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Institute
Chordomas are rare bone tumors with few therapeutic options. Here we show, using whole-exome and genome sequencing within a precision oncology program, that advanced chordomas (nβ=β11) may be characterized by genomic patterns indicative of defective homologous recombination (HR) DNA repair and alterations affecting HR-related genes, including, for example, deletions and pathogenic germline variants of BRCA2, NBN, and CHEK2. A mutational signature associated with HR deficiency was significantly enriched in 72.7% of samples and co-occurred with genomic instability. The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib, which is preferentially toxic to HR-incompetent cells, led to prolonged clinical benefit in a patient with refractory chordoma, and whole-genome analysis at progression revealed a PARP1 p.T910A mutation predicted to disrupt the autoinhibitory PARP1 helical domain. These findings uncover a therapeutic opportunity in chordoma that warrants further exploration, and provide insight into the mechanisms underlying PARP inhibitor resistance.
Background: To evaluate clinical outcomes after either immediate or deferred initiation of antiretroviral therapy in HIV-1-infected patients, presenting late with pneumocystis pneumonia (PCP) or toxoplasma encephalitis (TE).
Methods: Phase IV, multicenter, prospective, randomized open-label clinical trial. Patients were randomized into an immediate therapy arm (starting antiretroviral therapy (ART) within 7 days after initiation of OI treatment) versus a deferred arm (starting ART after completing the OI-therapy). All patients were followed for 24 weeks. The rates of clinical progression (death, new or relapsing opportunistic infections (OI) and other grade 4 clinical endpoints) were compared, using a combined primary endpoint. Secondary endpoints were hospitalization rates after completion of OI treatment, incidence of immune reconstitution inflammatory syndrome (IRIS), virologic and immunological outcome, adherence to proteinase-inhibitor based antiretroviral therapy (ART) protocol and quality of life.
Results: 61 patients (11 patients suffering TE, 50 with PCP) were enrolled. No differences between the two therapy groups in all examined primary and secondary endpoints could be identified: immunological and virologic outcome was similar in both groups, there was no significant difference in the incidence of IRIS (11 and 10 cases), furthermore 9 events (combined endpoint of death, new/relapsing OI and grade 4 events) occurred in each group.
Conclusions: In summary, this study supports the notion that immediate initiation of ART with a ritonavir-boosted proteinase-inhibitor and two nucleoside reverse transcriptase inhibitors is safe and has no negative effects on incidence of disease progression or IRIS, nor on immunological and virologic outcomes or on quality of life.
We present first data on sub-threshold production of Ks0 mesons and Ξ hyperons in Au+Au collisions at sNN=2.4 GeV. We observe an universal β©Apartβͺ scaling of hadrons containing strangeness, independent of their corresponding production thresholds. Comparing the yields, their β©Apartβͺ scaling, and the shapes of the rapidity and the pt spectra to state-of-the-art transport model (UrQMD, HSD, IQMD) predictions, we find that none of them can simultaneously describe these observables with reasonable Ο2 values.
We investigate identical pion HBT intensity interferometry in central Au+Au collisions at 1.23A GeV. High-statistics ΟβΟβ and Ο+Ο+ data are measured with HADES at SIS18/GSI. The radius parameters, derived from the correlation function depending on relative momenta in the longitudinally comoving system and parametrized as three-dimensional Gaussian distribution, are studied as function of transverse momentum. A substantial charge-sign difference of the source radii is found, particularly pronounced at low transverse momentum. The extracted source parameters agree well with a smooth extrapolation of the center-of-mass energy dependence established at higher energies, extending the corresponding excitation functions down towards a very low energy.
We report on new measurements of Cabibbo-suppressed semileptonic D+s decays using 3.19 fbβ1 of e+eβ annihilation data sample collected at a center-of-mass energy of 4.178~GeV with the BESIII detector at the BEPCII collider. Our results include branching fractions B(D+sβK0e+Ξ½e)=(3.25Β±0.38(stat.)Β±0.16(syst.))Γ10β3 and B(D+sβKβ0e+Ξ½e)=(2.37Β±0.26(stat.)Β±0.20(syst.))Γ10β3 which are much improved relative to previous measurements, and the first measurements of the hadronic form-factor parameters for these decays. For D+sβK0e+Ξ½e, we obtain f+(0)=0.720Β±0.084(stat.)Β±0.013(syst.), and for D+sβKβ0e+Ξ½e, we find form-factor ratios rV=V(0)/A1(0)=1.67Β±0.34(stat.)Β±0.16(syst.) and r2=A2(0)/A1(0)=0.77Β±0.28(stat.)Β±0.07(syst.).
We study the hadronic decays of Ξ+c to the final states Ξ£+Ξ· and Ξ£+Ξ·β², using an e+eβ annihilation data sample of 567 pbβ1 taken at a center-of-mass energy of 4.6 GeV with the BESIII detector at the BEPCII collider. We find evidence for the decays Ξ+cβΞ£+Ξ· and Ξ£+Ξ·β² with statistical significance of 2.5Ο and 3.2Ο, respectively. Normalizing to the reference decays Ξ+cβΞ£+Ο0 and Ξ£+Ο, we obtain the ratios of the branching fractions B(Ξ+cβΞ£+Ξ·)B(Ξ+cβΞ£+Ο0) and B(Ξ+cβΞ£+Ξ·β²)B(Ξ+cβΞ£+Ο) to be 0.35Β±0.16Β±0.03 and 0.86Β±0.34Β±0.07, respectively. The upper limits at the 90\% confidence level are set to be B(Ξ+cβΞ£+Ξ·)B(Ξ+cβΞ£+Ο0)<0.58 and B(Ξ+cβΞ£+Ξ·β²)B(Ξ+cβΞ£+Ο)<1.2. Using BESIII measurements of the branching fractions of the reference decays, we determine B(Ξ+cβΞ£+Ξ·)=(0.41Β±0.19Β±0.05)% (<0.68%) and B(Ξ+cβΞ£+Ξ·β²)=(1.34Β±0.53Β±0.21)% (<1.9%). Here, the first uncertainties are statistical and the second systematic. The obtained branching fraction of Ξ+cβΞ£+Ξ· is consistent with the previous measurement, and the branching fraction of Ξ+cβΞ£+Ξ·β² is measured for the first time.
Measurement of branching fractions for D meson decaying into Ο meson and a pseudoscalar meson
(2019)
The four decay modes D0 β ΟΟ0, D0 β ΟΞ·, D+ β ΟΟ+, and D+ β ΟK + are studied by using a data sample taken at the centre-of-mass energy βs = 3.773 GeV with the BESIII detector, corresponding to an integrated luminosity of 2.93 fbβ1. The branching fractions of the first three decay modes are measured to be B(D0 β ΟΟ0) = (1.168 Β± 0.028 Β± 0.028) Γ 10β3, B(D0 β ΟΞ·) = (1.81 Β± 0.46 Β± 0.06) Γ 10β4, and B(D+ β ΟΟ+) = (5.70 Β± 0.05 Β± 0.13) Γ 10β3, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the upper limit of the branching fraction for D+ β ΟK+ is given to be 2.1 Γ 10β5 at the 90% confidence level. The ratio of B(D0 β ΟΟ0) to B(D+ β ΟΟ+) is calculated to be (20.49 Β± 0.50 Β± 0.45)%, which is consistent with the theoretical prediction based on isospin symmetry between these two decay modes.
The cross section of the process e+eββK+Kβ is measured at a number of center-of-mass energies sβ from 2.00 to 3.08 GeV with the BESIII detector at the Beijing Electron Positron Collider (BEPCII). The results provide the best precision achieved so far. A resonant structure around 2.2 GeV is observed in the cross section line shape. A Breit-Wigner fit yields a mass of M=2239.2Β±7.1Β±11.3~and a width of Ξ=139.8Β±12.3Β±20.6 MeV, where the first uncertainties are statistical and the second ones are systematic. In addition, the time-like electromagnetic form factor of the kaon is determined at the individual center-of-mass energy points.
Using π+β’πββΞ+πβ’Β―Ξβπ production from a 567ββpbβ1 data sample collected by BESIII at 4.6 GeV, a full angular analysis is carried out simultaneously on the four decay modes of Ξ+πβπβ’πΎ0π, Ξβ’π+, Ξ£+β’π0, and Ξ£0β’π+. For the first time, the Ξ+π transverse polarization is studied in unpolarized π+β’πβ collisions, where a nonzero effect is observed with a statistical significance of 2.1β’π. The decay asymmetry parameters of the Ξ+π weak hadronic decays into πβ’πΎ0π, Ξβ’π+, Ξ£+β’π0 and Ξ£0β’π+ are measured to be 0.18Β±0.43β’(stat)Β±0.14β’(syst), β0.80Β±0.11β’(stat)Β±0.02β’(syst), β0.57Β±0.10β’(stat)Β±0.07β’(syst), and β0.73Β±0.17β’(stat)Β±0.07β’(syst), respectively. In comparison with previous results, the measurements for the Ξβ’π+ and Ξ£+β’π0 modes are consistent but with improved precision, while the parameters for the πβ’πΎ0π and Ξ£0β’π+ modes are measured for the first time.
We measure the Born cross sections of the process π+β’πββπΎ+β’πΎββ’πΎ+β’πΎβ at center-of-mass (c.m.) energies, βπ , between 2.100 and 3.080 GeV. The data were collected using the BESIII detector at the BEPCII collider. An enhancement at βπ =2.232ββGeV is observed, very close to the π+β’πββΞβ’Β―Ξ production threshold. A similar enhancement at the same c.m. energy is observed in the π+β’πββπβ’πΎ+β’πΎβ cross section. The energy dependence of the πΎ+β’πΎββ’πΎ+β’πΎβ and πβ’πΎ+β’πΎβ cross sections differs significantly from that of π+β’πββπβ’π+β’πβ.