RESULTS: The crowd identified errors as well as any single expert at about one-quarter of the cost. The inter-rater agreement (κ) between the crowd and the experts was 0.58; the inter-rater agreement between experts themselves was 0.59, suggesting that the crowd is nearly indistinguishable from any one expert. Furthermore, the crowd identified 39 previously undiscovered, critical errors in SNOMED CT (eg, 'septic shock is a soft-tissue infection').
DISCUSSION: The results show that the crowd can indeed identify errors in SNOMED CT that experts also find, and the results suggest that our method will likely perform well on similar ontologies. The crowd may be particularly useful in situations where an expert is unavailable, budget is limited, or an ontology is too large for manual error checking. Finally, our results suggest that the online anonymous crowd could successfully complete other domain-specific tasks.
CONCLUSIONS: We have demonstrated that the crowd can address the challenges of scalable ontology verification, completing not only intuitive, common-sense tasks, but also expert-level, knowledge-intensive tasks.
PMID: 25342179 [PubMed - as supplied by publisher]
Toward a science of learning systems: a research agenda for the high-functioning Learning Health System.
J Am Med Inform Assoc. 2014 Oct 23;
Authors: Friedman C, Rubin J, Brown J, Buntin M, Corn M, Etheredge L, Gunter C, Musen M, Platt R, Stead W, Sullivan K, Van Houweling D
OBJECTIVE: The capability to share data, and harness its potential to generate knowledge rapidly and inform decisions, can have transformative effects that improve health. The infrastructure to achieve this goal at scale-marrying technology, process, and policy-is commonly referred to as the Learning Health System (LHS). Achieving an LHS raises numerous scientific challenges.
MATERIALS AND METHODS: The National Science Foundation convened an invitational workshop to identify the fundamental scientific and engineering research challenges to achieving a national-scale LHS. The workshop was planned by a 12-member committee and ultimately engaged 45 prominent researchers spanning multiple disciplines over 2 days in Washington, DC on 11-12 April 2013.
RESULTS: The workshop participants collectively identified 106 research questions organized around four system-level requirements that a high-functioning LHS must satisfy. The workshop participants also identified a new cross-disciplinary integrative science of cyber-social ecosystems that will be required to address these challenges.
CONCLUSIONS: The intellectual merit and potential broad impacts of the innovations that will be driven by investments in an LHS are of great potential significance. The specific research questions that emerged from the workshop, alongside the potential for diverse communities to assemble to address them through a 'new science of learning systems', create an important agenda for informatics and related disciplines.
PMID: 25342177 [PubMed - as supplied by publisher]
Does a medial retraction blade transmit direct pressure to pharynx/esophagus wall during anterior cervical surgery?
Spine (Phila Pa 1976). 2014 Oct 22;
Authors: Han IH, Lee SH, Lee JM, Kim HS, Nam KH, Duetzmann S, Park J, Choi BK
Study Design. Prospective study of 25 patients who underwent anterior cervical surgery.Objective. To assess retraction pressure and the exposure of pharynx/esophagus (P/E) wall to the medial retractor blade to clarify whether medial retraction causes direct pressure transmission to the P/E wall.Summary of Background Data. Retraction pressure on P/E walls has been used to explain the relation between the retraction pressure and dysphagia or the efficacies of new retractor blades. However, it is doubtful whether the measured pressure represent real retraction pressure on the P/E wall because exposure of the P/E in the surgical field could be reduced by the shielding effect of thyroid cartilage.Methods. Epi- and endo-esophageal pressures were serially measured using online pressure transducers at 15minutes before retraction, immediately after retraction, and 30 minute after retraction. To measure the extent of P/E wall exposure to pressure transducer, we used posterior border of thyroid cartilage (PBTC) as a landmark. Intra-operative X-ray was used to mark the position of the posterior border of thyroid cartilage (PBTC). We checked out the marked location on retractors by measuring the distance from distal retractor tip.Results. The mean epi-esophageal pressure significantly increased after retraction (0 mmHg: 88.7±19.6 mmHg: 81.9±15.3 mmHg). The mean endo-esophageal pressure minimally changed after retraction (9.0±6.6 mmHg: 15.7±13.8 mmHg: 17.0±14.3 mmHg). The mean location of the posterior border of thyroid cartilage was 7.3±3.5mm on the retractor blade from the tip, which means epi-esophageal pressure was measured against the PBTC, not against the P/E wall.Conclusion. We suggest that a medial retraction blade does not transmit direct pressure on P/E wall due to minimal wall exposure and intervening thyroid cartilage. Our result should be considered when measuring retraction pressure during anterior cervical surgery or designing novel retractor systems.
PMID: 25341988 [PubMed - as supplied by publisher]
T-Cell Profile in Adipose Tissue Is Associated With Insulin Resistance and Systemic Inflammation in Humans.
Arterioscler Thromb Vasc Biol. 2014 Oct 23;
Authors: McLaughlin T, Liu LF, Lamendola C, Shen L, Morton J, Rivas H, Winer D, Tolentino L, Choi O, Zhang H, Ch'ng M, Engleman E
OBJECTIVE: The biological mechanisms linking obesity to insulin resistance have not been fully elucidated. We have shown that insulin resistance or glucose intolerance in diet-induced obese mice is related to a shift in the ratio of pro- and anti-inflammatory T cells in adipose tissue. We sought to test the hypothesis that the balance of T-cell phenotypes would be similarly related to insulin resistance in human obesity.
APPROACH AND RESULTS: Healthy overweight or obese human subjects underwent adipose-tissue biopsies and quantification of insulin-mediated glucose disposal by the modified insulin suppression test. T-cell subsets were quantified by flow cytometry in visceral (VAT) and subcutaneous adipose tissues (SATs). Results showed that CD4 and CD8 T cells infiltrate both depots, with proinflammatory T-helper (Th)-1, Th17, and CD8 T cells, significantly, more frequently in VAT as compared with SAT. T-cell profiles in SAT and VAT correlated significantly with one another and with peripheral blood. Th1 frequency in SAT and VAT correlated directly, whereas Th2 frequency in VAT correlated inversely with plasma high-sensitivity C-reactive protein concentrations. Th1 in SAT correlated with plasma interleukin-6. Th2 in both depots and peripheral blood was inversely associated with systemic insulin resistance. Relative expression of associated cytokines, measured by real-time polymerase chain reaction, reflected flow cytometry results. Most notably, adipose tissue expression of interleukin-10 was inversely associated with insulin resistance.
CONCLUSIONS: CD4 and CD8 T cells populate human adipose tissue and the relative frequency of Th1 and Th2 are highly associated with systemic inflammation and insulin resistance. These findings point to the adaptive immune system as a potential mediator between obesity and insulin resistance or inflammation. Identification of antigenic stimuli in adipose tissue may yield novel targets for treatment of obesity-associated metabolic disease.
PMID: 25341798 [PubMed - as supplied by publisher]
Waking sleeping algal cells.
Proc Natl Acad Sci U S A. 2014 Oct 23;
Authors: Li X, Umen JG, Jonikas MC
PMID: 25341728 [PubMed - as supplied by publisher]
Heparin Use in Hemodialysis Patients following Gastrointestinal Bleeding.
Am J Nephrol. 2014 Oct 17;40(4):300-307
Authors: Shen JI, Mitani AA, Winkelmayer WC
Background: Heparin is commonly given during hemodialysis (HD). Patients undergoing HD have a high rate of gastrointestinal bleeding (GIB). It is unclear whether or when it is safe to give heparin after acute GIB. We describe the patterns and safety of heparin use with outpatient HD following an acute GIB. Methods: We identified patients aged ≥67 who, from 2004-2008, experienced GIB requiring hospitalization within 2 days of receiving maintenance HD with heparin. We used Cox regression to estimate the risk of recurrent GIB and death associated with receiving heparin the day they resumed outpatient HD post-GIB. Results: Of the 1,342 patients who had GIB, 1,158 (86%) received heparin at a median dose of 4,000 units with their first outpatient HD session after discharge from GIB. On average, their post-GIB doses were slightly lower than their pre-GIB doses (mean change: -214 ± 3,266 units, p < 0.02). However, only 27% of patients had a decrease in their dose, while 21% had their dose increased. We did not find an increased risk of death or recurrent GIB associated with using heparin post-GIB (HR; 95% confidence interval (CI), for death: 1.01; 0.69-1.48; for recurrent GIB: 0.78; 0.39-1.57). Conclusions: The vast majority of these high-risk patients received heparin on the very first day they resumed outpatient HD post-GIB, and the majority at unchanged doses to those received pre-GIB. Even if the practice was not associated with increased risks of death or re-bleeding, it highlights an area for possible system-based improvement to the care for patients on HD. © 2014 S. Karger AG, Basel.
PMID: 25341418 [PubMed - as supplied by publisher]
Comparative analysis of regulatory information and circuits across distant species.
Nature. 2014 Aug 28;512(7515):453-6
Authors: Boyle AP, Araya CL, Brdlik C, Cayting P, Cheng C, Cheng Y, Gardner K, Hillier LW, Janette J, Jiang L, Kasper D, Kawli T, Kheradpour P, Kundaje A, Li JJ, Ma L, Niu W, Rehm EJ, Rozowsky J, Slattery M, Spokony R, Terrell R, Vafeados D, Wang D, Weisdepp P, Wu YC, Xie D, Yan KK, Feingold EA, Good PJ, Pazin MJ, Huang H, Bickel PJ, Brenner SE, Reinke V, Waterston RH, Gerstein M, White KP, Kellis M, Snyder M
Despite the large evolutionary distances between metazoan species, they can show remarkable commonalities in their biology, and this has helped to establish fly and worm as model organisms for human biology. Although studies of individual elements and factors have explored similarities in gene regulation, a large-scale comparative analysis of basic principles of transcriptional regulatory features is lacking. Here we map the genome-wide binding locations of 165 human, 93 worm and 52 fly transcription regulatory factors, generating a total of 1,019 data sets from diverse cell types, developmental stages, or conditions in the three species, of which 498 (48.9%) are presented here for the first time. We find that structural properties of regulatory networks are remarkably conserved and that orthologous regulatory factor families recognize similar binding motifs in vivo and show some similar co-associations. Our results suggest that gene-regulatory properties previously observed for individual factors are general principles of metazoan regulation that are remarkably well-preserved despite extensive functional divergence of individual network connections. The comparative maps of regulatory circuitry provided here will drive an improved understanding of the regulatory underpinnings of model organism biology and how these relate to human biology, development and disease.
PMID: 25164757 [PubMed - indexed for MEDLINE]
Comparative analysis of metazoan chromatin organization.
Nature. 2014 Aug 28;512(7515):449-52
Authors: Ho JW, Jung YL, Liu T, Alver BH, Lee S, Ikegami K, Sohn KA, Minoda A, Tolstorukov MY, Appert A, Parker SC, Gu T, Kundaje A, Riddle NC, Bishop E, Egelhofer TA, Hu SS, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen QB, Chen RA, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM, Strome S, Elgin SC, Liu XS, Lieb JD, Ahringer J, Karpen GH, Park PJ
Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
PMID: 25164756 [PubMed - indexed for MEDLINE]
Neural constraints on learning.
Nature. 2014 Aug 28;512(7515):423-6
Authors: Sadtler PT, Quick KM, Golub MD, Chase SM, Ryu SI, Tyler-Kabara EC, Yu BM, Batista AP
Learning, whether motor, sensory or cognitive, requires networks of neurons to generate new activity patterns. As some behaviours are easier to learn than others, we asked if some neural activity patterns are easier to generate than others. Here we investigate whether an existing network constrains the patterns that a subset of its neurons is capable of exhibiting, and if so, what principles define this constraint. We employed a closed-loop intracortical brain-computer interface learning paradigm in which Rhesus macaques (Macaca mulatta) controlled a computer cursor by modulating neural activity patterns in the primary motor cortex. Using the brain-computer interface paradigm, we could specify and alter how neural activity mapped to cursor velocity. At the start of each session, we observed the characteristic activity patterns of the recorded neural population. The activity of a neural population can be represented in a high-dimensional space (termed the neural space), wherein each dimension corresponds to the activity of one neuron. These characteristic activity patterns comprise a low-dimensional subspace (termed the intrinsic manifold) within the neural space. The intrinsic manifold presumably reflects constraints imposed by the underlying neural circuitry. Here we show that the animals could readily learn to proficiently control the cursor using neural activity patterns that were within the intrinsic manifold. However, animals were less able to learn to proficiently control the cursor using activity patterns that were outside of the intrinsic manifold. These results suggest that the existing structure of a network can shape learning. On a timescale of hours, it seems to be difficult to learn to generate neural activity patterns that are not consistent with the existing network structure. These findings offer a network-level explanation for the observation that we are more readily able to learn new skills when they are related to the skills that we already possess.
PMID: 25164754 [PubMed - indexed for MEDLINE]
Regulatory analysis of the C. elegans genome with spatiotemporal resolution.
Nature. 2014 Aug 28;512(7515):400-5
Authors: Araya CL, Kawli T, Kundaje A, Jiang L, Wu B, Vafeados D, Terrell R, Weissdepp P, Gevirtzman L, Mace D, Niu W, Boyle AP, Xie D, Ma L, Murray JI, Reinke V, Waterston RH, Snyder M
Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors and regulatory proteins across multiple stages of Caenorhabditis elegans development by performing 241 ChIP-seq (chromatin immunoprecipitation followed by sequencing) experiments. Integration of regulatory binding and cellular-resolution expression data produced a spatiotemporally resolved metazoan transcription factor binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of transcription factors, characterizing the genomic coverage and clustering of regulatory binding, the binding preferences of, and biological processes regulated by, transcription factors, the global transcription factor co-associations and genomic subdomains that suggest shared patterns of regulation, and identifying key transcription factors and transcription factor co-associations for fate specification of individual lineages and cell types.
PMID: 25164749 [PubMed - indexed for MEDLINE]
Re: co-existence of intramuscular spindle cell lipoma with an intramuscular ordinary lipoma. Report of a case.
Pol J Pathol. 2014 Jun;65(2):160-1
Authors: Chernev I, Mctighe S, Stanley DP
PMID: 25119179 [PubMed - indexed for MEDLINE]
Processing properties of ON and OFF pathways for Drosophila motion detection.
Nature. 2014 Aug 28;512(7515):427-30
Authors: Behnia R, Clark DA, Carter AG, Clandinin TR, Desplan C
The algorithms and neural circuits that process spatio-temporal changes in luminance to extract visual motion cues have been the focus of intense research. An influential model, the Hassenstein-Reichardt correlator, relies on differential temporal filtering of two spatially separated input channels, delaying one input signal with respect to the other. Motion in a particular direction causes these delayed and non-delayed luminance signals to arrive simultaneously at a subsequent processing step in the brain; these signals are then nonlinearly amplified to produce a direction-selective response. Recent work in Drosophila has identified two parallel pathways that selectively respond to either moving light or dark edges. Each of these pathways requires two critical processing steps to be applied to incoming signals: differential delay between the spatial input channels, and distinct processing of brightness increment and decrement signals. Here we demonstrate, using in vivo patch-clamp recordings, that four medulla neurons implement these two processing steps. The neurons Mi1 and Tm3 respond selectively to brightness increments, with the response of Mi1 delayed relative to Tm3. Conversely, Tm1 and Tm2 respond selectively to brightness decrements, with the response of Tm1 delayed compared with Tm2. Remarkably, constraining Hassenstein-Reichardt correlator models using these measurements produces outputs consistent with previously measured properties of motion detectors, including temporal frequency tuning and specificity for light versus dark edges. We propose that Mi1 and Tm3 perform critical processing of the delayed and non-delayed input channels of the correlator responsible for the detection of light edges, while Tm1 and Tm2 play analogous roles in the detection of moving dark edges. Our data show that specific medulla neurons possess response properties that allow them to implement the algorithmic steps that precede the correlative operation in the Hassenstein-Reichardt correlator, revealing elements of the long-sought neural substrates of motion detection in the fly.
PMID: 25043016 [PubMed - indexed for MEDLINE]
Hydrological controls on methylmercury distribution and flux in a tidal marsh.
Environ Sci Technol. 2014 Jun 17;48(12):6795-804
Authors: Zhang H, Moffett KB, Windham-Myers L, Gorelick SM
The San Francisco Estuary, California, contains mercury (Hg) contamination originating from historical regional gold and Hg mining operations. We measured hydrological and geochemical variables in a tidal marsh of the Palo Alto Baylands Nature Preserve to determine the sources, location, and magnitude of hydrological fluxes of methylmercury (MeHg), a bioavailable Hg species of ecological and health concern. Based on measured concentrations and detailed finite-element simulation of coupled surface water and saturated-unsaturated groundwater flow, we found pore water MeHg was concentrated in unsaturated pockets that persisted over tidal cycles. These pockets, occurring over 16% of the marsh plain area, corresponded to the marsh root zone. Groundwater discharge (e.g., exfiltration) to the tidal channel represented a significant source of MeHg during low tide. We found that nonchannelized flow accounted for up to 20% of the MeHg flux to the estuary. The estimated net flux of filter-passing (0.45 μm) MeHg toward estuary was 10 ± 5 ng m(-2) day(-1) during a single 12-h tidal cycle, suggesting an annual MeHg load of 1.17 ± 0.58 kg when the estimated flux was applied to present tidal marshes and planned marsh restorations throughout the San Francisco Estuary.
PMID: 24828335 [PubMed - indexed for MEDLINE]
Age-related macular degeneration and protective effect of HMG Co-A reductase inhibitors (statins): results from the National Health and Nutrition Examination Survey 2005-2008.
Eye (Lond). 2014 Apr;28(4):472-80
Authors: Barbosa DT, Mendes TS, Cíntron-Colon HR, Wang SY, Bhisitkul RB, Singh K, Lin SC
PURPOSE: To determine the association of hydroxymethylglutarylcoenzyme A (HMG Co-A) reductase inhibitor (statin) use with the prevalence of age-related macular degeneration (AMD).
METHODS: This cross-sectional study included 5604 participants in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008, ≥ 40 years of age, who were ascertained with regard to the diagnosis of AMD, the use of statins, and comorbidities and health-related behaviors such as smoking.
RESULTS: The mean age of participants denying or confirming a history of AMD was 68 (SEM 0.90) and 55 (SEM 0.36) years, respectively. Individuals 68 years of age or older who were classified as long-term users of statins had statistically significant less self-reported AMD (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.49-0.84; P=0.002), after adjusting for potential confounding variables. No significant association was found between the prevalence of AMD and statin consumption among subjects between 40 and 67 years of age (OR 1.61, 95% CI 0.85-3.03; P=0.137).
CONCLUSIONS: Our results suggest a possible beneficial effect of statin intake for the prevention of AMD in individuals 68 years of age or older.
PMID: 24503725 [PubMed - indexed for MEDLINE]
The impact of change in pregnancy body mass index on the development of gestational hypertensive disorders.
J Perinatol. 2014 Mar;34(3):181-5
Authors: Swank ML, Caughey AB, Farinelli CK, Main EK, Melsop KA, Gilbert WM, Chung JH
OBJECTIVE: To examine the impact of change in body mass index (BMI) during pregnancy on the incidence of gestational hypertension/preeclampsia.
STUDY DESIGN: This is a retrospective cohort study using linked California birth certificate and discharge diagnosis data from the year 2007. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated for the outcome of gestational hypertension/preeclampsia, as a function of a categorical change in pregnancy BMI: BMI loss (<-0.5), no change (-0.5 to 0.5), minimal (0.6 to 5), moderate (5.1 to 10) and excessive (>10). The impact of change in pregnancy BMI was evaluated for the entire cohort and then as a function of prepregnancy BMI category. Women with no change in pregnancy BMI served as the reference group.
RESULT: The study population consisted of 436 414 women with singleton gestations. Overall, women with excessive BMI change had a nearly twofold increased odds of gestational hypertension/preeclampsia (aOR=1.94; 95% CI=1.72 to 2.20). By prepregnancy BMI class, overweight and obese women who had a moderate change in pregnancy BMI also had increased odds of developing gestational hypertension/preeclampsia with aOR ranging from 1.73 to 1.97.
CONCLUSION: Regardless of prepregnancy BMI category, women with excessive BMI change have a higher chance of developing gestational hypertension/preeclampsia. Overweight and obese women with moderate BMI change may also be at increased risk.
PMID: 24384780 [PubMed - indexed for MEDLINE]
Outcomes of extremely preterm infants following severe intracranial hemorrhage.
J Perinatol. 2014 Mar;34(3):203-8
Authors: Davis AS, Hintz SR, Goldstein RF, Ambalavanan N, Bann CM, Stoll BJ, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Das A, Higgins RD, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
OBJECTIVE: Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH.
STUDY DESIGN: Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: (i) unilateral vs bilateral ICH; and (ii) presence vs absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI).
RESULT: Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI.
CONCLUSION: Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.
PMID: 24370654 [PubMed - indexed for MEDLINE]
Genetically encoded voltage sensor goes live.
Nat Biotechnol. 2013 Nov;31(11):994-5
Authors: Marshel JH, Deisseroth K
PMID: 24213775 [PubMed - indexed for MEDLINE]
A single-molecule long-read survey of the human transcriptome.
Nat Biotechnol. 2013 Nov;31(11):1009-14
Authors: Sharon D, Tilgner H, Grubert F, Snyder M
Global RNA studies have become central to understanding biological processes, but methods such as microarrays and short-read sequencing are unable to describe an entire RNA molecule from 5' to 3' end. Here we use single-molecule long-read sequencing technology from Pacific Biosciences to sequence the polyadenylated RNA complement of a pooled set of 20 human organs and tissues without the need for fragmentation or amplification. We show that full-length RNA molecules of up to 1.5 kb can readily be monitored with little sequence loss at the 5' ends. For longer RNA molecules more 5' nucleotides are missing, but complete intron structures are often preserved. In total, we identify ∼14,000 spliced GENCODE genes. High-confidence mappings are consistent with GENCODE annotations, but >10% of the alignments represent intron structures that were not previously annotated. As a group, transcripts mapping to unannotated regions have features of long, noncoding RNAs. Our results show the feasibility of deep sequencing full-length RNA from complex eukaryotic transcriptomes on a single-molecule level.
PMID: 24108091 [PubMed - indexed for MEDLINE]
Hypertension: Do calcium-channel blockers increase breast cancer risk?
Nat Rev Cardiol. 2013 Nov;10(11):621-2
Authors: Wang A, Manson JE
PMID: 24080583 [PubMed - indexed for MEDLINE]
Classic biphasic pulmonary blastoma demonstrated by 18F-FDG PET/CT.
Clin Nucl Med. 2014 Apr;39(4):346-8
Authors: Keu KV, Berry GJ, Quon A
A 75-year-old nonsmoker woman was referred for the evaluation of a nonsecretory left adrenal lesion. An abdominal contrast-enhanced CT showed an incidental left lower lobe mass, which was confirmed on a chest contrast-enhanced CT. A 18F-FDG PET/CT showed a hypermetabolic tumor without nodal or distant metastasis. She underwent a lobectomy, and the final pathology reported a classic biphasic pulmonary blastoma, which is an uncommon histological form of malignant lung neoplasm. This case highlighted the glucose avidity of this rare and aggressive cancer.
PMID: 23989445 [PubMed - indexed for MEDLINE]
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