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Verduin, Maikel, Inge Compter, Sergey Primakov, Sander van Kuijk, Maarten te Dorsthorst, Elles Revenich, Mark ter Laan, et al. "NIMG-65. PREDICTING PROGNOSIS AND CANCER HOTSPOT MUTATIONS USING QUALITATIVE MR IMAGING ANALYSIS IN GLIOBLASTOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi176. http://dx.doi.org/10.1093/neuonc/noz175.734.
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Abstract INTRODUCTION Tumor heterogeneity poses one of the major limitations in improving the treatment for glioblastoma (GBM), which calls for new clinically relevant predictive models. This study aims to investigate non-invasive diagnostic methods, including patient characteristics and qualitative imaging analysis as a prognostic classifier and predictor for druggable oncogenes. METHODS We performed a retrospective analysis on 143 GBM patients (discovery cohort). Diagnostic MRIs were re-analyzed for qualitative imaging features (VASARI features). DNA was extracted from formalin-fixed, paraffin-embedded GBM tissue of the discovery cohort for next-generation sequencing (Ion Torrent Cancer Hotspot panel v2Plus), TERT-promoter mutation and MGMT-methylation analysis. Multivariable regression analysis was used to determine the prognostic and predictive value of VASARI features. RESULTS Of the 143 patients, median age was 61.4 years (range 15.5–84.6) with a median overall survival of 12 months (range 0–142). We observed IDH1 R132H mutation in 8.5%, MGMT-promotor methylation in 26.1%, TERT-promotor mutation (C250T;C228T) in 69.5%, EGFR mutation in 20.3% and EGFR amplification in 37.5% of all patients. A set of eight VASARI features was identified to be associated with overall survival (p< 0.001), which is currently being validated in an external dataset (n= 184). Interestingly, VASARI features appeared to be associated with IDH1-mutation (four features, p=0.004), TERT-promotor mutation (five features, p-value < 0.001), EGFR mutation (five features, p-value < 0.001) and EGFR amplification (seven features, p-value < 0.001) but not with MGMT-methylation (two features, p-value=0.054). Additional cancer hotspots are currently being analyzed and internal validation is ongoing. CONCLUSION AND FUTURE PERSPECTIVES We propose an integrated prognostic classifier comprising MRI features, also associated with GBM-specific molecular alterations. Additionally, quantitative MRI radiomics features are being extracted from the discovery and validation set and incorporated in the prognostic classifier. Subsequently, radiomics and VASARI features will be correlated to intratumoral heterogeneity, assessed by tissue micro-array analysis of the discovery cohort.
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Linehan, Sheena A., Luisa Martínez-Pomares, Philip D. Stahl, and Siamon Gordon. "Mannose Receptor and Its Putative Ligands in Normal Murine Lymphoid and Nonlymphoid Organs: In Situ Expression of Mannose Receptor by Selected Macrophages, Endothelial Cells, Perivascular Microglia, and Mesangial Cells, but not Dendritic Cells." Journal of Experimental Medicine 189, no. 12 (June 21, 1999): 1961–72. http://dx.doi.org/10.1084/jem.189.12.1961.
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The mannose receptor (MR) has established roles in macrophage (Mφ) phagocytosis of microorganisms and endocytic clearance of host-derived glycoproteins, and has recently been implicated in antigen capture by dendritic cells (DCs) in vitro. MR is the founder member of a family of homologous proteins, and its recognition properties differ according to its tissue of origin. Given this heterogeneity and our recent discovery of a soluble form of MR in mouse serum, we studied the sites of synthesis of MR mRNA and expression of MR protein in normal mouse tissues. We demonstrate that synthesis and expression occur at identical sites, and that mature Mφ and endothelium are heterogeneous with respect to MR expression, additionally describing MR on perivascular microglia and glomerular mesangial cells. However, MR was not detected on DCs in situ, or on marginal zone or subcapsular sinus Mφ, both of which have MR-like binding activities. We also compared expression of MR to the binding of a recombinant probe containing the cysteine-rich domain of MR. We show that MR and its putative ligand(s) are expressed at nonoverlapping sites within lymphoid organs, consistent with a transfer function for soluble MR. Therefore, in addition to endocytic and phagocytic roles, MR may play an important role in antigen recognition and transport within lymphoid organs.
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Zhuang, He, Ying Zhang, Shuo Yang, Liang Cheng, and Shu-Lin Liu. "A Mendelian Randomization Study on Infant Length and Type 2 Diabetes Mellitus Risk." Current Gene Therapy 19, no. 4 (November 18, 2019): 224–31. http://dx.doi.org/10.2174/1566523219666190925115535.
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Objective: Infant length (IL) is a positively associated phenotype of type 2 diabetes mellitus (T2DM), but the causal relationship of which is still unclear. Here, we applied a Mendelian randomization (MR) study to explore the causal relationship between IL and T2DM, which has the potential to provide guidance for assessing T2DM activity and T2DM- prevention in young at-risk populations. Materials and Methods: To classify the study, a two-sample MR, using genetic instrumental variables (IVs) to explore the causal effect was applied to test the influence of IL on the risk of T2DM. In this study, MR was carried out on GWAS data using 8 independent IL SNPs as IVs. The pooled odds ratio (OR) of these SNPs was calculated by the inverse-variance weighted method for the assessment of the risk the shorter IL brings to T2DM. Sensitivity validation was conducted to identify the effect of individual SNPs. MR-Egger regression was used to detect pleiotropic bias of IVs. Results: The pooled odds ratio from the IVW method was 1.03 (95% CI 0.89-1.18, P = 0.0785), low intercept was -0.477, P = 0.252, and small fluctuation of ORs ranged from -0.062 ((0.966 - 1.03) / 1.03) to 0.05 ((1.081 - 1.03) / 1.03) in leave-one-out validation. Conclusion: We validated that the shorter IL causes no additional risk to T2DM. The sensitivity analysis and the MR-Egger regression analysis also provided adequate evidence that the above result was not due to any heterogeneity or pleiotropic effect of IVs.
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Polyanskaya, M. V., A. A. Demushkina, F. A. Kostylev, I. G. Vasilyev, V. A. Chadaev, N. N. Zavadenko, and A. A. Alikhanov. "The role of susceptibility-weighted imaging (SWI) in neuroimaging in children with focal epilepsy." Epilepsy and paroxysmal conditions 12, no. 2 (September 11, 2020): 105–16. http://dx.doi.org/10.17749/2077-8333/epi.par.con.2020.025.
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Aim. To approve of diagnostic effectiveness of SWAN (SWI) images in revealing of calcium containing epileptogenic substrates in children with resistant focal epilepsy.Materials and methods. The results of MRI in children with refractory focal epilepsy obtained in the Radiology Department of the Russian State Children Hospital in the period from 2018 to 2020 were observed retrospectively. High-resolution epileptological MR protocol used for investigation of 67 children. SWAN was applied in all cases for identification of calcium containing epileptogenic substrates, including cavernomas, DVA syndrome, cortical gangliogliomas, Sturge-Weber syndrome and tuberous sclerosis complex. All images were received by using MRI 3T 750 W Discovery GE.Results. In 17 cases (25%) SWAN provided important diagnostic information about the nature of the of epileptogenic lesion, its prevalence and borders. Additional earlier invisible structural changes were revealed in 2 cases of SWS and 1 cases of FCD; and in 13 cases SWAN gave us possibility to avoid CT for approving calcium in epileptogenic focus.Conclusion. We believe that adding SWAN in to the epileptological MR protocol is the necessary step for optimizing calcium and blood degradation products identification in the structure of potential epileptogenic focuses. Moreover, it would be very effective instrument for differential diagnosis of cerebral structural changes, specifying its etiology and, hence, would have influence on the therapeutic tactic and surgical strategy in children with focal epilepsy.
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Kotfis, Katarzyna, Kacper Lechowicz, Sylwester Drożdżal, Paulina Niedźwiedzka-Rystwej, Tomasz K. Wojdacz, Ewelina Grywalska, Jowita Biernawska, Magda Wiśniewska, and Miłosz Parczewski. "COVID-19—The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection." Pharmaceuticals 14, no. 1 (January 17, 2021): 71. http://dx.doi.org/10.3390/ph14010071.
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In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin–angiotensin–aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.
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Hulsey, Josiah, and M. Royhan Gani. "Applying modern interpretation techniques to old hydrocarbon fields to find new reserves: A case study in the onshore Gulf of Mexico, USA." Interpretation 4, no. 4 (November 1, 2016): T637—T655. http://dx.doi.org/10.1190/int-2016-0015.1.
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This study shows how the use of current geological investigative techniques, such as sequence stratigraphy and modern seismic interpretation methods, can potentially discover additional hydrocarbons in old fields that were previously considered depleted. Specifically, we examine the White Castle Field in South Louisiana, which has produced over 84.1 million barrels of oil and 63.1 billion cubic feet of gas but retains additional recoverable hydrocarbons. The field has pay sections ranging from late Oligocene to late Miocene. The upper Oligocene to early Miocene package, which was underexploited and understudied during the previous exploitation phase, contains three primary reservoirs (Cib Haz, MW, and MR). During most of the late Oligocene, the White Castle Salt Dome was located in a minibasin on the continental slope. The Cib Haz and MW reservoirs were deposited in this minibasin and offer great exploitation potential. The Cib Haz interval is an amalgamation of slumped shelfal limestones, sandstones, and shales interpreted to represent a lowstand systems tract (LST). The MW comprises a shelf-edge delta deposit that is also interpreted as part of a LST. The MR reservoir is interpreted as an incised valley fill located in the continental shelf that was deposited during a lowstand of sea level after the minibasin was filled. Finally, it appears that the minibasin acted as a self-contained hydrocarbon system during the late Oligocene, suggesting the possibility of a shale play. In this study, several new areas of interest are revealed that could contain economical amounts of hydrocarbons.
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Sarikaya-Seiwert, Sevgi, Bernd Turowski, Daniel Hänggi, Giesela Janssen, Hans-Jakob Steiger, and Walter Stummer. "Symptomatic intracystic hemorrhage in pineal cysts." Journal of Neurosurgery: Pediatrics 4, no. 2 (August 2009): 130–36. http://dx.doi.org/10.3171/2009.4.peds08309.
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Pineal cysts are benign and often asymptomatic intracranial entities. Occasionally they can lead to neurological symptoms through growth or due to intracystic hemorrhage. The purpose of the current report is to describe their clinical characteristics and treatment options. In the current study, the authors illustrate the course of disease in 3 patients who developed neurological symptoms due to hemorrhage into a pineal cyst. Two of their patients had additional cerebral disease, and regular MR imaging examinations were conducted. This circumstance allowed documentation of growth and intracystic hemorrhage. After the occurrence of new neurological symptoms with severe headache, MR images showed a fluid-fluid interface due to intracystic hemorrhage. The third patient presented with acute triventricular hydrocephalus and papilledema due to aqueductal stenosis caused by intracystic hemorrhage. In all 3 cases, excision of the pineal cysts via an infratentorial/supracerebellar approach was performed. Histological examination revealed the characteristic structure of pineal cyst in all cases, with hemorrhagic residues in the form of hemosiderin deposits. All patients recovered fully after surgical removal of the cysts. Furthermore, resolution of occlusive hydrocephalus could be demonstrated in those cases with ventricular enlargement. Pineal cysts without neurological symptoms are often discovered as incidental findings on cranial MR images. In contrast, neurological symptoms such as severe headache, diplopia, or Parinaud syndrome, may occur as a result of pineal apoplexy due to intracystic hemorrhage. The authors' cases confirm that MR imaging can identify intracystic hemorrhage by a characteristic fluid-fluid interface. Their experience suggests that microsurgical resection of cysts may be an effective and curative treatment option.
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Matías-García, Pamela R., Rory Wilson, Qi Guo, Shaza B. Zaghlool, James M. Eales, Xiaoguang Xu, Fadi J. Charchar, et al. "Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study." Journal of the American Society of Nephrology 32, no. 7 (June 16, 2021): 1747–63. http://dx.doi.org/10.1681/asn.2020071070.
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BackgroundStudies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed.MethodsA cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR.ResultsIn total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR.ConclusionsIn a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation.
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Sato, Enos Nobuo, Carlos Teixeira, Beck Nader, and Giorgio de Tomi. "Time Series Models to Obtain the Barrel Crude Oil Prices." Materials Science Forum 805 (September 2014): 422–28. http://dx.doi.org/10.4028/www.scientific.net/msf.805.422.
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The use of time series as an additional tool in decision making for the oil industry has been established as a mechanism for predicting the behavior of crude oil price. Especially in Brazil, after the discovery in this decade of the pre-salt reservoirs, the estimate of the price of a crude oil barrel through the use of modern techniques can minimize risks in exploration and production of oil. The more appropriate pricing for crude oil aims to minimize the risks to the economic activity for both exporters and importers of oil. This paper presents six different methods for obtaining crude oil future pricesi.e.Multiple regression (MR), Holt ́s method (HM), Holt-Winter (HW), Kalman filter (KF), Auto-Regression/Moving-Average (ARIMA) and stochastic simulation based on the use of the Monte Carlo method (SMC). The methods are compared to determine their advantages and disadvantages against each other, seeking to determine which of the generated models has the best potential to determine the future fair price of a barrel of oil. As a result, the most appropriate methodology capable of projecting a more precise future barrel oil fair price was determined, among the six alternatives studied.
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Dicks, Jonathan. "The Roman Villa at Woodham's Farm, Kings Worthy, Hampshire." Hampshire Studies 73, no. 1 (November 1, 2018): 145–55. http://dx.doi.org/10.24202/hs2018006.
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Additional information about the Romano-British villa at Woodham's Farm was discovered whilst researching the villas at Sparsholt and Twyford. Amongst the Sparsholt material held by the late David Johnston was an envelope containing coins from Woodham's Farm. Similarly, amongst the Twyford paper archive held by Martin Biddle was a letter from Mr. W. H. Blake of Woodham's Farm to Lieut. Colonel Montague dated 14th September 1925. The letter briefly described his excavation of the site and contains a sketch of the exposed ground plan of parts of the villa. This short report is based on the information held by Winchester Museum Services (History File ARCH 296). It documents the discoveries found and attempts to put the Romano-British Villa at Woodham's Farm into a regional context.
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Gentillon, Hugues, Ludomir Stefańczyk, Michał Strzelecki, and Maria Respondek-Liberska. "Prenatal brain MRI samples for development of automatic segmentation, target- recognition and machine-learning algorithms to detect anatomical structures." F1000Research 6 (January 31, 2017): 93. http://dx.doi.org/10.12688/f1000research.10723.1.
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In this data note, we present a sorted pool of fetal magnetic resonance imaging (MRI) specimens, selected for a project seeking to further develop a computer-vision software called MaZda, originally created for magnetic resonance (MR) image analysis. A link to download the samples is provided in the manuscript herein. This data descriptor further explains how and why these fetal MRI samples were selected. Firstly, thousands of cross-sectional images obtained from fetal MRI scans were processed and sorted semi-manually with other software. We did so because a built-in “samplesort” (sorting algorithm) is missing in MaZda version 5. Additionally, the software is unfortunately lacking effective and efficient algorithms to allow automatic identification and segmentation of anatomical structures in fetal MRI samples. Hence, the finals sorting steps were carried out manually via time-consuming methods — i.e. human- visual detection and classifications by the gestational age of pregnancy and the rotational plane of the MR scanner. Thus the latter correlates with the anatomical plane of the mother, rather than the hypothetical plane used to transect the fetus. In brief, we collated these fetal MRI samples in an effort to facilitate future research and discovery, especially to aid the improvement of MaZda.
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Gentillon, Hugues, Ludomir Stefańczyk, Michał Strzelecki, and Maria Respondek-Liberska. "Prenatal brain MRI samples for development of automatic segmentation, target-recognition, and machine-learning algorithms to detect anatomical structures." F1000Research 6 (September 8, 2017): 93. http://dx.doi.org/10.12688/f1000research.10723.2.
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In this data note, we present a sorted pool of fetal magnetic resonance imaging (MRI) specimens. These were selected for a project seeking to further develop computer vision software called MaZda, which was originally created for magnetic resonance (MR) image analysis. A link to download the samples is provided in the manuscript herein. This data descriptor further explains how and why these fetal MRI samples were selected. Firstly, thousands of cross-sectional images obtained from fetal MRI scans were processed and sorted semi-manually with other software. We did so because a built-in “samplesort” (sorting algorithm) is missing in MaZda version 5. Additionally, the software is unfortunately lacking effective and efficient algorithms to allow automatic identification and segmentation of anatomical structures in fetal MRI samples. Hence, the final sorting steps were carried out manually via time-consuming methods (i.e., human visual detection and classifications by the gestational age of pregnancy and the rotational plane of the MR scanner). Thus, the latter correlates with the anatomical plane of the mother, rather than the hypothetical plane used to transect the fetus. In brief, we collated these fetal MRI samples in an effort to facilitate future research and discovery, especially to aid the improvement of MaZda.
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Yuan, Shuai, and Susanna C. Larsson. "An atlas on risk factors for type 2 diabetes: a wide-angled Mendelian randomisation study." Diabetologia 63, no. 11 (September 8, 2020): 2359–71. http://dx.doi.org/10.1007/s00125-020-05253-x.
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Abstract Aims/hypothesis The aim of this study was to use Mendelian randomisation (MR) to identify the causal risk factors for type 2 diabetes. Methods We first conducted a review of meta-analyses and review articles to pinpoint possible risk factors for type 2 diabetes. Around 170 possible risk factors were identified of which 97 risk factors with available genetic instrumental variables were included in MR analyses. To reveal more risk factors that were not included in our MR analyses, we conducted a review of published MR studies of type 2 diabetes. For our MR analyses, we used summary-level data from the DIAbetes Genetics Replication And Meta-analysis consortium (74,124 type 2 diabetes cases and 824,006 controls of European ancestry). Potential causal associations were replicated using the FinnGen consortium (11,006 type 2 diabetes cases and 82,655 controls of European ancestry). The inverse-variance weighted method was used as the main analysis. Multivariable MR analysis was used to assess whether the observed associations with type 2 diabetes were mediated by BMI. We used the Benjamini–Hochberg method that controls false discovery rate for multiple testing. Results We found evidence of causal associations between 34 exposures (19 risk factors and 15 protective factors) and type 2 diabetes. Insomnia was identified as a novel risk factor (OR 1.17 [95% CI 1.11, 1.23]). The other 18 risk factors were depression, systolic BP, smoking initiation, lifetime smoking, coffee (caffeine) consumption, plasma isoleucine, valine and leucine, liver alanine aminotransferase, childhood and adulthood BMI, body fat percentage, visceral fat mass, resting heart rate, and four plasma fatty acids. The 15 exposures associated with a decreased risk of type 2 diabetes were plasma alanine, HDL- and total cholesterol, age at menarche, testosterone levels, sex hormone binding globulin levels (adjusted for BMI), birthweight, adulthood height, lean body mass (for women), four plasma fatty acids, circulating 25-hydroxyvitamin D and education years. Eight associations remained after adjustment for adulthood BMI. We additionally identified 21 suggestive risk factors (p < 0.05), such as alcohol consumption, breakfast skipping, daytime napping, short sleep, urinary sodium, and certain amino acids and inflammatory factors. Conclusions/interpretation The present study verified several previously reported risk factors and identified novel potential risk factors for type 2 diabetes. Prevention strategies for type 2 diabetes should be considered from multiple perspectives on obesity, mental health, sleep quality, education level, birthweight and smoking. Graphical abstract
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Tarnoki, David Laszlo, Adam Domonkos Tarnoki, Antje Richter, Kinga Karlinger, Viktor Berczi, and Dirk Pickuth. "Clinical value of whole-body magnetic resonance imaging in health screening of general adult population." Radiology and Oncology 49, no. 1 (March 1, 2015): 10–16. http://dx.doi.org/10.2478/raon-2014-0031.
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Abstract Background. Whole-body magnetic resonance imaging (WB-MRI) and angiography (WB-MRA) has become increasingly popular in population-based research. We evaluated retrospectively the frequency of potentially relevant incidental findings throughout the body. Materials and methods. 22 highly health-conscious managers (18 men, mean age 47±9 years) underwent WBMRI and WB-MRA between March 2012 and September 2013 on a Discovery MR750w wide bore 3 Tesla device (GE Healthcare) using T1 weighted, short tau inversion recovery (STIR) and diffusion weighted imaging (DWI) acquisitions according to a standardized protocol. Results. A suspicious (pararectal) malignancy was detected in one patient which was confirmed by an endorectal sonography. Incidental findings were described in 20 subjects, including hydrocele (11 patients), benign bony lesion (7 patients) and non-specific lymph nodes (5 patients). Further investigations were recommended in 68% (ultrasound: 36%, computed tomography: 28%, mammography: 9%, additional MRI: 9%). WB-MRA were negative in 16 subjects. Vascular normal variations were reported in 23%, and a 40% left proximal common carotid artery stenosis were described in one subject. Conclusions. WB-MRI and MRA lead to the detection of clinically relevant diseases and unexpected findings in a cohort of healthy adults that require further imaging or surveillance in 68%. WB-MR imaging may play a paramount role in health screening, especially in the future generation of (epi)genetic based screening of malignant and atherosclerotic disorders. Our study is the first which involved a highly selected patient group using a high field 3-T wide bore magnet system with T1, STIR, MRA and whole-body DWI acquisitions as well.
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Martel, Carlos, José A. Nicholás, and José M. Vega. "Surface wave damping in a brimful circular cylinder." Journal of Fluid Mechanics 373 (October 25, 1998): 379. http://dx.doi.org/10.1017/s0022112098002924.
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Journal of Fluid Mechanics, vol. 360 (1998), pp. 213–228As pointed out to us by Mr T. Heath, the following printing errors can be quite misleading when using the formulas in the paper to obtain eigenfrequencies and damping rates to compare with experiments:in (A 13) 1 should read −1 on the right-hand side;in (A 22) and (A 26) Ω20 should read Ω−20;in (A 25) the factor Ω40 must be omitted on the right-hand side.When revising again the printed version of the paper, we discovered several additional misprints:A factor C was omitted in the first two integrals in the expression for J2, immediately following equation (2.9).The sign of the second expression for I1 in (2.23) should be changed.The expression (W0Wz +3WW0z)z=0 should read 2(W0Wz +WW0z)z=0 in equation (2.24).The expression W0(1, z)W0z(1, z) in (2.26) should read W0(r, 0)W0z(r, 0).None of the misprints above affect the results of the paper, which were obtained with the correct expressions.
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Fehniger, Todd A., Kilannin Krysiak, Brian S. White, Matthew Matlock, Chris Miller, Robert Fulton, Friederike Kreisel, et al. "Recurrent Somatic Genomic Alterations in Follicular NHL (FL) Revealed By Exome and Custom-Capture Next Generation Sequencing." Blood 126, no. 23 (December 3, 2015): 574. http://dx.doi.org/10.1182/blood.v126.23.574.574.
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Abstract Background: Follicular lymphoma (FL) is the most common indolent NHL (iNHL), exhibits a variable clinical course, and remains largely incurable. The pathogenesis of FL is complex and involves over expression of Bcl2 via t(14;18) translocation, as well as copy number alterations, recurrent somatic mutations, and changes in the tumor microenvironment. In line with recent publications, we hypothesized that recurrent somatic genomic mutations in FL will be present and may impact FL development, progression, transformation, and clinical outcomes. Methods: To address this, we performed exome sequencing (NimbleGen SeqCap EZ V2.0) of tumor and normal frozen tissue pairs from 24 patients in a discovery cohort with untreated FL (12), relapsed FL (6), or transformed FL/iNHL (6). We developed a custom capture assay (NimbleGen) that targets 7.05 MB corresponding to the coding, 5' and 3' UTR regions of 1717 genes. The custom capture genes included somatic mutations identified in our exome discovery cohort (898 genes) or somatic mutations previously published to be recurrently mutated in B cell NHL (819 genes). Instrument data from the discovery cohort exome and re-sequenced custom capture were combined and analyzed using the McDonnell Genome Institute (MGI) somatic caller pipeline (5 SNV callers, 3 indel callers), filtered (minimum 20X coverage, minimum 2.5% VAF, maximum 10% normal VAF) and manually reviewed. Additionally, the 1717 custom capture strategy was used to sequence an extension cohort consisting of FFPE tumor samples from 80 patients with FL, achieving >20x coverage for >75% of the targeted region. All discovery and extension samples have clinical annotations that include FLIPI prognostic score, treatment, and clinical outcomes. Results: Combined analysis of exome and custom capture data for the discovery cohort yielded a robust data set with good sequence coverage of >78% of the targeted regions with at least 20x depth in all samples and a mean depth of 89x. Based upon somatic mutations identified and manually reviewed using this approach, we conservatively estimate 0.98 mutations per MB in FL. 23 genes were recurrently mutated in 3 or more cases, and an additional 75 genes recurrently mutated in 2 cases in the discovery cohort. Consistent with recent publications (Li H et. al., Blood, 2014; Green MR, PNAS, 2015; Yildiz M et al, Blood, 2015) we confirmed a number of genes that were highly recurrently mutated in FL [TNFRSF14 (50%), Bcl2 (25%), IRF8 (13%), TP53 (13%)] including chromatin modifying genes consisting of histone methyl transferases [KMT2D/MLL2 (58%), EZH2 (13%)], histone acetyltransferases [CREBBP (42%), EP300 (17%)], histone linkers [HIST1H1C (13%), HIST1H1E (8%), HIST1H2BO (8%), HIST1H3G (8%), HIST2H2AC (8%); collectively 42%]. We also confirmed (ATP6V1B2, 13%) and found unreported (ATP6AP2, 8%; ATP6V0A1, 4%; ATP6V1F, 4%) mutations in vacuolar ATPase proton pump genes and P5 or Ca++ ATPase genes (ATP13A2, 4%; ATP13A4, 4%, ATP2B4, 4%;). We confirmed (CD79B, 13%; BCL10, 8%) and found unreported (CD22, 13%) mutations in components of the B cell receptor signaling pathway. The previously unreported recurrent mutations in CD22 were consistent with loss-of function (2 missense, 1 nonsense, 1 frame shift deletion). As a negative regulator of BCR signaling, mutation of CD22 may represent a strategy of to enhance BCR signals in malignant germinal center B cells. We also identified members of the SWI/SNF complex mutated in 33% of this FL cohort: ARID1B (8%), BCL11A (4%), SMARCB1 (4%) in addition to previously reported members BCL7A (12%), SMARCA4 (8%), ARID1A (4%). Somatic mutations were also identified in the Notch pathway: DTX1 (29%), Notch2 (4%), Notch3 (4%), Notch4 (4%). We identified several genes that have not been reported as highly recurrent in FL CXCR4 (42%, mutation calls primarily in RNA), DMD (13%), DNAH9 (13%), FLG (13%), GON4L (13%), PCDH7 (13%), RLTPR (13%), SCN7A (13%), ST6GAL1 (13%). Conclusions: FL genomes harbor a large number of recurrent mutations, consistent with a role in the development and progression of this malignancy. Analysis of the extension cohort and association of recurrently mutated genes and pathways with clinical outcomes is ongoing and will be presented. Disclosures Bartlett: Gilead: Consultancy, Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Millennium: Research Funding; Colgene: Research Funding; Medimmune: Research Funding; Kite: Research Funding; Insight: Research Funding; Seattle Genetics: Consultancy, Research Funding; MERC: Research Funding; Dynavax: Research Funding; Idera: Research Funding; Portola: Research Funding; Bristol Meyers Squibb: Research Funding; Infinity: Research Funding; LAM Theapeutics: Research Funding.
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Kachuri, Linda, Soyoung Jeon, Andrew T. DeWan, Catherine Metayer, John S. Witte, Xiaomei Ma, Charleston W. K. Chiang, Joseph L. Wiemels, and Adam J. de Smith. "Genetic Determinants of Blood Cell Traits Play a Role in Susceptibility to Acute Lymphoblastic Leukemia." Blood 136, Supplement 1 (November 5, 2020): 10–11. http://dx.doi.org/10.1182/blood-2020-141443.
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Background: Genome-wide association studies (GWAS) have identified several genes associated with childhood acute lymphoblastic leukemia (ALL) that are also implicated in variation in hematological traits. We performed a comprehensive study of the shared heritability of blood cell traits and ALL, and investigated whether genetic variation in blood cell traits may underlie ALL risk. Methods: We leveraged genome-wide single nucleotide polymorphism (SNP) data from: 1) 335,332 European ancestry, cancer-free subjects without immune deficiencies or hematopoietic disorders in the UK Biobank (UKB); and 2) a childhood ALL GWAS meta-analysis including 2,121 cases and 59,965 controls of European ancestry, to investigate the shared genetic basis of blood cell trait variation and ALL susceptibility. Co-heritability between blood cell profiles and ALL susceptibility was evaluated by LD score regression. To formally test variation in blood cell traits as potential causal pathways in ALL development, we conducted Mendelian randomization (MR) analyses, which use genetic predictors of blood cell phenotypes to overcome potential confounding and reverse causation in directly measured blood counts. Genetic instruments for MR were developed using a two-stage GWAS of 6 cell types (lymphocytes, monocytes, neutrophils, eosinophils, basophils, platelets), and their ratios (lymphocyte/monocyte - LMR; neutrophil/monocyte - NLR; platelet/lymphocyte - PLR) in the UKB. Next we applied multi-trait analysis of GWAS (MTAG) to improve power for identifying trait-specific loci by exploiting the correlated nature of blood cell traits. Causal odds ratios (OR) for ALL were estimated per 1 standard deviation increase in normalized cell counts (109cells/L) or 1-unit increase in cell type ratios. Results: Using genome-wide SNP data, we found that ALL has a heritability of hg=0.235 (95% confidence intervals, CI:0.203-0.268) in European ancestry individuals. In LD score regression, ALL susceptibility was correlated at the genetic level with overall blood cell counts (rg=0.070, P=0.003), lymphocyte counts (rg=0.088, P=0.004), LMR (rg=0.065, P=0.012), and PLR (rg= -0.072, P=0.001). Genetic instruments for MR were selected from independent (LD r2<0.05) variants with P<5×10-8 in the discovery blood cell trait GWAS/MTAG (N=234,778) and P<0.05 in the replication analysis (N=100,554). The resulting genetic predictors explained between 4.0% (basophils, NSNP=144) and 23.9% (platelets, NSNP=661) of trait variation. Our findings lend support to a modest but significant causal effect of variation in lymphocyte counts (OR=1.16, 95% CI:1.01-1.33), LMR (OR=1.23, 95% CI:1.07-1.41), NLR (OR=0.67, 95% CI:0.54-0.83), and PLR (OR=0.80, 95% CI:0.70-0.92) on ALL risk. There was no evidence of directional pleiotropy based on the MR Egger intercept test (P>0.05). However, significant heterogeneity among SNP-specific causal effects (Cochran's Q P<0.05) indicated potential for confounding due to balanced pleiotropy. In sensitivity analyses using MR-PRESSO framework, which corrects for distortion in causal effects due to pleiotropy, the associations with ALL risk became attenuated for lymphocytes (OR=1.14, 95% CI:0.98-1.32), but persisted for LMR (OR=1.18, 95% CI:1.01-1.38), NLR (OR=0.76, 95% CI:0.60-0.97), and PLR (OR=0.82, 95% CI:0.70-0.95). Next, we searched for individual variants that may underlie the effects on ALL risk using heterogeneity-based clustering of genetic instruments. This analysis confirmed that regulation of blood cell traits partially mediates the effects of known ALL risk variants: rs4948492, rs4245597 (ARID5B), rs2239630 (CEBPE), and rs78697948 (IKZF1). We also identified putative novel ALL risk loci at chromosome 2q22 (OR=1.28, P=2.5×10-6), chr6q23 (OR=1.21, P=9.3×10-6), and chr13q12 (OR=1.79, P=3.2×10-5), though further analyses are required to confirm these associations and identify likely causal variants and genes at these loci. Conclusions: Our findings suggest that dysregulation of blood cell profiles characterized by a genetic predisposition to increased lymphocyte counts, particularly in relation to neutrophils, monocytes, and platelets, confers a modest but significant increase in ALL risk. Additional research is required to determine whether a genetic propensity to higher lymphocyte levels is associated with ALL subtypes or clinical outcomes in ALL patients. Disclosures Ma: Celgene/BMS: Research Funding; BMS: Consultancy.
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Kan, Hermien E., Esther Meeuwissen, Jack J. van Asten, Andor Veltien, Dirk Isbrandt, and Arend Heerschap. "Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy." Journal of Applied Physiology 102, no. 6 (June 2007): 2121–27. http://dx.doi.org/10.1152/japplphysiol.01327.2006.
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Creatine (Cr) levels in skeletal muscle and brain of a mouse model of Cr deficiency caused by guanidinoacetate methyltransferase absence (GAMT−/−) were studied after Cr supplementation with 2 g·kg body wt−1·day−1 Cr for 35 days. Localized 1H magnetic resonance spectroscopy (MRS) was performed in brain (cerebellum and thalamus/hippocampus) and in hind leg muscle of GAMT−/− mice before and after Cr supplementation and in control (Con) mice. As expected, a signal for Cr was hardly detectable in MR spectra of GAMT−/− mice before Cr supplementation. In the thalamus/hippocampus region of these mice, an increase in N-acetylasparate (NAA) was observed. During Cr administration, Cr levels increased faster in skeletal muscle compared with brain, but this occurred only during the first day of supplementation. Thereafter, Cr levels increased by 0.8 mM/day in all studied locations. After 35 days of Cr supplementation, Cr levels in all locations were higher compared with Con mice on a Cr-free diet and NAA levels normalized. Only because of the repeated MRS measurements performed in this longitudinal Cr supplementation study on GAMT−/− mice were we able to discover the initial faster uptake of Cr in skeletal muscle compared with brain, which may represent muscular Cr uptake independent of Cr transporter expression. Our results can provide the basis for additional experiments to optimize Cr supplementation in GAMT deficiency, as increases in brain Cr are slow in patients after Cr supplementation.
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Islam, AKM Monwarul, Dipal K. Adhikary, Shovan Rahman, Mohsin Ahmed, Md Toufiqur Rahman, Mohammad Ullah, and Abdullah AS Majumder. "Echocardiographic Profile of Hypertrophic Cardiomyopathy – A Single-Centre, Observational study." Cardiovascular Journal 14, no. 1 (September 15, 2021): 5–11. http://dx.doi.org/10.3329/cardio.v14i1.55367.
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Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease of left ventricular hypertrophy (LVH). Phenotypic expression varies widely from subclinical hypertrophy to gross asymmetric septal hypertrophy causing left ventricular outflow tract (LVOT) obstruction. On top of genetic and phenotypic heterogeneity, the prevalence of different types of HCM may have geographical, as well as, ethnic variation. Methods: This observational study was carried out during 2010 to 2020 to determine the echocardiographic profile of HCM in Bangladeshi population. All patients undergoing transthoracic echocardiography (TTE) in a private consultation centre of Dhaka, Bangladesh were included. HCM was defined as the presence of a maximal end-diastolic wall thickness of e”15 mm anywhere in the left ventricle (LV), in the absence of another cause of hypertrophy in adults. HCM was further classified according to the pattern of myocardial hypertrophy and presence or absence of LVOT, or mid-left ventricular cavity obstruction. Results: Out of 76 cases, non-obstructive HCM was the commonest type (65.8%), followed by HCM causing LVOT obstruction (13.2%), HCM causing mid-LV cavity obstruction (10.5%), and the apical variety ( 10.5%). Asymmetric septal hypertrophy (ASH) was found in 42.1%, systolic anterior motion (SAM) of anterior mitral leaflet (AML) in 14.5%, mitral regurgitation (MR) in 50%, left ventricular systolic dysfunction in 5.3%, and raised pulmonary artery systolic pressure (PASP) in 15.8% of cases. Maximum LV wall thickness ≥30 mm was found in 66 out of 76 cases. Conclusion: The study highlights the clinically useful profile of HCM in Bangladeshi population based on conventional echocardiography. Further studies involving clinical, newer echocardiographic modalities and genetic analyses are warranted to discover the additional information in this ethnicity. Cardiovasc j 2021; 14(1): 5-11
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Pungolino, Ester, Mariella D'adda, Alessandra Trojani, Alessandra Perego, Chiara Elena, Alessandra Iurlo, Simona Malato, et al. "Jak-2 and Nfkbia Gene Expression Play a Strategic Role in Chronic Myeloid Leukemia (CML) Molecular Response during Early Nilotinib Treatment: The PhilosoPhi34 Data." Blood 132, Supplement 1 (November 29, 2018): 5118. http://dx.doi.org/10.1182/blood-2018-99-113273.
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Abstract Background Targeted therapy with Tyrosine-Kinase-Inhibitors (TKIs) totally modified the course of treatment of Chronic Myeloid Leukemia (CML). The objectives and the needs of treatment have been modified during the last years and the discontinuation of therapy is now a feasible aim. However, a lot of biological data acquired in the last twenty years, showed that degree and mechanisms of Leukemic Stem Cells (LSCs) clearance during TKI treatment are not clearly established as well as the predictive criteria for a stable and prolonged Treatment Free Remission (TFR). The multicentre, prospective, single-arm PhilosoPhi34 study (EudraCT: 2012-005062-34) was designed by the Rete Ematologica Lombarda (REL), to verify the in-vivo activity and time-course of first-line Nilotinib (NIL) therapy on Bone Marrow (BM) CD34+/lin-Ph+ cells clearance. An exploratory Gene Expression Profiling (GEP) study of CD34+/lin- cells at diagnosis and at 12 months (mos) of treatment, for the first 30 evaluable pts, was included. Preliminary GEP data suggested a correlation between different NFKBIA expression at diagnosis and at 12 mos and the achievement of a deeper Molecular Response (MR) (Pungolino et al, AJH 2018). We report here some results of GEP analysis on all enrolled evaluable pts and their possible correlation with clinical data. Methods BM cells were collected and stored at diagnosis and at 12 mos of treatment. CD34+/lin- cells were purified with a Diamond CD34 Isolation Kit Miltenyi (97% of purity). For GEP analysis we used Affymetrix HG-U133 Plus 2.0 microarray and Genechip platform (Affymetrix) and the Affymetrix GeneChip Scanner 3000. Data was pre-processed and normalized using the Robust Multi-array Average (RMA) algorithm. The Significant Analysis of Microarrays (SAM) was used to identify genes with statistically significant changes in expression. P-values were corrected for multiple testing using false discovery rate, for differentially expressed genes confirmation. We chose to analyse different expression of NFKBIA (the inhibitor of NF-kB onco-gene) in order to confirm the preliminary data reported on the first 30 analysed pts. Pts were monitored according to ELN-recommendation. Biological data were correlated with MR at 3, 12 and 36 mos of therapy. We use Fishers test to compare unbalanced group. Results Out of the 87 enrolled pts, 80 completed the first 12 mos of treatment and 78 (1 failure and 77 CCyR) were evaluable for GEP analysis. We observed 2726 genes symbol differentially expressed of which 1868 are coding genes. Among these, JAK-2 showed a down regulation at 12 mos (p: .024). JAK-2 expression ranged from 2.62 to 4.95 at diagnosis and from 1.48 to 5.58 at 12 mos. Only 26/78 pts increased JAK-2 expression that was > 4 in 1/26 pts, at diagnosis; 2/26 (7.69%) pts showed a H Sokal. Other 52/78 pts decreased JAK-2 expression that was ≥ 4 in 21/52 pts, at diagnosis; 10/52 (19.23%) pts and 6/21 (28,57%) pts showed a H Sokal. Similarly, when we compared low JAK-2 expression (< 3.5) vs vary high expression (≥ 4) 2/21 vs 6/22 pts had H Sokal (9.52% vs 27.27%; p: .0057). Considering the role of JAK-2 and NFKBIA in cell regulation and survival, we evaluated how the combination of their different expression impact on MR (i.e. NFKBIA increased expression/JAK-2 decreased expression vs NFKBIA decreased expression/JAK-2 increased expression). Data are reported in Table 1 and 2. Conclusion GEP analysis showed a down regulation of JAK-2 expression after 12 mos of first line NIL treatment, in 78 early chronic phase CML pts. Data suggest that high expression of JAK-2, at diagnosis, correlate with H Sokal score. However, H Sokal pts with a JAK-2 down regulation, obtain during treatment similar MR compared to L Sokal pts. Additionally, the study confirms our preliminary observation on 30 pts , concerning the role of NKBIA up - regulation in increasing percentage of earlier and deeper MR . The better condition of NFKBIA and JAK-2 expression (up regulation of NFKBIA and down regulation of JAK-2) is associated with a higher percentage of early MR3 and optimal responses over time, despite the higher number of H Sokal pts in this group. A study with NIL as first line treatment combined with low dose of JAK-2 inhibitor and a natural inhibitor of NF-kB (such as curcuma), during the first year of treatment, to increase the deeper MR rate and the probability of TFR is warrented. Disclosures Rossi: Sandoz: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Teva: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Honoraria; Novartis: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees.
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Pollard, H. B., A. L. Burns, and E. Rojas. "A molecular basis for synexin-driven, calcium-dependent membrane fusion." Journal of Experimental Biology 139, no. 1 (September 1, 1988): 267–86. http://dx.doi.org/10.1242/jeb.139.1.267.
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Membranes of secretory vesicles fuse with each other and with plasma membranes during exocytosis in many different cell types. The probable role of calcium in the process is now widely accepted, and it is possible that at least one cytosolic mediator of calcium action is synexin. Synexin is a 47,000 Mr calcium-binding protein, initially discovered in the bovine adrenal medulla, which binds to granule membranes and to inner aspects of chromaffin cell plasma membranes. Synexin causes chromaffin granules to aggregate, and such aggregates can be caused to fuse in the additional presence of arachidonic acid. Synexin also mediates the direct fusion of liposomes and chromaffin granule ghosts. To understand better the mechanisms of membrane fusion promoted by synexin we have attempted to define the primary sequence of the protein. Our initial efforts were directed towards purification of bovine synexin in sufficient amounts to allow us to sequence tryptic peptides. However, as the project progressed we also directed our attention to human synexin, preparing peptides from this protein as well. From analysis of bovine peptides we learned that the synexin molecule might be closely related to a class of proteins including lipocortin I, calpactin (p36), endonexin II, protein II and calelectrin 67K. Complete analysis of a human synexin cDNA clone revealed strong homology with bovine synexin. The analysis also showed that synexin contained a unique, long, highly hydrophobic N-terminal leader sequence followed by a characteristic four-fold repeat homologous with those found in other members of the synexin gene family. The highly hydrophobic character of synexin seems consistent with information previously obtained that synexin is able to insert directly into the interior of bilayers prepared not only from purified phosphatidylserine but also from biological membranes. The evidence for such insertions is a dramatic increase in the capacitance of the membrane, formed at the tip of a patch pipette, when calcium-activated synexin is applied to the bilayer. Additional evidence is the fact that synexin also forms calcium-selective channels when the protein is applied to the cytosolic aspect of the plasmalemma when that side is also exposed to calcium at sub-millimolar concentrations. Thus, the synexin molecule not only enters the membrane, but also spans it. From these and other data we have developed the concept that the fusion process may involve synexin forming a ‘hydrophobic bridge’ between two fusing membranes. Lipid movement across this bridge may then be the material basis for final fusion.(ABSTRACT TRUNCATED AT 400 WORDS)
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Fluegge, Keith. "Autism in 2016: additional discovery." Jornal de Pediatria 93, no. 3 (May 2017): 308–9. http://dx.doi.org/10.1016/j.jped.2016.12.001.
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Fluegge, Keith. "Autism in 2016: additional discovery." Jornal de Pediatria (Versão em Português) 93, no. 3 (May 2017): 308–9. http://dx.doi.org/10.1016/j.jpedp.2016.12.004.
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Pralle, Ryan S., Wenli Li, Brianna N. Murphy, Henry T. Holdorf, and Heather M. White. "Novel Facets of the Liver Transcriptome Are Associated with the Susceptibility and Resistance to Lipid-Related Metabolic Disorders in Periparturient Holstein Cows." Animals 11, no. 9 (August 31, 2021): 2558. http://dx.doi.org/10.3390/ani11092558.
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Lipid-related metabolic disorders (LRMD) are prevalent in early lactation dairy cows, and have detrimental effects on productivity and health. Our objectives were to identify cows resistant or susceptible to LRMD using a ketosis induction protocol (KIP) to discover differentially expressed liver genes and metabolic pathways associated with disposition. Clustering cows based on postpartum lipid metabolite concentrations within dietary treatments identified cows more or less susceptible (MS vs. LS) to LRMD within the control treatment, and more or less resistant (MR vs. LR) within the KIP treatment. Whole-transcriptome RNA sequencing was performed on liver samples (−28, +1, and +14 days relative to calving) to assess differential gene and pathway expression (LS vs. MS; MR vs. LR; n = 3 cows per cluster). Cows within the MS and LR clusters had evidence of greater blood serum β-hydroxybutyrate concentration and liver triglyceride content than the LS and MR clusters, respectively. The inferred metabolism of differentially expressed genes suggested a role of immune response (i.e., interferon-inducible proteins and major histocompatibility complex molecules). Additionally, unique roles for glutathione metabolism and eicosanoid metabolism in modulating susceptibility and resistance, respectively, were implicated. Overall, this research provides novel insight into the role of immunometabolism in LRMD pathology, and suggests the potential for unique control points for LRMD progression and severity.
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Kordonsky, W. I., and S. A. Demchuk. "Additional Magnetic Dispersed Phase Improves the Mr-Fluid Properties." Journal of Intelligent Material Systems and Structures 7, no. 5 (September 1996): 522–25. http://dx.doi.org/10.1177/1045389x9600700509.
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Buhl, Ralf, Andreas Martin Stark, Heinz Hermann Hugo, Axel Rohr, and Hubertus Maximilian Mehdorn. "Gliosarcoma: clinical experiences and additional information with MR spectroscopy." Neurological Research 31, no. 8 (October 2009): 873–77. http://dx.doi.org/10.1179/174313209x395490.
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Kouyoumdjian, João Aris, Maria P. A. Morita, and Amalia F. P. Molina. "Usefulness of additional nerve conduction techniques in mild carpal tunnel syndrome." Arquivos de Neuro-Psiquiatria 60, no. 4 (December 2002): 923–27. http://dx.doi.org/10.1590/s0004-282x2002000600007.
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This study was done to assess the percentage of abnormality in additional nerve conduction techniques after normal median distal latency (routine) in mild carpal tunnel syndrome (CTS). Bilateral nerve conduction studies were carried out in 116 consecutive symptomatic CTS patients (153 hands). Mild cases were based on normal routine (< 3.7 ms, peak-measured, 14 cm) and at least one technique abnormal of the following: sensory median-radial difference (MR); sensory median-ulnar difference (MU4); mixed palm median-ulnar difference (MUP); median palm latency (PW); and motor median distal latency (MDL). After normal cut-off values for routine, 3.1 to 3.6 ms (< 3.7 ms), we found an abnormal MR, ranging from 86.6 to 93.4%, followed by MU4 (40 to 81.7%), MUP (20 to 71.2%), PW (0 to 41.1%), and MDL (0 to 19.6%). The most frequent abnormal association were MR plus MU4 in 90.1%, followed by MR plus MUP and MU4 plus MUP. The most frequent abnormal additional nerve conduction technique for mild CTS electrodiagnosis was MR, followed by MU4 and MUP. Percentage of MR abnormality was very high regardless of the median routine latency cut-off (< 3.1 to < 3.6 ms).
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Van Eck, S., S. Goriely, A. Jorissen, and B. Plez. "Discovery of additional lead-rich stars." Nuclear Physics A 718 (May 2003): 521–23. http://dx.doi.org/10.1016/s0375-9474(03)00830-3.
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Alexandersen, M., B. Gladman, C. Veillet, R. Jacobson, M. Brozović, and P. Rousselot. "DISCOVERY OF TWO ADDITIONAL JOVIAN IRREGULARS." Astronomical Journal 144, no. 1 (June 11, 2012): 21. http://dx.doi.org/10.1088/0004-6256/144/1/21.
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Rand, T., S. Trattnig, J. Haller, N. K. Nguyen, and H. Imhof. "MR imaging in shoulder trauma." Acta Radiologica 39, no. 3 (May 1998): 273–75. http://dx.doi.org/10.1080/02841859809172193.
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Purpose: To determine the adequacy of MR standard protocols by analyzing conventional T1— and T2-weighted SE sequences, and to evaluate the usefulness of additional fat-suppressed (STIR) images in shoulder trauma Material and Methods: Paracoronal T1-weighted, T2-weighted SE, and STIR images were obtained on a 0.5 T superconductive system in 25 patients with shoulder trauma. In a separate evaluation of T1/T2 images and a combined evaluation of T1/T2 SE- and STIR images, we compared the number of patients with evidence of Hill-Sachs lesions, bone bruises, and/or rotator-cuff lesions Results: Compared to the combined evaluation of T1/T2 and STIR images, the separate evaluation of T1/T2 SE images revealed identical results for rotator-cuff lesions and Hill-Sachs lesions, but different results for the bone bruises in the area of the major tubercle Conclusion: Occult fractures of the major tubercle, indicated by areas of bone bruising, might be missed with MR using conventional SE images. We recommend the use of additional paracoronal fat-suppressed sequences in patients with clinically suspected lesions and equivocal findings on plain radiographs and on standard SE sequences
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Sohn, Jung Woo, Jong-Seok Oh, and Seung-Bok Choi. "Damping Force Characteristics of MR Damper with Additional Flow Path." Transactions of the Korean Society for Noise and Vibration Engineering 25, no. 6 (June 20, 2015): 426–31. http://dx.doi.org/10.5050/ksnve.2015.25.6.426.
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Kirby, William F. "XIII. Additional Notes on Mr. Distant's Collection of African Locustidae." Transactions of the Royal Entomological Society of London 50, no. 2 (April 24, 2009): 231–42. http://dx.doi.org/10.1111/j.1365-2311.1902.tb01383.x.
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Salvin, Osbert. "Additional Notes on Mr. Lawrence's List of Costa-Rica Birds." Ibis 12, no. 1 (June 28, 2008): 107–16. http://dx.doi.org/10.1111/j.1474-919x.1870.tb05786.x.
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Nenezić, Dragoslav, and Igor Kocijancic. "The value of the sagittal-oblique MRI technique for injuries of the anterior cruciate ligament in the knee." Radiology and Oncology 47, no. 1 (January 1, 2013): 19–25. http://dx.doi.org/10.2478/raon-2013-0006.
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Abstract Background. Complete rupture of the anterior cruciate ligament (ACL) does not represent a diagnostic problem for the standard magnetic resonance (MR) protocol of the knee. Lower accuracy of the standard MR protocol for partial rupture of the ACL can be improved by using additional, dedicated MR techniques. The study goal was to draw a comparison between sagittal-oblique MR technique of ACL imaging versus flexion MR technique of ACL imaging and, versus ACL imaging obtained with standard MR protocol of the knee. Patients and methods. In this prospective study we included 149 patients who were referred to magnetic resonance imaging (MRI) examination due to knee soft tissues trauma during 12 months period. MRI signs of ACL trauma, especially detection of partial tears, number of slices per technique showing the whole ACL, duration of applied additional protocols, and reproducibility of examination were analysed. Results. Accuracy of standard MRI protocol of the knee comparing to both additional techniques is identical in detection of a complete ACL rupture. Presentations of the partial ruptures of ACL using flexion technique and sagittaloblique technique were more sensitive (p<0.001) than presentation using standard MR protocol. There was no statistically significant difference between MRI detection of the ruptured ACL between additional techniques (p> 0.65). Sagittal-oblique technique provides a higher number of MRI slices showing the whole course of the ACL and requires a shorter scan time compared to flexion technique (p<0.001). Conclusions. Both additional techniques (flexion and sagittal-oblique) are just as precise as the standard MR protocol for the evaluation of a complete rupture of the ACL, so they should be used in cases of suspicion of partial rupture of the ACL. Our study showed sagittal-oblique technique was superior, because it did not depend on patient’s ability to exactly repeat the same external rotation if standard MR protocol was used or to repeat exactly the same flexion in flexion MR technique in further MR examinations. Sagittal-oblique technique does not require the patient’s knee to be repositioned, which makes this technique faster. We propose this technique in addition to the standard MR protocol for detection of partial ACL tears.
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A. Tzacheva, Angelina, Arunkumar Bagavathi, and Punniya D. Ganesan. "MR - Random Forest Algorithm for Distributed Action Rules Discovery." International Journal of Data Mining & Knowledge Management Process 6, no. 5 (September 30, 2016): 15–30. http://dx.doi.org/10.5121/ijdkp.2016.6502.
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Omura, S. "Philosophy of new drug discovery." Microbiological Reviews 50, no. 3 (1986): 259–79. http://dx.doi.org/10.1128/mr.50.3.259-279.1986.
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Moulopoulos, L. A., M. A. Dimopoulos, D. Weber, L. Fuller, H. I. Libshitz, and R. Alexanian. "Magnetic resonance imaging in the staging of solitary plasmacytoma of bone." Journal of Clinical Oncology 11, no. 7 (July 1993): 1311–15. http://dx.doi.org/10.1200/jco.1993.11.7.1311.
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PURPOSE To assess prospectively the role of magnetic resonance (MR) imaging in the staging of patients with a solitary bone plasmacytoma (SBP). PATIENTS AND METHODS Twelve consecutive patients with an apparent SBP underwent MR imaging of both the primary tumor and the thoracic and lumbosacral spine to seek additional foci of marrow involvement that might have been undetected by standard skeletal survey. All patients received megavoltage irradiation (total dose, 40 Gy) to the primary lesion. RESULTS MR imaging of the thoracic and lumbosacral spine showed additional foci of marrow replacement in four of 12 patients, with signal characteristics identical to those of the primary tumor. In all four patients, the abnormal protein persisted at greater than 50% of the pretreatment value following radiation treatment. In contrast, the myeloma protein disappeared or was reduced by greater than 50% in five of the six patients with secretory disease and without additional marrow abnormalities. One of four patients progressed to multiple myeloma 10 months after diagnosis with new lesions on conventional radiographs in the same areas as detected previously by MR imaging. CONCLUSION Four of 12 patients considered to have a SBP by standard criteria may have been understaged, because MR imaging showed additional marrow abnormalities consistent with myeloma. MR imaging of the spine may contribute to the initial staging of SBP, especially since some patients may be cured with radiotherapy.
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Posar, Annio, and Paola Visconti. "Authors’ reply: “Autism in 2016: additional discovery”." Jornal de Pediatria 93, no. 3 (May 2017): 309–10. http://dx.doi.org/10.1016/j.jped.2016.12.002.
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Posar, Annio, and Paola Visconti. "Authors’ reply: “Autism in 2016: additional discovery”." Jornal de Pediatria (Versão em Português) 93, no. 3 (May 2017): 309–10. http://dx.doi.org/10.1016/j.jpedp.2016.12.005.
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Brauner, R., V. Barral, R. Rappaport, and D. Lallemand. "MAGNETIC RESONANCE (MR) AS AN ADDITIONAL DIAGNOSTIC TOOL FOR HYPOTHALAMIC HAMARTOMA." Pediatric Research 20, no. 11 (November 1986): 1188. http://dx.doi.org/10.1203/00006450-198611000-00088.
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Butler, Arthur G. "VI. Additional notes on Bombyces collected in Chili by Mr. Edmonds." Transactions of the Royal Entomological Society of London 30, no. 1 (April 24, 2009): 101–8. http://dx.doi.org/10.1111/j.1365-2311.1882.tb01571.x.
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Hung, Alice L., Wuyang Yang, Tomas Garzon-Muvdi, Justin M. Caplan, Geoffrey P. Colby, Alexander Lewis Coon, Rafael Jesus Tamargo, and Judy Huang. "123 Outcome Comparison for Single versus Multiple Radiosurgery for Brain Arteriovenous Malformation (AVM): A Propensity-Matched Cohort Analysis." Neurosurgery 64, CN_suppl_1 (August 24, 2017): 227. http://dx.doi.org/10.1093/neuros/nyx417.123.
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Abstract INTRODUCTION Radiosurgery has been shown as an effective definitive treatment for brain AVMs However, for patients with residual AVMs after a single radiosurgery treatment, the benefit of receiving additional radiosurgery treatments is less clear. In this study, we aim to determine the comparative outcome of multiple radiosurgery procedures. METHODS We retrospectively reviewed patients with brain AVMs from 1990–2015 at our institution. Three groups of patients were included: conservative management (CS), single radiosurgery (SR), and multiple radiosurgery (MR). We included treatment-propensity-related variables determined through univariable analysis into propensity-score-matching. MR was consecutively matched to other two groups in approximately 1:2 ratio. The matched groups were combined and examined in univariable analysis to test for balance. Patient outcomes were then compared. RESULTS >Younger patients with larger AVMs and deep drainage were more likely to receive MR. There were 35 patients in MR, and 51 were matched in SR and 44 matched in CS; therefore, our cohort consisted of 130 patients. There was no significant difference in distribution of baseline variables (p > 0.05) between different treatment groups. The average total dose received was 2760.0cGy and 2074.4cGy respectively for MR(n = 30) and SR(n = 43). More hemorrhages occurred during the follow-up period in the MR (14.3%) than in SR (2.0%, P = 0.039) group, compared to 31.8% in conservative management (P< 0.001). Of note, all follow-up hemorrhages in MR occurred between first and second treatment. Although no difference in overall obliteration(43.1% versus 45.7%, P = 0.937) was found, 60% who hemorrhaged in MR experienced eventual obliteration. No difference in last follow-up mRS (P = 0.653) was found between SR and MR. CONCLUSION Additional radiosurgery for patients with residual AVMs after first radiosurgery should be considered on individual basis. For patients with hemorrhage after initial radiosurgery, additional radiosurgery may achieve obliteration and prevent further hemorrhage. However, for patients without post-treatment hemorrhage, it is less clear whether receiving additional treatment will benefit the patient within the context of obliteration and functional outcome.
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Cruz-Monteagudo, Maykel, José L. Medina-Franco, Yunierkis Pérez-Castillo, Orazio Nicolotti, M. Natália D. S. Cordeiro, and Fernanda Borges. "Activity cliffs in drug discovery: Dr Jekyll or Mr Hyde?" Drug Discovery Today 19, no. 8 (August 2014): 1069–80. http://dx.doi.org/10.1016/j.drudis.2014.02.003.
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Beachy, Roger N. "Coat–protein–mediated resistance to tobacco mosaic virus: discovery mechanisms and exploitation." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 354, no. 1383 (March 29, 1999): 659–64. http://dx.doi.org/10.1098/rstb.1999.0418.
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In 1986 we reported that transgenic plants which accumulate the coat protein of tobacco mosaic virus (TMV) are protected from infection by TMV, and by closely related tobamoviruses. The phenomenon is referred to as coat–protein–mediated resistance (CP–MR), and bears certain similarities to cross protection, a phenomenon described by plant pathologists early in this century. Our studies of CP–MR against TMV have demonstrated that transgenically expressed CP interferes with disassembly of TMV particles in the inoculated transgenic cell. However, there is little resistance to local, cell–to–cell spread of infection. CP–MR involves interaction between the transgenic CP and the CP of the challenge virus, and resistance to TMV is greater than to tobamoviruses that have CP genes more distantly related to the transgene. Using the known coordinates of the three–dimensional structure of TMV we developed mutant forms of CP that have stronger inter–subunit interactions, and confer increased levels of CP–MR compared with wild–type CP. Similarly, it is predicted that understanding the cellular and structural basis of CP–MR will lead to the development of variant CP transgenes that each can confer high levels of resistance against a range of tobamoviruses.
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Kaiser, S., H. Jorulf, and G. Hirsch. "Clinical value of imaging techniques in childhood osteomyelitis." Acta Radiologica 39, no. 5 (September 1998): 523–31. http://dx.doi.org/10.1080/02841859809172219.
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Purpose: the traditional approach to investigating suspected osteomyelitis in children includes conventional radiography and bone scintigraphy. the roles of US, CT and MR imaging are controversial. Our objective was to determine whether the additional use of these modalities would yield information likely to lead to treatment modification Material and Methods: Sixty-five children with clinically suspected osteomyelitis took part in a prospective study. All patients underwent conventional radiography and bone scintigraphy. in addition to this, US, CT and MR imaging were all performed in 33 patients; the remaining 32 patients were examined with various combinations of these three modalities. the value of the additional information obtained was estimated retrospectively by a pediatric orthopedic surgeon in terms of possible modification of treatment Results: MR imaging was the modality with the highest sensitivity and specificity for detecting osteomyelitis. MR yielded information likely to influence treatment in the greatest proportion of patients (45%) followed by US (30%) Conclusion: the standard investigation protocol with the addition of US (because of its ability to detect subperiosteal abscesses early and simply) is adequate in uncomplicated cases. When additional imaging is required to outline a lesion, or in complicated cases, and when bone scintigraphy is inconclusive, MR imaging should also be performed. CT should be considered when MR investigation is not available or when anesthesia is required but cannot be provided
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Mittal, Puneet, Amit Mittal, Kapish Mittal, Ranjana Gupta, Sharad Gupta, and Ravleen Kaur. "Additional merit of coronal STIR imaging for MR imaging of lumbar spine." Journal of Craniovertebral Junction and Spine 6, no. 1 (2015): 12. http://dx.doi.org/10.4103/0974-8237.151582.
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Shellock, Frank G., and Vincent J. Shellock. "Additional information pertaining to the MR-compatibility of biopsy needles and devices." Journal of Magnetic Resonance Imaging 6, no. 2 (March 1996): 411. http://dx.doi.org/10.1002/jmri.1880060224.
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Walraven, Th, J. Walraven, and L. A. Balona. "Discovery of additional pulsation modes in AI Velorum." Monthly Notices of the Royal Astronomical Society 254, no. 1 (January 1992): 59–66. http://dx.doi.org/10.1093/mnras/254.1.59.
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Margelí, M., B. Cirauqui, V. Vallejos, C. Sánchez, A. Mariscal, E. Castellà, M. Rull, A. Torrente, M. Fraile, and A. Barnadas. "Monitorization of primary therapy (PT) by additional imaging methods in locally advanced breast cancer (LABC)." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 10580. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.10580.
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10580 Introduction: The response of locally advanced breast cancer (LABC) to Primary therapy (PT) may be monitored clinically and by mammography (MG). Magnetic resonance (MR) and 99mTc-sestamibi scintimammography (SMM) are increasingly being used. The aim of this study was to determine whether MG, MR and SMM are accurate indicators of tumour response to PT and whether they are predictors of histological response. Patients and Methods: A prospective observational study was approved at our institution and 52 patients( p) with core biopsy diagnostic of LABC and written consent were enrolled (mean age 52 years, SD 13) All p had clinical, MG, MR, SM assessment pre- and post- PT. Primary chemotherapy based on anthracyclines was administered as follows: 19 p FEC, 17 p AC-Docetaxel, 8 p Gemcitabine- Doxorubicine- Paclitaxel, 1 p FEC- Docetaxel and 1 p Carboplatin- VP16. 6 p were treated with hormone-therapy. RECIST criteria were considered for clinical response assessment and the same criteria was adapted for imaging and pathologic response. Results: After PT 33 tumours were considered not suitable for breast-conserving surgery. Based on histopathological findings, 10 (19%) lesions showed complete pathologic response, 30 (58%) partial response, 12 (23%) stabilization. No progression was detected. Clinical assessment of tumour complete response agreed with pathology in 40 of 52 tumours (78%), and with MG in 39 (78%). Correlation between MG and pathological findings was observed in 42 p (84%). Correlation between MR and pathological findings was observed in 42 p (82%). Correlation between SMM and pathological findings was observed in 31 p (66%). Among patients with complete pathologic remission, 9 of ten patients achieve a complete response by MR and SMM. Conclusion: In conclusion, our results don’t show that MR and SMM add any benefit to the diagnostic arsenal for predicting histopathological complete response to PT. However these new diagnostic methods should be considered in selected cases. No significant financial relationships to disclose.
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Perks, Julian R., Tianxiao Liu, William H. Hall, and Allan Y. Chen. "Clinical impact of magnetic resonance imaging on Gamma Knife surgery for brain metastases." Journal of Neurosurgery 105, Supplement (December 2006): 69–74. http://dx.doi.org/10.3171/sup.2006.105.7.69.
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ObjectStereotactic radiosurgery is beneficial for patients with a limited number of small brain metastases. Increased numbers of brain metastases, not infrequently at unreachable locations, are identified using thin-section magnetic resonance (MR) imaging on the day of Gamma Knife surgery (GKS). To improve patient selection and design better treatment strategies, a retrospective study was conducted to determine factors that may contribute to detecting additional brain metastases on the day of GKS.MethodsA total of 100 patients with brain metastases who underwent GKS between October 2003 and May 2006 at the University of California Davis Medical Center were included in the present study. Patients were categorized by age, sex, Karnofsky Performance Scale score, status of systemic disease, histological characteristics of the primary tumor, and whether they received previous whole-brain radiotherapy (WBRT). The number of lesions identified by diagnostic MR imaging at referral, by thin-section double-contrast MR imaging on the day of GKS, and the actual lesions treated by GKS were recorded. The diagnostic MR images were categorized in terms of section thickness and time interval before GKS.Conclusions The characteristics of this patient population match well with the general GKS practice. Fifty-six had been treated with WBRT. On average, patients presented with 2.2 ± 1.7 lesions, a number based on their original diagnostic MR imaging, had 3.6 ± 3.4 lesions identified on the thin-section treatment MR imaging (p < 0.05), and underwent treatment of 3.1 ± 2.6 lesions on the day of GKS. Significantly, treatment was compromised in 21 patients, in whom not all additional lesions could be treated with the initial headframe placement. Analysis shows that a significantly greater number of lesions were detected using thin-section MR imaging on the day of GKS in patients who had undergone thick-section diagnostic MR imaging, did not receive WBRT, and had progressive systemic disease. To optimize treatment planning and minimize additional treatment, the number of metastases needs to be determined accurately before frame placement, ideally by performing thin-section MR imaging, as used on the day of GKS.