Is there any advantage to combined trastuzumab and chemotherapy in perioperative setting her 2neu positive localized gastric adenocarcinoma?

We report here a 44-year-old Moroccan man with resectable gastric adenocarcinoma with overexpression of human epidermal growth factor receptor 2 (HER2) by immunohistochemistry who was treated with trastuzumab in combination with chemotherapy in perioperative setting. He received 3 cycles of neoadjuvant chemotherapy consisting of trastuzumab, oxaliplatin, and capecitabine. Afterwards, he received total gastrectomy with extended D2 lymphadenectomy without spleno-pancreatectomy. A pathologic complete response was obtained with a combination of trastuzumab and oxaliplatin and capecitabine. He received 3 more cycles of trastuzumab containing regimen postoperatively

4D Flow cardiovascular magnetic resonance consensus statement: 2023 update

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 '4D Flow CMR Consensus Statement'. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards

Extracellular signal-regulated kinase 1/2-mediated phosphorylation of p300 enhances myosin heavy chain I/β gene expression via acetylation of nuclear factor of activated T cells c1

The nuclear factor of activated T-cells (NFAT) c1 has been shown to be essential for Ca2+-dependent upregulation of myosin heavy chain (MyHC) I/β expression during skeletal muscle fiber type transformation. Here, we report activation of extracellular signal-regulated kinase (ERK) 1/2 in Ca2+-ionophore-treated C2C12 myotubes and electrostimulated soleus muscle. Activated ERK1/2 enhanced NFATc1-dependent upregulation of a −2.4 kb MyHCI/β promoter construct without affecting subcellular localization of endogenous NFATc1. Instead, ERK1/2-augmented phosphorylation of transcriptional coactivator p300, promoted its recruitment to NFATc1 and increased NFATc1–DNA binding to a NFAT site of the MyHCI/β promoter. In line, inhibition of ERK1/2 signaling abolished the effects of p300. Comparison between wild-type p300 and an acetyltransferase-deficient mutant (p300DY) indicated increased NFATc1–DNA binding as a consequence of p300-mediated acetylation of NFATc1. Activation of the MyHCI/β promoter by p300 depends on two conserved acetylation sites in NFATc1, which affect DNA binding and transcriptional stimulation. NFATc1 acetylation occurred in Ca2+-ionophore treated C2C12 myotubes or electrostimulated soleus. Finally, endogenous MyHCI/β gene expression in C2C12 myotubes was strongly inhibited by p300DY and a mutant deficient in ERK phosphorylation sites. In conclusion, ERK1/2-mediated phosphorylation of p300 is crucial for enhancing NFATc1 transactivation function by acetylation, which is essential for Ca2+-induced MyHCI/β expression

Acetonic Extract of Buxus sempervirens Induces Cell Cycle Arrest, Apoptosis and Autophagy in Breast Cancer Cells

Plants are an invaluable source of potential new anti-cancer drugs. Here, we investigated the cytotoxic activity of the acetonic extract of Buxus sempervirens on five breast cancer cell lines, MCF7, MCF10CA1a and T47D, three aggressive triple positive breast cancer cell lines, and BT-20 and MDA-MB-435, which are triple negative breast cancer cell lines. As a control, MCF10A, a spontaneously immortalized but non-tumoral cell line has been used. The acetonic extract of Buxus sempervirens showed cytotoxic activity towards all the five studied breast cancer cell lines with an IC50 ranging from 7.74 µg/ml to 12.5 µg/ml. Most importantly, the plant extract was less toxic towards MCF10A with an IC50 of 19.24 µg/ml. Fluorescence-activated cell sorting (FACS) analysis showed that the plant extract induced cell death and cell cycle arrest in G0/G1 phase in MCF7, T47D, MCF10CA1a and BT-20 cell lines, concomitant to cyclin D1 downregulation. Application of MCF7 and MCF10CA1a respective IC50 did not show such effects on the control cell line MCF10A. Propidium iodide/Annexin V double staining revealed a pre-apoptotic cell population with extract-treated MCF10CA1a, T47D and BT-20 cells. Transmission electron microscopy analyses indicated the occurrence of autophagy in MCF7 and MCF10CA1a cell lines. Immunofluorescence and Western blot assays confirmed the processing of microtubule-associated protein LC3 in the treated cancer cells. Moreover, we have demonstrated the upregulation of Beclin-1 in these cell lines and downregulation of Survivin and p21. Also, Caspase-3 detection in treated BT-20 and T47D confirmed the occurrence of apoptosis in these cells. Our findings indicate that Buxus sempervirens extract exhibit promising anti-cancer activity by triggering both autophagic cell death and apoptosis, suggesting that this plant may contain potential anti-cancer agents for single or combinatory cancer therapy against breast cancer

Search for non-resonant Higgs boson pair production in the 2b+2ℓ+ETmiss final state in pp collisions at s = 13 TeV with the ATLAS detector

A search for non-resonant Higgs boson pair (HH) production is presented, in which one of the Higgs bosons decays to a b-quark pair (bb¯) and the other decays to WW*, ZZ*, or τ+τ−, with in each case a final state with ℓ+ℓ−+ neutrinos (ℓ = e, μ). The analysis targets separately the gluon-gluon fusion and vector boson fusion production modes. Data recorded by the ATLAS detector in proton-proton collisions at a centre-of-mass energy of 13 TeV at the Large Hadron Collider, corresponding to an integrated luminosity of 140 fb−1, are used in this analysis. Events are selected to have exactly two b-tagged jets and two leptons with opposite electric charge and missing transverse momentum in the final state. These events are classified using multivariate analysis algorithms to separate the HH events from other Standard Model processes. No evidence of the signal is found. The observed (expected) upper limit on the cross-section for non-resonant Higgs boson pair production is determined to be 9.7 (16.2) times the Standard Model prediction at 95% confidence level. The Higgs boson self-interaction coupling parameter κλ and the quadrilinear coupling parameter κ2V are each separately constrained by this analysis to be within the ranges [−6.2, 13.3] and [−0.17, 2.4], respectively, at 95% confidence level, when all other parameters are fixed

Search for resonant production of dark quarks in the dijet final state with the ATLAS detector

This paper presents a search for a new Z′ resonance decaying into a pair of dark quarks which hadronise into dark hadrons before promptly decaying back as Standard Model particles. This analysis is based on proton-proton collision data recorded at s = 13 TeV with the ATLAS detector at the Large Hadron Collider between 2015 and 2018, corresponding to an integrated luminosity of 139 fb−1. After selecting events containing large-radius jets with high track multiplicity, the invariant mass distribution of the two highest-transverse-momentum jets is scanned to look for an excess above a data-driven estimate of the Standard Model multijet background. No significant excess of events is observed and the results are thus used to set 95% confidence-level upper limits on the production cross-section times branching ratio of the Z′ to dark quarks as a function of the Z′ mass for various dark-quark scenarios

Search for a CP-odd Higgs boson decaying into a heavy CP-even Higgs boson and a Z boson in the ℓ+ℓ−tt¯ and νν¯bb¯ final states using 140 fb⁻¹ of data collected with the ATLAS detector

A search for a heavy CP-odd Higgs boson, A, decaying into a Z boson and a heavy CP-even Higgs boson, H, is presented. It uses the full LHC Run 2 dataset of pp collisions at s = 13 TeV collected with the ATLAS detector, corresponding to an integrated luminosity of 140 fb−1. The search for A → ZH is performed in the ℓ+ℓ−tt¯ and νν¯bb¯ final states and surpasses the reach of previous searches in different final states in the region with mH > 350 GeV and mA > 800 GeV. No significant deviation from the Standard Model expectation is found. Upper limits are placed on the production cross-section times the decay branching ratios. Limits with less model dependence are also presented as functions of the reconstructed m(tt¯) and m(bb¯) distributions in the ℓ+ℓ−tt¯ and νν¯bb¯ channels, respectively. In addition, the results are interpreted in the context of two-Higgs-doublet models

Measurement of the production cross-section of J/ψ and ψ(2S) mesons in pp collisions at s=13 TeV with the ATLAS detector

Measurements of the differential production cross-sections of prompt and non-prompt J/ψ and ψ(2S) mesons with transverse momenta between 8 and 360 GeV and rapidity in the range |y|<2 are reported. Furthermore, measurements of the non-prompt fractions of J/ψ and ψ(2S), and the prompt and non-prompt ψ(2S)-to-J/ψ production ratios, are presented. The analysis is performed using 140 fb-1 of s=13 TeV pp collision data recorded by the ATLAS detector at the LHC during the years 2015–2018

A precise measurement of the Z-boson double-differential transverse momentum and rapidity distributions in the full phase space of the decay leptons with the ATLAS experiment at s=8 TeV

This paper presents for the first time a precise measurement of the production properties of the Z boson in the full phase space of the decay leptons. This is in contrast to the many previous precise unfolded measurements performed in the fiducial phase space of the decay leptons. The measurement is obtained from proton–proton collision data collected by the ATLAS experiment in 2012 at s=8 TeV at the LHC and corresponding to an integrated luminosity of 20.2 fb-1. The results, based on a total of 15.3 million Z-boson decays to electron and muon pairs, extend and improve a previous measurement of the full set of angular coefficients describing Z-boson decay. The double-differential cross-section distributions in Z-boson transverse momentum pT and rapidity y are measured in the pole region, defined as 80<mℓℓ<100 GeV, over the range |y|<3.6. The total uncertainty of the normalised cross-section measurements in the peak region of the pT distribution is dominated by statistical uncertainties over the full range and increases as a function of rapidity from 0.5–1.0% for |y|<2.0 to 2-7% at higher rapidities. The results for the rapidity-dependent transverse momentum distributions are compared to state-of-the-art QCD predictions, which combine in the best cases approximate N4LL resummation with N3LO fixed-order perturbative calculations. The differential rapidity distributions integrated over pT are even more precise, with accuracies from 0.2–0.3% for |y|<2.0 to 0.4–0.9% at higher rapidities, and are compared to fixed-order QCD predictions using the most recent parton distribution functions. The agreement between data and predictions is quite good in most cases