Novel immortalized human fetal liver cell line, cBAL111, has the potential to differentiate into functional hepatocytes

BACKGROUND: A clonal cell line that combines both stable hepatic function and proliferation capacity is desirable for in vitro applications that depend on hepatic function, such as pharmacological or toxicological assays and bioartificial liver systems. Here we describe the generation and characterization of a clonal human cell line for in vitro hepatocyte applications. RESULTS: Cell clones derived from human fetal liver cells were immortalized by over-expression of telomerase reverse transcriptase. The resulting cell line, cBAL111, displayed hepatic functionality similar to the parental cells prior to immortalization, and did not grow in soft agar. Cell line cBAL111 produced urea, albumin, cytokeratin 18 and 19 and showed high glutathione S transferase pi mRNA levels. In contrast to hepatic cell lines NKNT-3 and HepG2, all hepatic functions were expressed in cBAL111, although there was considerable variation in their levels compared with primary mature hepatocytes. When transplanted in the spleen of immunodeficient mice, cBAL111 engrafted into the liver and partly differentiated into hepatocytes showing expression of human albumin and carbamoylphosphate synthetase without signs of cell fusion. CONCLUSION: This novel liver cell line has the potential to differentiate into mature hepatocytes to be used for in vitro hepatocyte applications

Tissue engineering for the diaphragm and its various therapeutic possibilities - a systematic review

Diaphragmatic impairments exhibit high morbidity as well as mortality while current treatment options remain unsatisfactory. Tissue engineering (TE) approaches have explored the generation of an optimal biocompatible scaffold for diaphragmatic repair through tissue decellularization or de novo construction, with or without the addition of cells. We conducted a systematic review on the current state of the art in diaphragmatic tissue engineering (DTE) and found 24 articles eligible for final synthesis. The included approaches studied decellularization-based graft generation (9) and de novo bioscaffold construction (9). Three studies focused on in vitro host-scaffold interaction with synthesized, recellularized grafts (2) and decellularized extracellular matrix scaffolds (1). Another three studies investigated evaluation tools for decellularization efficacy. Among all studies, recellularization was performed in both decellularization-based (4) and de novo generated scaffolds (4). De novo constructed biocomposites as well as decellularized and recellularized scaffolds induced pro-regenerative remodeling and recovery of diaphragmatic function in all examined animal models. Potential therapeutic applications comprise substance defects requiring patch repair, such as congenital diaphragmatic hernia, and functional diseases demanding an entire organ transplant, like muscular dystrophies or dysfunction after prolonged artificial respiration

FIRE-9 - PORT / AIO-KRK-0418: a prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of adjuvant/additive chemotherapy in patients with definitely-treated metastatic colorectal cancer

BACKGROUND: Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer. METHODS: Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer-either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3-10 weeks before randomization-and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm. DISCUSSION: Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov ( NCT05008809 ) and EudraCT (2020-006,144-18)

Search for heavy resonances decaying into a Z or W boson and a Higgs boson in final states with leptons and b-jets in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

This article presents a search for new resonances decaying into a Z or W boson and a 125 GeV Higgs boson h, and it targets the νν¯¯¯bb¯¯, ℓ+ℓ−bb¯¯, or ℓ±νbb¯¯ final states, where ℓ = e or μ, in proton-proton collisions at s√ = 13 TeV. The data used correspond to a total integrated luminosity of 139 fb−1 collected by the ATLAS detector during Run 2 of the LHC at CERN. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Zh or Wh candidates for evidence of a localised excess in the mass range from 220 GeV to 5 TeV. No significant excess is observed and 95% confidence-level upper limits between 1.3 pb and 0.3 fb are placed on the production cross section times branching fraction of neutral and charged spin-1 resonances and CP-odd scalar bosons. These limits are converted into constraints on the parameter space of the Heavy Vector Triplet model and the two-Higgs-doublet model

Search for the Zγ decay mode of new high-mass resonances in pp collisions at √s = 13 TeV with the ATLAS detector

This letter presents a search for narrow, high-mass resonances in the Zγ final state with the Z boson decaying into a pair of electrons or muons. The √s = 13 TeV pp collision data were recorded by the ATLAS detector at the CERN Large Hadron Collider and have an integrated luminosity of 140 fb−1. The data are found to be in agreement with the Standard Model background expectation. Upper limits are set on the resonance production cross section times the decay branching ratio into Zγ. For spin-0 resonances produced via gluon–gluon fusion, the observed limits at 95% confidence level vary between 65.5 fb and 0.6 fb, while for spin-2 resonances produced via gluon–gluon fusion (or quark–antiquark initial states) limits vary between 77.4 (76.1) fb and 0.6 (0.5) fb, for the mass range from 220 GeV to 3400 GeV

Search for single vector-like B quark production and decay via B → bH(b¯b) in pp collisions at √s = 13 TeV with the ATLAS detector

A search is presented for single production of a vector-like B quark decaying into a Standard Model b-quark and a Standard Model Higgs boson, which decays into a b¯b pair. The search is carried out in 139 fb−1 of √s = 13 TeV proton-proton collision data collected by the ATLAS detector at the LHC between 2015 and 2018. No significant deviation from the Standard Model background prediction is observed, and mass-dependent exclusion limits at the 95% confidence level are set on the resonance production cross-section in several theoretical scenarios determined by the couplings cW, cZ and cH between the B quark and the Standard Model W, Z and Higgs bosons, respectively. For a vector-like B occurring as an isospin singlet, the search excludes values of cW greater than 0.45 for a B resonance mass (mB) between 1.0 and 1.2 TeV. For 1.2 TeV < mB < 2.0 TeV, cW values larger than 0.50–0.65 are excluded. If the B occurs as part of a (B, Y) doublet, the smallest excluded cZ coupling values range between 0.3 and 0.5 across the investigated resonance mass range 1.0 TeV < mB < 2.0 TeV

Search for single production of vector-like T quarks decaying into Ht or Zt in pp collisions at s√ = 13 TeV with the ATLAS detector

This paper describes a search for the single production of an up-type vector-like quark (T) decaying as T → Ht or T → Zt. The search utilises a dataset of pp collisions at s√ = 13 TeV collected with the ATLAS detector during the 2015–2018 data-taking period of the Large Hadron Collider, corresponding to an integrated luminosity of 139 fb−1. Data are analysed in final states containing a single lepton with multiple jets and b-jets. The presence of boosted heavy resonances in the event is exploited to discriminate the signal from the Standard Model background. No significant excess above the Standard Model expectation is observed, and 95% CL upper limits are set on the production cross section of T quarks in different decay channels. The results are interpreted in several benchmark scenarios to set limits on the mass and universal coupling strength (κ) of the vector-like quark. For singlet T quarks, κ values above 0.53 are excluded for all masses below 2.3 TeV. At a mass of 1.6 TeV, κ values as low as 0.35 are excluded. For T quarks in the doublet scenario, where the production cross section is much lower, κ values above 0.72 are excluded for all masses below 1.7 TeV, and this exclusion is extended to κ above 0.55 for low masses around 1.0 TeV

Search for excited τ-leptons and leptoquarks in the final state with τ-leptons and jets in pp collisions at s√ = 13 TeV with the ATLAS detector

A search is reported for excited τ-leptons and leptoquarks in events with two hadronically decaying τ-leptons and two or more jets. The search uses proton-proton (pp) collision data at s√ = 13 TeV recorded by the ATLAS experiment during the Run 2 of the Large Hadron Collider in 2015–2018. The total integrated luminosity is 139 fb−1. The excited τ-lepton is assumed to be produced and to decay via a four-fermion contact interaction into an ordinary τ-lepton and a quark-antiquark pair. The leptoquarks are assumed to be produced in pairs via the strong interaction, and each leptoquark is assumed to couple to a charm or lighter quark and a τ-lepton. No excess over the background prediction is observed. Excited τ-leptons with masses below 2.8 TeV are excluded at 95% CL in scenarios with the contact interaction scale Λ set to 10 TeV. At the extreme limit of model validity where Λ is set equal to the excited τ-lepton mass, excited τ-leptons with masses below 4.6 TeV are excluded. Leptoquarks with masses below 1.3 TeV are excluded at 95% CL if their branching ratio to a charm quark and a τ-lepton equals 1. The analysis does not exploit flavour-tagging in the signal region

Measurement of the cross-sections of the electroweak and total production of a Zγ pair in association with two jets in pp collisions at √s = 13 TeV with the ATLAS detector

This Letter presents the measurement of the fiducial and differential cross-sections of the electroweak production of a Zγ pair in association with two jets. The analysis uses 140 fb−1 of LHC proton–proton collision data taken at √s = 13 TeV recorded by the ATLAS detector during the years 2015–2018. Events with a Z boson candidate decaying into either an e+e− or μ+μ− pair, a photon and two jets are selected. The electroweak component is extracted by requiring a large dijet invariant mass and by using the information about the centrality of the system and is measured with an observed and expected significance well above five standard deviations. The fiducial pp → Zγ jj cross-section for the electroweak production is measured to be 3.6 ± 0.5 fb. The total fiducial cross-section that also includes contributions where the jets arise from strong interactions is measured to be 16.8+2.0 −1.8 fb. The results are consistent with the Standard Model predictions. Differential cross-sections are also measured using the same events and are compared with parton-shower Monte Carlo simulations. Good agreement is observed between data and predictions

Search for light long-lived neutral particles that decay to collimated pairs of leptons or light hadrons in pp collisions at s√ = 13 TeV with the ATLAS detector

A search for light long-lived neutral particles with masses in the O(MeV–GeV) range is presented. The analysis targets the production of long-lived dark photons in the decay of a Higgs boson produced via gluon–gluon fusion or in association with a W boson. Events that contain displaced collimated Standard Model fermions reconstructed in the calorimeter or muon spectrometer are selected in 139 fb−1 of s√ = 13 TeV pp collision data collected by the ATLAS detector at the LHC. Background estimates for contributions from Standard Model processes and instrumental effects are extracted from data. The observed event yields are consistent with the expected background. Exclusion limits are reported on the production cross-section times branching fraction as a function of the mean proper decay length cτ of the dark photon, or as a function of the dark-photon mass and kinetic mixing parameter that quantifies the coupling between the Standard Model and potential hidden (dark) sectors. A Higgs boson branching fraction above 1% is excluded at 95% CL for a Higgs boson decaying into two dark photons for dark-photon mean proper decay lengths between 10 mm and 250 mm and dark photons with masses between 0.4 GeV and 2 GeV