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Sökning: WFRF:(Kumar Ashish)

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61.
  • Lévy, Romain, et al. (författare)
  • Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
  • 2023
  • Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.
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62.
  • Li, Man, et al. (författare)
  • SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function
  • 2017
  • Ingår i: Journal of the American Society of Nephrology: JASN. - 1533-3450. ; 28:3, s. 981-994
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3.7×10-7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10-8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.
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63.
  • Meena, Ashish Kumar, et al. (författare)
  • Two Lensed Star Candidates at z similar or equal to 4.8 behind the Galaxy Cluster MACS J0647.7+7015
  • 2023
  • Ingår i: Astrophysical Journal Letters. - : Institute of Physics (IOP). - 2041-8205 .- 2041-8213. ; 944:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of two extremely magnified lensed star candidates behind the galaxy cluster MACS J0647.7+015 using recent multiband James Webb Space Telescope (JWST) NIRCam observations. The star candidates are seen in a previously known, z (phot) similar or equal to 4.8 dropout giant arc that straddles the critical curve. The candidates lie near the expected critical curve position, but lack clear counter-images on the other side of it, suggesting these are possibly stars undergoing caustic crossings. We present revised lensing models for the cluster, including multiply imaged galaxies newly identified in the JWST data, and use them to estimate background macro-magnifications of at least greater than or similar to 90 and greater than or similar to 50 at the positions of the two candidates, respectively. With these values, we expect effective, caustic-crossing magnifications of similar to[10(3)-10(5)] for the two star candidates. The spectral energy distributions of the two candidates match well the spectra of B-type stars with best-fit surface temperatures of similar to 10,000 K, and similar to 12,000 K, respectively, and we show that such stars with masses greater than or similar to 20 M (circle dot) and greater than or similar to 50 M (circle dot), respectively, can become sufficiently magnified to be observable. We briefly discuss other alternative explanations and conclude that these objects are likely lensed stars, but also acknowledge that the less-magnified candidate may alternatively reside in a star cluster. These star candidates constitute the second highest-redshift examples to date after Earendel at z (phot) similar or equal to 6.2, establishing further the potential of studying extremely magnified stars at high redshifts with JWST. Planned future observations, including with NIRSpec, will enable a more detailed view of these candidates in the near future.
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64.
  • Meena, Ashish Kumar, et al. (författare)
  • Two Lensed Star Candidates at z ≃ 4.8 behind the Galaxy Cluster MACS J0647.7+7015
  • 2023
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 944:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the discovery of two extremely magnified lensed star candidates behind the galaxy cluster MACS J0647.7+015 using recent multiband James Webb Space Telescope (JWST) NIRCam observations. The star candidates are seen in a previously known, zphot ≃ 4.8 dropout giant arc that straddles the critical curve. The candidates lie near the expected critical curve position, but lack clear counter-images on the other side of it, suggesting these are possibly stars undergoing caustic crossings. We present revised lensing models for the cluster, including multiply imaged galaxies newly identified in the JWST data, and use them to estimate background macro-magnifications of at least ≳90 and ≳50 at the positions of the two candidates, respectively. With these values, we expect effective, caustic-crossing magnifications of ∼[103–105] for the two star candidates. The spectral energy distributions of the two candidates match well the spectra of B-type stars with best-fit surface temperatures of ∼10,000 K, and ∼12,000 K, respectively, and we show that such stars with masses ≳20 M⊙ and ≳50 M⊙, respectively, can become sufficiently magnified to be observable. We briefly discuss other alternative explanations and conclude that these objects are likely lensed stars, but also acknowledge that the less-magnified candidate may alternatively reside in a star cluster. These star candidates constitute the second highest-redshift examples to date after Earendel at zphot ≃ 6.2, establishing further the potential of studying extremely magnified stars at high redshifts with JWST. Planned future observations, including with NIRSpec, will enable a more detailed view of these candidates in the near future.
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65.
  • Merid, Simon Kebede, et al. (författare)
  • Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
  • 2020
  • Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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66.
  • Middeldorp, Christel M., et al. (författare)
  • The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
  • 2019
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
  • Tidskriftsartikel (refereegranskat)abstract
    • The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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67.
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68.
  • Mokdad, Ali H., et al. (författare)
  • Diabetes mellitus and chronic kidney disease in the Eastern Mediterranean Region : findings from the Global Burden of Disease 2015 study
  • 2018
  • Ingår i: International Journal of Public Health. - : SPRINGER BASEL AG. - 1661-8556 .- 1661-8564. ; 63, s. 177-186
  • Tidskriftsartikel (refereegranskat)abstract
    • We used findings from the Global Burden of Disease 2015 study to update our previous publication on the burden of diabetes and chronic kidney disease due to diabetes (CKD-DM) during 1990-2015. We extracted GBD 2015 estimates for prevalence, mortality, and disability-adjusted life years (DALYs) of diabetes (including burden of low vision due to diabetes, neuropathy, and amputations and CKD-DM for 22 countries of the EMR from the GBD visualization tools. In 2015, 135,230 (95% UI 123,034-148,184) individuals died from diabetes and 16,470 (95% UI 13,977-18,961) from CKD-DM, 216 and 179% increases, respectively, compared to 1990. The total number of people with diabetes was 42.3 million (95% UI 38.6-46.4 million) in 2015. DALY rates of diabetes in 2015 were significantly higher than the expected rates based on Socio-demographic Index (SDI). Our study showed a large and increasing burden of diabetes in the region. There is an urgency in dealing with diabetes and its consequences, and these efforts should be at the forefront of health prevention and promotion.
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69.
  • Pathak, Ashish, 1973-, et al. (författare)
  • Incidence and factors associated with surgical site infections in a teaching hospital in Ujjain, India
  • 2014
  • Ingår i: American Journal of Infection Control. - : Elsevier BV. - 0196-6553 .- 1527-3296. ; 42:1, s. E11-E15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Surgical site infections (SSI) are among the most commonly reported health care-associated infections; however, there is a paucity of data on SSI from India. This study aimed to determine the incidence of SSI and explore its associated factors at a teaching hospital in India. Methods: Direct and indirect surveillance methods, based on Centers for Disease Control and Prevention guidelines, were used to define SSI. Patients were followed up for 30 days postsurgery. Prescribing and resistance data were collected. Results: The SSI rate among the 720 patients investigated was 5%. Risk factors for SSI identified were as follows: severity of disease (P = .001), presence of drains (P = .020), history of previous hospitalization (P = .003), preoperative stay (P = .005), wound classification (P < .001), and surgical duration (P < .001). Independent risk factors identified included wound classification (odds ratio - 4.525; P <. 001) and surgical duration (odds ratio = 2.554; P = .015). Most patients (99%) were prescribed antibiotics. Metronidazole (24.5%), ciprofloxacin (11%), and amikacin (9%) were the most commonly prescribed antibiotics. Most commonly isolated bacteria were Staphylococcus aureus (n = 14), of which 34% were methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa (n = 6), which showed resistance to ceftazidime (70%), ciprofloxacin (63%), and gentamicin (57%). Conclusion: Incidence of SSI at the hospital was lower than reported in many low-and middle-income countries, although higher than reported in most high-income countries. Targeted implementation strategies to decrease incidence of preventable SSI are needed to further improve quality and safety of health care in this hospital and similar hospitals elsewhere. 
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70.
  • Patil, Sayali Ashok, et al. (författare)
  • 2D Zinc Oxide - Synthesis, Methodologies, Reaction Mechanism, and Applications
  • 2023
  • Ingår i: Small. - : WILEY-V C H VERLAG GMBH. - 1613-6810 .- 1613-6829. ; 19:14
  • Forskningsöversikt (refereegranskat)abstract
    • Zinc oxide (ZnO) is a thermally stable n-type semiconducting material. ZnO 2D nanosheets have mainly gained substantial attention due to their unique properties, such as direct bandgap and strong excitonic binding energy at room temperature. These are widely utilized in piezotronics, energy storage, photodetectors, light-emitting diodes, solar cells, gas sensors, and photocatalysis. Notably, the chemical properties and performances of ZnO nanosheets largely depend on the nano-structuring that can be regulated and controlled through modulating synthetic strategies. Two synthetic approaches, top-down and bottom-up, are mainly employed for preparing ZnO 2D nanomaterials. However, owing to better results in producing defect-free nanostructures, homogenous chemical composition, etc., the bottom-up approach is extensively used compared to the top-down method for preparing ZnO 2D nanosheets. This review presents a comprehensive study on designing and developing 2D ZnO nanomaterials, followed by accenting its potential applications. To begin with, various synthetic strategies and attributes of ZnO 2D nanosheets are discussed, followed by focusing on methodologies and reaction mechanisms. Then, their deliberation toward batteries, supercapacitors, electronics/optoelectronics, photocatalysis, sensing, and piezoelectronic platforms are further discussed. Finally, the challenges and future opportunities are featured based on its current development.
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