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Kamijo, Hiroaki, and Makoto Sugaya. "Two distinct variants of mycosis fungoides (MF): Folliculotropic MF and erythrodermic MF." Journal of Dermatology 46, no. 12 (October 17, 2019): 1136–40. http://dx.doi.org/10.1111/1346-8138.15114.
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Bose, Prithviraj, and Srdan Verstovsek. "MF management." HemaSphere 3 (June 2019): 149–52. http://dx.doi.org/10.1097/hs9.0000000000000210.
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Longo, Dan L. "Watch out, MF!" Blood 110, no. 6 (September 15, 2007): 1708–9. http://dx.doi.org/10.1182/blood-2007-06-094896.
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Schmeitz, A. J. C., I. J. M. Besselink, and S. T. H. Jansen. "TNO MF-SWIFT." Vehicle System Dynamics 45, sup1 (January 2007): 121–37. http://dx.doi.org/10.1080/00423110701725208.
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Passamonti, Francesco, Barbara Mora, and Margherita Maffioli. "Management of Post ET/PV MF: Different from Primary MF." Clinical Lymphoma Myeloma and Leukemia 17 (September 2017): S24—S26. http://dx.doi.org/10.1016/j.clml.2017.08.016.
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周, 彩霞. "Gorenstein MF-Projective Modules." Pure Mathematics 12, no. 04 (2022): 565–71. http://dx.doi.org/10.12677/pm.2022.124063.
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Lemire, Francine, Jeff Sisler, and G. Michael Allan. "CMFCApprendre : n’importe quand, n’importe où, par les MF, pour les MF." Canadian Family Physician 67, no. 2 (February 2021): 145. http://dx.doi.org/10.46747/cfp.6702145.
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Kang, Sang-Mo, Arjun Adhikari, Dibya Bhatta, Ho-Jun Gam, Min-Ji Gim, Joon-Ik Son, Jin Y. Shin, and In-Jung Lee. "Comparison of Effects of Chemical and Food Waste-Derived Fertilizers on the Growth and Nutrient Content of Lettuce (Lactuca sativa L.)." Resources 11, no. 2 (February 11, 2022): 21. http://dx.doi.org/10.3390/resources11020021.
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The current high rate of food waste production, concomitant with the global increase in population and food demand, has adverse effects on environmental and socio-economic conditions. However, food waste has been shown to be an efficient and safe source of fertilizer in agriculture practice. Moreover, minimizing the application of chemical fertilizers is a goal of sustainable agriculture. Considering these facts, we aimed to compare the effect of chemical fertilizer (CF-3,8 g·pot−1) and different doses of mixed food waste-derived fertilizer (MF-10.6 g·pot−1), two-fold MF (MF × 2), four-fold MF (MF × 4), and six-fold MF (MF × 6) in a popular salad crop, Lactuca sativa (lettuce). Our results showed the growth rates of lettuce plants receiving CF, MF, and MF×2 applications were essentially the same; however, plant biomass significantly dropped with MF × 6 treatment. The CF, MF, and MF × 2 treatments enhanced the chlorophyll content, chlorophyll fluorescence, and photosynthetic rate of the plants and improved transpiration efficiency and stomatal conductance. With respect to mineral elements, the K+ content was significantly enhanced with MF × 2 and MF × 4 treatment, whereas MF × 6-treated plants showed lower concentrations of Ca, P, Mg, and K+ as well as higher Na+ concentration. Biochemical analysis showed the elevation of abscisic acid level with increasing dose of MF, except in the MF × 6 treatment. The level of super oxide dismutase (SOD) dropped with CF treatment, was unchanged with MF, and significantly increased in MF×2 and MF × 4 treated plants. Subsequently, higher flavonoid content was observed in MF×2 and MF×4 plants. The current results demonstrate the potential of food waste as a source of organic fertilizer and a significant substitute for chemical fertilizer in the conventional agricultural practice driven by high production cost and environmental pollution.
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Chang, Alex R., Mariana Lazo, Lawrence J. Appel, Orlando M. Gutiérrez, and Morgan E. Grams. "Reply to MF McCarty." American Journal of Clinical Nutrition 99, no. 4 (April 1, 2014): 966–67. http://dx.doi.org/10.3945/ajcn.113.082131.
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Jéquier, Eric. "Reply to MF McCarty." American Journal of Clinical Nutrition 70, no. 5 (November 1, 1999): 941–42. http://dx.doi.org/10.1093/ajcn/70.5.941.
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Janssen, Hennie CJP, Monique M. Samson, and Harald JJ Verhaar. "Reply to MF McCarty." American Journal of Clinical Nutrition 76, no. 6 (December 1, 2002): 1455–56. http://dx.doi.org/10.1093/ajcn/76.6.1455.
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Bray, George A., Samara Joy Nielsen, and Barry M. Popkin. "Reply to MF Jacobson." American Journal of Clinical Nutrition 80, no. 4 (October 1, 2004): 1081–82. http://dx.doi.org/10.1093/ajcn/80.4.1081a.
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Scherber, R. M., A. C. Dueck, P. Johansson, T. Barbui, G. Barosi, A. M. Vannucchi, F. Passamonti, et al. "Symptomatic burden in myelofibrosis (MF): Prospective international assessment in 128 MF patients." Journal of Clinical Oncology 29, no. 15_suppl (May 20, 2011): 6610. http://dx.doi.org/10.1200/jco.2011.29.15_suppl.6610.
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Calarco, Patricia G. "The Role of Microfilaments in Early Meiotic Maturation of Mouse Oocytes." Microscopy and Microanalysis 11, no. 2 (March 8, 2005): 146–53. http://dx.doi.org/10.1017/s1431927605050154.
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Mouse oocyte microfilaments (MF) were perturbed by depolymerization (cytochalasin B) or stabilization (jasplakinolide) and correlated meiotic defects examined by confocal microscopy. MF, microtubules, and mitochondria were vitally stained; centrosomes (γ-tubulin), after fixation. MF depolymerization by cytochalasin in culture medium did not affect central migration of centrosomes, mitochondria, or nuclear breakdown (GVBD); some MF signal was localized around the germinal vesicle (GV). In maturation-blocking medium (containing IBMX), central movement was curtailed and cortical MF aggregations made the plasma membrane wavy. Occasional long MF suggested that not all MF were depolymerized. MF stabilization by jasplakinolide led to MF aggregations throughout the cytoplasm. GVBD occurred (unless IBMX was present) but no spindle formed. Over time, most oocytes constricted creating a dumbbell shape with MF concentrated under one-half of the oocyte cortex and on either side of the constriction. In IBMX medium, the MF-containing half of the dumbbell over time sequestered the GV, MF, mitochondria, and one to two large cortical centrosomes; the non-MF half appeared empty. Cumulus processes contacted the oocyte surface (detected by microtubule content) and mirrored MF distribution. Results demonstrated that MF play an essential role in meiosis, primarily through cortically mediated events, including centrosome localization, spindle (or GV) movement to the periphery, activation of (polar body) constriction, and establishment of oocyte polarity. The presence of a cortical “organizing pole” is hypothesized.
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Kurjan, J. "Alpha-factor structural gene mutations in Saccharomyces cerevisiae: effects on alpha-factor production and mating." Molecular and Cellular Biology 5, no. 4 (April 1985): 787–96. http://dx.doi.org/10.1128/mcb.5.4.787-796.1985.
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The role of alpha-factor structural genes MF alpha 1 and MF alpha 2 in alpha-factor production and mating has been investigated by the construction of mf alpha 1 and mf alpha 2 mutations that totally eliminate gene function. An mf alpha 1 mutant in which the entire coding region is deleted shows a considerable decrease in alpha-factor production and a 75% decrease in mating. Mutations in mf alpha 2 have little or no effect on alpha-factor production or mating. The mf alpha 1 mf alpha 2 double mutants are completely defective in mating and alpha-factor production. These results indicate that at least one alpha-factor structural gene product is required for mating in MAT alpha cells, that MF alpha 1 is responsible for the majority of alpha-factor production, and that MF alpha 1 and MF alpha 2 are the only active alpha-factor genes.
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Kurjan, J. "Alpha-factor structural gene mutations in Saccharomyces cerevisiae: effects on alpha-factor production and mating." Molecular and Cellular Biology 5, no. 4 (April 1985): 787–96. http://dx.doi.org/10.1128/mcb.5.4.787.
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The role of alpha-factor structural genes MF alpha 1 and MF alpha 2 in alpha-factor production and mating has been investigated by the construction of mf alpha 1 and mf alpha 2 mutations that totally eliminate gene function. An mf alpha 1 mutant in which the entire coding region is deleted shows a considerable decrease in alpha-factor production and a 75% decrease in mating. Mutations in mf alpha 2 have little or no effect on alpha-factor production or mating. The mf alpha 1 mf alpha 2 double mutants are completely defective in mating and alpha-factor production. These results indicate that at least one alpha-factor structural gene product is required for mating in MAT alpha cells, that MF alpha 1 is responsible for the majority of alpha-factor production, and that MF alpha 1 and MF alpha 2 are the only active alpha-factor genes.
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Shimozono, Yoshiharu, Hao Huang, Timothy Deyer, and John G. Kennedy. "Comparison of Functional and MRI Outcomes of Microfracture with and without BioCartilage for Osteochondral Lesions of the Talus." Foot & Ankle Orthopaedics 4, no. 4 (October 1, 2019): 2473011419S0038. http://dx.doi.org/10.1177/2473011419s00389.
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Category: Ankle, Arthroscopy, Sports Introduction/Purpose: Microfracture (MF) remains a dominant treatment strategy for symptomatic osteochondral lesions of the talus (OLT). Micronized cartilage allograft (BioCartilage) is a biologic scaffold and is utilized for MF augmentation to improve the quality for cartilage regeneration. However, there is still lack of evidence on efficacy of BioCartilage as an adjunct to MF, as no comparative studies have been reported to date. The purpose of this study is to clarify the effectiveness of BioCartilage as an adjuvant to MF compared to MF alone in the treatment of OLT. Methods: A retrospective cohort study comparing patients treated with MF with BioCartilage and MF alone between 2014 and 2017 was undertaken. Patients with a minimum follow-up time of 12 months were included. All patients received concentrated bone marrow aspirate injection at the time of surgery. Clinical outcome was evaluated with the Foot and Ankle Outcome Score (FAOS) pre- and postoperatively. Postoperative MRIs were evaluated using a modified Magnetic Resonance Observation of Cartilage Tissue (MOCART) score. Comparisons between groups were made with the Man-Whitney U test for continuous variables and the Chi-squared test or Fisher exact test for categorical variables. Results: Twenty-four patients underwent MF with BioCartilage (MF-BC group) and 24 patients underwent MF alone (MF group). The mean age was 40.8 years in MF-BC group and 47.8 years in MF group (p=0.068). The mean follow-up time was 19.2 months in MF-BC group and 24.5 months in MF group (p=0.042). Both groups showed significant improvements in all FAOS subscales. No significant differences between groups were found in postoperative FAOS subscales including symptoms, pain, daily activities, sports activities and quality of life (MF-BC; 72.8, 77.8, 87.4, 60.8, 56.6, MF; 73.3, 79.3, 86.0, 60.9, 60.6, respectively, p>0.05). The mean MOCART score in MF-BC group was higher (73.2vs64.1), but not statistically significant (p=0.315). When assessing each MOCART parameter individually, MF-BC group had significant better infill in the defect (p=0.028). Conclusion: MF with BioCartilage is an effective treatment strategy for the treatment of OLT and results in similar functional outcomes compared with MF alone in the short-term. However, MF with BioCartilage provides better cartilage infill in the defect on MRI. This finding suggests that the repair seen in a cartilage defect treated with BioCartilage augmentation may be superior to treatment with MF alone. Further long-term follow-up studies are warranted.
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MUMMERT, CARL. "REVERSE MATHEMATICS OF MF SPACES." Journal of Mathematical Logic 06, no. 02 (December 2006): 203–32. http://dx.doi.org/10.1142/s0219061306000578.
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This paper gives a formalization of general topology in second-order arithmetic using countably based MF spaces. This formalization is used to study the reverse mathematics of general topology. For each poset P we let MF (P) denote the set of maximal filters on P endowed with the topology generated by {Np | p ∈ P}, where Np = {F ∈ MF (P) | p ∈ F}. We define a countably based MF space to be a space of the form MF (P) for some countable poset P. The class of countably based MF spaces includes all complete separable metric spaces as well as many nonmetrizable spaces. The following reverse mathematics results are obtained. The proposition that every nonempty Gδ subset of a countably based MF space is homeomorphic to a countably based MF space is equivalent to [Formula: see text] over ACA0. The proposition that every uncountable closed subset of a countably based MF space contains a perfect set is equivalent over [Formula: see text] to the proposition that [Formula: see text] is countable for all A ⊆ ℕ. The proposition that every regular countably based MF space is homeomorphic to a complete separable metric space is equivalent to [Formula: see text] over [Formula: see text].
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Fath, K. R., and R. J. Lasek. "Two classes of actin microfilaments are associated with the inner cytoskeleton of axons." Journal of Cell Biology 107, no. 2 (August 1, 1988): 613–21. http://dx.doi.org/10.1083/jcb.107.2.613.
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The distribution and length of actin microfilaments (MF) was determined in axoplasm extruded from the giant axons of the squid (Loligo pealeii). Extruded axoplasm that was separated from the axonal cortex contains approximately 92% of the total axonal actin, and 60% of this actin is polymerized (Morris, J., and R. Lasek. 1984. J. Cell Biol. 98:2064-2076). Localization of MF with rhodamine-phalloidin indicated that the MF were organized in fine columns oriented longitudinally within the axoplasm. In the electron microscope, MF were surrounded by a dense matrix and they were associated with the microtubule domains of the axoplasm. The surrounding matrix tended to obscure the MF which may explain why MF have rarely been recognized before in the inner regions of the axon. The axoplasmic MF are relatively short (number average length of 0.55 micron). Length measurements of MF prepared either in the presence or absence of the actin-filament stabilizing drug phalloidin indicate that axoplasm contains two populations of MF: stable MF (number average length of 0.79 micron) and metastable MF (number average length of 0.41 micron). Although individual axonal MF are much shorter than axonal microtubules, the combined length of the total MF is twice that of the total microtubules. Apparently, these numerous short MF have an important structural role in the architecture of the inner axonal cytoskeleton.
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Wang, Xiaoli, Sool Yeon Cho, Daniel Chen, John Roboz, and Ronald Hoffman. "An Altered Microenvironment Within The Spleens Of Patients With Myelofibrosis Affects CD34+ Cell Trafficking." Blood 122, no. 21 (November 15, 2013): 2848. http://dx.doi.org/10.1182/blood.v122.21.2848.2848.
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Abstract We have demonstrated that the homing of peripheral blood (PB) myelofibrosis (MF) CD34+ cells to the marrow but not the spleen is altered (Wang X, et al. Cancer Res. 2009;69:7612-8). The defective homing to the marrow was further found to be associated with both the down-regulation of CXCR4 expression by PB MF CD34+ cells (Wang X, et al. Cancer Res. 2009;69:7612-8) and the proteolytic degradation of CXCL12 in the plasma of MF patients (Cho SY, et al. Cancer Res. 2010;70:3402-10). However, the mechanism underlying the preferential homing, retention and engraftment of the MF HSCs/HPCs to extramedullary sites has not been clarified. Cancer stem cell behavior is thought to be determined by both intrinsic properties and by regulatory signals provided by the microenvironment. The effect of alterations within the splenic microenvironment on the trafficking of MF-stem cells (MF-SC) was, therefore, investigated. The homing of spleen and PB MF CD34+ cells to the marrow and spleens of sublethally irradiated NOD/SCID mice was first evaluated. Following the infusion of paired spleen or PB MF CD34+ cells (n=5) or normal G-CSF mobilized PB CD34+ cells (mPB: n=6, 5×105/mouse), reduced numbers of spleen MF CD34+ cells were detected in the marrows of these mice as compared with mPB CD34+ cells (No. of CD34+ Cells/106 BMCs: PB MF:74±6; mPB: 196±32; P=0.007). However, the number of spleen MF CD34+ cells that homed to the marrow of recipient mice were even lower than PB MF CD34+ cells (No. of CD34+ Cells/106 BMCs: spleen MF: 74±6; PB MF: 102±13; P=0.08). By contrast, similar numbers of spleen MF, PB MF and mPB CD34+ cells were detected in the spleens of these mice. These findings suggest that both spleen MF and PB MF CD34+ cells preferentially migrate towards spleen rather than to the marrow. To determine if the expression of chemokine receptors and adhesion molecules could account for the homing and location of MF CD34+ cells to the spleen, the expression of CXCR4, CD47, CD44 and CD49d by spleen and PB MF CD34+ cells was evaluated and was shown to be similar. These findings suggest that the greater number of MF-SCs that were observed in the spleen as compared to PB of MF patients (Wang X, et al. J Clin Invest. 2012;122:3888-99) is not due to aberrant expression of adhesion molecules or chemokine receptors by MF-SCs and that microenvironmental conditions within the MF spleen might be responsible for MF-SC and progenitor cell homing, retention and engraftment. Unlike intact CXCL12, truncated forms of CXCL12 either lack the ability to act as a chemo-attractant for CD34+ cells or act as an antagonist to the action of CXCL12. The intact and truncated forms (loss of 2 aa, 3 aa, 4 aa, and 5 aa, aa = amino acid) of CXCL12 in paired spleen and PB MF plasma (n=5) were quantified using mass spectrometry. The concentration of intact CXCL12 in spleen MF plasma was 39.6 ±13.9ng/ml, which was higher than that detected in PB MF plasma (5.5 ± 2.6ng/ml, P=0.08). However, the concentrations of the 4 truncated forms of CXC12 were comparable in spleen and PB MF plasma. The concentrations of CXCL12 were further normalized based on the albumin level of the corresponding plasma to exclude the influence of different methods used to prepare these two sources of plasmas. The normalized concentration of intact CXCL12 in spleen MF plasma was significantly higher than that of PB MF plasma (P=0.03), while the normalized concentrations of the 4 truncated forms of CXCR4 were found again similar in both spleen and PB MF plasma. However, comparable levels of serine proteases, including active MMP-9 and NE, each of which are responsible for the degradation of a number of marrow matrix proteins such as CXCL12, were detected in spleen and PB MF plasma, suggesting that the splenic microenvironment acted to blunt their proteolytic actions. The migratory behavior of spleen MF CD34+ cells towards spleen and PB MF plasma was also determined in vitro using transwell plates. A greater number of spleen MF CD34+ cells from each individual patient migrated towards spleen plasma than PB plasma. Moreover, the percentage of JAK2V617F+ colonies cloned from patient CD34+ cells (JAK2V617F allele burden: 90%) that had migrated towards spleen plasma was similar to that observed with PB plasma. These findings suggest that the MF spleen is characterized by increased levels of intact CXCL12 which contributes to the preferential homing of spleen MF CD34+ cells to the spleen and the retention of such cells within the spleens of MF patients. Disclosures: No relevant conflicts of interest to declare.
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Wang, Jingyi, Yu Meng, Tao Lu, Jiabin Zhang, Huajin Wang, Jialiang Sheng, Chunhui Huang, and Zusheng Hang. "Influence of melamine formaldehyde microsphere on the vulcanization kinetics and mechanical properties of nitrile butadiene rubber." Journal of Elastomers & Plastics 51, no. 2 (April 11, 2018): 143–56. http://dx.doi.org/10.1177/0095244318769959.
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The melamine formaldehyde (MF) microsphere/nitrile butadiene rubber (NBR) vulcanizates were prepared by adding MF into NBR through mechanical mixing, followed by a vulcanization process. The influences of MF on the vulcanization characteristics, vulcanization kinetics, and mechanical properties were investigated. The results showed that MF interacted with NBR through hydrogen bonds. In addition, parameter b calculated by the ratio of modulus and strains also demonstrated the strong interaction between MF and NBR. Adding MF into NBR would reduce the curing time of NBR compounds, and increase the curing rate, as well as the cross-linked density. The vulcanization kinetics of MF/NBR compounds could be simulated accurately by Ghoreishy’s model. The mechanical properties of MF/NBR increased with the incorporation of MF. The modulus at 100%, modulus at 300%, and tensile strength of NBR vulcanizates with 20 parts per hundred rubber MF had 155, 90, and 110% increment, respectively, compared with those of neat NBR. The MF also enhanced the tear strength of NBR by 80% with a rough tear-fractured surface of NBR recorded by scanning electron microscope.
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Caramazza, Domenica, Margherita Maffioli, Mario Cazzola, Alessandro Maria Vannucchi, Alessandro Rambaldi, Enrica Morra, Jean-Jacques Kiladjian, et al. "Post-Polycythemia and Post-Thrombocythemia Myelofibrosis Have Distinctive Clinical Phenotypes: An International Multicenter Study on 718 Patients." Blood 124, no. 21 (December 6, 2014): 1824. http://dx.doi.org/10.1182/blood.v124.21.1824.1824.
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Abstract Background. Progression to myelofibrosis (MF) represents a natural evolution of polycytemia vera (PV) and essential thrombocytemia (ET), named post-PV (PPV) MF and post-ET (PET) MF, respectively. Information on secondary MF (SMF) is scant. The objective of this study is to define the clinical phenotype and outcome of SMF on a large number of patients and to investigate differences between PPV-MF and PET-MF. Patients and Methods. A total of 718 patients with SMF from 16 Centers have been collected. Diagnosis of PPV-MF and PET-MF was made according to the IWGMRT criteria. Differences in the distribution of variables between categories were properly analyzed by Mann-Whitney test or Fisher exact test. The cumulative incidence of thrombosis and of leukemia was estimated with a competing risk approach according to the Kalbfleisch-Prentice method. The study was approved by the Institutional Review Boards of each participating center and conducted in accordance with the principles of the Declaration of Helsinki. Results. Among 718 SMF, 354 (49%) were PPV-MF and 364 (51%) were PET-MF. Median follow-up from SMF diagnosis was 2.5 (range, 0.6-14.7) years in PET-MF and 2.3 (range, 0.6-20.1) in PPV-MF. Demographics are reported in Table 1. Median time from PV/ET diagnosis to SMF was 10.5 years (range, 0.7-40) in PET-MF and 11.1 years (range, 0.7-41) in PPV-MF. As illustrated in Table 1, patients with PPV-MF have significantly higher leukocyte and hemoglobin, while those with post-ET MF have higher platelet counts. Enlargement of spleen and liver was significantly more frequent in PPV-MF than in post-ET MF as well as the presence of constitutional symptoms. Concerning cytogenetics, we found a higher rate of abnormal karyotype in PPV-MF, but no differences in the rate of unfavorable versus favorable, according to the DIPSS-plus definition (Gangat, JCO 2011). As expected, there was an imbalance in JAK2(V617F) distribution (96.7% in PPV-MF and 47% in PET-MF, p< 0.001). The 3- and 5-year cumulative incidence of thrombosis, estimated with death as a competing risk, was 7.5 (95% CI: 4.6-11.3) x100 p/y and 10.4 (95% CI: 6.6-15.1) x100 p/y in PET-MF and 9.7 (95% CI: 6.3-14.1) x100 p/y and 13.1 (95% CI: 8.8-18.2) x100 p/y in PPV-MF without statistically significant difference. The 5- and 10-year cumulative incidence of leukemia, estimated with death as a competing risk was 13.1 (95% CI: 8.8-18.4) x100 p/y and 18.7 (95% CI: 11.8-26.8) x100 p/y in PET-MF and 6.6 (95% CI: 3.9-10.3) x100 p/y and 11.3 (95% CI: 6.2-18) x100 p/y in PPV-MF, resulting in an excess of event in PET-MF (Pepe and Mori test, p=0.001). Median survival was 14.5 years (95% CI: 7.9-NR) in PET-MF and 7.2 (95%CI: 6.2-9.3) in PPV-MF, without a statistically significant difference (Figure 1). Survival of patients undergoing treatment was censored at date of hematopoietic stem cell transplant, splenectomy or experimental drug enrollment. Conclusions. This study on 718 patients with SMF showed that PET-MF and PPV-MF have distinctive clinical phenotypes: more myeloproliferative (leukocytosis, higher hemoglobin levels, splenomegaly, hepatomegaly and symptomatology) in PPV-MF. Leukemia occurred more frequently in PET-MF, while thrombosis incidence was similar. Finally, no differences in survival between PPV-MF and PET-MF have been found. Table 1: Demographics of 718 patients with secondary myelofibrosis. Variables PET-MF(n=364) PPV-MF(n=354) P value Age in years; median (range) 64 (25-93) 65 (34-96) 0.08 Males; n (%) 175 (48) 195 (55) 0.06 Hemoglobin, g/dL; median (range) 10.7 (5-17.4) 11.9 (6.8-17.7) <0.00001 Leukocytes, x109/L; median (range) 7.95 (1.1-97.3) 13 (1.7-98.4) <0.00001 Platelets, x109/L; median (range) 387 (25-1908) 293.5 (16-1689) <0.00001 Circulating blasts; median (range) 0 (0-19) 0 (0-13) 0.8 LDH^ upper the normal range, U/L; n (%) 228 (82) 195 (76) 0.05 Constitutional symptoms; n (%) 147 (41) 182 (53) 0.002 Spleen, cm bcm#; median (range) 4 (0-27) 8 (0-34) <0.00001 Splenomegaly; n (%) 282 (80) 324 (94) <0.0001 Hepatomegaly; n (%) 89 (29) 125 (40) 0.002 Unfavourable cytogenetic/normal karyotype; n (%)n evaluable=320 19 (12)/145 (88) 21 (13)/135 (86) 0.36 Normal karyotype/abnormal karyotype; n (%)n evaluable=338 124 (72)/47 (27) 98 (59)/69 (41) 0.005 Time to myelofibrosis in years; median (range) 10.5 (0.7-40) 11.1 (0.7-41) 0.17 ^Lactic dehydrogenase #Below costal margin Figure 1: Survival of patients with PPV-MF and PET-MF. Figure 1:. Survival of patients with PPV-MF and PET-MF. Disclosures No relevant conflicts of interest to declare.
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Mesa, Ruben A., Hagop Kantarjian, Ayalew Tefferi, Richard Levy, Kris Vaddi, Susan Erickson-Viitanen, Deborah A. Thomas, et al. "Validation of the Serial Use of the Myelofibrosis Symptom Assessment Form (MF-SAF) for Measuring Symptomatic Improvement: Performance in 86 Myelofibrosis Patients On INCB018424 Clinical Trial." Blood 114, no. 22 (November 20, 2009): 3917. http://dx.doi.org/10.1182/blood.v114.22.3917.3917.
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Abstract Abstract 3917 Poster Board III-853 Background Patients with Myelofibrosis (MF) suffer from significant fatigue, constitutional symptoms and splenomegaly (Mesa et. al. Cancer 2007) not improved by current therapy. The MF-SAF is a 19 item self administered instrument specific to MF associated symptoms previously validated for use at a single time point (Mesa et. al. Leukemia Research 2009). We sought to assess the performance characteristics of the MF-SAF when administered sequentially in the context of a prospective clinical trial. Methods Sequential MF patients enrolled in the prospective, uncontrolled Phase II, trial were given a 15 item modified MF-SAF to complete at enrollment, and after 15 days, 1 month, 2 months, 3 months and every 3 months thereafter. The MF-SAF was scored as previously published on a 0 (absent) to 10 (maximal) scale. Cross validation of serial change in MF-SAF scores was undertaken by comparison to objective measurements made as part of the therapeutic drug trial. Results Patients Eighty six MF patients were enrolled and had 2 or more MF-SAF instruments completed to allow for sequential analysis. Patients were of a median age (65 years), gender distribution (35 % females), and disease subtype (53 % PMF) typical for a clinical trial in MF. Baseline MF-SAF Responses: Baseline assessment of the most frequent MF abnormalities reported by patients completing the MF-SAF (see Table 1) confirmed the wide prevalence of MF associated symptoms, and their significant severity. General fatigue was the most frequent symptom cited (91%), while cough was the least frequently observed symptom (44%). 95% of patients had at least 2 symptoms present on the MF-SAF. Serial MF-SAF Changes in Response to Therapy Therapy with INCB018424 resulted in a significant and rapid reduction in MF associated symptoms with 46% to 85% of patients experiencing improvement in a given symptom. The greatest improvements in MFSAF score improvements were reported by patients experiencing abdominal discomfort, night sweats, pruritus and fever (see Table 1), and corresponded to significant improvements in the individual MF symptom scales as well as the patient's overall assessment of quality of life (QOL). Correlation of MF-SAF to Objective Changes during INCB018424 Therapy Objective measurements obtained on the INCB018424 trial included MRI measurements of splenic reduction, the six minute walk test (6MWT) for inactivity, and serial weights. Reduction in spleen size (by ≥ 35% by volume or ≥ 50% by palpable length) corresponded to improvement in MF-SAF scores of abdominal discomfort and fatigue (50% of patients, median score decrease of -1.2, and -1.8, respectively). Improvement in the 6MWT by > 50 meters was associated with a 2-fold greater improvement in inactivity score on the MF-SAF compared to subjects who improved 6MWT performance by <50 meters. Finally, improvements in weight loss and fever were corroborated by objective measurements made at physician visits on the trial. Conclusions The MF-SAF is a brief, easily self administered, MF specific instrument which was successfully administered sequentially in the conduct of a large Phase II clinical trial. The significant symptomatic improvements reported by patients in the open label trial of INCB018424 corresponded to both improvements in symptom specific scores on the MF-SAF and objective measurements. Further validation of the MF-SAF will be possible by inclusion in upcoming randomized placebo controlled trials in MF patients. Parallel trials performed in MF patients should consider use of this instrument to allow for comparisons. Disclosures: Levy: Incyte Corporation: Employment, Equity Ownership. Vaddi:Incyte Corporation: Employment, Equity Ownership. Erickson-Viitanen:Incyte Corporation: Employment, Equity Ownership. Verstovsek:Incyte: Research Funding.
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Habay, Jelle, Matthias Proost, Jonas De Wachter, Jesús Díaz-García, Kevin De Pauw, Romain Meeusen, Jeroen Van Cutsem, and Bart Roelands. "Mental Fatigue-Associated Decrease in Table Tennis Performance: Is There an Electrophysiological Signature?" International Journal of Environmental Research and Public Health 18, no. 24 (December 7, 2021): 12906. http://dx.doi.org/10.3390/ijerph182412906.
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Mental fatigue (MF) is a psychobiological state negatively impacting both cognitive and physical performance. Although recent research implies that some table tennis (TT) performance outcomes are impaired by MF, open skill sports such as TT require a more detailed overview of MF-related performance decrements. Moreover, research into MF and sport-specific psychomotor performance lacks the inclusion of brain-related measurements to identify MF mechanisms. Eleven experienced TT players participated in this randomized counterbalanced crossover trial. Participants were either required to perform an individualized Stroop task (MF condition) or watch a documentary (control condition). The primary outcomes were reaction time on a sport-specific visuomotor task and EEG activity throughout the trial. The subjective feeling of MF was significantly different between both conditions and confirmed that the MF condition induced the mentally fatigue state of participants (p < 0.001), though no behavioral indicators (i.e., decrease in performance on Stroop and flanker task) of MF. MF worsened reaction time on the visuomotor task, while other secondary measurements remained largely ambiguous. Spectral power (i.e., decreases in upper α band and θ band) was influenced by MF, while ERPs measured during the visuomotor task remained unaltered. The present study confirms that MF negatively impacts table tennis performance, specifically inhibitory stimuli during the visuomotor task. These findings also further augment our understanding of the effects of MF on human performance.
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Lehmann, T., M. S. Cupp, and E. W. Cupp. "Analysis of migration success of Onchocerca lienalis microfilariae in the haemocoel of Simulium vittatum." Journal of Helminthology 69, no. 1 (March 1995): 47–52. http://dx.doi.org/10.1017/s0022149x00013821.
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AbstractMigration success (i.e. the proportion of worms that reach the thorax) of Onchocerca lienalis microfilariae (mf) in the haemocoel of Simulium vittatum was studied by inoculating mf into the posterior abdomen, and recording their distribution in the blackfly body at predetermined time points. Mf arrive into the thorax by active locomotion rather than by drifting in haemolymph currents. Migration into the thorax was completed by 12 h post inoculation (pi) but was not continuous throughout this period. Migration proceeded in two phases; the first occurred 0–2 h pi and the second at 6–12 h pi. Overall, migration success 12–24 h pi was only 36%, indicating thata substantial number of mf failed to reach the thorax, either because they were eliminated by the fly's defensive response or because they remained in the abdomen. Migration success was density independent Mf that arrive into the thorax within 2 h pi did not differ in their migration potential from mf that remained in the abdomen at this time. In flies where more mf migrated successfully there was lower mf loss, indicating that migration success was linked to mf loss. Moreover, the proportion of mf in the thorax was not correlated with mf loss, suggesting that mf loss affected the number of mf that migrated successfully, rather than the reverse causal relationship.
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He, Ling-Yun, and Shu-Peng Chen. "Are crude oil markets multifractal? Evidence from MF-DFA and MF-SSA perspectives." Physica A: Statistical Mechanics and its Applications 389, no. 16 (August 2010): 3218–29. http://dx.doi.org/10.1016/j.physa.2010.04.007.
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Mlynáriková, Jarmila, Miroslav Boča, Eva Mikšíková, and Zuzana Netriová. "Volume properties of the molten systems MF–K2TaF7 (MF = LiF, NaF and KF)." Journal of Thermal Analysis and Calorimetry 129, no. 1 (February 15, 2017): 475–86. http://dx.doi.org/10.1007/s10973-017-6137-3.
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Lu, Min, Lijuan Xia, Mohamed E. Salama, and Ronald Hoffman. "Enriched Populations of Human Megakaryocytic Cells Affect the Behavior of Myelofibrosis CD34+ Cells As Well As Cells Belonging to the MF Supportive Microenvironment." Blood 132, Supplement 1 (November 29, 2018): 3057. http://dx.doi.org/10.1182/blood-2018-99-117062.
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Abstract Objective The marrows and spleens of myelofibrosis (MF) patients are characterized by megakaryocytic (MK) hyperplasia as well as microenvironment (MicroE) abnormalities including increased micro-vessel density, stromal cell (SC) hyperplasia and fibrosis. MF is accompanied by dysregulation of inflammatory cytokines (INF-CyKs) which alter the tissue specific MicroE niches in which MF HSC reside. We hypothesized that MF MKs play a critical role in MF pathobiology and examined their potential to affect MF and normal CD34+ cells as well as marrow and splenic endothelial cells (EC) and SCs. Methods & Results MF MKP/MKs elaborate specific INF-CyKs. CD34+ cells were cultured in serum free medium with stem cell factor and thrombopoietin (TPO) for 7 days, and then cultured with TPO alone for an additional 7 days to generate cell population enriched for MK progenitor cells (MKPs) (CD34+CD41+) and MKs (CD34-/CD41+) (MKP/MK: 22-61% in normal and 27.6-54% in MF). MF MKP/MKs as compared to normal MKPs (nMKP/MKs) contained increased transcripts for several INF-CyKs including: IL-8 (31 fold), TGF-β (8 fold) and VEGF (93 fold). The transcripts for the P53 antagonist MDM2 (112 fold) and the activity of the transcription factor NF-κB were also increased. Furthermore, media conditioned by MF MKP/MKs contained increased protein levels of IL-8, TGF-β and VEGF (5.8, 1.4 and 5.2 fold, respectively) as compared to nMKP/MKs. Using immunohistochemistry, we demonstrated that IL-8 protein was present in normal and MF splenic SCs and ECs, but was exclusively present in MF splenic MKs. Plasma IL-8 levels were significantly elevated in MF patient plasma (p=0.0008). These data indicate that MF MKP/MKs elaborate a series of INF-CyKs which promote the development of MF. IL-8 promotes MF CD34+ cells proliferation. CXCR1 and CXCR2 are two receptors that bind IL-8. Flow cytometric analyses showed that MF CD34+ cells expressed higher levels of CXCR1 and CXCR2 than normal CD34+ cells (3.3 and 3.1 fold, respectively). Addition of IL-8 increased MF CD34+ cell numbers by 2 fold and assayable CFU-GM by 40% (p=0.033), but this effect was eliminated by the addition of reparixin, a CXCR1/CXCR2 antagonist (p=0.0055). MF MKP/MKs can alter the HSC MicroE. Using IHC and flow cytometry we observed that CXCR1 and CXCR2 were also expressed by splenic SCs and ECs and marrow mesenchymal stem cells. When SCs and ECs were incubated with equal numbers of normal or MF MKP/MKs, higher levels of SCF and VEGF were elaborated by SCs but not ECs. This effect was more pronounced with MF MKP/MKs as compared to nMKP/MKs (p=0.02 for SCF and p=0.003 for VEGF). By contrast, higher levels of IL-8 were elaborated by both ECs and SCs following co-cultivation with MF MKP/MKs (p=0.047 and p=0.03). The addition of reparixin to these co-cultures decreased the levels of VEGF and IL-8 to baseline. Co-culturing MF CD34+ cells with either SCs or ECs significantly increased the numbers of CD34+ cells, an effect which could be blocked by the addition of reparixin. These data indicate that MF MKP/MKs provide inflammatory signals that alter the MF MicroE which supports MF CD34+ cells and that these signals can be disrupted by drugs blocking IL-8-CXCR1/2 interactions. MF MKP/MKs and CD34+ cells can be targeted with ruxolitinib, the nutlin-RG7112 and a BET inhibitor. Treatment of MF CD34+ cells with low doses of RG7112, ruxolitinib, or JQ1 alone or in combinations decreased MF but not normal hematopoietic colony formation. Treatment of MF MKP/MKs with each of these agents decreased phosphor-NF-kB p65 levels as demonstrated by western blot and decreased the elaboration of IL-8 by 20 to 60%. Conclusion These data indicate that MF MKPs are characterized by increased transcripts for MDM2 as well as NF-κB activity contributing / leading to the MK hyperplasia characteristic of MF and the elaboration of a group of lineage specific cytokines (TGF-β, IL-8, VEGF) that not only affect MF CD34+ cells but also cells belonging to the MicroE (ECs and SCs) (Figure 1). The MF promoting activities of MF MKP/MKs can be effectively targeted with ruxolitinib, RG7112, and BET inhibitors. Furthermore reparixin can be utilized to interrupt the interactions between IL-8 and CXCR1/2 expressing cells (CD34+ cells, ECs and SCs). These data provide the preclinical rationale for the evaluation of combinations of drugs which can dampen the cascade of events that result when MF MKP/MKs interact with CD34+ cells and MicroE cells. Disclosures Hoffman: Summer Road: Research Funding; Merus: Research Funding; Janssen: Research Funding; Incyte: Research Funding; Formation Biologics: Research Funding.
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Jung, Chul Won, Lee-Yung Shih, Zhijian Xiao, Jie Jin, Hsin-An Hou, Xin Du, Ming-Chung Wang, et al. "A Multinational, Open-Label Phase 2 Study Of Ruxolitinib In Asian Patients (Pts) With Primary Myelofibrosis (PMF), Post–Polycythemia Vera MF (PPV-MF), Or Post–Essential Thrombocythemia MF (PET-MF)." Blood 122, no. 21 (November 15, 2013): 4086. http://dx.doi.org/10.1182/blood.v122.21.4086.4086.
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Abstract Background Ruxolitinib is a potent JAK1/JAK2 inhibitor that has demonstrated rapid and durable reductions in splenomegaly, improved MF-related symptoms and quality of life (QoL), and prolonged survival in 2 phase 3 studies comparing ruxolitinib with placebo (COMFORT-I) and best available therapy (COMFORT-II). However, no clinical trial in pts with MF had been conducted in Asian countries, and only a limited number of Asian pts or healthy volunteers had been enrolled in any ruxolitinib study. Methods This study was an open-label phase 2 study evaluating ruxolitinib in Asian pts with PMF, PPV-MF, or PET-MF who had palpable splenomegaly ≥ 5 cm below the costal margin and intermediate-2– or high-risk MF by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria. Pts received starting doses of ruxolitinib 15 or 20 mg twice daily (bid) based on baseline platelet count (100-200 or > 200 × 109/L, respectively); dose adjustments balancing safety and efficacy were allowed to titrate each pt to their most appropriate dose. The primary endpoint was met if the proportion of pts achieving ≥ 35% reduction in spleen volume from baseline at week 24 was ≥ 27.5% as measured by MRI/CT. Symptomatic response was assessed as a secondary endpoint using the 7-day modified MF Symptom Assessment Form (MFSAF) v2.0 total symptom score (TSS) and European Organisation for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30). The study was conducted in China (n = 63), Japan (n = 30), Korea (n = 17), and Taiwan (n = 10). The data cutoff date for this analysis was 7 June 2013. Results Overall, 120 pts were enrolled (PMF, n = 80; PPV-MF, n = 21; PET-MF, n = 19), and their baseline characteristics were as follows: median age, 61 years (range, 25-80 years); 51.7% female; 69.2% intermediate-2 and 30.8% high risk by IWG-MRT criteria; median palpable spleen size, 15 cm (range, 5-45 cm); median spleen volume, 2159 cm3; 55.8% of pts had prior exposure to hydroxyurea. The median follow-up was 8.44 months; 22.5% of pts discontinued treatment, primarily for adverse events (AEs; 9.2%) and disease progression (7.5%). The median duration of treatment was 8.44 months (range, 0.5-21.7 months), and the median daily dose was 20.64 mg/day in the 15 mg bid group (n = 46) and 36.11 mg/day in the 20 mg bid group (n = 74). All pts were evaluable for achievement of the primary endpoint, 101 pts remained on study and were evaluable at week 24, and 96 pts had nonzero scores on the MFSAF-TSS and were evaluable for a reduction from baseline. Most pts who had assessments at week 24 (91% [92/101]) had a reduction from baseline in spleen volume (Figure). The study met the primary endpoint, with 31.7% (38/120) of all pts achieving ≥ 35% reduction from baseline at week 24. Overall, 38.3% (46/120) of pts achieved ≥ 35% reduction from baseline in spleen volume at any time on study. As measured by the 7-day MFSAF, 49% (47/96) of pts achieved ≥ 50% reduction from baseline in TSS (median reduction, 47.2%). Pts experienced an improvement from baseline at week 24 in EORTC global health status/QoL (mean change, 5.2). The most common nonhematologic AEs (≥ 10%) regardless of relationship to study medication included diarrhea (25.8%), upper respiratory tract infection (17.5%), ALT level increased (15.0%), pyrexia (15.0%), AST level increased (13.3%), cough (11.7%), herpes zoster infection (11.7%), nasopharyngitis (10.8%), constipation (10.0%), gamma-glutamyl transferase level increased (10.0%), and headache (10.0%), and most were grade 1/2. Serious AEs were reported for 24.2% of pts, and 65.8% of all pts had grade 3/4 AEs. The most common new or worsening laboratory abnormalities were low hemoglobin (all grade 3, 55.7%), low lymphocyte (grade 3/4, 19.5%), low platelet (grade 3/4, 15.3%), and low ANC (grade 3/4, 7.6%) levels. AEs observed in this study were consistent with those observed in the 2 large phase 3 COMFORT studies. Six pts (5%) died on treatment or within 30 days of discontinuation. Summary/conclusions Findings from this study demonstrated that ruxolitinib was relatively well tolerated in Asian pts with MF and provided substantial reductions in splenomegaly and modest improvements in MF-associated symptoms. The AEs observed with ruxolitinib treatment in this study are consistent with those observed in the large phase 3 COMFORT studies, and there were no new AEs associated with ruxolitinib in Asian pts with MF. Disclosures: Okamoto: Novartis: Honoraria, Research Funding. Sirulnik:Novartis: Employment. Ruiz:Novartis: Employment. Amagasaki:Novartis: Employment. Ito:Novartis: Employment. Akashi:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding.
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Hess, Gregory, Eileen Fonseca, Andrew Lee, Hongwei Wang, Ravinder Dhawan, Stephen F. Thompson, Sheikh Usman Iqbal, and Sean Redmond. "Characteristics Of Patients Included In The Myelofibrosis Real-World Practice-Based Network Research (ENRiCH) Data Platform." Blood 122, no. 21 (November 15, 2013): 1580. http://dx.doi.org/10.1182/blood.v122.21.1580.1580.
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Abstract Introduction The prevalence of myelofibrosis (MF) is 3.6 to 5.6 cases per 100,000 in the United States. Overall median survival is 3 years and 1.3 years for patients with intermediate-2 and high-risk disease, respectively. The MF PracticE-Based Network ResearCH (ENRiCH) platform is an adaptive, dynamic, data hub designed to accumulate real-world data to identify MF patients, understand their treatment patterns and unmet needs, inform clinical trial design, and conduct research using clinically relevant outcomes. A descriptive analysis of the demographic and clinical characteristics of MF patients from the ENRiCH platform is reported in this study. Methods The ENRiCH platform was developed from patient-level data representing approximately 1 billion US private practitioner medical claims, >1.6 billion pharmacy claims, and electronic medical records from >500,000 cancer patients treated in community oncology practices at 344 locations in 37 states and encompassing approximately 550 treating providers. ENRiCH includes patients with a diagnosis of MF, polycythemia vera (PV), or essential thrombocytopenia (ET), and/or a ruxolitinib prescription between November 1, 2010 and October 31, 2012; patients who received ruxolitinib in a clinical trial were excluded. Results As of March 2013, 6362 MF and 299 ruxolitinib patients were identified. Mean (SD) age was 67.0 (12.6) years for MF patients and 65.8 (15.0) years for the ruxolitinib subgroup, with 45% females. Hematologic comorbidities included myeloid disorders (80% MF; 70% ruxolitinib) and lymphoid disorders (10% MF; 5% ruxolitinib). The most common myeloid disorders were primary MF (47% MF; 29% ruxolitinib), myelodysplastic syndrome (35% MF; 26% ruxolitinib), ET (25% MF; 17% ruxolitinib), and PV (25% MF; 17% ruxolitinib). Common comorbidities of interest that were observed included infectious diseases (35% MF; 35% ruxolitinib), thrombocytopenia (33% MF; 23% ruxolitinib), pulmonary hypertension (7% MF; 7% ruxolitinib), and vitamin D deficiency (7% MF; 8% ruxolitinib). The mean (SD) Charlson comorbidity index (CCI) was 4.36 (2.4) for MF patients and 4.28 (2.4) for the ruxolitinib subgroup. Clinical characteristics and laboratory results among patients with diagnostic or clinical data from the index date forward are shown in the table. The 5 most common concomitant medication groups for ruxolitinib patients were loop diuretics (11%), gout agents (10%), hydrocodone combinations (9%), opioid agonists (9%), and proton pump inhibitors (9%). The top 5 most common medications taken within 180 days prior to new ruxolitinib starts were hydrocodone combinations (21%), antineoplastics (19%), gout agents (18%), glucocorticosteroids (15%), and fluoroquinolones (14%). The predominant [MF (ruxolitinib)] payer types observed were Medicare [48% (37%)], Medicaid [4% (1%)], and commercial insurance [37% (21%)]. Conclusions The observed demographic and clinical characteristics of MF patients are similar to prior MF epidemiological studies (Mehta J et al. Leuk Lymphoma. 2013;Early Online: 1-6), suggesting that the sample of MF ENRiCH patients is reflective of the broader US MF population and will allow for broad-based quantification of unmet needs and treatment outcomes. The addition of more MF patients and longer follow-up data will further enhance the value of this large US real-world MF patient data hub including those on current MF therapies. This study was sponsored by Sanofi. Disclosures: Fonseca: IMS Health - a company that received funds from Sanofi to conduct the study: Employment. Lee:Sanofi: Employment. Wang:Sanofi: Employment, Equity Ownership. Dhawan:Sanofi: Employment. Thompson:Sanofi: Employment. Iqbal:Sanofi: Employment, Equity Ownership. Redmond:IMS Health: Consultancy, Employment.
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Li, Zixuan, Hao Li, Kenli Li, Fan Wu, Lydia Chen, and Keqin Li. "Locality Sensitive Hash Aggregated Nonlinear Neighborhood Matrix Factorization for Online Sparse Big Data Analysis." ACM/IMS Transactions on Data Science 2, no. 4 (November 30, 2021): 1–27. http://dx.doi.org/10.1145/3497749.
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Matrix factorization (MF) can extract the low-rank features and integrate the information of the data manifold distribution from high-dimensional data, which can consider the nonlinear neighborhood information. Thus, MF has drawn wide attention for low-rank analysis of sparse big data, e.g., Collaborative Filtering (CF) Recommender Systems, Social Networks, and Quality of Service. However, the following two problems exist: (1) huge computational overhead for the construction of the Graph Similarity Matrix (GSM) and (2) huge memory overhead for the intermediate GSM. Therefore, GSM-based MF, e.g., kernel MF, graph regularized MF, and so on, cannot be directly applied to the low-rank analysis of sparse big data on cloud and edge platforms. To solve this intractable problem for sparse big data analysis, we propose Locality Sensitive Hashing (LSH) aggregated MF (LSH-MF), which can solve the following problems: (1) The proposed probabilistic projection strategy of LSH-MF can avoid the construction of the GSM. Furthermore, LSH-MF can satisfy the requirement for the accurate projection of sparse big data. (2) To run LSH-MF for fine-grained parallelization and online learning on GPUs, we also propose CULSH-MF, which works on CUDA parallelization. Experimental results show that CULSH-MF can not only reduce the computational time and memory overhead but also obtain higher accuracy. Compared with deep learning models, CULSH-MF can not only save training time but also achieve the same accuracy performance.
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Ulberth, Franz. "Detection of Milk Fat Adulteration by Linear Discriminant Analysis of Fatty Acid Data." Journal of AOAC INTERNATIONAL 77, no. 5 (September 1, 1994): 1326–34. http://dx.doi.org/10.1093/jaoac/77.5.1326.
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Abstract Analysis of the fatty acid (FA) profile of milk fat (MF) by gas-liquid chromatography is widely used to detect adulteration with foreign fats. On the basis of the FA spectra of 352 genuine Austrian MF samples collected over a 4-year period, the effectiveness of concentration ranges of the major FA of MF and of certain FA ratios to identify non-MF/MF mixtures was tested. FA ratios proved useful for the detection of coconut fat in MF and admixture of vegetable oils rich in linoleic acid down to a level of 2%. This approach failed to identify non-MF/MF blends containing beef tallow, lard, olive oil, or palm oil at a level less than 10% commingling. Linear discriminant analysis applied to FA data was successful in distinguishing pure MFfrom adulterated MF. Computer-simulated data were used to derive the discriminant functions. Saturated and un-saturated FA with 18 C atoms were the most useful discriminating variables selected by a stepwise variable selection procedure. More than 95% of a data set composed of pure MF, and non-MF/MF blends containing 3% of either tallow, lard, olive oil, or palm oil were correctly classified. The validity of the classification rule was also tested by 206 gravimetrically prepared fat mixtures. Mixtures containing >3% foreign fat were detected in all cases.
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SAHOO, P. K., J. J. BABU GEDDAM, A. K. SATAPATHY, M. C. MOHANTY, B. K. DAS, A. S. ACHARYA, N. MISHRA, and B. RAVINDRAN. "Bancroftian filariasis: a 13-year follow-up study of asymptomatic microfilariae carriers and endemic normals in Orissa, India." Parasitology 124, no. 2 (February 2002): 191–201. http://dx.doi.org/10.1017/s0031182001001007.
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The natural history of human filarial infections leading to development of disease has been a subject of intense debate. The models proposed so far have largely been based on cross-sectional data on microfilariae (Mf) and disease prevalence in filariasis endemic areas. In an attempt to study the parasitological and clinical consequences of filarial infection in Beldal (Orissa, India), an area endemic for Bancroftian filariasis, cohorts of 59 asymptomatic Mf carriers (AS) and 187 asymptomatic and amicrofilaraemic subjects or ‘endemic normals’ (‘EN’), were followed-up and a fraction (73% and 46% respectively) re-examined after 13 years to monitor (a) Mf prevalence, (b) Mf density, (c) circulating filarial antigen (CFA) and (d) chronic disease manifestations. The Mf prevalence and density were also monitored in Mf carriers after 1 and 4 years. Both Mf prevalence and density decreased progressively in the cohort of Mf carriers over a period of 13 years in Beldal. Only 37% of them continued to be microfilaraemic and the Mf density in these subjects was only 10% of the original level. However, loss of circulating Mf in this cohort did not result in loss of CFA and 95% remained CFA positive regardless of Mf status. About 23% of males in the ‘EN’ cohort developed hydrocoele while only 5·7% of male Mf carriers, who were not treated with DEC, had developed hydrocoele after 13 years. A cohort of Mf carriers in another area, Jatni, was also examined after 10 years to study the parasitological and clinical outcome. In this area, about 59% of the Mf carriers continued to be microfilaraemic after 10 years. These results reveal that in Mf carriers adult filarial worms persist for several years and that loss of circulating Mf with or without chemotherapy with DEC (single 12-day course) does not influence adult worm survival. The findings have been discussed in the context of ‘static’ and ‘dynamic’ models describing the relationship between infection and disease in human filariasis.
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Guglielmelli, Paola, Giada Rotunno, Annalisa Pacilli, Elisa Rumi, Vittorio Rosti, Federica Delaini, Margherita Maffioli, et al. "Prognostic Impact of Bone Marrow Fibrosis in Primary Myelofibrosis: A Study of Agimm Group on 540 Patients." Blood 126, no. 23 (December 3, 2015): 351. http://dx.doi.org/10.1182/blood.v126.23.351.351.
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Abstract Background. The prognostic significance of bone marrow (BM) fibrosis grade in pts with primary myelofibrosis (PMF) is debated. A fibrosis grade greater than 1 was associated with a 2-fold higher risk of death compared with pts with early/prefibrotic MF (grade 0) [Thiele J, Ann Hematol 2006]. Recent data suggest that more accurate prediction of survival is achieved when fibrosis grade is added to IPSS [Verner C, Blood 2008; Giannelli U, Mod Pathol 2012]. Aim. To analyze the prognostic impact of fibrosis in diagnostic BM samples of 540 WHO-2008 diagnosed PMF pts with extensive clinical and molecular information collected in 6 Italian centers belonging to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative). Methods. The clinical variables assessed were those previously identified as prognostically relevant in the IPSS score. Published methods were used to screen mutations of JAK2, MPL, CALR, EZH2, ASXL1, IDH1/2 and SRSF2. European consensus scoring system was used to grade fibrosis (on a scale of MF-0 to MF-3). The prognostic value of fibrosis with regard to overall survival (OS) was estimated by Kaplan-Meier method and Cox regression. Results. Pts' median age was 61y; median follow-up 3.7y; median OS 10.5y; 184 pts (34.1%) died. IPSS risk category: low 33.7%, Int-1 27.7%, Int-2 19.1%, High-risk 19.5%. Mutational rate: JAK2 V617F 62.6%, CALR 20.7% (type-1/1-like 77.7%, type2/2-like-2 21.4%), MPL W515 5.9%; 62 (11.5%) were triple negative (TN). 171 pts (31.7%) were High-Molecular Risk (HMR) category (Vannucchi AM, Leukemia 2013); mutation rate: EZH2 7.2%, ASXL1 22.2%, IDH1-2 2.4%, SRSF2 8.3%. According to fibrosis grading, 50 pts were MF-0 (9.3%), 180 MF-1 (33.3%), 196 MF-2 (36.3%), 114 MF-3 (21.1%). Compared with both MF-0 and MF-1, MF-2 and MF-3 pts presented more frequently constitutional symptoms (P<.0001), larger splenomegaly (P<.0001), greater risk of developing anemia (P<.0001) or thrombocytopenia (P=.003). We found a significant association (P<.0001) between IPSS higher/Int-2 risk categories and MF-2 and -3 (20.5% and 37.8%, respectively, vs 14.8% and 6.0% for MF-0 and -1). There was no correlation between fibrosis grade and phenotypic driver mutations; in particular, TN pts were equally distributed among MF fibrosis grades (10%, 10.6%, 14.3% and 8.8% from MF-0 to -3, respectively). Conversely, the frequency of HMR pts increased progressively according to fibrosis grade: 8 pts MF-0 (16%), 46 MF-1 (25.6%), 66 MF-2 (33.7%) and 51 MF-3 (44.7%) (P<.0001). In particular, we found a significant association between fibrosis grade and ASXL1 (12%, 15%, 23.5% and 36% from MF-0 to -3; P<.0001) and EZH2 (2%, 3.9%, 8.2%, 13.2%; P=.01) mutations. Also, pts with 2 or more HMR mutated genes were preferentially MF-2 or -3 ( 0%, 4.4% 10.2% and 10.5% from MF-0 to -3; P=.001). Median OS was significantly shorter in pts with MF-2 (OS 6.7y, HR 7.3, IC95% 2.7-20.0; P<.0001) and MF-3 (OS 7.2y, HR 8.7, IC95% 3.1-24.2; P<.0001) compared with MF-1 (14.7y; HR 3.9, IC95% 1.4-10.9, P=.008) and MF-0 (P<.0001) used as reference group (OS not reached) (Figure). Excluding MF-0, MF-2 and -3 maintained negative prognostic impact with HR 1.9 (1.3-2.6; P=.001) and 2.2 (1.5-3.3; P<.0001) respectively vs MF-1. The impact of fibrosis on OS was maintained when analysis was restricted to younger (≤65y) pts. In multivariate analysis using the individual IPSS variables, grade MF-2 and -3 were independently predictive of survival (HR 3.9 (1.4-10.8), and HR 4.2 (1.5-12.0), respectively, P=.008 for both). The negative impact on survival of MF-2/-3 was maintained regardless of IPSS category, HMR status, number of HMR mutated genes and driver mutations, included as covariates (Table). In low, Int-1 and Int-2, but not high-risk IPSS categories, MF-2/-3 associated with reduced survival (P<.03). Conclusions. Overall, these results indicate that higher grades (MF-2 and MF-3) of fibrosis correlate with defined clinical and molecular variables and independently negatively impact on OS in PMF, suggesting the opportunity to explore its value in the setting of clinical and molecular prognostic scores for PMF. Table. Multivariate Analysis Variables HR 95% CI P value HMR status 2.4 1.5-3.7 <.0001 HMR≥2mutations 4.3 2.8-6.4 .009 IPSS scoring Int1 2.9 1.6-5.1 <.0001 Int2 10.0 5.6-17.7 <.0001 High 9.7 5.5-17.2 <.0001 Driver mutations CALR type2 3.4 1.3-8.6 .010 JAK2/MPL 2.4 1.4-4.3 .003 TN 4.5 2.3-8.8 <.0001 Fibrosis MF-2/MF-3 3.8 1.4-10.6 .010 Figure 1. Figure 1. Disclosures Passamonti: Novartis: Consultancy, Honoraria, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Vannucchi:Shire: Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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Cai, Yan Hua. "Study on Effect of Rice Flour on Isothermal Crystallization Kinetics of Biodegradable Poly(L-Lactic Acid)." Advanced Materials Research 887-888 (February 2014): 627–31. http://dx.doi.org/10.4028/www.scientific.net/amr.887-888.627.
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The Ultra-fine rice flour (MF) was processed using supersonic speed airflow grinding technology, and the average size of the particles was 8 μm. The Poly (L-lactic acid)(PLLA)/MF composites were fabricated by blending, and the isothermal crystallization behavior of PLLA/MF was investigated in detail. The results showed that the half time of overall PLLA crystallization t1/2 was affected by Tc and content of MF. Upon the addition of 3%MF at 100°C, t1/2 decreased to minimum value. In addition, the kinetic of isothermal crystallization of PLLA/MF composites showed that there existed complicated nucleation mechanism of PLLA and PLLA/MF composite.
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Hettihewa, Samanthala, and Christopher S. Wright. "Socio-Economic Differences and Deployment of the LDC Micro-Finance Bottom-up Approach in DCs." Journal of Electronic Commerce in Organizations 8, no. 2 (April 2010): 41–53. http://dx.doi.org/10.4018/jeco.2010040104.
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Microfinance (MF), after showing great success in poverty-relief in less-developed countries (LDCs), has experiencing rapid growth and interest in developed countries (DCs). However, current DC MF literature gives the impression that survival concerns are diverting DC MF from its original poverty-relief intent. As e-technology evolves, further threats and opportunities are created for MF by changing cost structures and relationships. This study uses descriptive analysis to infer that DC MF needs redesigning for DC socio-economic conditions or it will continue gaining a reputation of being too poorly focused, ineffective, and inefficient for use in DCs. After showing that LDC poverty is harsher than DC poverty, this paper reviews current-performance concerns of DC MF, links those issues with the effect of regulatory and other socio-economic factors on micro-enterprise, discusses how MF can relieve poverty in DCs, and concludes that MF needs refocusing before DCs investing in further developing/adapting MF infrastructure.
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Ryu, Hyang-Joo, Sun-Il Kim, Hyung-Ook Jang, Se-Hoon Kim, Sang-Ho Oh, Sujin Park, and Sang-Kyum Kim. "Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides." Cells 10, no. 10 (October 15, 2021): 2758. http://dx.doi.org/10.3390/cells10102758.
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The International Society for Cutaneous Lymphoma (ISCL) proposes a diagnostic algorithm for early mycosis fungoides (MF) that includes clinical, histological, immunophenotypical, and molecular criteria. Here, we analyzed the immunologic markers and features of T-cell clonality in 38 early MF cases and 22 non-MF cases to validate the ISCL algorithm. We found that CD5 and CD7 expression differed significantly between early MF and non-MF cases, with epidermal discordance of CD7 expression more frequently identified in early MF. Notably, increasing the cut-off value for CD7 expression from 10% to 22.5% improved its sensitivity. Furthermore, TCR-γ and β chain rearrangements were more frequently detected in early MF than in non-MF cases. Based on these findings, we propose CD5 and CD7 deficiency as mandatory immunopathologic criteria and PCR-based testing for TCR-γ and β chains as required molecular/biologic criteria to improve the efficiency of early MF diagnosis using the ISCL algorithm.
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Ford, J. L., and R. B. Claydon. "Inheritance of multifoliolate leaves in white clover." NZGA: Research and Practice Series 6 (January 1, 1996): 167–70. http://dx.doi.org/10.33584/rps.6.1995.3361.
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During 1988/89 selected white clover (Trifolium repens L.) genotypes were studied to determine their inheritance of multifoliolate (mf) leaves in relation to the multifoliolate percentage of the parent material. Genotypes differing in multifoliolate frequency were crossed in an incomplete diallel with plants from three Grasslands white clover cultivars, Huia, Kopu and Tahora. Each cultivar was used in three separate pair crosses, with genotypes expressing multifoliolate leaf percentages of 25%, 50% and 75% respectively. These mf plants were also pair crossed and plants from within each cultivar were pair crossed 3 times. All plants in the total of 21 pair crosses were bee pollinated. Harvested seed from each genotype was sown and raised under glasshouse conditions, and after ninety days each young plant was evaluated for mf leaf production. Leaf count results showed that 31% of cultivar x mf genotypes expressed mf leaves, while in the mf x mf programme 90% of genotypes displayed mf leaves. A distinct increase in the percentage of multifoliolate leaves occurred in crosses between mf plants and the trifoliolate cultivars when the mf genotype was the maternal parent. It is apparent that the multifoliolate character is heritable and that the percentage of mf leaves can be increased through breeding and selection. Keywords: expression levels, inheritance, multifoliolate, white clover
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Ohyashiki, Kazuma, Yasuo Aota, Akihiko Gotoh, Keisuke Miyazawa, Yukihiko Kimura, and Junko H. Ohyashiki. "Myelodysplastic Syndromes with Myelofibrosis May Be a Target for the JAK2 V617F Tyrosine Kinase Mutation." Blood 106, no. 11 (November 16, 2005): 4895. http://dx.doi.org/10.1182/blood.v106.11.4895.4895.
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Abstract The JAK V617F tyrosine kinase mutation is responsible for development of the disease in chronic myeloproliferative disorders, including myelofibrosis (MF). Since MF is associated with various hematologic diseases as a terminal hematologic condition and is an important issue in managing patients, we searched for the V617F mutation in primary and secondary MF in various hematologic diseases using the sequence-specific primer-single molecule fluorescence detection assay (SSP-SMFD). Of the MF patients associated with acute myeloid leukemia and (n = 3), lymphoma (n = 3), and chronic myeloid leukemia (n = 3), none of them showed the mutation at the time of the diagnosis of MF. Approximately 40% of essential thrombocythemia (ET: n = 16) and primary MF (n = 4) showed the JAK2 V617F mutation, whereas 6 of 8 patients with polycythemia vera showed the mutation. Of note is that 2 of 6 patients with myelodysplastic syndromes (MDS) terminating in MF showed the mutation, while no MDS patient without MF (MDS: n = 3) had the JAK2 V617F mutation. Our study clearly demonstrated that MF in MDS patients is sometimes associated with JAK2 V617F mutation, while other underlying diseases developing MF may involve other pathways. Moreover, it permits speculation that clonal evolution in some MDS patients with the JAK2 V617F tyrosine kinase mutation may be responsible for secondary MF.
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LAWRENCE, R. A., J. E. ALLEN, and C. A. GRAY. "Requirements for in vivo IFN-γ induction by live microfilariae of the parasitic nematode, Brugia malayi." Parasitology 120, no. 6 (June 2000): 631–40. http://dx.doi.org/10.1017/s003118209900596x.
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Lymphatic filariasis caused by the parasitic nematode, Brugia malayi, is a chronic human disease immunologically characterized by stimulation of Th2 cells and reduced antigen-specific T cell responses. Single stage intra-peritoneal infections with infective larvae (L3) or adult nematodes induce Th2 cells, while the microfilarial stage (Mf) stimulates IFN-γ and Mf-specific IgG1, IgG2a, IgG2b, IgG3 and IgM, but not IgE. To investigate whether IFN-γ is elicited by live Mf in their natural site of infection, mice were infected intravenously. Intravenous infection had a striking effect on the response to Mf and high levels of IgE were induced even in the presence of IFN-γ. Indeed IgE levels to Mf increased markedly with the number of immunizations, higher doses of Mf and prolonged exposure to Mf suggesting that under conditions of chronic antigen exposure, typical of human disease, Mf will stimulate high levels of IgE. The ability of Mf-induced IFN-γ to modulate or regulate a pre-existing Th2 response, was investigated by infecting mice initially with adult male worms to induce a Th2 response, followed 14 days later by infection with Mf. Although Mf stimulated IFN-γ in the presence of male adults, the antibody isotypes elicited did not reflect IFN-γ induction and IgG1and IgE dominated the response. Although it cannot be discounted that IFN-γ induction by Mf may act locally as an inflammatory mediator or modulator of Th2 cells, these data suggest that Mf-stimulated IFN-γ does not have a profound effect overall on progression of the Th2-dominated immune response to filarial infection.
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P., Torsten, Benedikt A. Aulinger, Eric P. Smith, Deborah L. Drazen, Yve Ulrich-Lai, Randy J. Seeley, Stephen C. Woods, and David A. D'Alessio. "Meal feeding improves oral glucose tolerance in male rats and causes adaptations in postprandial islet hormone secretion that are independent of plasma incretins or glycemia." American Journal of Physiology-Endocrinology and Metabolism 307, no. 9 (November 1, 2014): E784—E792. http://dx.doi.org/10.1152/ajpendo.00339.2014.
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Meal-fed (MF) rats with access to food for only 4 consecutive hours during the light cycle learn to eat large meals to maintain energy balance. MF animals develop behavioral and endocrine changes that permit glucose tolerance despite increased meal size. We hypothesized that enhanced activity of the enteroinsular axis mediates glucose homeostasis during MF. Cohorts of rats were allocated to MF or ad libitum (AL) regimens for 2–4 wk. Insulin secretion and glucose tolerance were determined after oral carbohydrate and intraperitoneal (ip) and intravenous (iv) glucose. MF rats ate less than AL in the first week but maintained a comparable weight trajectory thereafter. MF rats had decreased glucose excursions after a liquid mixed meal (AUC: MF 75 ± 7, AL 461 ± 28 mmol·l−1·min, P < 0.001), with left-shifted insulin secretion (AUC0–15: MF 31.0 ± 4.9, AL 9.6 ± 4.4 pM·min, P < 0.02), which peaked before a significant rise in blood glucose. Both groups had comparable fasting glucagon levels, but postprandial responses were lower with MF. However, neither intestinal expression of proGIP and proglucagon mRNA nor plasma incretin levels differed between MF and AL groups. There were no differences in the insulin response to ip or iv glucose between MF and AL rats. These findings demonstrate that MF improves oral glucose tolerance and is associated with significant changes in postprandial islet hormone secretion. Because MF enhanced β-cell function during oral but not parenteral carbohydrate administration, and was not accounted for by changes in circulating incretins, these results support a neural mechanism of adaptive insulin secretion.
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Reynolds, Samuel B., and Kristen Pettit. "New approaches to tackle cytopenic myelofibrosis." Hematology 2022, no. 1 (December 9, 2022): 235–44. http://dx.doi.org/10.1182/hematology.2022000340.
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Abstract Myelofibrosis (MF) is a clonal hematopoietic stem cell neoplasm characterized by constitutional symptoms, splenomegaly, and risks of marrow failure or leukemic transformation and is universally driven by Jak/STAT pathway activation. Despite sharing this pathogenic feature, MF disease behavior can vary widely. MF can generally be categorized into 2 distinct subgroups based on clinical phenotype: proliferative MF and cytopenic (myelodepletive) MF. Compared to proliferative phenotypes, cytopenic MF is characterized by lower blood counts (specifically anemia and thrombocytopenia), more frequent additional somatic mutations outside the Jak/STAT pathway, and a worse prognosis. Cytopenic MF presents unique therapeutic challenges. The first approved Jak inhibitors, ruxolitinib and fedratinib, can both improve constitutional symptoms and splenomegaly but carry on-target risks of worsening anemia and thrombocytopenia, limiting their use in patients with cytopenic MF. Supportive care measures that aim to improve anemia or thrombocytopenia are often ineffective. Fortunately, new treatment strategies for cytopenic MF are on the horizon. Pacritinib, selective Jak2 inhibitor, was approved in 2022 to treat patients with symptomatic MF and a platelet count lower than 50 × 109/L. Several other Jak inhibitors are in development to extend therapeutic benefits to those with either anemia or thrombocytopenia. While many other novel non–Jak inhibitor therapies are in development for MF, most carry a risk of hematologic toxicities and often exclude patients with baseline thrombocytopenia. As a result, significant unmet needs remain for cytopenic MF. Here, we discuss clinical implications of the cytopenic MF phenotype and present existing and future strategies to tackle this challenging disease.
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Yang, Mengdie, Yudong Zhang, and Jian Wang. "Sign Retention in Classical MF-DFA." Fractal and Fractional 6, no. 7 (June 30, 2022): 365. http://dx.doi.org/10.3390/fractalfract6070365.
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In this paper, we propose a one-dimensional (1D) multifractal sign retention detrending fluctuation analysis algorithm (MF-S-DFA). The proposed method is based on conventional multifractal detrending fluctuation analysis (MF-DFA). As negative values may exist in the calculation in the original MF-DFA model, sign retention is considered to improve performance. We evaluate the two methods based on time series constructed by p-model multiplication cascades. The results indicate that the generalized Hurst exponent H(q), the scale exponent τ(q) and the singular spectrum f(α) estimated by MF-S-DFA behave almost consistently with the theoretical values. Moreover, we also employ distance functions such as DH and Dτ. The results prove that MF-S-DFA achieves more accurate estimation. In addition, we present various numerical experiments by transforming parameters such as nmax, q and p. The results imply that MF-S-DFA obtains more excellent performance than that of conventional MF-DFA in all cases. Finally, we also verify the high feasibility of MF-S-DFA in ECG signal classification. Through classification of normal and abnormal ECG signals, we further corroborate that MF-S-DFA is more effective than conventional MF-DFA.
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Ghanima, Waleed, Julia Turbiner Geyer, Christina Soo Lee, Attilio Orazi, Leonardo Boiocchi, Allison Imahiyerobo, and James B. Bussel. "Bone Marrow Fibrosis In Immune Thrombocytopenia (ITP) Patients Treated With Thrombopoietin Receptor Agonists (TRA) – a Single Center Long-Term Follow-Up." Blood 122, no. 21 (November 15, 2013): 3527. http://dx.doi.org/10.1182/blood.v122.21.3527.3527.
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Abstract Introduction TRAs increase platelet counts by stimulating the TPO-receptor. A known effect of TRA treatment is increased bone marrow fibrosis (MF). This study explored extent of MF, its clinical relevance, and incidence of phenotypic or karyotypic abnormalities in TRA-treated ITP patients. Methods This single-center study was carried out at the Platelet Disorders Center of Weill Cornell Medical College (WCMC), NY, USA. Eligibility criteria were: diagnosis of ITP; treatment with a TRA (romiplostim, eltrombopag, AKR 501 (Eisai) or Shionogi agent), ≥ 1 bone marrow biopsy (BMB) performed during TRA treatment. BMBs were performed every 1–2 years as standard f/u procedure for our ITP patients on TRA. MF grade was assessed from MF-0 to MF-3 according to the European Consensus Grading System in 141 BMBs acquired prior to (n=15), during (n=117) and after (n=9) TRA-treatment from 66 patients. Fifty disease-free staging BMBs served as controls. BMBs were separately reviewed by 3 pathologists to assess the grade of MF and then reviewed concurrently as needed to reach consensus. The study was approved by the IRB of WCMC; informed written consent was obtained from patients. Results Median (Q1-Q3) age at the time of 1st BMB was 38 years (18-63); 34 males 32 females. 32 patients had > 2 on-treatment BMBs. The distribution of MF-grades is shown in the figure. The proportion of MF-0 decreased from 67% in pretreatment biopsies (BM0) to 21% in the first set of BMBs (BM1); in the 15 patients with pre- and on-treatment BMBs there was a significantly higher number of MF-0 in BM0 as compared to BM1 (10/15 vs. 3/15;p=0.016) suggesting that TRAs induce fibrosis in treated patients. In patients with multiple on-treatment BMBs (n=32), first on-treatment BMB was graded as MF-1 in 24. In the last set of biopsies (BM-Last) 8 had progressed to MF-2/3, 12 remained MF-1, and 4 became MF-0 illustrating the unpredictability of the future course of MF from the first on-treatment marrow. Nonetheless, a higher number of MF-2/3 BMB was found in BM-Last as compared to BM1 [10 (31%) vs. 3 (9%) of 32; p=0.039]. In 5 patients with MF-2/3 BMB, TRA were discontinued: on f/u 2 had less fibrosis, 1 remained the same, and 2 are awaiting f/u BMB. BMB was graded MF-0 in 54% and MF-1 in 46% of control BMB; no difference was found in the proportion of MF-0/1 and 2/3 in BM0 compared to controls, but increased MF-2/3 was seen in BM-last compared to controls (p<0.001). At BM-last in patients dichotomized by MF-0/1 vs. MF-2/3, differences in hemoglobin levels (13.6 vs. 12.4 g/dl, respectively), absolute neutrophil counts (4.8 vs. 7 x109/L), platelet counts (92 vs. 123 x109/L), and LDH levels (212 vs. 219 U/L) were not significantly different. Of the following 6 clinical factors: age, duration of disease, duration of treatment, splenectomy status, type and dose of agent; only age was significantly higher in patients with MF-2/3 as opposed to MF0/1 at time of BM-last [57 vs. 38 years; p=0.01]. There was a tendency toward longer duration of treatment in patients with MF-2/3 as compared to MF-0/1 (3.6 y vs. 2.7y; p=0.16). Flow cytometric immunophenotyping of BMB in 89 examinations did not reveal emergence of clonal abnormalities. Cytogenetic analysis in 72 BMBs did not show any clonal karyotypic abnormalities. Conclusions This large single center experience indicates that TRAs induce some degree of MF as supported by: 1) decreasing fraction of MF-0 after initiation of TRA, 2) decreasing fraction of MF-0/1 (normal grades of MF) in subsequent on-treatment BMBs, 3) increasing fraction of MF-2/3 (pathological grades) in patients with multiple on-treatment BMBs. Only older age was associated with higher grades of fibrosis. However, MF remained stable in most patients within the range found in normal individuals. Higher grades of MF (MF-2/3) observed in some patients were not clinically significant based on peripheral blood counts. Overall, since a number of patients developed MF-2 and even MF-3, this suggests a risk of progressive fibrosis in approximately 20% of patients. No neoplastic immunophenotypic or karyotypic abnormalities emerged during treatment with TRAs. Annual or bi-annual follow-up with BMB should be carefully considered in TRA-treated patients. Discontinuation of TRA should be encouraged in those who develop/progress to MF-3 and possibly even MF-2 to avoid potential further progression of MF Disclosures: Bussel: Amgen: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Genzyme: Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Eisai: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Shionogi: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Sysmex: Research Funding; Symphogen: Membership on an entity’s Board of Directors or advisory committees.
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Stroup, Bridget M., Emily A. Sawin, Sangita G. Murali, Neil Binkley, Karen E. Hansen, and Denise M. Ney. "Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria." Journal of Nutrition and Metabolism 2017 (2017): 1–12. http://dx.doi.org/10.1155/2017/1909101.
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Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p=0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p=0.012) and magnesium by 30% (p=0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258.
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Medeiros, Jessie J. F., Amanda Mitchell, Aaron Trotman-Grant, Tristan Woo, Jenny M. Ho, Andrea Arruda, Mark D. Minden, John E. Dick, Vikas Gupta, and Liran I. Shlush. "Myelofibrosis Is Initiated and Sustained By Rare Multipotent Stem Cells." Blood 132, Supplement 1 (November 29, 2018): 1790. http://dx.doi.org/10.1182/blood-2018-99-119088.
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Abstract Background: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm (MPN) characterized by marked bone marrow fibrosis, extramedullary hematopoiesis and significant risk for leukemic transformation. Most patients carry recurrent MPN driver mutations in JAK2, CALR and MPL and many carry additional mutations in epigenetic regulators, splicing and signaling pathways. MF pathophysiology remains poorly understood, particularly with respect to the cellular identity of the MF clone(s) bearing mutations that initiate and maintain the disease. Therefore, here we tracked somatic mutations from nine MF patients in sorted hematopoietic cell populations from serial time-points as well as patient-derived xenografts (PDXs), to identify clinically relevant MF cell populations for future targeted therapies. Methods: Genomic DNA was isolated from the peripheral blood mononuclear cells (PBMCs) of nine chronic-phase MF patients (5 JAK2+ and 4 CALR+) and sequenced using the 54-gene TruSight Myeloid targeted panel. PBMCs from the same patients at serial time-points (if available) were sorted into hematopoietic stem and progenitor cell (HSPC) and mature cell populations. In addition, PDXs were generated following injection of CD34+ peripheral blood cells into sub-lethally irradiated NSG and/or NSG-SGM3 mice. Human myeloid (CD45+33+) and B (CD45+19+) cells were isolated from PDXs after 8-16 weeks. Digital droplet PCR was used to interrogate known oncogenic variants, identified from the targeted sequencing, in all sorted primary and PDX cell fractions. Results: We reveal that the vast majority of genetic lesions used to interrogate the hierarchy were acquired at the level of immunophenotypically defined hematopoietic stem/multipotent progenitor cells (HSC/MPP) (CD45+34+38-RA-, termed MF-HSC). MF-HSC variants were generally shared with most HSPC, differentiated myeloid (CD33+) and lymphoid (B and/or T cell) populations sorted from primary patient samples. In our cohort, MPN driver mutations were invariably acquired in MF-HSC and consistently maintained over longitudinal clinical follow-up (median of 17 months) in both MF-HSCs and differentiated myeloid cells (CD33+). Interestingly however, in 2 cases (1 CALR+ and 1 JAK2+ MF), ASXL1 mutations in MF-HSCs were observed at the first time-point but restricted to the CD33+ compartment at a later time-point. Further, in one patient, SF3B1 mutation was restricted to the CD33+ fraction at the first time-point and was completely absent at the second time-point. Thus, certain mutations, like ASXL1, may be required for MF initiation but not necessarily disease maintenance; or alternatively, independent MF-HSC clones may outcompete others over time. Additionally, some acquired downstream mutations may be transient in nature and not clinically relevant. Together these data suggest that MF-HSCs are essential for MF clonal maintenance. To complement our genetic interrogation of the hematopoietic hierarchy in MF, we demonstrate that CD34+ HSPCs generate multi-lineage grafts in xenotransplanted mice bearing mutations identified in MF-HSCs. CALR+ samples invariably demonstrate multi-lineage potential and clonal dynamics in PDXs suggest that CALR mutations are likely the first genetic lesion acquired in multipotent MF-HSCs. JAK2+ samples generated more variable data, but by combining the genetic data of both PDXs and lymphoid cells sorted from primary patient samples, we show that JAK2+ MF-HSCs may also be multipotent. Taken together, these data suggest that MF-HSCs are multipotent, functionally relevant MF-initiating cells capable of propagating downstream HSPC populations and the CD33+ MF-disease clone that harbors all interrogated mutations. Thus, rare MF-HSCs are both disease-initiating and disease-maintaining cells. Conclusions: Our approach combining high-resolution cell sorting and xenograft assays with genomic interrogation demonstrates that MF is initiated and maintained by rare multipotent MF-HSCs. Our study underscores the complex evolutionary events that occur in the stem cell compartment during disease progression and identifies MF-HSCs as the relevant cellular target for future therapeutic intervention. Disclosures Gupta: Novartis: Consultancy, Honoraria, Research Funding; Incyte: Research Funding.
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Pöschl, Marek, Shibulal Gopi Sathi, Radek Stoček, and Ondřej Kratina. "Rheometer Evidences for the Co-Curing Effect of a Bismaleimide in Conjunction with the Accelerated Sulfur on Natural Rubber/Chloroprene Rubber Blends." Polymers 13, no. 9 (May 7, 2021): 1510. http://dx.doi.org/10.3390/polym13091510.
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The rheometer curing curves of neat natural rubber (NR) and neat chloroprene rubber (CR) with maleide F (MF) exhibit considerable crosslinking torque at 180 °C. This indicates that MF can crosslink both these rubbers via Alder-ene reactions. Based on this knowledge, MF has been introduced as a co-crosslinking agent for a 50/50 blend of NR and CR in conjunction with accelerated sulfur. The delta (Δ) torque obtained from the curing curves of a blend with the addition of 1 phr MF was around 62% higher than those without MF. As the content of MF increased to 3 phr, the Δ torque was further raised to 236%. Moreover, the mechanical properties, particularly the tensile strength of the blend with the addition of 1 phr MF in conjunction with the accelerated sulfur, was around 201% higher than the blend without MF. The overall tensile properties of the blends cured with MF were almost retained even after ageing the samples at 70 °C for 72 h. This significant improvement in the curing torque and the tensile properties of the blends indicates that MF can co-crosslink between NR and CR via the Diels–Alder reaction.
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Feng, Jianguo, Huaying Sheng, Chihong Zhu, Hao Jiang, and Shenglin Ma. "Effect of Adjuvant Magnetic Fields in Radiotherapy on Non-Small-Cell Lung Cancer CellsIn Vitro." BioMed Research International 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/657259.
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Objectives. To explore sensitization and possible mechanisms of adjuvant magnetic fields (MFs) in radiotherapy (RT) of non-small-cell lung cancer.Methods. Human A549 lung adenocarcinoma cells were treated with MF, RT, and combined MF-RT. Colony-forming efficiency was calculated, cell cycle and apoptosis were measured, and changes in cell cycle- and apoptosis-related gene expression were measured by microarray.Results. A 0.5 T, 8 Hz stationary MF showed a duration-dependent inhibitory effect lasting for 1–4 hours. The MF-treated groups had significantly greater cell inhibition than did controls (). Surviving fractions and growth curves derived from colony-forming assay showed that the MF-only, RT-only, and MF-RT groups had inhibited cell growth; the MF-RT group showed a synergetic effect. Microarray of A549 cells exposed for 1 hour to MF showed that 19 cell cycle- and apoptosis-related genes had 2-fold upregulation and 40 genes had 2-fold downregulation. MF significantly arrested cells in G2and M phases, apparently sensitizing the cells to RT.Conclusions. MF may inhibit A549 cells and can increase their sensitivity to RT, possibly by affecting cell cycle- and apoptosis-related signaling pathways.
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Verstovsek, Srdan, Moshe Talpaz, Ellen Ritchie, Martha Wadleigh, Olatoyosi M. Odenike, Catriona Jamieson, Brady Stein, Tomonori Uno, and Ruben A. Mesa. "Phase 1/2, dose-escalation study of oral NS-018 in patients with primary myelofibrosis (PMF), post-polycythemia vera MF (post-PV MF), or post-essential thrombocythemia MF(post-ET MF)." Clinical Lymphoma Myeloma and Leukemia 15 (September 2015): S58. http://dx.doi.org/10.1016/j.clml.2015.07.118.
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Lee, Byung-Hyun, Hyemi Moon, Ka-Won Kang, Byung Soo Kim, and Yong Park. "Clinical Efficacy of Ruxolitinib in Patients with Myelofibrosis: A Nationwide Population-Based Study in Korea." Blood 134, Supplement_1 (November 13, 2019): 2951. http://dx.doi.org/10.1182/blood-2019-122156.
Full textAbstract:
Background: The survival benefit of ruxolitinib, approved for treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera (PV) MF, and post-essential thrombocythemia (ET) MF, has been reported in phase-3 studies. However, population-based comparison data of its efficacy in primary and secondary MF are limited. We analyzed the effects of ruxolitinib in MF patients from a real-world population using National Health Insurance Research Database of Korea. Methods: A total of 1171 patients who diagnosed MF (ICD-10 code D47.4) from January 1, 2011 to December 31, 2017 were identified. Of these, 291 patients previously diagnosed with leukemia, myelodysplastic syndromes, or lymphoma were excluded. The remaining 880 patients (361 patients with primary MF and 519 with secondary MF) were included in the study and divided into 2 group according to ruxolitinib treatment. Patients who received ruxolitinib (n = 276) were matched with those who did not receive ruxolitinib (n = 604) using the 1:1 greedy matching algorithm. Propensity scores were formulated using six variables: age, sex, previous history of arterial/venous thrombosis, red blood cell (RBC) or platelet (PLT) transfusion dependence, and previous hydroxyurea treatment. Overall survival (OS) and occurrence of acute leukemia and thrombotic complications were evaluated using stratified Cox-regression analysis between patients who received ruxolitinib and those who did not. Among the former, we evaluated the risk factors for OS as the primary outcome and occurrence of acute leukemia, thrombotic complications, and RBC and PLT transfusion response as secondary outcomes using multivariable Cox-regression analysis. Primary MF was defined as MF without a prior diagnosis of PV (ICD-10 code D45), ET (ICD-10 code D47.3), and chronic myeloproliferative disease (ICD-10 code D47.1). Secondary MF was defined as MF, which was not included in primary MF. Results: In the Cox-regression analysis for OS, non-ruxolitinib treatment (adjusted hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.22-2.10; P <0.001) was a significant prognostic factor for shorter survival. In the subgroup analysis, non-ruxolitinib treatment was a significant prognostic factor for poor survival in patients with secondary MF (adjusted HR, 1.78; 95% CI, 1.28-2.48; P <0.001). Contrastingly, no significant difference was observed in patients with primary MF (adjusted HR, 1.00; 95% CI, 0.73-1.94; P = 0.478). Ruxolitinib treatment did not affect the occurrence of leukemia and thrombotic complications in patients with both primary and secondary MF. In the multivariable Cox-regression analysis for OS in patients treated with ruxolitinib, older age (adjusted HR, 1.06; P <0.001), RBC (adjusted HR, 2.91; P <0.001), and PLT (adjusted HR, 9.65; P <0.001) transfusion dependence were significantly associated with poor survival, although MF type did not significantly affect survival. In the multivariable analysis for secondary outcomes, PLT transfusion dependency was the only significant risk factor for the occurrence of acute leukemia (adjusted HR, 4.78; P = 0.046) and thrombotic complications (adjusted HR, 14.16; P = 0.002). Older age (adjusted HR, 1.05; P <0.001) and previous hydroxyurea treatment (adjusted HR, 0.41; P = 0.005) significantly affected the response to RBC transfusion. Patients with secondary MF who received ruxolitinib showed a better RBC transfusion response than those with primary MF (adjusted HR, 0.51; P = 0.055). Conclusions: Ruxolitinib treatment led to better survival in patients with MF and might be more beneficial in secondary MF. Moreover, ruxolitinib was more efficacious in reducing RBC transfusion requirement in secondary MF than in primary MF. Further studies on the efficacy of ruxolitinib in other populations are needed. Disclosures No relevant conflicts of interest to declare.