Notes

Revisiting the particular genome-wide importance tolerance for common different GWAS.
Multiple myeloma (MM) is a common hematological malignancy with poorly understood recurrence and relapse mechanisms. Notably, bortezomib resistance leading to relapse makes MM treatment significantly challenging. To clarify the drug resistance mechanism, we employed a quantitative proteomics approach to identify differentially expressed protein candidates implicated in bortezomib-resistant recurrent and relapsed MM (RRMM). Bone marrow aspirates from five patients newly diagnosed with MM (NDMM) were compared with those from five patients diagnosed with bortezomib-resistant RRMM using tandem mass tag-mass spectrometry (TMT-MS). Subcellular localization and functional classification of the differentially expressed proteins were determined by gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and hierarchical clustering analyses. The top candidates identified were validated with parallel reaction monitoring (PRM) analysis using tissue samples from 11 NDMM and 8 RRMM patients, followed by comparison with the NCBI Gene Expression Omnibus (GEO) dataset of 10 MM patients and 10 healthy controls (accession no. GSE80608). Thirty-four differentially expressed proteins in RRMM, including proteinase inhibitor 9 (SERPINB9), were identified by TMT-MS. Subsequent functional enrichment analyses of the identified protein candidates indicated their involvement in regulating cellular metabolism, apoptosis, programmed cell death, lymphocyte-mediated immunity, and defense response pathways in RRMM. The top protein candidate SERPINB9 was confirmed by PRM analysis and western blotting as well as by comparison with an NCBI GEO dataset. We elucidated the proteome landscape of bortezomib-resistant RRMM and identified SERPINB9 as a promising novel therapeutic target. Our results provide a resource for future studies on the mechanism of RRMM.Lithium iron phosphate (LiFePO4) is broadly used as a low-cost cathode material for lithium-ion batteries, but its low ionic and electronic conductivity limit the rate performance. We report herein the synthesis of LiFePO4/graphite composites in which LiFePO4 nanoparticles were grown within a graphite matrix. The graphite matrix is porous, highly conductive, and mechanically robust, giving electrodes outstanding cycle performance and high rate capability. High-mass-loading electrodes with high reversible capacity (160 mA h g-1 under 0.2 C), ultrahigh rate capability (107 mA h g-1 under 60 C), and outstanding cycle performance (>95% reversible capacity retention over 2000 cycles) were achieved, providing a new strategy toward low-cost, long-life, and high-power batteries. Adoption of such material leads to electrodes with volumetric energy density as high as 427 W h L-1 under 60 C, which is of great interest for electric vehicles and other applications.Two series of poly(vinyl amine) (PVAm)-based block copolymers with zwitterionic and thermoresponsive segments were synthesized by the reversible addition-fragmentation chain transfer polymerization. A mixture of the two copolymers, poly(N-acryloyl-l-lysine) (PALysOH) and poly(N-isopropylacrylamide) (PNIPAM), which have the same cationic PVAm chain but different shell-forming segments, were used to prepare mixed polyplex micelles with DNA. Both PVAm-b-PALysOH and PVAm-b-PNIPAM showed low cytotoxicity, with characteristic assembled structures and stimuli-responsive properties. The cationic PVAm segment in both block copolymers showed site-specific interactions with DNA, which were evaluated by dynamic light scattering, zeta potential, circular dichroism, agarose gel electrophoresis, atomic force microscopy, and transmission electron microscopy measurements. The PVAm-b-PNIPAM/DNA polyplexes showed the characteristic temperature-induced formation of assembled structures in which the polyplex size, surface charge, chiroptical property of DNA, and polymer-DNA binding were governed by the nitrogen/phosphate (N/P) ratio. The DNA binding strength and colloidal stability of the PVAm-b-PALysOH/DNA polyplexes could be tuned by introducing an appropriate amount of zwitterionic PALysOH functionality, while maintaining the polyplex size, surface charge, and chiroptical property, regardless of the N/P ratio. The mixed polyplex micelles showed temperature-induced stability originating from the hydrophobic (dehydrated) PNIPAM chains upon heating, and remarkable stability under salty conditions owing to the presence of the zwitterionic PALysOH chain on the polyplex surface.Null.Null.The objective of this study was to find out the association of ABO blood groups with the severity and outcome of corona virus disease 2019 (COVID-19) in children. selleck kinase inhibitor It included all laboratory-confirmed cases of COVID-19 and post-COVID multisystem inflammatory syndrome in children (MIS-C)/ Kawasaki disease (KD) like illness, admitted from March to September, 2020 to The Children's Hospital, Lahore. Out of 66 children, 45 (68.2%) were COVID-19 and 21 (31.8%) MIS-C/KD temporally associated with SARS-C0V-2. The mean age was 7.9 ± 4.2 years. Majority of children had mild to moderate illness 38 (57.6%), while 23 (34.8%) had severe or critical disease. Among all patients, 24 (36.4%) had some underlying comorbidity. Blood group A was significantly associated with severe and critical disease (p=0.030). COVID-19 in children had generally a good outcome, but children with blood group A were more susceptible to severe/critical disease. Key Words Coronavirus disease 2019, ABO blood groups, Children, Severity, Outcome.ABSTARCT Four hundred and fifty-three SARS CoV-2 antibodies tests were conducted using Roche Elecsys® Anti SARS CoV-2 kits (detecting total antibodies) between June 13 to July 8, 2020 (25 days) on Cobas® e411 automatic analyser, based on electrochemiluminescence immunoassay (ECLIA) principle. Samples were collected from walk-in patients at our facility. Among them, 2 (0.4%) were found equivocal, 289 (63.8%) were found reactive, while 162 (35.8%) were found non-reactive. Moreover, reactive (symptomatic) cases were 262 (57.8%), reactive (asymptomatic) were 27 (6.0%), non-reactive (symptomatic) were 34 (7.5%), while non-reactive (asymptomatic) were 128 (28.3%). Most common symptom was fever, found in 262 (87.9%) individuals, followed by dry cough 146 (49.0%). Most number of reactive cases, i.e. 110 (42.6%) were those who got themselves tested between 15-21 days after onset of first symptom. Key Words COVID-19, Coronavirus, Antibodies testing.
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