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Sökning: WFRF:(Mehra A.) > (2020-2024)

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1.
  • 2021
  • swepub:Mat__t
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2.
  • 2021
  • swepub:Mat__t
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3.
  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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4.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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5.
  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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8.
  • In ’t Veld, Sjors G.J.G., et al. (författare)
  • Detection and localization of early- and late-stage cancers using platelet RNA
  • 2022
  • Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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9.
  • Mehra, A., et al. (författare)
  • Using highly time-resolved online mass spectrometry to examine biogenic and anthropogenic contributions to organic aerosol in Beijing
  • 2021
  • Ingår i: Faraday Discussions. - 1359-6640. ; 226, s. 382-408
  • Tidskriftsartikel (refereegranskat)abstract
    • Organic aerosols, a major constituent of fine particulate mass in megacities, can be directly emitted or formed from secondary processing of biogenic and anthropogenic volatile organic compound emissions. The complexity of volatile organic compound emission sources, speciation and oxidation pathways leads to uncertainties in the key sources and chemistry leading to formation of organic aerosol in urban areas. Historically, online measurements of organic aerosol composition have been unable to resolve specific markers of volatile organic compound oxidation, while offline analysis of markers focus on a small proportion of organic aerosol and lack the time resolution to carry out detailed statistical analysis required to study the dynamic changes in aerosol sources and chemistry. Here we use data collected as part of the joint UK-China Air Pollution and Human Health (APHH-Beijing) collaboration during a field campaign in urban Beijing in the summer of 2017 alongside laboratory measurements of secondary organic aerosol from oxidation of key aromatic precursors (1,3,5-trimethyl benzene, 1,2,4-trimethyl benzene, propyl benzene, isopropyl benzene and 1-methyl naphthalene) to study the anthropogenic and biogenic contributions to organic aerosol. For the first time in Beijing, this study applies positive matrix factorisation to online measurements of organic aerosol composition from a time-of-flight iodide chemical ionisation mass spectrometer fitted with a filter inlet for gases and aerosols (FIGAERO-ToF-I-CIMS). This approach identifies the real-time variations in sources and oxidation processes influencing aerosol composition at a near-molecular level. We identify eight factors with distinct temporal variability, highlighting episodic differences in OA composition attributed to regional influences and in situ formation. These have average carbon numbers ranging from C-5-C-9 and can be associated with oxidation of anthropogenic aromatic hydrocarbons alongside biogenic emissions of isoprene, alpha -pinene and sesquiterpenes.
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10.
  • Mehra, A., et al. (författare)
  • The persistence of a proxy for cooking emissions in megacities: a kinetic study of the ozonolysis of self-assembled films by simultaneous small and wide angle X-ray scattering (SAXS/WAXS) and Raman microscopy
  • 2021
  • Ingår i: Faraday Discussions. - 1359-6640. ; 226, s. 382-408
  • Tidskriftsartikel (refereegranskat)abstract
    • Cooking emissions account for a significant proportion of the organic aerosols emitted into the urban environment and high pollution events have been linked to an increased organic content on urban particulate matter surfaces. We present a kinetic study on surface coatings of self-assembled (semi-solid) oleic acid-sodium oleate cooking aerosol proxies undergoing ozonolysis. We found clear film thickness-dependent kinetic behaviour and measured the effect of the organic phase on the kinetics for this system. In addition to the thickness-dependent kinetics, we show that significant fractions of unreacted proxy remain after extensive ozone exposure and that this effect scales approximately linearly with film thickness, suggesting that a late-stage inert reaction product may form and inhibit reaction progress - effectively building up an inert crust. We determine this by using a range of simultaneous analytical techniques; most notably Small-Angle X-ray Scattering (SAXS) has been used for the first time to measure the reaction kinetics of films of a wide range of thicknesses from ca. 0.59 to 73 mu m with films <10 mu m thick being of potential atmospheric relevance. These observations have implications for the evolution of particulate matter in the urban environment, potentially extending the atmospheric lifetimes of harmful aerosol components and affecting the local urban air quality and climate.
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11.
  • Priestley, Michael, et al. (författare)
  • Chemical characterisation of benzene oxidation products under high- and low-NOx conditions using chemical ionisation mass spectrometry
  • 2021
  • Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 21:5, s. 3473-3490
  • Tidskriftsartikel (refereegranskat)abstract
    • Aromatic hydrocarbons are a class of volatile organic compounds associated with anthropogenic activity and make up a significant fraction of urban volatile organic compound (VOC) emissions that contribute to the formation of secondary organic aerosol (SOA). Benzene is one of the most abundant species emitted from vehicles, biomass burning and industry. An iodide time-of-flight chemical ionisation mass spectrometer (ToF-CIMS) and nitrate ToF-CIMS were deployed at the Julich Plant Atmosphere Chamber as part of a series of experiments examining benzene oxidation by OH under high- and low-NOx conditions, where a range of organic oxidation products were detected. The nitrate scheme detects many oxidation products with high masses, ranging from intermediate volatile organic compounds (IVOCs) to extremely low volatile organic compounds (ELVOCs), including C-12 dimers. In comparison, very few species with C->= 6 and O-> 8 were detected with the iodide scheme, which detected many more IVOCs and semi-volatile organic compounds (SVOCs) but very few ELVOCs and low volatile organic compounds (LVOCs). A total of 132 and 195 CHO
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12.
  • Akgul, M, et al. (författare)
  • Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey
  • 2021
  • Ingår i: Journal of clinical pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 74:5, s. 291-299
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.
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  • Faulx, M. D., et al. (författare)
  • Obstructive sleep apnea and its management in patients with atrial fibrillation: An International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT) global survey of practicing cardiologists
  • 2022
  • Ingår i: International journal of cardiology: Heart and Vasculature (IJCHA). - : Elsevier BV. - 2352-9067. ; 42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations.
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15.
  • Gupta, Rajeev Kumar, et al. (författare)
  • Biochar influences nitrogen and phosphorus dynamics in two texturally different soils
  • 2024
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitrogen (N) and phosphorus (P) are vital for crop growth. However, most agricultural systems have limited inherent ability to supply N and P to crops. Biochars (BCs) are strongly advocated in agrosystems and are known to improve the availability of N and P in crops through different chemical transformations. Herein, a soil-biochar incubation experiment was carried out to investigate the transformations of N and P in two different textured soils, namely clay loam and loamy sand, on mixing with rice straw biochar (RSB) and acacia wood biochar (ACB) at each level (0, 0.5, and 1.0% w/w). Ammonium N (NH4-N) decreased continuously with the increasing incubation period. The ammonium N content disappeared rapidly in both the soils incubated with biochars compared to the unamended soil. RSB increased the nitrate N (NO3–N) content significantly compared to ACB for the entire study period in both texturally divergent soils. The nitrate N content increased with the enhanced biochar addition rate in clay loam soil until 15 days after incubation; however, it was reduced for the biochar addition rate of 1% compared to 0.5% at 30 and 60 days after incubation in loamy sand soil. With ACB, the net increase in nitrate N content with the biochar addition rate of 1% remained higher than the 0.5% rate for 60 days in clay loam and 30 days in loamy sand soil. The phosphorus content remained consistently higher in both the soils amended with two types of biochars till the completion of the experiment.
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16.
  • Harms, H. J., et al. (författare)
  • Cardiopulmonary transit time : A novel PET imaging biomarker of in vivo physiology for risk stratification of heart transplant recipients
  • 2022
  • Ingår i: Journal of Nuclear Cardiology. - : Springer Nature. - 1071-3581 .- 1532-6551. ; 29, s. 1234-1244
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myocardial blood flow (MBF) can be quantified using dynamic PET studies. These studies also inherently contain tomographic images of early bolus displacement, which can provide cardiopulmonary transit times (CPTT) as measure of cardiopulmonary physiology. The aim of this study was to assess the incremental prognostic value of CPTT in heart transplant (OHT) recipients.Methods: 94 patients (age 56 +/- 16 years, 78% male) undergoing dynamic N-13-ammonia stress/rest studies were included, of which 68 underwent right-heart catherization. A recently validated cardiac allograft vasculopathy (CAV) score based on PET measures of regional perfusion, peak MBF and left-ventricular (LV) ejection fraction (LVEF) was used to identify patients with no, mild or moderate-severe CAV. Time-activity curves of the LV and right ventricular (RV) cavities were obtained and used to calculate the difference between the LV and RV bolus midpoint times, which represents the CPTT and is expressed in heartbeats. Patients were followed for a median of 2.5 years for the occurrence of major adverse cardiac events (MACE), including cardiovascular death, hospitalization for heart failure or acute coronary syndrome, or re-transplantation.Results: CPTT was significantly correlated with cardiac filling pressures (r = .434, P = .0002 and r = .439, P = .0002 for right atrial and pulmonary wedge pressure), cardiac output (r = - .315, P = .01) and LVEF (r = - .513, P < .0001). CPTT was prolonged in patients with MACE (19.4 +/- 6.0 vs 14.5 +/- 3.0 heartbeats, P < .001, N = 15) with CPTT >= 17.75 beats showing optimal discriminatory value in ROC analysis. CPTT >= 17.75 heartbeats was associated with a 10.1-fold increased risk (P < .001) of MACE and a 7.3-fold increased risk (P < .001) after adjusting for PET-CAV, age, sex and time since transplant.Conclusion: Measurements of cardiopulmonary transit time provide incremental risk stratification in OHT recipients and enhance the value of multiparametric dynamic PET imaging, particularly in identifying high-risk patients.
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  • Mehra, Archit, et al. (författare)
  • Evaluation of the chemical composition of gas- and particle-phase products of aromatic oxidation
  • 2020
  • Ingår i: ATMOSPHERIC CHEMISTRY AND PHYSICS. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:16, s. 9783-9803
  • Tidskriftsartikel (refereegranskat)abstract
    • Aromatic volatile organic compounds (VOCs) are key anthropogenic pollutants emitted to the atmosphere and are important for both ozone and secondary organic aerosol (SOA) formation in urban areas. Recent studies have indicated that aromatic hydrocarbons may follow previously unknown oxidation chemistry pathways, including autoxidation that can lead to the formation of highly oxidised products. In this study we evaluate the gas- and particle-phase ions measured by online mass spectrometry during the hydroxyl radical oxidation of substituted C-9-aromatic isomers (1,3,5-trimethylbenzene, 1,2,4-trimethylbenzene, propylbenzene and isopropylbenzene) and a substituted polyaromatic hydrocarbon (1-methylnaphthalene) under low- and medium-NO x conditions. A time-of-flight chemical ionisation mass spectrometer (ToF-CIMS) with iodide-anion ionisation was used with a filter inlet for gases and aerosols (FIGAERO) for the detection of products in the particle phase, while a Vocus protontransfer-reaction mass spectrometer (Vocus-PTR-MS) was used for the detection of products in the gas phase. The signal of product ions observed in the mass spectra were compared for the different precursors and experimental conditions. The majority of mass spectral product signal in both the gas and particle phases comes from ions which are common to all precursors, though signal distributions are distinct for different VOCs. Gas- and particle-phase composition are distinct from one another. Ions corresponding to products contained in the near-explicit gas phase Master Chemical Mechanism (MCM version 3.3.1) are utilised as a benchmark of current scientific understanding, and a comparison of these with observations shows that the MCM is missing a range of highly oxidised products from its mechanism. In the particle phase, the bulk of the product signal from all precursors comes from ring scission ions, a large proportion of which are more oxidised than previously reported and have undergone further oxidation to form highly oxygenated organic molecules (HOMs). Under the perturbation of OH oxidation with increased NOx, the contribution of HOM-ion signals to the particle-phase signal remains elevated for more substituted aromatic precursors. Up to 43% of product signal comes from ring-retaining ions including HOMs; this is most important for the more substituted aromatics. Unique products are a minor component in these systems, and many of the dominant ions have ion formulae concurrent with other systems, highlighting the challenges in utilising marker ions for SOA.
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  • Mehra, Surabhi, et al. (författare)
  • Convergent generation of atypical prions in knockin mouse models of genetic prion disease
  • 2024
  • Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 134:15
  • Tidskriftsartikel (refereegranskat)abstract
    • Most cases of human prion disease arise due to spontaneous misfolding of WT or mutant prion protein, yet recapitulating this event in animal models has proven challenging. It remains unclear whether spontaneous prion generation can occur within the mouse lifespan in the absence of protein overexpression and how disease-causing mutations affect prion strain properties. To address these issues, we generated knockin mice that express the misfolding-prone bank vole prion protein (BVPrP). While mice expressing WT BVPrP (I109 variant) remained free from neurological disease, a subset of mice expressing BVPrP with mutations (D178N or E200K) causing genetic prion disease developed progressive neurological illness. Brains from spontaneously ill knockin mice contained prion disease-specific neuropathological changes as well as atypical protease- resistant BVPrP. Moreover, brain extracts from spontaneously ill D178N- or E200K-mutant BVPrP-knockin mice exhibited prion seeding activity and transmitted disease to mice expressing WT BVPrP. Surprisingly, the properties of the D178N- and E200K-mutant prions appeared identical before and after transmission, suggesting that both mutations guide the formation of a similar atypical prion strain. These findings imply that knockin mice expressing mutant BVPrP spontaneously develop a bona fide prion disease and that mutations causing prion diseases may share a uniform initial mechanism of action.
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  • Xiao, Wenming, et al. (författare)
  • Toward best practice in cancer mutation detection with whole-genome and whole-exome sequencing
  • 2021
  • Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 39:9, s. 1141-1150
  • Tidskriftsartikel (refereegranskat)abstract
    • Recommendations are given on optimal read coverage and selection of calling algorithm to maximize the reproducibility of cancer mutation detection in whole-genome or whole-exome sequencing. Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
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