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Sökning: WFRF:(Salvatore Stefano)

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2.
  • Soffitta, Paolo, et al. (författare)
  • XIPE : the X-ray imaging polarimetry explorer
  • 2013
  • Ingår i: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 36:3, s. 523-567
  • Tidskriftsartikel (refereegranskat)abstract
    • X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017. The proposal was, unfortunately, not selected. To be compliant with this schedule, we designed the payload mostly with existing items. The XIPE proposal takes advantage of the completed phase A of POLARIX for an ASI small mission program that was cancelled, but is different in many aspects: the detectors, the presence of a solar flare polarimeter and photometer and the use of a light platform derived by a mass production for a cluster of satellites. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus. Two additional GPDs filled with a 3-bar Ar-DME mixture always face the Sun to detect polarization from solar flares. The Minimum Detectable Polarization of a 1 mCrab source reaches 14 % in the 2-10 keV band in 10(5) s for pointed observations, and 0.6 % for an X10 class solar flare in the 15-35 keV energy band. The imaging capability is 24 arcsec Half Energy Width (HEW) in a Field of View of 14.7 arcmin x 14.7 arcmin. The spectral resolution is 20 % at 6 keV and the time resolution is 8 mu s. The imaging capabilities of the JET-X optics and of the GPD have been demonstrated by a recent calibration campaign at PANTER X-ray test facility of the Max-Planck-Institut fur extraterrestrische Physik (MPE, Germany). XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil). The data policy is organized with a Core Program that comprises three months of Science Verification Phase and 25 % of net observing time in the following 2 years. A competitive Guest Observer program covers the remaining 75 % of the net observing time.
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3.
  • Grasso, Silvia, et al. (författare)
  • The scaffold protein p140Cap limits ERBB2-mediated breast cancer progression interfering with Rac GTPase-controlled circuitries
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The docking protein p140Cap negatively regulates tumour cell features. Its relevance on breast cancer patient survival, as well as its ability to counteract relevant cancer signalling pathways, are not fully understood. Here we report that in patients with ERBB2-amplified breast cancer, a p140Cap-positive status associates with a significantly lower probability of developing a distant event, and a clear difference in survival. p140Cap dampens ERBB2-positive tumour cell progression, impairing tumour onset and growth in the NeuT mouse model, and counteracting epithelial mesenchymal transition, resulting in decreased metastasis formation. One major mechanism is the ability of p140Cap to interfere with ERBB2-dependent activation of Rac GTPase-controlled circuitries. Our findings point to a specific role of p140Cap in curbing the aggressiveness of ERBB2-amplified breast cancers and suggest that, due to its ability to impinge on specific molecular pathways, p140Cap may represent a predictive biomarker of response to targeted anti-ERBB2 therapies.
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4.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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5.
  • Landi, Antonio, et al. (författare)
  • Transient vs In-Hospital Persistent AcuteKidney Injury in Patients With Acute Coronary Syndrome.
  • 2023
  • Ingår i: JACC. Cardiovascular interventions. - : Elsevier BV. - 1876-7605 .- 1936-8798. ; 16:2, s. 193-205
  • Tidskriftsartikel (refereegranskat)abstract
    • The occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ.The aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS.In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding.Persistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95%CI: 1.48-3.64; P< 0.001; NACE: adjusted HR: 2.29; 95%CI: 1.48-3.52; P< 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95%CI: 2.03-5.82; P< 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria.Among patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627).
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6.
  • Stefania, Grimaudo, et al. (författare)
  • PCSK9 rs11591147 R46L Loss-of-Function Variant Protects Against Liver Damage in Individuals with NAFLD.
  • 2021
  • Ingår i: Liver international : official journal of the International Association for the Study of the Liver. - : Wiley. - 1478-3231. ; 41:2, s. 321-332
  • Tidskriftsartikel (refereegranskat)abstract
    • The proproteinconvertasesubtilisin/kexin type 9(PCSK9) plays a key role in cholesterol homeostasis, and its inhibition represents an effective therapy to lower LDL-C levels. In this study, we examined the impact of the PCSK9 rs11591147 loss-of-function (LOF) variant on liver damage in a multicenter collection of patients at risk of nonalcoholic steatohepatitis (NASH), in clinical samples and experimental models.We considered 1,874 consecutive individuals at risk of NASH as determined by histology. The SNP rs11591147, encoding for the p.R46L variant of PCSK9,was genotyped by TaqMan assays. We also evaluated 1)PCSK9 mRNA hepatic expression in human liver, and 2)the impact of a NASH-inducing diet in mice with hepatic overexpression of human PCSK9.Carriers of PCSK9 rs11591147 had lower circulating LDL-C levels and were protected against NAFLD (OR0.42; 95%C.I0.22-0.81; P=0.01), NASH (OR0.48;95%C.I.0.26-0.87;P=0.01)and more severe fibrosis (OR0.55; 95%C.I.0.32-0.94; P=0.03) independently of clinical, metabolic and genetic confounding factors. PCSK9 hepatic expression was directly correlated with liver steatosis(P=0.03). Finally, liver-specific overexpression of human PCSK9 in male mice drives NAFLD and fibrosis upon a dietary challenge.In individuals at risk of NASH, PCSK9 was induced with hepatic fat accumulation and PCSK9 rs11591147 LOF variant was protective against liver steatosis, NASH and fibrosis, suggesting PCSK9 inhibition may be a new therapeutic strategy to treat NASH.
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7.
  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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8.
  • Abelev, Betty, et al. (författare)
  • Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
  • 2013
  • Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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9.
  • Abelev, Betty, et al. (författare)
  • Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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10.
  • Abelev, Betty, et al. (författare)
  • Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
  • 2012
  • Ingår i: Journal of High Energy Physics. - 1029-8479. ; :7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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12.
  • Baselli, Guido A, et al. (författare)
  • Rare ATG7 genetic variants predispose patients to severe fatty liver disease.
  • 2022
  • Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 77:3, s. 596-606
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci contributing to severe NAFLD by examining rare variants.We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n=301) and examined the enrichment of likely pathogenic rare variants vs. the general population, followed by validation at gene level.In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; OR 5.26, 2.1-12.6; p=0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9, 1.9-612; p=0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30, 1.1-7.5 and OR 12.30, 2.6-36, respectively; p<0.001 for both). The low-frequency loss-of-function p.V471A variant (rs36117895 T>C) was also associated with severe NAFLD in the clinical cohort (OR=1.7, 1.2-2.5; p=0.003), predisposed to hepatocellular ballooning (p=0.007) evolving to fibrosis in a Liver biopsy cohort (n=2268), and was associated with liver injury in the UK Biobank (AST levels, p<0.001), with a larger effect in severely obese individuals where it was linked to hepatocellular carcinoma (p=0.009). ATG7 protein localized to periportal hepatocytes, more so in the presence of ballooning. In the Liver Transcriptomic cohort (n=125) ATG7 expression correlated with suppression of the TNFα pathway, which was conversely upregulated in p.V471A carriers.We identified rare and low-frequency ATG7 loss-of-function variants as modifiers of NAFLD progression by impairing autophagy and facilitating ballooning and inflammation.•We found that rare mutations in a gene called autophagy related (ATG7) increase the risk of developing severe liver disease in individuals with dysmetabolism. •These mutations cause an alteration in protein function and impairment of self-renewal of cellular content, leading to liver damage and inflammation.
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13.
  • Bianco, Cristina, et al. (författare)
  • Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores.
  • 2021
  • Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 74:4, s. 775-782
  • Tidskriftsartikel (refereegranskat)abstract
    • Hepatocellular carcinoma (HCC) risk stratification in individuals with dysmetabolism is a major unmet need. Genetic predisposition contributes to non-alcoholic fatty liver disease (NAFLD). We aimed to exploit robust polygenic risk scores (PRS) that can be evaluated in the clinic to gain insight into the causal relationship between NAFLD and HCC, and to improve HCC risk stratification.We examined at-risk individuals (NAFLD cohort, n=2,566; 226 with HCC; and a replication cohort of 427 German patients with NAFLD) and the general population (UK Biobank [UKBB] cohort, n=364,048; 202 with HCC). Variants in PNPLA3-TM6SF2-GCKR-MBOAT7 were combined in a hepatic fat PRS (PRS-HFC), and then adjusted for HSD17B13 (PRS-5).In the NAFLD cohort, the adjusted impact of genetic risk variants on HCC was proportional to the predisposition to fatty liver (p=0.002) with some heterogeneity in the effect. PRS predicted HCC more robustly than single variants (p<10-13). The association between PRS and HCC was mainly mediated through severe fibrosis, but was independent of fibrosis in clinically relevant subgroups, and was also observed in those without severe fibrosis (p<0.05). In the UKBB cohort, PRS predicted HCC independently of classical risk factors and cirrhosis (p<10-7). In the NAFLD cohort, we identified high PRS cut-offs (≥0.532/0.495 for PRS-HFC/PRS-5) that in the UKBB cohort detected HCC with ∼90% specificity but limited sensitivity; PRS predicted HCC both in individuals with (p<10-5) and without cirrhosis (p<0.05).Our results are consistent with a causal relationship between hepatic fat and HCC. PRS improved the accuracy to detect HCC and may help stratify HCC risk in individuals with dysmetabolism, including those without severe liver fibrosis. Further studies are needed to validate our findings.
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16.
  • Blösch, Günter, et al. (författare)
  • Twenty-three unsolved problems in hydrology (UPH) - a community perspective
  • 2019
  • Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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17.
  • Brito-Zerón, Pilar, et al. (författare)
  • Early diagnosis of primary Sjögren's syndrome: EULAR-SS task force clinical recommendations.
  • 2016
  • Ingår i: Expert Review of Clinical Immunology. - 1744-8409. ; 12:2, s. 137-156
  • Forskningsöversikt (refereegranskat)abstract
    • Sjögren's syndrome (SjS) is a systemic autoimmune disease that mainly affects the exocrine glands, leading to generalized mucosal dryness. However, primary SjS may initially present with non-sicca (systemic) manifestations. When these features appear before the onset of an overt sicca syndrome, we may talk of an underlying 'occult' SjS. The European League Against Rheumatism (EULAR) has promoted and supported an international collaborative study group (EULAR-SS Task Force) aimed at developing consensual recommendations to provide a homogeneous approach to the patient with primary SjS presenting with systemic involvement. This review summarizes the key factors that should be taken into account in the diagnostic approach in a patient with suspected SjS according to the main clinical patterns of presentation, and is especially focused on organ-specific systemic disease presentations, including a consensus set of recommendations in order to reach an early diagnosis. Close collaboration with the different specialties involved through a comprehensive multidisciplinary approach is essential in SjS patients presenting with systemic involvements.
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18.
  • Calabrese, Salvatore, et al. (författare)
  • Energetic scaling in microbial growth
  • 2021
  • 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. ; 118:47
  • Tidskriftsartikel (refereegranskat)abstract
    • Microbial growth is a clear example of organization and structure arising in nonequilibrium conditions. Due to the complexity of the microbial metabolic network, elucidating the fundamental principles governing microbial growth remains a challenge. Here, we present a systematic analysis of microbial growth thermodynamics, leveraging an extensive dataset on energy-limited monoculture growth. A consistent thermodynamic framework based on reaction stoichiometry allows us to quantify how much of the available energy microbes can efficiently convert into new biomass while dissipating the remaining energy into the environment and producing entropy. We show that dissipation mechanisms can be linked to the electron donor uptake rate, a fact leading to the central result that the thermodynamic efficiency is related to the electron donor uptake rate by the scaling law eta proportional to M-1/2 ED and to the growth yield by eta proportional to Y4/5. These findings allow us to rederive the Pirt equation from a thermodynamic perspective, providing a means to compute its coefficients, as well as a deeper understanding of the relationship between growth rate and yield. Our results provide rather general insights into the relation between mass and energy conversion in microbial growth with potentially wide application, especially in ecology and biotechnology.
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19.
  • Chakrawal, Arjun, 1992-, et al. (författare)
  • Interacting Bioenergetic and Stoichiometric Controls on Microbial Growth
  • 2022
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Microorganisms function as open systems that exchange matter and energy with their surrounding environment. Even though mass (carbon and nutrients) and energy exchanges are tightly linked, there is a lack of integrated approaches that combine these fluxes and explore how they jointly impact microbial growth. Such links are essential to predicting how the growth rate of microorganisms varies, especially when the stoichiometry of carbon- (C) and nitrogen (N)-uptake is not balanced. Here, we present a theoretical framework to quantify the microbial growth rate for conditions of C-, N-, and energy-(co-) limitations. We use this framework to show how the C:N ratio and the degree of reduction of the organic matter (OM), which is also the electron donor, availability of electron acceptors (EAs), and the different sources of N together control the microbial growth rate under C, nutrient, and energy-limited conditions. We show that the growth rate peaks at intermediate values of the degree of reduction of OM under oxic and C-limited conditions, but not under N-limited conditions. Under oxic conditions and with N-poor OM, the growth rate is higher when the inorganic N (NInorg)-source is ammonium compared to nitrate due to the additional energetic cost involved in nitrate reduction. Under anoxic conditions, when nitrate is both EA and NInorg-source, the growth rates of denitrifiers and microbes performing the dissimilatory nitrate reduction to ammonia (DNRA) are determined by both OM degree of reduction and nitrate-availability. Consistent with the data, DNRA is predicted to foster growth under extreme nitrate-limitation and with a reduced OM, whereas denitrifiers are favored as nitrate becomes more available and in the presence of oxidized OM. Furthermore, the growth rate is reduced when catabolism is coupled to low energy yielding EAs (e.g., sulfate) because of the low carbon use efficiency (CUE). However, the low CUE also decreases the nutrient demand for growth, thereby reducing N-limitation. We conclude that bioenergetics provides a useful conceptual framework for explaining growth rates under different metabolisms and multiple resource-limitations.
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20.
  • Chinazzo, Giorgia, et al. (författare)
  • Quality criteria for multi-domain studies in the indoor environment: Critical review towards research guidelines and recommendations
  • 2022
  • Ingår i: Building and Environment. - : Elsevier BV. - 0360-1323. ; 226
  • Forskningsöversikt (refereegranskat)abstract
    • The perception, physiology, behavior, and performance of building occupants are influenced by multi-domain exposures: the simultaneous presence of multiple environmental stimuli, i.e., visual, thermal, acoustic, and air quality. Despite being extensive, the literature on multi-domain exposures presents heterogeneous methodological approaches and inconsistent study reporting, which hinder direct comparison between studies and meta-analyses. Therefore, in addition to carrying out more multi-domain studies, such investigations need to be designed, conducted, and documented in a systematic and transparent way. With the goal to facilitate and support future multi-domain studies and their meta-analyses, this work provides (1) a range of criteria for multi-domain study design and reporting (i.e., defined as quality criteria), and (2) a critical review of the multi-domain literature based on the described criteria, which can serve as guidelines and recommendations for future studies on the topic. The identified quality criteria encompass study set-up, study deployment and analysis, and study outcome, stressing the importance of adopting a consistent terminology and result reporting style. The developed critical review highlights several shortcomings in the design, deployment, and documentation of multi-domain studies, emphasizing the need for quality improvements of future multi-domain research. The ultimate goal of this work is to consolidate our knowledge on multi-domain exposures for its integration into regulatory resources and guidelines, which are currently dominated by single-domain knowledge.
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21.
  • Damschen, Marvin, et al. (författare)
  • Business Model
  • 2021
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The objective of X2Rail-3 (Grant Agreement No. 826141) Task 7.5 is an analysis of the businessmodel for the Virtually Coupled Train Sets (VCTS) concept. The VCTS concept was developed inX2Rail-3 Work Packages 6 and 7. The MOVINGRAIL project, which was the only project fundedunder the IP2 open call S2R-OC-IP2-01-2018, provided inputs concerning the cost effectiveness,application roadmap as well as business risks and overall market potential of VCTS. Thisdeliverable (D7.5) is the outcome of Task 7.5. First, it provides an analysis of the inputs providedby MOVINGRAIL, putting them in context with previous X2Rail-3 work. Then, taking theconclusions of the analysis into account, two different application cases for VCTS are presented.Strategies to implement the application cases are detailed, including a vision for implementingVCTS within the RCA and OCORA reference architectures. Finally, the business case of VCTS iscompared against business objectives identified within the LinX4Rail project.The application cases for VCTS presented in this deliverable are standalone VCTS and ETCS-based VCTS. Standalone VCTS is an application of VCTS that focuses on low-traffic lines thatare today using Class B signalling systems that cannot be upgraded to ETCS in a cost-effectiveway. In summary, it is a low-cost onboard train protection system which has the objectives ofproviding an economically interesting upgrade path for Class B systems and raising the maturityof the underlying technology required for VCTS, thus, fostering the wide-scale introduction. ETCS-based VCTS is an application of VCTS that focuses on high-traffic lines and bases on ETCS Level2 or Level 3. ETCS-based VCTS is the actual goal of the VCTS concept and has the mainobjectives of reducing headway and improving flexibility of operation in order to increase linecapacity and provide the technical basis for innovative business models.For each application case, a migration strategy is presented, detailing the non-technical andtechnical steps required for implementing and on-site testing a first complete demonstrator withina period of three to five years. The migration strategies provide details for train protection, trafficmanagement, automatic train operation, on-board train integrity, communication and VCTS (on-board and trackside, if applicable) sub-systems. As detailed in Deliverable 7.4 “Impact Analysis”which was prepared in parallel to this deliverable, the introduction of VCTS does not change thefundamental principles of any of the existing sub-systems, i.e., a full rework is not required.Beyond the migration strategies, the vision of implementing ETCS-based VCTS within the RCAand OCORA reference architectures is presented, which would imply software changes only and,thus, simplify the migration considerably. Finally, the impact of VCTS is compared against thebusiness objectives identified in the LinX4Rail project. Taking the presented migration strategiesand MOVINGRAIL input into account, it is shown that VCTS is in line with the RUs’, IMs’ andsuppliers’ business objectives.Ultimately, VCTS is an innovative concept that can raise scepticism by operators and the generalpublic. Its safety can be achieved within the near future, but this needs to be communicated clearlyto foster the acceptance of VCTS. Only then, VCTS cannot only improve current railway operationwith increased capacity, reliability and lower operational costs, but even provide the basis for novelbusiness models that benefit from the increased flexibility.
  •  
22.
  • De Vincentis, Antonio, et al. (författare)
  • Genetic variants in the MTHFR are not associated with fatty liver disease.
  • 2020
  • Ingår i: Liver international : official journal of the International Association for the Study of the Liver. - : Wiley. - 1478-3231. ; 40:8, s. 1934-1940
  • Tidskriftsartikel (refereegranskat)abstract
    • The common missense sequence variants of methylenetetrahydrofolate-reductase (MTHFR), rs1801131 (c.A1298C) and rs1801133 (c.C677T), favor the development of hyperhomocysteinemia and diminished DNA methylation. Previous studies, carried out in small series and with suboptimal characterization of the hepatic phenotype, tested the association of these genetic variants with fatty liver disease (FLD), with conflicting results. Here, we assessed the association of rs1801131 and rs1801133 with hepatic phenotype in the Liver Biopsy Cross-Sectional Cohort, a large cohort (n=1375 from Italy and 411 from Finland) of European individuals with suspect FLD associated with dysmetabolism. A total of 1786 subjects were analyzed by ordinal regression analyses. The rs1801131 and the rs1801133 variants were not associated with steatosis, inflammation, ballooning, or fibrosis. The present study suggests that changes in folate and methionine metabolism resulting from these 2 variants are not associated with a clinically significant impact on FLD in Europeans.
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23.
  • Di Stefano, Omar, et al. (författare)
  • Interaction of Mechanical Oscillators Mediated by the Exchange of Virtual Photon Pairs
  • 2019
  • Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 122:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Two close parallel mirrors attract due to a small force (Casimir effect) originating from the quantum vacuum fluctuations of the electromagnetic field. These vacuum fluctuations can also induce motional forces exerted upon one mirror when the other one moves. Here, we consider an optomechanical system consisting of two vibrating mirrors constituting an optical resonator. We find that motional forces can determine noticeable coupling rates between the two spatially separated vibrating mirrors. We show that, by tuning the two mechanical oscillators into resonance, energy is exchanged between them at the quantum level. This coherent motional coupling is enabled by the exchange of virtual photon pairs, originating from the dynamical Casimir effect. The process proposed here shows that the electromagnetic quantum vacuum is able to transfer mechanical energy somewhat like an ordinary fluid. We show that this system can also operate as a mechanical parametric down-converter even at very weak excitations. These results demonstrate that vacuum-induced motional forces open up new possibilities for the development of optomechanical quantum technologies.
  •  
24.
  • Di Stefano, Omar, et al. (författare)
  • Photodetection probability in quantum systems with arbitrarily strong light-matter interaction
  • 2018
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Cavity-QED systems have recently reached a regime where the light-matter interaction strength amounts to a non-negligible fraction of the resonance frequencies of the bare subsystems. In this regime, it is known that the usual normal-order correlation functions for the cavity-photon operators fail to describe both the rate and the statistics of emitted photons. Following Glauber's original approach, we derive a simple and general quantum theory of photodetection, valid for arbitrary lightmatter interaction strengths. Our derivation uses Fermi's golden rule, together with an expansion of system operators in the eigenbasis of the interacting light-matter system, to arrive at the correct photodetection probabilities. We consider both narrow-and wide-band photodetectors. Our description is also valid for point-like detectors placed inside the optical cavity. As an application, we propose a gedanken experiment confirming the virtual nature of the bare excitations that enrich the ground state of the quantum Rabi model.
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25.
  • Donati, Benedetta, et al. (författare)
  • Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease.
  • 2017
  • Ingår i: Cancer medicine. - : Wiley. - 2045-7634. ; 6:8, s. 1930-1940
  • Tidskriftsartikel (refereegranskat)abstract
    • In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD-HCC. In 40 patients with NAFLD-HCC, 45 with NAFLD-cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT-PCR and hTERT coding regions and intron-exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD-PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequency <0.001) was evaluated by Burden test. Functional consequences were estimated in silico and by over-expressing protein variants in HEK-293 cells. We found that telomere length was reduced in individuals with NAFLD-HCC versus those with cirrhosis (P=0.048) and healthy controls (P=0.0006), independently of age and sex. We detected an enrichment of hTERT mutations in NAFLD-HCC, that was confirmed when we further considered a larger cohort of NAFLD-PLC, and was more marked in female patients (P=0.03). No mutations were found in cirrhosis and local controls, and only one in 503 healthy Europeans from the 1000 Genomes Project (allelic frequency=0.025 vs. <0.001; P=0.0005). Mutations with predicted functional impact, including the frameshift Glu113Argfs*79 and missense Glu668Asp, cosegregated with liver disease in two families. Three patients carried missense mutations (Ala67Val in homozygosity, Pro193Leu and His296Pro in heterozygosity) in the N-terminal template-binding domain (P=0.037 for specific enrichment). Besides Glu668Asp, the Ala67Val variant resulted in reduced intracellular protein levels. In conclusion, we detected an association between shorter telomeres in peripheral blood and rare germline hTERT mutations and NAFLD-HCC.
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26.
  • Donati, Benedetta, et al. (författare)
  • The rs2294918 E434K variant modulates PNPLA3 expression and liver damage.
  • 2016
  • Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 63:3, s. 787-798
  • Tidskriftsartikel (refereegranskat)abstract
    • The PNPLA3 rs738409 polymorphism (I148M) is a major determinant of hepatic fat and predisposes to the full spectrum of liver damage in nonalcoholic fatty liver disease (NAFLD). Aim of this study was to evaluate whether additional PNPLA3 coding variants contribute to NAFLD susceptibility, first in individuals with contrasting phenotypes (with early onset NAFLD vs. very low aminotransferases), and then in a large validation cohort. Rare PNPLA3 variants were not detected by sequencing coding regions and intron-exon boundaries either in 142 patients with early-onset NAFLD, nor in 100 healthy individuals with ALT <22/20 IU/ml. Besides rs738409 I148M, the rs2294918 G>A polymorphism (E434K sequence variant) was over-represented in NAFLD (adjusted p=0.01). In 1447 subjects with and without NAFLD, the 148M-434E (p<0.0001), but not the 148M-434K haplotype (p>0.9), was associated with histological NAFLD and steatohepatitis. Both the I148M (p=0.0002) and E434K variants (p=0.044) were associated with serum ALT levels, by interacting each other, in that the 434K hampered the association with liver damage of the 148M allele (p=0.006). The E434K variant did not affect PNPLA3 enzymatic activity, but carriers of the rs2294918 A allele (434K) displayed lower hepatic PNPLA3 mRNA and protein levels (p<0.05).
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27.
  • Dongiovanni, Paola, et al. (författare)
  • PCSK7 gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients.
  • 2019
  • Ingår i: Journal of lipid research. - 1539-7262. ; 60:June, s. 1144-1153
  • Tidskriftsartikel (refereegranskat)abstract
    • Dyslipidemia and altered iron metabolism are typical features of non-alcoholic fatty liver disease (NAFLD). Proprotein Convertase Subtilisin/Kexin Type 7 (PCSK7) gene variation has been associated with circulating lipids and liver damage during iron overload. Aim of this study was to examine the impact of the PCSK7 rs236918 variant on NAFLD-related traits in 1,801 individuals from the Liver Biopsy Cohort (LBC), 500,000 from the UK Biobank Cohort (UKBBC), and 4,580 from the Dallas Heart Study (DHS). The minor PCSK7 rs236918 C allele was associated with higher triglycerides, aminotransferases and hepatic inflammation in the LBC (p<0.05) and with hypercholesterolemia and liver disease in the UKBBC. In the DHS, PCSK7 missense variants were associated with circulating lipids. PCSK7 was expressed in hepatocytes and its hepatic expression correlated with that of lipogenic genes (p<0.05). The rs236918 C allele was associated with upregulation of a new 'intra-PCSK7' lnc-RNA predicted to interact with the protein, higher hepatic and circulating PCSK7 protein (p<0.01), and the latter correlated with triglycerides (p=0.04). In HepG2, PCSK7 deletion reduced lipogenesis, fat accumulation, inflammation, TGFB pathway activation and fibrogenesis. In conclusion, PCSK7 gene variation is associated with dyslipidemia and more severe liver disease in high risk individuals, likely by modulating PCSK7 expression/activity.
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28.
  • Dongiovanni, Paola, et al. (författare)
  • Protein phosphatase 1 regulatory subunit 3B gene variation protects against hepatic fat accumulation and fibrosis in individuals at high risk of nonalcoholic fatty liver disease.
  • 2018
  • Ingår i: Hepatology communications. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 2:6, s. 666-675
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver damage and has a strong genetic component. The rs4841132 G>A variant, modulating the expression of protein phosphatase 1 regulatory subunit 3B (PPP1R3B), which is involved in glycogen synthesis, has been reported to reduce the risk of NAFLD but at the same time may favor liver disease by facilitating glycogen accumulation. The aim of this study was to assess the impact of rs4841132 on development of histologic steatosis and fibrosis in 1,388 European individuals in a liver biopsy cohort, on NAFLD hepatocellular carcinoma in a cross-sectional Italian cohort (n = 132 cases), and on liver disease at the population level in the United Kingdom Biobank cohort. We investigated the underlying mechanism by examining the impact of the variant on gene expression profiles. In the liver biopsy cohort, the rs4841132 minor A allele was associated with protection against steatosis (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.42-0.95; P = 0.03) and clinically significant fibrosis (OR, 0.35; 95% CI, 0.14-0.87; P = 0.02) and with reduced circulating cholesterol (P = 0.02). This translated into protection against hepatocellular carcinoma development (OR, 0.22; 95% CI, 0.07-0.70; P = 0.01). At the population level, the rs4841132 variation was not associated with nonalcoholic or nonviral diseases of the liver but was associated with lower cholesterol (P = 1.7 × 10-8). In individuals with obesity, the A allele protecting against steatosis was associated with increased PPP1R3B messenger RNA expression and activation of lipid oxidation and with down-regulation of pathways related to lipid metabolism, inflammation, and cell cycle. Conclusion: The rs4841132 A allele is associated with protection against hepatic steatosis and fibrosis in individuals at high risk of NAFLD but not in the general population and against dyslipidemia. The mechanism may be related to modulation of PPP1R3B expression and hepatic lipid metabolism. (Hepatology Communications 2018;2:666-675).
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29.
  • Dongiovanni, Paola, et al. (författare)
  • Statin use and nonalcoholic steatohepatitis in at risk individuals.
  • 2015
  • Ingår i: Journal of hepatology. - : Elsevier BV. - 1600-0641 .- 0168-8278. ; 63:3, s. 705-712
  • Tidskriftsartikel (refereegranskat)abstract
    • Excess hepatic free cholesterol contributes to the pathogenesis of nonalcoholic steatohepatitis, and statins reduce cholesterol synthesis. Aim of this study was to assess whether statin use is associated with histological liver damage related to steatohepatitis.
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30.
  • Földváry Ličina, Veronika, et al. (författare)
  • Development of the ASHRAE Global Thermal Comfort Database II
  • 2018
  • Ingår i: Building and Environment. - : Elsevier BV. - 0360-1323. ; 142, s. 502-512
  • Tidskriftsartikel (refereegranskat)abstract
    • Recognizing the value of open-source research databases in advancing the art and science of HVAC, in 2014 the ASHRAE Global Thermal Comfort Database II project was launched under the leadership of University of California at Berkeley's Center for the Built Environment and The University of Sydney's Indoor Environmental Quality (IEQ) Laboratory. The exercise began with a systematic collection and harmonization of raw data from the last two decades of thermal comfort field studies around the world. The ASHRAE Global Thermal Comfort Database II (Comfort Database), now an online, open-source database, includes approximately 81,846 complete sets of objective indoor climatic observations with accompanying “right-here-right-now” subjective evaluations by the building occupants who were exposed to them. The database is intended to support diverse inquiries about thermal comfort in field settings. A simple web-based interface to the database enables filtering on multiple criteria, including building typology, occupancy type, subjects' demographic variables, subjective thermal comfort states, indoor thermal environmental criteria, calculated comfort indices, environmental control criteria and outdoor meteorological information. Furthermore, a web-based interactive thermal comfort visualization tool has been developed that allows end-users to quickly and interactively explore the data.
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31.
  • Gheit, Tarik, et al. (författare)
  • Development of a sensitive and specific multiplex PCR method combined with DNA microarray primer extension to detect beta-papillomavirus types.
  • 2007
  • Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 45:8, s. 2537-2544
  • Tidskriftsartikel (refereegranskat)abstract
    • Emerging lines of evidence indicate that the cutaneous human papillomavirus (HPV) types that belong to the genus Betapapillomavirus (beta HPV) are involved in the development of nonmelanoma skin cancer. Unlike the situation for mucosal HPV types, highly sensitive and reliable methods to identify characterized cutaneous HPV types in a single assay are limited. Here, we describe a novel one-shot method for the detection of all characterized beta HPV types, namely, HPV type 5 (HPV5), 8, 9, 12, 14, 15, 17, 19, 20, 21, 22, 23, 24, 25, 36, 37, 38, 47, 49, 75, 76, 80, 92, 93, and 96. This assay combines two different techniques: multiplex PCR using HPV type-specific primers for amplification of each E7 gene and array primer extension (APEX) for typing. This method has been validated using clinical samples which were analyzed simultaneously for the presence of cutaneous HPV types by two additional methods, i.e., the FAP59/64 PCR protocol and a commercially available PCR-reverse hybridization assay (PM-PCR RHA). Our data show good agreement between the results obtained with the multiplex PCR/APEX assay and the PM-PCR RHA method (overall HPV positivity of 92.2% for multiplex PCR/APEX assay versus 90.6% with the PM-PCR RHA) (kappa value, 50; 95% confidence interval, 13 to 88). In addition, the multiplex PCR/APEX assay showed higher sensitivity than the PM-PCR RHA did. This favorable feature and the high-throughput potential make this assay ideal for large-scale clinical and epidemiological studies aimed at determining the spectrum of cutaneous types in skin cancer.
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32.
  • Grimaudo, Stefania, et al. (författare)
  • NR1H4 rs35724 G>C variant modulates liver damage in nonalcoholic fatty liver disease.
  • 2021
  • Ingår i: Liver international. - : Wiley. - 1478-3231 .- 1478-3223. ; 41:11, s. 2712-2719
  • Tidskriftsartikel (refereegranskat)abstract
    • Farnesoid X receptor (FXR) plays a key role in bile acid and lipid homeostasis. Experimental evidence suggests that it can modulate liver damage related to nonalcoholic fatty liver disease (NAFLD). We examined the impact of the NR1H4 rs35724 G>C, encoding for FXR, on liver damage in a large cohort of patients at risk of steatohepatitis.We considered 2,660 consecutive individuals at risk of steatohepatitis with liver histology. The rs35724 G>C polymorphisms were genotyped by TaqMan assays. Gene expression was evaluated by RNASeq in a subset of patients (n=124).The NR1H4 rs35724 CC genotype, after adjusting for clinic-metabolic and genetic confounders and for enrolling centre, was protective against severity of steatosis (GG vs CC OR 0.77, 95% CI 0.62-0.95; P=.01), steatohepatitis (GG vs CC OR 0.62, 95% CI 0.47-0.83; P=.001) and severity of fibrosis (GG vs CC OR 0.83, 95% CI 0.67-0.98; P=.04). The C allele was associated with higher total circulating cholesterol (P=.01). Patients carrying the NR1H4 rs35724 C allele had significantly higher hepatic mRNA levels of FXR and were associated with higher hepatic FGFR4 and Cyp39A1 that are in turn involved in bile acid synthesis.Increased hepatic FXR expression due to the NR1H4 rs35724 C allele is linked to higher serum cholesterol but protects against steatosis, steatohepatitis and liver fibrosis. The translational relevance of these results for patient risk stratification and FXR-targeted therapy warrants further investigation.
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33.
  • Kirby, Michael G, et al. (författare)
  • Overactive bladder: Is there a link to the metabolic syndrome in men?
  • 2010
  • Ingår i: Neurourology and urodynamics. - : Wiley. - 1520-6777 .- 0733-2467. ; 29:8, s. 1360-4
  • Tidskriftsartikel (refereegranskat)abstract
    • It is becoming increasingly clear that a variety of metabolic, cardiovascular, and endocrine factors contribute to male pelvic health. In particular, a growing body of evidence suggests a relationship between lower urinary tract symptoms, benign prostatic hyperplasia, overactive bladder, erectile dysfunction, and the metabolic syndrome. This article explores these relationships, focusing on the role of the autonomic nervous system and hyperinsulinemia, together with their implications for urological practice.
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34.
  • Lembrechts, Jonas J., et al. (författare)
  • Global maps of soil temperature
  • 2022
  • Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
  • Tidskriftsartikel (refereegranskat)abstract
    • Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean=3.0±2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6±2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7±2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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35.
  • Mancina, Rosellina Margherita, et al. (författare)
  • PSD3 downregulation confers protection against fatty liver disease.
  • 2022
  • Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:1, s. 60-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD.
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36.
  • Mancina, Rosellina Margherita, et al. (författare)
  • The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent.
  • 2016
  • Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 150:5, s. 1219-1230
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain-containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7-TMC4 is a susceptibility locus for the development and progression of NAFLD.
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37.
  • McKenzie, Fiona, et al. (författare)
  • Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study
  • 2015
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:11, s. 2640-2648
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR=0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR=0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR=0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported. What's new? How much does behavior really affect cancer risk? These authors set out to measure just that. First, they created a Healthy Lifestyle Index, which quantified five modifiable behaviors, such as smoking and physical activity. Then, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), they assigned each participant a score between 0 and 4 on each of the behaviors. It turned out that with each point added to a person's Healthy Lifestyle Index score, breast cancer risk fell by 3%, suggesting that public programs to help women maintain these behaviors could be worthwhile for cancer prevention.
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38.
  • Moschetto, Salvatore, et al. (författare)
  • Interplay between Charge Injection, Electron Transport, and Quantum Efficiency in Ambipolar Trilayer Organic Light-Emitting Transistors
  • 2022
  • Ingår i: Advanced Materials Interfaces. - : Wiley. - 2196-7350. ; 9:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The fascinating characteristic of organic light-emitting transistors (OLETs) of being electrical switches with an intrinsic light-emitting capability makes them attractive candidates for a wide variety of applications, ranging from sensors to displays. To date, the OLET ambipolar trilayer heterostructure is the most developed architecture for maximizing device performance. However, a major challenge of trilayer OLETs remains the inverse correlation between external quantum efficiency and brightness under ambipolar conditions. The complex interconnection between electroluminescent and ambipolar charge transport properties, in conjunction with the limited availability of electron transport semiconducting materials, has indeed hampered the disruptive evolution of the OLET technology. Here, an in-depth study of the interplay of the key fundamental features that determine the device performance is reported by exploring electron transport semiconductors with different properties in ambipolar trilayer OLETs. Through the selection of compounds with tailored chemical structures, the relation between intrinsic optoelectronic characteristics of the electron transport semiconductor, energy level alignment within the structure, and morphological features is unraveled. Furthermore, the introduction of a suitable electron injector at the emissive/semiconducting layers interface sheds light into the bidimensional nature of OLETs that is a distinguishing factor of this class of devices with respect to prototypical organic light-emitting diodes.
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39.
  •  
40.
  • Neeraj, Kumar, 1991-, et al. (författare)
  • Magnetization switching in the inertial regime
  • 2022
  • Ingår i: Physical Review B. - 2469-9950 .- 2469-9969. ; 105:5
  • Tidskriftsartikel (refereegranskat)abstract
    • We have numerically solved the Landau-Lifshitz-Gilbert (LLG) equation in its standard and inertial forms to study the magnetization switching dynamics in a 3d thin film ferromagnet. The dynamics is triggered by ultrashort magnetic field pulses of varying width and amplitude in the picosecond and Tesla range. We have compared the solutions of the two equations in terms of switching characteristic, speed, and energy analysis. Both equations return qualitatively similar switching dynamics, characterized by regions of slower precessional behavior and faster ballistic motion. In the case of inertial dynamics, ballistic switching is found in a 25% wider region in the parameter space given by the magnetic field amplitude and width. The energy analysis of the dynamics is qualitatively different for the standard and inertial LLG equations. In the latter case, an extra energy channel, interpreted as the kinetic energy of the system, is available. Such an extra channel is responsible for a resonant energy absorption at THz frequencies, consistent with the occurrence of spin nutation.
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41.
  • Oveis, Jamialahmadi, et al. (författare)
  • Exome-wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated with Fatty Liver Disease.
  • 2021
  • Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 160:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered.To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine aminotransferase (ALT) at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants with liver fat content in 8,930 participants in whom liver fat measurement was available, and replicated two genetic variants in three independent cohorts comprising 2,621 individuals with available liver biopsy.We identified 190 genetic variants independently associated with ALT after correcting for multiple testing with Bonferroni method. The majority of these variants were not previously associated with this trait. Among those associated, there was a striking enrichment of genetic variants influencing lipid metabolism. We identified the variants rs2792751 in GPAM/GPAT1, the gene encoding glycerol-3-phosphate acyltransferase, mitochondrial, and rs429358 in APOE, the gene encoding apolipoprotein E, as robustly associated with liver fat content and liver disease after adjusting for multiple testing. Both genes affect lipid metabolism in the liver.We identified two novel genetic variants in GPAM and APOE that are robustly associated with steatosis and liver damage. These findings may help to better elucidate the genetic susceptibility to FLD onset and progression.
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42.
  • Pelusi, Serena, et al. (författare)
  • Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease.
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonalcoholic fatty liver disease (NAFLD) is a rising cause of hepatocellular carcinoma (HCC). We examined whether inherited pathogenic variants in candidate genes (n=181) were enriched in patients with NAFLD-HCC. To this end, we resequenced peripheral blood DNA of 142 NAFLD-HCC, 59 NAFLD with advanced fibrosis, and 50 controls, and considered 404 healthy individuals from 1000G. Pathogenic variants were defined according to ClinVar, likely pathogenic as rare variants predicted to alter protein activity. In NAFLD-HCC patients, we detected an enrichment in pathogenic (p=0.024), and likely pathogenic variants (p=1.9*10-6), particularly in APOB (p=0.047). APOB variants were associated with lower circulating triglycerides and higher HDL cholesterol (p<0.01). A genetic risk score predicted NAFLD-HCC (OR 4.96, 3.29-7.55; p=5.1*10-16), outperforming the diagnostic accuracy of common genetic risk variants, and of clinical risk factors (p<0.05). In conclusion, rare pathogenic variants in genes involved in liver disease and cancer predisposition are associated with NAFLD-HCC development.
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43.
  • Pennisi, Grazia, et al. (författare)
  • ANGPTL3 Downregulation Increases Intracellular Lipids by Reducing Energy Utilization.
  • 2024
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642. ; 44:5, s. 1086-1097
  • Tidskriftsartikel (refereegranskat)abstract
    • ANGPTL3 (angiopoietin-like protein 3) is a circulating protein with a key role in maintaining lipoprotein homeostasis. A monoclonal antibody against ANGPTL3 is an approved and well-tolerated treatment to reduce lipoproteins in familial hypercholesterolemia homozygotes. However, the reduction of hepatic ANGPTL3 synthesis using an antisense oligonucleotide unexpectedly resulted in a dose-dependent increase in liver lipid content and circulating transaminases, resulting in the termination of the clinical trial. Meanwhile, the use of silencing RNAs remains an area of active investigation. Our study sought to investigate whether intracellular downregulation of ANGPTL3 may lead to a primary increase in neutral lipids within the hepatocyte.We downregulated ANGPTL3 by silencing RNA in primary human hepatocytes 3-dimensional spheroids, HepG2/LX-2 3-dimensional spheroids, and in HepG2, Hep3B2, and Huh7 cultured in 2 dimensions.ANGPTL3 downregulation increased neutral lipids in all models investigated. Interestingly, ANGPTL3 induced lower intracellular deiodinase type 1 protein levels resulting in a reduction in beta-oxidation and causing an increase in triglycerides stored in lipid droplets.In conclusion, intracellular ANGPTL3 downregulation by silencing RNA led to an increase in triglycerides content due to a reduction in energy substrate utilization resembling a primary intracellular hepatocyte hypothyroidism.
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44.
  • Petta, Salvatore, et al. (författare)
  • The first MASH drug therapy on the horizon: Current perspectives of resmetirom.
  • 2024
  • Ingår i: Liver international. - 1478-3223. ; 44:7, s. 1526-1536
  • Tidskriftsartikel (refereegranskat)abstract
    • The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant global health challenge, affecting over 30% of adults worldwide. MASLD is linked to increased mortality rates and substantial healthcare costs, primarily driven by its progression to metabolic dysfunction-associated steatohepatitis (MASH), which can lead to severe liver complications including cirrhosis and hepatocellular carcinoma. Despite its growing burden, effective pharmacotherapy for MASLD/MASH has been lacking until the recent conditional approval of resmetirom by the FDA. Resmetirom, a liver-targeted thyroid hormone receptor-β selective drug, has shown promise in clinical trials for treating non-cirrhotic MASH with moderate to advanced fibrosis. It has demonstrated efficacy in reducing hepatic fat content, improving liver histology (both MASH resolution and fibrosis improvement), and ameliorating biomarkers of liver damage without significant effects on body weight or glucose metabolism. Notably, resmetirom also exhibits favourable effects on circulating lipids, potentially reducing cardiovascular risk in MASLD/MASH patients. The safety profile of resmetirom appears acceptable, with gastrointestinal adverse events being the most common, though generally mild or moderate. However, long-term surveillance is warranted to monitor for potential risks related to thyroid, gonadal, or bone diseases. Clinical implementation of resmetirom faces challenges in patient selection and monitoring treatment response, and will heavily rely on non-invasive tests for liver fibrosis assessment. Nonetheless, resmetirom represents a landmark breakthrough in MASLD/MASH treatment, paving the way for future therapeutic strategies aiming to mitigate the multifaceted risks associated with this complex metabolic liver disease.
  •  
45.
  • Pilotto, Andrea, et al. (författare)
  • SARS-CoV-2 encephalitis is a cytokine release syndrome: evidences from cerebrospinal fluid analyses.
  • 2021
  • Ingår i: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - : Oxford University Press (OUP). - 1537-6591. ; 73:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent findings indicated that SARS-CoV-2 related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the CSF correlates of SARS-CoV-2 encephalitis.Patients with PCR-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC) and healthy controls (HC) underwent an extended panel of CSF neuronal (NfL, T-tau), glial (GFAP, TREM2, YKL-40) and inflammatory biomarkers (IL-1β, IL-6, Il-8, TNF- α, CXCL-13 and β2-microglobulin).Thirteen COV-Enc, 21 ENC and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and β2-microglobulin and glial markers (GFAP, sTREM-2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-Tau were abnormal only in severe cases.SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2 related encephalitis.
  •  
46.
  • Pipitone, Rosaria M., et al. (författare)
  • Programmed cell death 1 genetic variant and liver damage in nonalcoholic fatty liver disease
  • 2023
  • Ingår i: Liver International. - 1478-3223 .- 1478-3231. ; 43:8, s. 1761-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Programmed cell death 1/programmed cell death-ligand 1 (PD-1/PDL-1) axis has been reported to modulate liver inflammation and progression to hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease (NAFLD). Here, we examined whether the PDCD1 variation is associated with NAFLD severity in individuals with liver biopsy. Methods: We examined the impact of PDCD1 gene variants on HCC, as robust severe liver disease phenotype in UK Biobank participants. The strongest genetic association with the rs13023138 G>C variation was subsequently tested for association with liver damage in 2889 individuals who underwent liver biopsy for suspected nonalcoholic steatohepatitis (NASH). Hepatic transcriptome was examined by RNA-Seq in a subset of NAFLD individuals (n = 121). Transcriptomic and deconvolution analyses were performed to identify biological pathways modulated by the risk allele. Results: The rs13023138 C>G showed the most robust association with HCC in UK Biobank (p = 5.28E-4, OR = 1.32, 95% CI [1.1, 1.5]). In the liver biopsy cohort, rs13023138 G allele was independently associated with severe steatosis (OR 1.17, 95% CI 1.02-1.34; p =.01), NASH (OR 1.22, 95% CI 1.09-1.37; p <.001) and advanced fibrosis (OR 1.26, 95% CI 1.06-1.50; p =.007). At deconvolution analysis, rs13023138 G>C allele was linked to higher hepatic representation of M1 macrophages, paralleled by upregulation of pathways related to inflammation and higher expression of CXCR6. Conclusions: The PDCD1 rs13023138 G allele was associated with HCC development in the general population and with liver disease severity in patients at high risk of NASH.
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47.
  •  
48.
  • Ramos-Casals, Manuel, et al. (författare)
  • EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies.
  • 2020
  • Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:1, s. 3-18
  • Tidskriftsartikel (refereegranskat)abstract
    • The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.
  •  
49.
  • Rothman, Nathaniel, et al. (författare)
  • A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 978-984
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
  •  
50.
  • Sasidharan, Kavitha, et al. (författare)
  • IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids.
  • 2024
  • Ingår i: Cell reports. Medicine. - 2666-3791. ; 5:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate invitro that incubation with IL-32β protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD.
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