| 1. |
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| 2. |
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| 3. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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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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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
-
Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 8. |
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| 9. |
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| 10. |
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Zang, ZL, et al.
(författare)
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Valproic acid exposure decreases neurogenic potential of outer radial glia in human brain organoids
- 2022
-
Ingår i: Frontiers in molecular neuroscience. - : Frontiers Media SA. - 1662-5099. ; 15, s. 1023765-
-
Tidskriftsartikel (refereegranskat)abstract
- Valproic acid (VPA) exposure during pregnancy leads to a higher risk of autism spectrum disorder (ASD) susceptibility in offspring. Human dorsal forebrain organoids were used to recapitulate course of cortical neurogenesis in the developing human brain. Combining morphological characterization with massive parallel RNA sequencing (RNA-seq) on organoids to analyze the pathogenic effects caused by VPA exposure and critical signaling pathway. We found that VPA exposure in organoids caused a reduction in the size and impairment in the proliferation and expansion of neural progenitor cells (NPCs) in a dose-dependent manner. VPA exposure typically decreased the production of outer radial glia-like cells (oRGs), a subtype of NPCs contributing to mammalian neocortical expansion and delayed their fate toward upper-layer neurons. Transcriptomics analysis revealed that VPA exposure influenced ASD risk gene expression in organoids, which markedly overlapped with irregulated genes in brains or organoids originating from ASD patients. We also identified that VPA-mediated Wnt/β-catenin signaling pathway activation is essential for sustaining cortical neurogenesis and oRGs output. Taken together, our study establishes the use of dorsal forebrain organoids as an effective platform for modeling VPA-induced teratogenic pathways involved in the cortical neurogenesis and oRGs output, which might contribute to ASD pathogenesis in the developing brain.
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| 18. |
- Adcox, K, et al.
(författare)
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Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX Collaboration
- 2005
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Ingår i: Nuclear Physics, Section A. - : Elsevier BV. - 0375-9474. ; 757:1-2, s. 184-283
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Forskningsöversikt (refereegranskat)abstract
- Extensive experimental data from high-energy nucleus-nucleus collisions were recorded using the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC). The comprehensive set of measurements from the first three years of RHIC operation includes charged particle multiplicities, transverse energy, yield ratios and spectra of identified hadrons in a wide range of transverse momenta (PT), elliptic flow, two-particle correlations, nonstatistical fluctuations, and suppression of particle production at high PT. The results are examined with an emphasis on implications for the formation of a new state of dense matter. We find that the state of matter created at RHIC cannot be described in terms of ordinary color neutral hadrons.
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| 19. |
- Adcox, K, et al.
(författare)
-
PHENIX detector overview
- 2003
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 20. |
- Adler, SS, et al.
(författare)
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Bose-Einstein correlations of charged pion pairs in Au+Au collisions at root(NN)-N-s = 200 GeV
- 2004
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Ingår i: Physical Review Letters. - 1079-7114. ; 93:15
-
Tidskriftsartikel (refereegranskat)abstract
- Bose-Einstein correlations of identically charged pion pairs were measured by the PHENIX experiment at midrapidity in Au+Au collisions at roots(NN)=200 GeV. The Bertsch-Pratt radius parameters were determined as a function of the transverse momentum of the pair and as a function of the centrality of the collision. Using the standard core-halo partial Coulomb fits, and a new parametrization which constrains the Coulomb fraction as determined from the unlike-sign pion correlation, the ratio R-out/R-side is within 0.8-1.1 for 0.25<<1.2 GeV/c. The centrality dependence of all radii is well described by a linear scaling in N-part(1/3), and R-out/R-side for similar to0.45 GeV/c is approximately constant at unity as a function of centrality.
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| 21. |
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| 22. |
- Adler, SS, et al.
(författare)
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Common suppression pattern of eta and pi(0) mesons at high transverse momentum in Au plus Au collisions at root SNN=200 GeV
- 2006
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Ingår i: Physical Review Letters. - 1079-7114. ; 96:20
-
Tidskriftsartikel (refereegranskat)abstract
- Inclusive transverse momentum spectra of eta mesons have been measured within p(T)=2-10 GeV/c at midrapidity by the PHENIX experiment in Au+Au collisions at root s(NN) = 200 GeV. In central Au+Au the eta yields are significantly suppressed compared to peripheral Au+Au, d+Au, and p+p yields scaled by the corresponding number of nucleon-nucleon collisions. The magnitude, centrality, and p(T) dependence of the suppression is common, within errors, for eta and pi(0). The ratio of eta to pi(0) spectra at high p(T) amounts to 0.40 < R-eta/pi(0)< 0.48 for the three systems, in agreement with the world average measured in hadronic and nuclear reactions and, at large scaled momentum, in e(+)e(-) collisions.
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| 23. |
- Adler, SS, et al.
(författare)
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Deuteron and antideuteron production in Au+Au collisions at root s(NN)=200 GeV
- 2005
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Ingår i: Physical Review Letters. - 1079-7114. ; 94:12
-
Tidskriftsartikel (refereegranskat)abstract
- The production of deuterons and antideuterons in the transverse momentum range 1.1 < p(T)< 4.3 GeV/c at midrapidity in Au+Au collisions at root s(NN) = 200 GeV has been studied by the PHENIX experiment at RHIC. A coalescence analysis, comparing the deuteron and antideuteron spectra with that of proton and antiproton, has been performed. The coalescence probability is equal for both deuterons and antideuterons and it increases as a function of p(T), which is consistent with an expanding collision zone. Comparing (anti)proton yields, (p) over bar /p = 0.73 +/- 0.01, with (anti)deuteron yields, (d) over bar /d = 0.47 +/- 0.03, we estimate that (n) over bar /n = 0.64 +/- 0.04. The nucleon phase space density is estimated from the coalescence measurement.
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| 24. |
- Adler, SS, et al.
(författare)
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Elliptic flow of identified hadrons in Au+Au collisions at root s(NN)=200 GeV
- 2003
-
Ingår i: Physical Review Letters. - 1079-7114. ; 91:18: 182301
-
Tidskriftsartikel (refereegranskat)abstract
- The anisotropy parameter (v(2)), the second harmonic of the azimuthal particle distribution, has been measured with the PHENIX detector in Au+Au collisions at roots(NN)=200 GeV for identified and inclusive charged particle production at central rapidities (eta<0.35) with respect to the reaction plane defined at high rapidities (eta=3-4 ). We observe that the v(2) of mesons falls below that of (anti)baryons for p(T)>2 GeV/c, in marked contrast to the predictions of a hydrodynamical model. A quark-coalescence model is also investigated.
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| 25. |
- Adler, SS, et al.
(författare)
-
J/psi production from proton-proton collisions at root s=200 GeV
- 2004
-
Ingår i: Physical Review Letters. - 1079-7114. ; 92:5
-
Tidskriftsartikel (refereegranskat)abstract
- J/psi production has been measured in proton-proton collisions at roots=200 GeV over a wide rapidity and transverse momentum range by the PHENIX experiment at the Relativistic Heavy Ion Collider. Distributions of the rapidity and transverse momentum, along with measurements of the mean transverse momentum and total production cross section are presented and compared to available theoretical calculations. The total J/psi cross section is 4.0+/-0.6(stat)+/-0.6(syst)+/-0.4(abs) mub. The mean transverse momentum is 1.80+/-0.23(stat)+/-0.16(syst) GeV/c.
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| 26. |
- Adler, SS, et al.
(författare)
-
J/psi production in Au-Au collisions at root s(NN)=200 GeV
- 2004
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 69:1
-
Tidskriftsartikel (refereegranskat)abstract
- First results on charm quarkonia production in heavy ion collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The yield of J/psi's measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au-Au reactions at roots(NN) = 200 GeV is analyzed as a function of collision centrality. For this analysis we have studied 49.3x10(6) minimum bias Au-Au reactions. We present the J/psi invariant yield dN/dy for peripheral and midcentral reactions. For the most central collisions where we observe no signal above background, we quote 90% confidence level upper limits. We compare these results with our J/psi measurement from proton-proton reactions at the same energy. We find that our measurements are not consistent with models that predict strong enhancement relative to binary collision scaling.
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| 27. |
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| 28. |
- Adler, SS, et al.
(författare)
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Measurement of single electron event anisotropy in Au plus Au collisions at root s(NN)=200 GeV
- 2005
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 72:2
-
Tidskriftsartikel (refereegranskat)abstract
- The transverse momentum dependence of the azimuthal anisotropy parameter v(2), the second harmonic of the azimuthal distribution, for electrons at midrapidity (vertical bar eta vertical bar < 0.35) has been measured with the PHENIX detector in Au+Au collisions at root s(NN) = 200 GeV. The measurement was made with respect to the reaction plane defined at high rapidities (vertical bar eta vertical bar = 3.1-3.9). From the result we have measured the v(2) of electrons from heavy flavor decay after subtraction of the v(2) of electrons from other sources such as photon conversions and Dalitz decay from light neutral mesons. We observe a nonzero single electron v(2) with a 90% confidence level in the intermediate-p(T) region. The precision of the present data set does not permit us to conclude definitively that heavy quarks exhibit thermalization with the transverse flow of the bulk matter.
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| 29. |
- Adler, SS, et al.
(författare)
-
Measurement of transverse single-spin asymmetries for midrapidity production of neutral pions and charged hadrons in polarized p+p collisions at root s=200 GeV
- 2005
-
Ingår i: Physical Review Letters. - 1079-7114. ; 95
-
Tidskriftsartikel (refereegranskat)abstract
- Transverse single-spin asymmetries to probe the transverse-spin structure of the proton have been measured for neutral pions and nonidentified charged hadrons from polarized proton-proton collisions at midrapidity and root s = 200 GeV. The data cover a transverse momentum (pT) range 1.0-5.0 GeV/c for neutral pions and 0.5-5.0 GeV/c for charged hadrons, at a Feynman-x value of approximately zero. The asymmetries seen in this previously unexplored kinematic region are consistent with zero within errors of a few percent. In addition, the inclusive charged hadron cross section at midrapidity from 0.5 < P-T < 7.0 GeV/c is presented and compared to next-to-leading order perturbative QCD ( pQCD) calculations. Successful description of the unpolarized cross section above similar to 2 GeV/c suggests that pQCD is applicable in the interpretation of the asymmetry results in the relevant kinematic range.
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| 30. |
- Adler, SS, et al.
(författare)
-
Midrapidity direct-photon production in p+p collisions at root s=200 GeV
- 2005
-
Ingår i: Physical Review D (Particles and Fields). - 0556-2821. ; 71:7
-
Tidskriftsartikel (refereegranskat)abstract
- A measurement of direct photons in p+p collisions at root s=200 GeV is presented. A photon excess above background from pi(0)->gamma+gamma, eta ->gamma+gamma and other decays is observed in the transverse momentum range 5.5 < p(T)< 7 GeV/c. The result is compared to a next-to-leading-order perturbative QCD calculation. Within errors, good agreement is found between the QCD calculation and the measured result.
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| 31. |
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| 32. |
- Adler, SS, et al.
(författare)
-
Production of phi mesons at midrapidity in root S-NN=200 GeVAu+Au collisions at relativistic energies
- 2005
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 72:1
-
Tidskriftsartikel (refereegranskat)abstract
- We present the results of phi meson production in the K+K- decay channel from Au+Au collisions at root s(NN) =200 GeV as measured at midrapidity by the PHENIX detector at Brookhaven National Laboratory's Relativistic Heavy Ion Collider. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the Particle Data Group accepted values is observed, contrary to some model predictions. The phi transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. However, when these data are fitted by a hydrodynamic model the result is that the centrality-dependent freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting identified charged hadron data. As a function of transverse momentum the collisions scaled peripheral-to-central yield ratio R-CP for the phi is comparable to that of pions rather than that of protons. This result lends support to theoretical models that distinguish between baryons and mesons instead of particle mass for explaining the anomalous (anti) proton yield.
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| 33. |
- Adler, SS, et al.
(författare)
-
Scaling properties of proton and antiproton production in root s(NN)=200 GeV Au+Au collisions
- 2003
-
Ingår i: Physical Review Letters. - 1079-7114. ; 91:17: 172301
-
Tidskriftsartikel (refereegranskat)abstract
- We report on the yield of protons and antiprotons, as a function of centrality and transverse momentum, in Au+Au collisions at rootS(NN)=200 GeV measured at midrapidity by the PHENIX experiment at the BNL Relativistic Heavy Ion Collider. In central collisions at intermediate transverse momenta (1.5
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| 34. |
- Adler, SS, et al.
(författare)
-
Single electrons from heavy-flavor decays in p + p collisions at root s=200 GeV
- 2006
-
Ingår i: Physical Review Letters. - 1079-7114. ; 96:3
-
Tidskriftsartikel (refereegranskat)abstract
- The invariant differential cross section for inclusive electron production in p+p collisions at root s=200 GeV has been measured by the PHENIX experiment at the BNL Relativistic Heavy Ion Collider over the transverse momentum range 0.4 <= p(T) <= 5.0 GeV/c in the central rapidity region (vertical bar eta vertical bar <= 0.35). The contribution to the inclusive electron spectrum from semileptonic decays of hadrons carrying heavy flavor, i.e., charm quarks or, at high p(T), bottom quarks, is determined via three independent methods. The resulting electron spectrum from heavy-flavor decays is compared to recent leading and next-to-leading order perturbative QCD calculations. The total cross section of charm quark-antiquark pair production is determined to be sigma(c (c) over bar) = 0.92 +/- 0.15(stat) +/- 0.54(syst) mb.
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| 35. |
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| 36. |
- Beral, V, et al.
(författare)
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Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
- 2002
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
-
Tidskriftsartikel (refereegranskat)abstract
- Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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| 37. |
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| 38. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 39. |
- Chen, TT, et al.
(författare)
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Family history of esophageal cancer increases the risk of esophageal squamous cell carcinoma
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 16038-
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Tidskriftsartikel (refereegranskat)abstract
- A population-based case-control was performed to explore familial aggregation of esophageal squamous cell carcinoma (ESCC). Family history of cancer was assessed by a structured questionnaire and from which 2 cohorts of relatives of cases and controls were reconstructed. Unconditional logistic regression and Cox proportional hazards regression were applied for case-control design and reconstructed cohort design, respectively. We observed a close to doubled risk of ESCC associated with a positive family history of esophageal cancer among first degree relatives (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.42–2.41), after adjusting age, sex, family size and other confounders. The excess risks of ESCC increased with the increasing of first-degree relatives affected by esophageal cancer (p < 0.001). In particular, those individuals whose both parents with esophageal cancer had an 8-fold excess risk of ESCC (95% CI: 1.74–36.32). The reconstructed cohort analysis showed that the cumulative risk of esophageal cancer to age 75 was 12.2% in the first-degree relatives of cases and 7.0% in those of controls (hazard ratio = 1.91, 95% CI: 1.54–2.37). Our results suggest family history of esophageal cancer significantly increases the risk for ESCC. Future studies are needed to understand how the shared genetic susceptibility and/or environmental exposures contribute to the observed excess risk.
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| 40. |
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| 41. |
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| 42. |
- Ge, CT, et al.
(författare)
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Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 116:39, s. 19635-19645
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Tidskriftsartikel (refereegranskat)abstract
- Substance P (SP) regulates multiple biological processes through its high-affinity neurokinin-1 receptor (NK-1R). While the SP/NK-1R signaling axis is involved in the pathogenesis of solid cancer, the role of this signaling pathway in hematological malignancy remains unknown. Here, we demonstrate that NK-1R expression is markedly elevated in the white blood cells from acute myeloid leukemia patients and a panel of human leukemia cell lines. Blocking NK-1R induces apoptosis in vitro and in vivo via increase of mitochondrial reactive oxygen species. This oxidative stress was triggered by rapid calcium flux from the endoplasmic reticulum into mitochondria and, consequently, impairment of mitochondrial function, a mechanism underlying the cytotoxicity of NK-1R antagonists. Besides anticancer activity, blocking NK-1R produces a potent antinociceptive effect in myeloid leukemia-induced bone pain by alleviating inflammation and inducing apoptosis. These findings thus raise the exciting possibility that the NK-1R antagonists, drugs currently used in the clinic for preventing chemotherapy-induced nausea and vomiting, may provide a therapeutic option for treating human myeloid leukemia.
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| 43. |
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| 44. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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- Pelaz, B, et al.
(författare)
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Diverse Applications of Nanomedicine
- 2017
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Ingår i: ACS nano. - : American Chemical Society (ACS). - 1936-086X .- 1936-0851. ; 11:3, s. 2313-2381
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Tidskriftsartikel (refereegranskat)
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