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  • Lind, Lars, et al. (författare)
  • Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
  • 2021
  • Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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  • Fenstermacher, M.E., et al. (författare)
  • DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
  • 2022
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
  • Tidskriftsartikel (refereegranskat)abstract
    • DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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  • Campbell, PJ, et al. (författare)
  • Pan-cancer analysis of whole genomes
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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  • Ramdas, S., et al. (författare)
  • A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
  • 2022
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 109:8, s. 1366-1387
  • Tidskriftsartikel (refereegranskat)abstract
    • A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.
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  • Han, L., et al. (författare)
  • Cell transcriptomic atlas of the non-human primate Macaca fascicularis
  • 2022
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 604:7907, s. 723-731
  • Tidskriftsartikel (refereegranskat)abstract
    • Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell–cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs. 
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  • He, YQ, et al. (författare)
  • A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
  • 2022
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
  • Tidskriftsartikel (refereegranskat)abstract
    • Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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  • Mishra, A, et al. (författare)
  • Diminishing benefits of urban living for children and adolescents' growth and development
  • 2023
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
  • Tidskriftsartikel (refereegranskat)abstract
    • Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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  • Kanai, M, et al. (författare)
  • 2023
  • swepub:Mat__t
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  • Ikuta, K. S., et al. (författare)
  • Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019
  • 2022
  • Ingår i: Lancet. - : Elsevier BV. - 0140-6736. ; 400:10369, s. 2221-2248
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2.5th and 97.5th percentiles across 1000 posterior draws for each quantity of interest. Findings From an estimated 13.7 million (95% UI 10.9-17.1) infection-related deaths in 2019, there were 7.7 million deaths (5.7-10.2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13.6% (10.2-18.1) of all global deaths and 56.2% (52.1-60.1) of all sepsis-related deaths in 2019. Five leading pathogens-Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa-were responsible for 54.9% (52.9-56.9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185-285) per 100 000 population, and lowest in the high-income super-region, with 52.2 deaths (37.4-71.5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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  • Li, XB, et al. (författare)
  • Novel TCF21high pericyte subpopulation promotes colorectal cancer metastasis by remodelling perivascular matrix
  • 2023
  • Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 72:4, s. 710-721
  • Tidskriftsartikel (refereegranskat)abstract
    • Haematogenous dissemination is a prevalent route of colorectal cancer (CRC) metastasis. However, as the gatekeeper of vessels, the role of tumour pericytes (TPCs) in haematogenous metastasis remains largely unknown. Here, we aimed to investigate the heterogeneity of TPCs and their effects on CRC metastasis.DesignTPCs were isolated from patients with CRC with or without liver metastases and analysed by single-cell RNA sequencing (scRNA-seq). Clinical CRC specimens were collected to analyse the association between the molecular profiling of TPCs and CRC metastasis. RNA-sequencing, chromatin immunoprecipitation-sequencing and bisulfite-sequencing were performed to investigate the TCF21-regulated genes and mechanisms underlying integrin α5 onTCF21DNA hypermethylation. Pericyte-conditionalTcf21-knockout mice were constructed to investigate the effects of TCF21 in TPCs on CRC metastasis. Masson staining, atomic force microscopy, second-harmonic generation and two-photon fluorescence microscopy were employed to observe perivascular extracellular matrix (ECM) remodelling.ResultsThirteen TPC subpopulations were identified by scRNA-seq. A novel subset of TCF21highTPCs, termed ‘matrix–pericytes’, was associated with liver metastasis in patients with CRC. TCF21 in TPCs increased perivascular ECM stiffness, collagen rearrangement and basement membrane degradation, establishing a perivascular metastatic microenvironment to instigate colorectal cancer liver metastasis (CRCLM).Tcf21depletion in TPCs mitigated perivascular ECM remodelling and CRCLM, whereas the coinjection of TCF21highTPCs and CRC cells markedly promoted CRCLM. Mechanistically, loss of integrin α5 inhibited the FAK/PI3K/AKT/DNMT1 axis to impairTCF21DNA hypermethylation in TCF21highTPCs.ConclusionThis study uncovers a previously unidentified role of TPCs in haematogenous metastasis and provides a potential diagnostic marker and therapeutic target for CRC metastasis.
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  • Shu, X, et al. (författare)
  • Identification of novel breast cancer susceptibility loci in meta-analyses conducted among Asian and European descendants
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 1217-
  • Tidskriftsartikel (refereegranskat)abstract
    • Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10−8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.
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  • Sliz, E., et al. (författare)
  • Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
  • 2023
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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  • Song, G. S., et al. (författare)
  • Simultaneous determination of various heavy metal and arsenic ions in seafood using functionalized fibrous silica (KCC-1) coated stir bar sorptive extraction prior to inductively coupled plasma mass spectrometry
  • 2023
  • Ingår i: Food Control. - 0956-7135. ; 152
  • Tidskriftsartikel (refereegranskat)abstract
    • Heavy metal ions (HMIs) and arsenic ion with high bioavailability and toxicity in seafood pose a serious threat to human health by food chain. Herein, the functionalized fibrous silica (KCC-1) nanoparticles bearing thiol (-SH) and amine (-NH2) groups respectively were synthesized, characterized, and coated on stir bar sorptive extraction (SBSE) of trace cadmium (Cd), mercury (Hg), lead (Pb), copper (Cu), and arsenic (As) ions simultaneously in seafood prior to inductively coupled plasma mass spectrometry (ICP-MS). The optimal SBSE variables, such as sample pH (3-7), elution composition (1 M HNO3 and 0-4% (m/v) thiourea), and sample volume (5-25 mL), were optimized. The optimal sample pH (6), elution composition (1 M HNO3 and 2% (m/v) thiourea), and sample volume (20 mL), were obtained. The performance of KCC-1-SH SBSE method was superior to the KCC-1-NH2 SBSE method in terms of linearity (0.9981-0.9992), limit of detection (LOD, <0.08 mu g kg-1), limit of quantification (LOQ, <0.60 mu g kg -1), recovery (85.6-106.6%), and repeatability and reusability (no apparent loss in extraction efficiency after 18 times). The maximum residual limits of Cd, Hg, Pb, Cu, and As (V) in mussel, shellfish, and shrimp were all below 1, 1, 1.5, 20, and 76 mg kg-1, respectively. The results demonstrated that the method has a great potential for the daily monitoring of trace HMIs in these seafood products.
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  • Thoma, B, et al. (författare)
  • An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
  • 2020
  • Ingår i: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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  • Thomas, M, et al. (författare)
  • Combining Asian-European Genome-Wide Association Studies of Colorectal Cancer Improves Risk Prediction Across Race and Ethnicity
  • 2023
  • Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expanded PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS were 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1,681-3,651 cases and 8,696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They were significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values<0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
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  • Wu, Mousong, et al. (författare)
  • Improved soil hydrological modeling with the implementation of salt-induced freezing point depression in CoupModel : Model calibration and validation
  • 2020
  • Ingår i: Journal of Hydrology. - : Elsevier B.V.. - 0022-1694 .- 1879-2707.
  • Tidskriftsartikel (refereegranskat)abstract
    • Soil freezing/thawing is an important mechanism to control soil water and heat redistribution in mid-to-high latitudes. Salt in the agricultural soil from mid-to-high latitudes can alter characteristics of soil freezing/thawing cycle and then affect soil thermal and hydrological processes in winter and finally cause salinization in spring. To quantify the impacts of soil salinization on soil water and heat transport in saline soils, we conducted field experiments on soil water and heat dynamics in two typical agricultural regions of northern China with different climate and soil conditions. The coupled soil heat and water model—CoupModel has been extended to account for the dynamic impacts of salt on freezing point depression. The newly-added module improved the representation of soil freezing point depression by significantly improving model performance between simulated and measured soil temperatures, especially around freezing point, with mean error (ME) for the soil temperature at various depths reduced by 16% to 77% for the entire winter period. With a systematic model calibration approach, processes related to energy balance and soil freezing/thawing have been well constrained for both study sites with different characteristics for soil hydrology and energy balance. The model generally showed good performance with respect to soil moisture and temperature for both the calibration and validation periods. Our study has demonstrated a new modeling approach to successfully account for the impacts of salt on soil freezing/thawing and the new module can be a useful tool to address the salinization problems in mid-to-high latitudes with respect to climate change and water management.
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  • Zheng, X. Q., et al. (författare)
  • Greenhouse gas emissions from extractive industries in a globalized era
  • 2023
  • Ingår i: Journal of Environmental Management. - 0301-4797. ; 343
  • Tidskriftsartikel (refereegranskat)abstract
    • The extractive industry consumes vast amounts of energy and is a major contributor to greenhouse gas (GHG) emissions. However, its climatic impacts have not yet been fully accounted for. In this study, we estimated the GHG emissions from extractive activities globally with a focus on China, and assessed the main emission drivers. In addition, we predicted the Chinese extractive industry emissions in the context of global mineral demand and cycling. As of 2020, GHG emissions from the global extractive industry had reached 7.7 billion tons of CO2 equivalents (CO2e), accounting for approximately 15.0% of the global anthropogenic GHG emissions (excluding GHG emissions from land use, land-use change, and forestry activities (LULUCF), with China being the largest emitter, accounting for 3.5% of global emissions. Extractive industry GHG emissions are projected to peak by 2030 or even earlier to achieve low-carbon peak targets. The most critical pathway for reducing GHG emissions in the extractive industry is to control emissions from coal mining. Therefore, reducing methane emissions from mining and washing coal (MWC) should be prioritized.
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  • Zhou, XY, et al. (författare)
  • Mechanisms of Anergic Inflammatory Response in Nasopharyngeal Carcinoma Cells Despite Ubiquitous Constitutive NF-κB Activation
  • 2022
  • Ingår i: Frontiers in cell and developmental biology. - : Frontiers Media SA. - 2296-634X. ; 10, s. 861916-
  • Tidskriftsartikel (refereegranskat)abstract
    • Commensal microbes cross talk with their colonized mucosa. We show that microbes and their cell wall components induce an inflammatory response in cultured human mucosal cells derived from the nonmalignant nasopharyngeal epithelium (NNE) cells in vitro. NNE cells show significant induction of NF-κB with nuclear shuttling and inflammatory gene response when exposed to Gram-positive bacteria (streptococci) or peptidoglycan (PGN), a component of the Gram-positive bacterial cell wall. This response is abrogated in nasopharyngeal carcinoma (NPC)–derived cell lines. The inflammatory response induced by NF-κB signaling was blocked at two levels in the tumor-derived cells. We found that NF-κB was largely trapped in lipid droplets (LDs) in the cytoplasm of the NPC-derived cells, while the increased expression of lysine-specific histone demethylase 1 (LSD1, a repressive nuclear factor) reduces the response mediated by remaining NF-κB at the promoters responding to inflammatory stimuli. This refractory response in NPC cells might be a consequence of long-term exposure to microbes in vivo during carcinogenic progression. It may contribute to the decreased antitumor immune responses in NPC, among others despite heavy T-helper cell infiltration, and thus facilitate tumor progression.
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  • Niemi, MEK, et al. (författare)
  • 2021
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  • Coignard, J, et al. (författare)
  • A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
  • 2021
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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  • Delios, A., et al. (författare)
  • Examining the generalizability of research findings from archival data
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
  • Tidskriftsartikel (refereegranskat)abstract
    • This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples. 
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38.
  • Dennis, J, et al. (författare)
  • Rare germline copy number variants (CNVs) and breast cancer risk
  • 2022
  • Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 65-
  • Tidskriftsartikel (refereegranskat)abstract
    • Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E−18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
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39.
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40.
  • Dong, X., et al. (författare)
  • A novel design of a metal hydride reactor integrated with phase change material for H2 storage
  • 2024
  • Ingår i: Applied Energy. - : Elsevier Ltd. - 0306-2619 .- 1872-9118. ; 367
  • Tidskriftsartikel (refereegranskat)abstract
    • Using metal hydride for hydrogen storage in stationary applications and for transportation is a promising technology due to its advantages of large hydrogen storage capacity, low pressure and low energy consumption. Combining the metal hydride reactor with PCM is expected to recover the heat generated during the hydrogen absorption and use it for hydrogen desorption, thus improving the energy efficiency of the system. This paper proposes a metal hydride reactor integrated with honeycomb fins and PCM to enhance heat transfer. Based on simulations, the results show that the achieved hydrogen storage capacity is 1.326 wt%, the gravimetric and volumetric storage densities are 0.411% and 14.76 kg of H2 per m3, respectively, and the mean saturated rates are 1.222 × 10−3 g s−1 and 0.773 × 10−3 g s−1 for absorption and desorption processes. Compared with the reactor without fins, the mass and volume of the reactor using honeycomb fins are increased, resulting in a decrease in gravimetric and volumetric storage density, but a increase in reaction rate during hydrogen absorption and desorption processes. Based on this structure, we also propose a honeycomb fin reactor filled with sandwich PCM to further accelerate the heat transfer in the reaction process. Compare to the reactor with PCM only filled on the periphery of the honeycomb fins, the hydrogen absorption and desorption times are shortened by about 86.4% and 81.1%, respectively. In addition, different reactor structures are compared using multiple KPIs to provide relevant suggestions for the reactor optimization. The obtained research results can provide a reference for effective thermal management methods in MH storage systems.
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41.
  • Du, J., et al. (författare)
  • A theory-guided deep-learning method for predicting power generation of multi-region photovoltaic plants
  • 2023
  • Ingår i: Engineering applications of artificial intelligence. - : Elsevier Ltd. - 0952-1976 .- 1873-6769. ; 118
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, clean solar energy has aroused wide attention due to its excellent potential for electricity production. A highly accurate prediction of photovoltaic power generation (PVPG) is the basis of the production and transmission of electricity. However, the current works neglect the regional correlation characteristics of PVPG and few studies propose an effective framework by incorporating prior knowledge for more physically reasonable results. In this work, a hybrid deep learning framework is proposed for simultaneously capturing the spatial correlations among different regions and temporal dependency patterns with various importance. The scientific theory and domain knowledge are incorporated into the deep learning model to make the predicted results possess physical reasonability. Subsequently, the theory-guided and attention-based CNN-LSTM (TG-A-CNN-LSTM) is constructed for PVPG prediction. In the training process, data mismatch and boundary constraint are incorporated into the loss function, and the positive constraint is utilized to restrict the output of the model. After receiving the parameters of the neural network, a TG-A-CNN-LSTM model, whose predicted results obey the physical law, is constructed. A real energy system in five regions is used to verify the accuracy of the proposed model. The predicted results indicate that TG-A-CNN-LSTM can achieve higher precision of PVPG prediction than other prediction models, with RMSE being 11.07, MAE being 4.98, and R2 being 0.94, respectively. Moreover, the performance of prediction models with sparse data is tested to illustrate the stability and robustness of TG-A-CNN-LSTM. 
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42.
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43.
  • Escartin, C., et al. (författare)
  • Reactive astrocyte nomenclature, definitions, and future directions
  • 2021
  • Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 24, s. 312-325
  • Tidskriftsartikel (refereegranskat)abstract
    • Reactive astrocytes are astrocytes undergoing morphological, molecular, and functional remodeling in response to injury, disease, or infection of the CNS. Although this remodeling was first described over a century ago, uncertainties and controversies remain regarding the contribution of reactive astrocytes to CNS diseases, repair, and aging. It is also unclear whether fixed categories of reactive astrocytes exist and, if so, how to identify them. We point out the shortcomings of binary divisions of reactive astrocytes into good-vs-bad, neurotoxic-vs-neuroprotective or A1-vs-A2. We advocate, instead, that research on reactive astrocytes include assessment of multiple molecular and functional parameters-preferably in vivo-plus multivariate statistics and determination of impact on pathological hallmarks in relevant models. These guidelines may spur the discovery of astrocyte-based biomarkers as well as astrocyte-targeting therapies that abrogate detrimental actions of reactive astrocytes, potentiate their neuro- and glioprotective actions, and restore or augment their homeostatic, modulatory, and defensive functions. Good-bad binary classifications fail to describe reactive astrocytes in CNS disorders. Here, 81 researchers reach consensus on widespread misconceptions and provide definitions and recommendations for future research on reactive astrocytes.
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44.
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45.
  • Fang, Keyan, et al. (författare)
  • ENSO modulates wildfire activity in China
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • China is a key region for understanding fire activity and the drivers of its variability under strict fire suppression policies. Here, we present a detailed fire occurrence dataset for China, the Wildfire Atlas of China (WFAC; 2005-2018), based on continuous monitoring from multiple satellites and calibrated against field observations. We find that wildfires across China mostly occur in the winter season from January to April and those fire occurrences generally show a decreasing trend after reaching a peak in 2007. Most wildfires (84%) occur in subtropical China, with two distinct clusters in its southwestern and southeastern parts. In southeastern China, wildfires are mainly promoted by low precipitation and high diurnal temperature ranges, the combination of which dries out plant tissue and fuel. In southwestern China, wildfires are mainly promoted by warm conditions that enhance evaporation from litter and dormant plant tissues. We further find a fire occurrence dipole between southwestern and southeastern China that is modulated by the El Nino-Southern Oscillation (ENSO). Fire activity in China and its associations with climate are not well quantified at a local scale. Here, the authors present a detailed fire occurrence dataset for China and find a dipole fire pattern between southwestern and southeastern China that is modulated by the El Nino-Southern Oscillation (ENSO).
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46.
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47.
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48.
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49.
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50.
  • Goyal, A., et al. (författare)
  • Mechanochemical synthesis of stable, quantum-confined CsPbBr3perovskite nanocrystals with blue-green emission and high PLQY
  • 2022
  • Ingår i: JPhys Materials. - : IOP Publishing. - 2515-7639. ; 5:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Cesium lead halides are a family of bright, visible-light emitting materials with near-unity photoluminescence quantum yield (PLQY) in nanocrystals (NCs). The usual way to achieve visible light-emission tunability is by mixing halides, which often leads to phase separation and poor stability. While the NCs should also show size-dependent PL emission, reports on strong quantum confinement in these materials are scarce. Here, we report the synthesis of quantum-confined cesium lead bromide (CsPbBr3) NCs via a facile, environment-friendly, and scalable high-energy mechanochemical synthesis route. The PLQY measured is ∼85%, even after 90 days of synthesis, and the emission wavelength is shifted from green, 520 nm, to blue, 460 nm by quantum confinement in NCs of size 3-5 nm. Micro-PL optical spectroscopy and atomic force microscopy confirm the size tunability of PL on a single-dot scale. Our work demonstrates the potential of mechanochemical synthesis in the medium-scale production of bright luminescent quantum-confined NCs that could be extended to other materials as well.
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