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We search for an axion-like particle (ALP) a through the process ψ(3686)→π+π−J/ψ, J/ψ→γa, a→γγ in a data sample of (2.71±0.01)×109 ψ(3686) events collected by the BESIII detector. No significant ALP signal is observed over the expected background, and the upper limits on the branching fraction of the decay J/ψ→γa and the ALP-photon coupling constant gaγγ are set at 95% confidence level in the mass range of 0.165≤ma≤2.84GeV/c2. The limits on B(J/ψ→γa) range from 8.3×10−8 to 1.8×10−6 over the search region, and the constraints on the ALP-photon coupling are the most stringent to date for 0.165≤ma≤1.468GeV/c2.
We search for an axion-like particle (ALP) a through the process ψ(3686)→π+π−J/ψ, J/ψ→γa, a→γγ in a data sample of (2.71±0.01)×109 ψ(3686) events collected by the BESIII detector. No significant ALP signal is observed over the expected background, and the upper limits on the branching fraction of the decay J/ψ→γa and the ALP-photon coupling constant gaγγ are set at 95% confidence level in the mass range of 0.165≤ma≤2.84GeV/c2. The limits on B(J/ψ→γa) range from 8.3×10−8 to 1.8×10−6 over the search region, and the constraints on the ALP-photon coupling are the most stringent to date for 0.165≤ma≤1.468GeV/c2.
Using e+e− annihilation data sets collected with the BESIII detector, we measure the cross sections of the processes e+e−→e+e− and e+e−→μ+μ− at fifteen center-of-mass energy points in the vicinity of the J/ψ resonance. By a simultaneous fit to the measured, center-of-mass energy dependent cross sections of the two processes, the combined quantities ΓeeΓee/Γtot and ΓeeΓμμ/Γtot are determined to be (0.346±0.009) and (0.335±0.006) keV, respectively, where Γee, Γμμ, and Γtot are the electronic, muonic, and total decay widths of the J/ψ resonance, respectively. Using the resultant ΓeeΓμμ/Γtot and ΓeeΓee/Γtot, the ratio Γee/Γμμ is calculated to be 1.031±0.015, which is consistent with the expectation of lepton universality within about two standard deviations. Assuming lepton universality and using the branching fraction of the J/ψ leptonic decay measured by BESIII in 2013, Γtot and Γll are determined to be (93.0±2.1) and (5.56±0.11) keV, respectively, where Γll is the average leptonic decay width of the J/ψ resonance.
Observation of 𝜒𝑐𝐽→Λ¯Λ𝜂
(2022)
By analyzing (448.1±2.9)×106 𝜓(3686) events collected with the BESIII detector operating at the BEPCII collider, the decays of 𝜒𝑐𝐽→Λ
¯Λ𝜂 (𝐽=0, 1, and 2) are observed for the first time with statistical significances of 13.9𝜎, 6.7𝜎, and 8.2𝜎, respectively. The product branching fractions of 𝜓(3686)→𝛾𝜒𝑐𝐽 and 𝜒𝑐𝐽→Λ¯Λ𝜂 are measured. Dividing by the world averages of the branching fractions of 𝜓(3686)→𝛾𝜒𝑐𝐽, the branching fractions of 𝜒𝑐𝐽→Λ¯Λ𝜂 decays are determined to be (2.31±0.30±0.21)×10−4, (5.86±1.38±0.68)×10−5, and (1.05±0.21±0.15)×10−4 for 𝐽=0, 1 and 2, respectively, where the first uncertainties are statistical and the second systematic.
The radiative hyperon decay Λ→nγ is studied using (10087±44)×106 J/ψ events collected with the BESIII detector operating at BEPCII. The absolute branching fraction of the decay Λ→nγ is determined with a significance of 5.6σ to be [0.832±0.038(stat.)±0.054(syst.)]×10−3, which lies significantly below the current PDG value. By analyzing the joint angular distribution of the decay products, the first determination of the decay asymmetry αγ is reported with a value of −0.16±0.10(stat.)±0.05(syst.).
We report a search for a heavier partner of the recently observed Zcs(3985)− state, denoted as Z′−cs, in the process e+e−→K+D∗−sD∗0+c.c., based on e+e− collision data collected at the center-of-mass energies of s√=4.661, 4.682 and 4.699 GeV with the BESIII detector. The Z′−cs is of interest as it is expected to be a candidate for a hidden-charm and open-strange tetraquark. A partial-reconstruction technique is used to isolate K+ recoil-mass spectra, which are probed for a potential contribution from Z′−cs→D∗−sD∗0 (c.c.). We find an excess of Z′−cs→D∗−sD∗0 (c.c.) candidates with a significance of 2.1σ, after considering systematic uncertainties, at a mass of (4123.5±0.7stat.±4.7syst.) MeV/c2. As the data set is limited in size, the upper limits are evaluated at the 90\% confidence level on the product of the Born cross sections (σBorn) and the branching fraction (B) of Z′−cs→D∗−sD∗0, under different assumptions of the Z′−cs mass from 4.120 to 4.140 MeV and of the width from 10 to 50 MeV at the three center-of-mass energies. The upper limits of σBorn⋅B are found to be at the level of O(1) pb at each energy. Larger data samples are needed to confirm the Z′−cs state and clarify its nature in the coming years.
We report a search for a heavier partner of the recently observed Zcs(3985)− state, denoted as Z′−cs, in the process e+e−→K+D∗−sD∗0+c.c., based on e+e− collision data collected at the center-of-mass energies of s√=4.661, 4.682 and 4.699 GeV with the BESIII detector. The Z′−cs is of interest as it is expected to be a candidate for a hidden-charm and open-strange tetraquark. A partial-reconstruction technique is used to isolate K+ recoil-mass spectra, which are probed for a potential contribution from Z′−cs→D∗−sD∗0 (c.c.). We find an excess of Z′−cs→D∗−sD∗0 (c.c.) candidates with a significance of 2.1σ, after considering systematic uncertainties, at a mass of (4123.5±0.7stat.±4.7syst.) MeV/c2. As the data set is limited in size, the upper limits are evaluated at the 90\% confidence level on the product of the Born cross sections (σBorn) and the branching fraction (B) of Z′−cs→D∗−sD∗0, under different assumptions of the Z′−cs mass from 4.120 to 4.140 MeV and of the width from 10 to 50 MeV at the three center-of-mass energies. The upper limits of σBorn⋅B are found to be at the level of O(1) pb at each energy. Larger data samples are needed to confirm the Z′−cs state and clarify its nature in the coming years.
Using about 23 fb−1 of data collected with the BESIII detector operating at the BEPCII storage ring, a precise measurement of the e+e−→π+π−J/ψ Born cross section is performed at center-of-mass energies from 3.7730 to 4.7008 GeV. Two structures, identified as the Y(4220) and the Y(4320) states, are observed in the energy-dependent cross section with a significance larger than 10σ. The masses and widths of the two structures are determined to be (M,Γ) = (4221.4±1.5±2.0 MeV/c2, 41.8±2.9±2.7 MeV) and (M,Γ) = (4298±12±26 MeV/c2, 127±17±10 MeV), respectively. A small enhancement around 4.5 GeV with a significance about 3σ, compatible with the ψ(4415), might also indicate the presence of an additional resonance in the spectrum. The inclusion of this additional contribution in the fit to the cross section affects the resonance parameters of the Y(4320) state.
Using about 23 fb−1 of data collected with the BESIII detector operating at the BEPCII storage ring, a precise measurement of the e+e−→π+π−J/ψ Born cross section is performed at center-of-mass energies from 3.7730 to 4.7008 GeV. Two structures, identified as the Y(4220) and the Y(4320) states, are observed in the energy-dependent cross section with a significance larger than 10σ. The masses and widths of the two structures are determined to be (M,Γ) = (4221.4±1.5±2.0 MeV/c2, 41.8±2.9±2.7 MeV) and (M,Γ) = (4298±12±26 MeV/c2, 127±17±10 MeV), respectively. A small enhancement around 4.5 GeV with a significance about 3σ, compatible with the ψ(4415), might also indicate the presence of an additional resonance in the spectrum. The inclusion of this additional contribution in the fit to the cross section affects the resonance parameters of the Y(4320) state.
We search for an axion-like particle (ALP) a through the process ψ(3686)→π+π−J/ψ, J/ψ→γa, a→γγ in a data sample of (2.71±0.01)×109 ψ(3686) events collected by the BESIII detector. No significant ALP signal is observed over the expected background, and the upper limits on the branching fraction of the decay J/ψ→γa and the ALP-photon coupling constant gaγγ are set at 95% confidence level in the mass range of 0.165≤ma≤2.84GeV/c2. The limits on B(J/ψ→γa) range from 8.3×10−8 to 1.8×10−6 over the search region, and the constraints on the ALP-photon coupling are the most stringent to date for 0.165 ≤ ma ≤ 1.468GeV/c2.
Using about 23 fb−1 of data collected with the BESIII detector operating at the BEPCII storage ring, a precise measurement of the 𝑒+𝑒−→𝜋+𝜋−𝐽/𝜓 Born cross section is performed at center-of-mass energies from 3.7730 to 4.7008 GeV. Two structures, identified as the 𝑌(4220) and the 𝑌(4320) states, are observed in the energy-dependent cross section with a significance larger than 10𝜎. The masses and widths of the two structures are determined to be (𝑀,Γ)=(4221.4±1.5±2.0 MeV/𝑐2,41.8±2.9±2.7 MeV) and (𝑀,Γ)=(4298±12±26 MeV/𝑐2,127±17±10 MeV), respectively. A small enhancement around 4.5 GeV with a significance about 3𝜎, compatible with the 𝜓(4415), might also indicate the presence of an additional resonance in the spectrum. The inclusion of this additional contribution in the fit to the cross section affects the resonance parameters of the 𝑌(4320) state.
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay 𝜂𝑐(2𝑆)→3(𝜋+𝜋−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 𝜓(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of 𝜂𝑐(2𝑆) are (3643.4±2.3 (stat)±4.4 (syst)) MeV/𝑐2 and (19.8±3.9 (stat)±3.1 (syst)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]×ℬ[𝜂𝑐(2𝑆)→3(𝜋+𝜋−)] is measured to be (9.2±1.0 (stat)±1.2 (syst))×10−6. Using ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]=(7.0+3.4−2.5)×10−4, we obtain ℬ[𝜂𝑐(2𝑆)→3(𝜋+𝜋−)]=(1.31±0.15 (stat)±0.17 (syst) (+0.64−0.47) (extr))×10−2, where the third uncertainty is from ℬ[𝜓(3686)→𝛾𝜂𝑐(2𝑆)]. We also measure the 𝜒𝑐𝐽→3(𝜋+𝜋−) (𝐽=0, 1, 2) decays via 𝜓′→𝛾𝜒𝑐𝐽 transitions. The branching fractions are ℬ[𝜒𝑐0→3(𝜋+𝜋−)]=(2.080±0.006 (stat)±0.068 (syst))×10−2, ℬ[𝜒𝑐1→3(𝜋+𝜋−)]=(1.092±0.004 (stat)±0.035 (syst))×10−2, and ℬ[𝜒𝑐2→3(𝜋+𝜋−)]=(1.565±0.005 (stat)±0.048 (syst))×10−2.
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay ηc(2S)→3(π+π−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of ηc(2S) are (3643.4±2.3(stat.)±4.4(syst.)) MeV/c2 and (19.8±3.9(stat.)±3.1(syst.)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction B[ψ(3686) → γηc(2S)]×B[ηc(2S)→3(π+π−)] is measured to be (9.2±1.0(stat.)±0.9(syst.))×10−6. Using B[ψ(3686)→γηc(2S)]=(7.0+3.4−2.5)×10−4, we obtain B[ηc(2S)→3(π+π−)]=(1.31±0.15(stat.)±0.13(syst.)(+0.64−0.47)(extr))×10−2, where the third uncertainty is from B[ψ(3686)→γηc(2S)]. We also measure the χcJ→3(π+π−) (J=0,1,2) decays via ψ(3686)→γχcJ transitions. The branching fractions are B[χc0→3(π+π−)]=(2.080±0.006(stat.)±0.068(syst.))×10−2, B[χc1→3(π+π−)]=(1.092±0.004(stat.)±0.035(syst.))×10−2, and B[χc2→3(π+π−)]=(1.565±0.005(stat.)±0.048(syst.))×10−2.
Observation of ηc(2S) → 3(π⁺π⁻) and measurements of χcJ → 3(π⁺π⁻) in ψ(3686) radiative transitions
(2022)
The hadronic decay ηc(2S)→3(π+π−) is observed with a statistical significance of 9.3 standard deviations using (448.1±2.9)×106 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The measured mass and width of ηc(2S) are (3643.4±2.3(stat.)±4.4(syst.)) MeV/c2 and (19.8±3.9(stat.)±3.1(syst.)) MeV, respectively, which are consistent with the world average values within two standard deviations. The product branching fraction B[ψ(3686)→γηc(2S)]×B[ηc(2S)→3(π+π−)] is measured to be (9.2±1.0(stat.)±0.9(syst.))×10−6. Using B[ψ(3686)→γηc(2S)]=(7.0+3.4−2.5)×10−4, we obtain B[ηc(2S)→3(π+π−)]=(1.31±0.15(stat.)±0.13(syst.)(+0.64−0.47)(extr))×10−2, where the third uncertainty is from B[ψ(3686)→γηc(2S)]. We also measure the χcJ→3(π+π−) (J=0,1,2) decays via ψ(3686)→γχcJ transitions. The branching fractions are B[χc0→3(π+π−)]=(2.080±0.006(stat.)±0.068(syst.))×10−2, B[χc1→3(π+π−)]=(1.092±0.004(stat.)±0.035(syst.))×10−2, and B[χc2→3(π+π−)]=(1.565±0.005(stat.)±0.048(syst.))×10−2.
Using an 𝑒+𝑒− collision data sample with a total integrated luminosity of 3.19 fb−1 collected with the BESIII detector at a center-of-mass energy of 4.178 GeV, the branching fraction of the inclusive decay of the 𝐷+𝑠 meson to final states including at least three charged pions is measured for the first time to be ℬ(𝐷+𝑠→𝜋+𝜋+𝜋−𝑋)=(32.81±0.35stat±0.63syst)%. In this measurement the charged pions from 𝐾0𝑆 meson decays are excluded. The partial branching fractions of 𝐷+𝑠→𝜋+𝜋+𝜋−𝑋 are also measured as a function of the 𝜋+𝜋+𝜋− invariant mass.
By analyzing 𝑒+𝑒− annihilation data with an integrated luminosity of 2.93 fb−1 collected at the center-of-mass energy √𝑠=3.773 GeV with the BESIII detector, we present the first absolute measurements of the branching fractions of twenty Cabibbo-suppressed hadronic 𝐷0(+) decays involving multiple pions. The highest four branching fractions obtained are ℬ(𝐷0→𝜋+𝜋−𝜋0) = (1.343±0.013stat±0.016syst)%, ℬ(𝐷0→𝜋+𝜋−2𝜋0) = (1.002±0.019stat±0.024syst)%, ℬ(𝐷+→2𝜋+𝜋−𝜋0) = (1.165±0.021stat±0.021syst)%, and ℬ(𝐷+→2𝜋+𝜋−2𝜋0) = (1.074±0.040stat±0.030syst)%. The 𝐶𝑃 asymmetries for the six decays with highest signal yields are also determined and found to be compatible with zero.
By analyzing e+e− annihilation data with an integrated luminosity of 2.93 fb−1 collected at the center-of-mass energy s√= 3.773 GeV with the BESIII detector, we present the first absolute measurements of the branching fractions of twenty Cabibbo-suppressed hadronic D0(+) decays involving multiple pions. The largest four branching fractions obtained are B(D0→π+π−π0) = >(1.343±0.013stat±0.016syst)%, B(D0→π+π−2π0) = (0.998±0.019stat±0.024syst)%, B(D+→2π+π−π0)
(1.174±0.021stat±0.021syst)%, and B(D+→2π+π−2π0) = (1.074±0.040stat±0.030syst)%. The CP asymmetries for the six decays with highest event yields are also determined.
Using a sample of (448.1±2.9)×106 𝜓(3686) decays collected with the BESIII detector at BEPCII, we report an observation of Ξ− transverse polarization with a significance of 7.3𝜎 in the decay 𝜓(3686)→Ξ− ¯Ξ+ (Ξ−→Λ𝜋−, ¯Ξ+→¯Λ𝜋+, Λ→𝑝𝜋−, ¯Λ→¯𝑝𝜋+). The relative phase of the electric and magnetic form factors is determined to be ΔΦ=(0.667±0.111±0.058) rad. This is the first measurement of the relative phase for a 𝜓(3686) decay into a pair of Ξ−¯Ξ+ hyperons. The Ξ− decay parameters (𝛼Ξ−, 𝜙Ξ−) and their conjugates (𝛼¯Ξ+, 𝜙¯Ξ+), the angular-distribution parameter 𝛼𝜓, and the strong-phase difference 𝛿𝑝−𝛿𝑠 for Λ𝜋− scattering are measured to be consistent with previous BESIII results.
We report a measurement of the cross section for the process e+e−→π+π−J/ψ around the X(3872) mass in search for the direct formation of e+e−→X(3872) through the two-photon fusion process. No enhancement of the cross section is observed at the X(3872) peak and an upper limit on the product of electronic width and branching fraction of X(3872)→π+π−J/ψ is determined to be Γee×B(X(3872)→π+π−J/ψ)<7.5×10−3eV at 90% confidence level under an assumption of total width of 1.19±0.21 MeV. This is an improvement of a factor of about 17 compared to the previous limit. Furthermore, using the latest result of B(X(3872)→π+π−J/ψ), an upper limit on the electronic width Γee of X(3872) is obtained to be <0.32eV at the 90% confidence level.
Luminosities and energies of e⁺e⁻ collision data taken between √s=4.61 GeV and 4.95 GeV at BESIII
(2022)
From December 2019 to June 2021, the BESIII experiment collected about 5.85 fb−1 of data at center-of-mass energies between 4.61 GeV and 4.95 GeV. This is the highest collision energy BEPCII has reached so far. The accumulated e+e− annihilation data samples are useful for studying charmonium(-like) states and charmed-hadron decays. By adopting a novel method of analyzing the production of Λ+cΛ¯−c pairs in e+e− annihilation, the center-of-mass energies are measured with a precision of ∼0.6 MeV. Integrated luminosities are measured with a precision of better than 1\% by analyzing the events of large-angle Bhabha scattering. These measurements provide important inputs to the analyses based on these data samples.
Background: Does the dogma of nephron sparing surgery (NSS) still stand for large renal masses? Available studies dealing with that issue are considerably biased often mixing imperative with elective indications for NSS and also including less malignant variants or even benign renal tumors. Here, we analyzed the oncological long-term outcomes of patients undergoing elective NSS or radical tumor nephrectomy (RN) for non-endophytic, large (≥7cm) clear cell renal carcinoma (ccRCC).
Methods: Prospectively acquired, clinical databases from two academic high-volume centers were screened for patients from 1980 to 2010. The query was strictly limited to patients with elective indications. Surgical complications were retrospectively assessed and classified using the Clavien-Dindo-classification system (CDS). Overall survival (OS) and cancer specific survival (CSS) were analyzed using the Kaplan-Meier-method and the log-rank test.
Results: Out of in total 8664 patients in the databases, 123 patients were identified (elective NSS (n = 18) or elective RN (n = 105)) for ≥7cm ccRCC. The median follow-up over all was 102 months (range 3–367 months). Compared to the RN group, the NSS group had a significantly longer median OS (p = 0.014) and median CSS (p = 0.04).
Conclusions: In large renal masses, NSS can be performed safely with acceptable complication rates. In terms of long-term OS and CSS, NSS was at least not inferior to RN. Our findings suggest that NSS should also be performed in patients presenting with renal tumors ≥7cm whenever technically feasible. Limitations include its retrospective nature and the limited availability of data concerning long-term development of renal function in the two groups.
Objective: To investigate temporal trends in prostate cancer (PCa) radical prostatectomy (RP) candidates.
Materials and Methods: Patients who underwent RP for PCa between January 2014 and December 2019 were identified form our institutional database. Trend analysis and logistic regression models assessed RP trends after stratification of PCa patients according to D'Amico classification and Gleason score. Patients with neoadjuvant androgen deprivation or radiotherapy prior to RP were excluded from the analysis.
Results: Overall, 528 PCa patients that underwent RP were identified. Temporal trend analysis revealed a significant decrease in low-risk PCa patients from 17 to 9% (EAPC: −14.6%, p < 0.05) and GS6 PCa patients from 30 to 14% (EAPC: −17.6%, p < 0.01). This remained significant even after multivariable adjustment [low-risk PCa: (OR): 0.85, p < 0.05 and GS6 PCa: (OR): 0.79, p < 0.001]. Furthermore, a trend toward a higher proportion of intermediate-risk PCa undergoing RP was recorded.
Conclusion: Our results confirm that inverse stage migration represents an ongoing phenomenon in a contemporary RP cohort in a European tertiary care PCa center. Our results demonstrate a significant decrease in the proportion of low-risk and GS6 PCa undergoing RP and a trend toward a higher proportion of intermediate-risk PCa patients undergoing RP. This indicates a more precise patient selection when it comes to selecting suitable candidates for definite surgical treatment with RP.
Objective: We aimed to assess the correlation between serum prostate-specific antigen (PSA) and tumor burden in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), because estimation of tumor burden is of high value, e.g., in men undergoing RP or with biochemical recurrence after RP. Patients and Methods: From January 2019 to June 2020, 179 consecutive PCa patients after RP with information on tumor and prostate weight were retrospectively identified from our prospective institutional RP database. Patients with preoperative systemic therapy (n=19), metastases (cM1, n=5), and locally progressed PCa (pT4 or pN1, n=50) were excluded from analyses. Histopathological features, including total weight of the prostate and specific tumor weight, were recorded by specialized uro-pathologists. Linear regression models were performed to evaluate the effect of PSA on tumor burden, measured by tumor weight after adjustment for patient and tumor characteristics. Results: Overall, median preoperative PSA was 7.0 ng/ml (interquartile range [IQR]: 5.41–10) and median age at surgery was 66 years (IQR: 61-71). Median prostate weight was 34 g (IQR: 26–46) and median tumor weight was 3.7 g (IQR: 1.8–7.1), respectively. In multivariable linear regression analysis after adjustment for patients and tumor characteristics, a significant, positive correlation could be detected between preoperative PSA and tumor weight (coefficient [coef.]: 0.37, CI: 0.15–0.6, p=0.001), indicating a robust increase in PSA of almost 0.4 ng/ml per 1g tumor weight. Conclusion: Preoperative PSA was significantly correlated with tumor weight in PCa patients undergoing RP, with an increase in PSA of almost 0.4 ng/ml per 1 g tumor weight. This might help to estimate both tumor burden before undergoing RP and in case of biochemical recurrence.
Objective: Many patients with localized prostate cancer (PCa) do not immediately undergo radical prostatectomy (RP) after biopsy confirmation. The aim of this study was to investigate the influence of “time-from-biopsy-to- prostatectomy” on adverse pathological outcomes.
Materials and Methods: Between January 2014 and December 2019, 437 patients with intermediate- and high risk PCa who underwent RP were retrospectively identified within our prospective institutional database. For the aim of our study, we focused on patients with intermediate- (n = 285) and high-risk (n = 151) PCa using D'Amico risk stratification. Endpoints were adverse pathological outcomes and proportion of nerve-sparing procedures after RP stratified by “time-from-biopsy-to-prostatectomy”: ≤3 months vs. >3 and < 6 months. Medians and interquartile ranges (IQR) were reported for continuously coded variables. The chi-square test examined the statistical significance of the differences in proportions while the Kruskal-Wallis test was used to examine differences in medians. Multivariable (ordered) logistic regressions, analyzing the impact of time between diagnosis and prostatectomy, were separately run for all relevant outcome variables (ISUP specimen, margin status, pathological stage, pathological nodal status, LVI, perineural invasion, nerve-sparing).
Results: We observed no difference between patients undergoing RP ≤3 months vs. >3 and <6 months after diagnosis for the following oncological endpoints: pT-stage, ISUP grading, probability of a positive surgical margin, probability of lymph node invasion (LNI), lymphovascular invasion (LVI), and perineural invasion (pn) in patients with intermediate- and high-risk PCa. Likewise, the rates of nerve sparing procedures were 84.3 vs. 87.4% (p = 0.778) and 61.0% vs. 78.8% (p = 0.211), for intermediate- and high-risk PCa patients undergoing surgery after ≤3 months vs. >3 and <6 months, respectively. In multivariable adjusted analyses, a time to surgery >3 months did not significantly worsen any of the outcome variables in patients with intermediate- or high-risk PCa (all p > 0.05).
Conclusion: A “time-from-biopsy-to-prostatectomy” of >3 and <6 months is neither associated with adverse pathological outcomes nor poorer chances of nerve sparing RP in intermediate- and high-risk PCa patients.
hintergrund: Männer in Deutschland sterben früher als Frauen und nehmen weniger häufig Krebsvorsorgeuntersuchungen wahr.
Fragestellung: Ziel war die prospektive Evaluation einer „Movember-Gesundheitsinitiative“ am Universitätsklinikum Frankfurt (UKF) im November 2019.
Methoden: Im Rahmen der „Movember-Gesundheitsinitiative“ wurde allen männlichen Mitarbeitern des UKF ab dem 45. Lebensjahr und bei erstgradiger familiärer Vorbelastung eines Prostatakarzinoms ab dem 40. Lebensjahr im November 2019 gemäß S3-Leitlinien der Deutschen Gesellschaft für Urologie (DGU) eine Prostatakarzinom-Vorsorgeuntersuchung angeboten.
Ergebnisse: Insgesamt nahmen 14,4 % der Mitarbeiter teil. Eine familiäre Vorbelastung gaben insgesamt 14,0 % Teilnehmer an. Das mediane Alter betrug 54 Jahre. Der mediane PSA(prostataspezifisches Antigen)-Wert lag bei 0,9 ng/ml, der mediane PSA-Quotient bei 30 %. Bei 5 % (n = 6) zeigte sich ein suspekter Tastbefund in der DRU (digital-rektale Untersuchung). Nach Altersstratifizierung (≤ 50 vs. > 50 Lebensjahre) zeigten sich signifikante Unterschiede im medianen PSA-Wert (0,7 ng/ml vs. 1,0 ng/ml, p < 0,01) und der bereits zuvor durchgeführten urologischen Vorsorge (12,1 vs. 42,0 %, p < 0,01). Vier Teilnehmer (3,3 %) zeigten erhöhte Gesamt-PSA-Werte. Bei 32,2 % der Teilnehmer zeigte sich mindestens ein kontrollbedürftiger Befund. Insgesamt wurden 6 Prostatabiopsien durchgeführt. Hierbei zeigte sich in einem Fall ein intermediate-risk Prostatakarzinom (Gleason 3 + 4, pT3a, pPn1, pNx, R0).
Schlussfolgerungung: Im Rahmen der UKF-Movember-Gesundheitsinitiative 2019 konnten durch ein Vorsorgeangebot 121 Männer für eine Prostatakrebs-Vorsorge inklusive PSA-Testung gewonnen werden. Auffällige/kontrollbedürftige Befunde zeigten sich bei 32,2 %. Bei einem Mitarbeiter wurde ein therapiebedürftiges Prostatakarzinom entdeckt und therapiert.
In vivo inducible reverse genetics in patients' tumors to identify individual therapeutic targets
(2021)
High-throughput sequencing describes multiple alterations in individual tumors, but their functional relevance is often unclear. Clinic-close, individualized molecular model systems are required for functional validation and to identify therapeutic targets of high significance for each patient. Here, we establish a Cre-ERT2-loxP (causes recombination, estrogen receptor mutant T2, locus of X-over P1) based inducible RNAi- (ribonucleic acid interference) mediated gene silencing system in patient-derived xenograft (PDX) models of acute leukemias in vivo. Mimicking anti-cancer therapy in patients, gene inhibition is initiated in mice harboring orthotopic tumors. In fluorochrome guided, competitive in vivo trials, silencing of the apoptosis regulator MCL1 (myeloid cell leukemia sequence 1) correlates to pharmacological MCL1 inhibition in patients´ tumors, demonstrating the ability of the method to detect therapeutic vulnerabilities. The technique identifies a major tumor-maintaining potency of the MLL-AF4 (mixed lineage leukemia, ALL1-fused gene from chromosome 4) fusion, restricted to samples carrying the translocation. DUX4 (double homeobox 4) plays an essential role in patients’ leukemias carrying the recently described DUX4-IGH (immunoglobulin heavy chain) translocation, while the downstream mediator DDIT4L (DNA-damage-inducible transcript 4 like) is identified as therapeutic vulnerability. By individualizing functional genomics in established tumors in vivo, our technique decisively complements the value chain of precision oncology. Being broadly applicable to tumors of all kinds, it will considerably reinforce personalizing anti-cancer treatment in the future.
Siebenmeilenstiefel gab es einmal in zwei Welten: zum einen im Märchen, wo sie Wunderdinge sind, die übernatürliche Fähigkeiten verleihen; zum anderen wurden die Reitstiefel der Postreiter so genannt, "die nur alle sieben Meilen den Boden berührten, wenn Postreiter oder Gespanne an Stationen die Pferde wechselten". Als literarisches Motiv haben die Siebenmeilenstiefel eine lange Geschichte, die mindestens bis in den griechischen Mythos zurückreicht, wo Perseus von den Nymphen Flügelsandalen erhält - zum Dank dafür, dass er die übelriechenden Graien ins Meer wirft. In der Science-Fiction des 20. Jahrhunderts kehrt das Motiv auf - zeitgemäß - abstrakterer Ebene wieder, in der Figur der Teleportation, also des Reisens durch den Raum ohne zeitliche Verzögerung - und ohne ein bestimmtes Schuhwerk.
The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium–aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1–38) vs. a median of 15 (range 2–74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.
Background: To test the value of immunohistochemistry (IHC) staining in prostate biopsies for changes in biopsy results and its impact on treatment decision-making. Methods: Between January 2017–June 2020, all patients undergoing prostate biopsies were identified and evaluated regarding additional IHC staining for diagnostic purpose. Final pathologic results after radical prostatectomy (RP) were analyzed regarding the effect of IHC at biopsy. Results: Of 606 biopsies, 350 (58.7%) received additional IHC staining. Of those, prostate cancer (PCa) was found in 208 patients (59.4%); while in 142 patients (40.6%), PCa could be ruled out through IHC. IHC patients harbored significantly more often Gleason 6 in biopsy (p < 0.01) and less suspicious baseline characteristics than patients without IHC. Of 185 patients with positive IHC and PCa detection, IHC led to a change in biopsy results in 81 (43.8%) patients. Of these patients with changes in biopsy results due to IHC, 42 (51.9%) underwent RP with 59.5% harboring ≥pT3 and/or Gleason 7–10. Conclusions: Patients with IHC stains had less suspicious characteristics than patients without IHC. Moreover, in patients with positive IHC and PCa detection, a change in biopsy results was observed in >40%. Patients with changes in biopsy results partly underwent RP, in which 60% harbored significant PCa.
Background: The impact of MRI-lesion targeted (TB) and systematic biopsy (SB) Gleason score (GS) as a predictor for final pathological GS still remains unclear. Methods: All patients with TB + SB, and subsequent radical prostatectomy (RP) between 01/2014-12/2020 were analyzed. Rank correlation coefficient predicted concordance with pathological GS for patients’ TB and SB GS, as well as for the combined effect of SB + TB. Results: Of 159 eligible patients, 77% were biopsy naïve. For SB taken in addition to TB, a Spearman’s correlation of +0.33 was observed regarding final GS. Rates of concordance, upgrading, and downgrading were 37.1, 37.1 and 25.8%, respectively. For TB, a +0.52 correlation was computed regarding final GS. Rates of concordance, upgrading and downgrading for TB biopsy GS were 45.9, 33.3, and 20.8%, respectively. For the combination of SB + TB, a correlation of +0.59 was observed. Rates of concordance, upgrading and downgrading were 49.7, 15.1 and 35.2%, respectively. The combined effect of SB + TB resulted in a lower upgrading rate, relative to TB and SB (both p < 0.001), but a higher downgrading rate, relative to TB (p < 0.01). Conclusions: GS obtained from TB provided higher concordance and lower upgrading and downgrading rates, relative to SB GS with regard to final pathology. The combined effect of SB + TB led to the highest concordance rate and the lowest upgrading rate.
In March 2019 the HADES experiment recorded 14 billion Ag+Ag collisions at √sNN = 2.55 GeV as a part of the FAIR phase-0 physics program. In this contribution, we present and investigate our capabilities to reconstruct and analyze weakly decaying strange hadrons and hypernuclei emerging from these collisions. The focus is put on measuring the mean lifetimes of these particles.
Startle disease or hereditary hyperekplexia has been shown to result from mutations in the α1‐subunit gene of the inhibitory glycine receptor (GlyR). In hyperekplexia patients, neuromotor symptoms generally become apparent at birth, improve with age, and often disappear in adulthood. Loss‐of‐function mutations of GlyR α or β‐subunits in mice show rather severe neuromotor phenotypes. Here, we generated mutant mice with a transient neuromotor deficiency by introducing a GlyR β transgene into the spastic mouse (spa/spa), a recessive mutant carrying a transposon insertion within the GlyR β‐subunit gene. In spa/spa TG456 mice, one of three strains generated with this construct, which expressed very low levels of GlyR β transgene‐dependent mRNA and protein, the spastic phenotype was found to depend upon the transgene copy number. Notably, mice carrying two copies of the transgene showed an age‐dependent sensitivity to tremor induction, which peaked at ∼ 3–4 weeks postnatally. This closely resembles the development of symptoms in human hyperekplexia patients, where motor coordination significantly improves after adolescence. The spa/spa TG456 line thus may serve as an animal model of human startle disease.
Abstract
Natural plant populations often harbour substantial heritable variation in DNA methylation. However, a thorough understanding of the genetic and environmental drivers of this epigenetic variation requires large-scale and high-resolution data, which currently exist only for a few model species. Here, we studied 207 lines of the annual weed Thlaspi arvense (field pennycress), collected across a large latitudinal gradient in Europe and propagated in a common environment. By screening for variation in DNA sequence and DNA methylation using whole-genome (bisulfite) sequencing, we found significant epigenetic population structure across Europe. Average levels of DNA methylation were strongly context-dependent, with highest DNA methylation in CG context, particularly in transposable elements and in intergenic regions. Residual DNA methylation variation within all contexts was associated with genetic variants, which often co-localized with annotated methylation machinery genes but also with new candidates. Variation in DNA methylation was also significantly associated with climate of origin, with methylation levels being higher in warmer regions and lower in more variable climates. Finally, we used variance decomposition to assess genetic versus environmental associations with differentially methylation regions (DMRs). We found that while genetic variation was generally the strongest predictor of DMRs, the strength of environmental associations increased from CG to CHG and CHH, with climate-of-origin as the strongest predictor in about one third of the CHH DMRs. In summary, our data show that natural epigenetic variation in Thlaspi arvense is significantly associated with both DNA sequence and environment of origin, and that the relative importance of the two factors strongly depends on the sequence context of DNA methylation. T. arvense is an emerging biofuel and winter cover crop; our results may hence be relevant for breeding efforts and agricultural practices in the context of rapidly changing environmental conditions.
Author Summary: Variation within species is an important level of biodiversity, and it is key for future adaptation. Besides variation in DNA sequence, plants also harbour heritable variation in DNA methylation, and we want to understand the evolutionary significance of this epigenetic variation, in particular how much of it is under genetic control, and how much is associated with the environment. We addressed these questions in a high-resolution molecular analysis of 207 lines of the common plant field pennycress (Thlaspi arvense), which we collected across Europe, propagated under standardized conditions, and sequenced for their genetic and epigenetic variation. We found large geographic variation in DNA methylation, associated with both DNA sequence and climate of origin. Genetic variation was generally the stronger predictor of DNA methylation variation, but the strength of environmental association varied between different sequence contexts. Climate-of-origin was the strongest predictor in about one third of the differentially methylated regions in the CHH context, which suggests that epigenetic variation may play a role in the short-term climate adaptation of pennycress. As pennycress is currently being domesticated as a new biofuel and winter cover crop, our results may be relevant also for agriculture, particularly in changing environments.
Abstract
Natural plant populations often harbour substantial heritable variation in DNA methylation. However, a thorough understanding of the genetic and environmental drivers of this epigenetic variation requires large-scale and high-resolution data, which currently exist only for a few model species. Here, we studied 207 lines of the annual weed Thlaspi arvense (field pennycress), collected across a large latitudinal gradient in Europe and propagated in a common environment. By screening for variation in DNA sequence and DNA methylation using whole-genome (bisulfite) sequencing, we found significant epigenetic population structure across Europe. Average levels of DNA methylation were strongly context-dependent, with highest DNA methylation in CG context, particularly in transposable elements and in intergenic regions. Residual DNA methylation variation within all contexts was associated with genetic variants, which often co-localized with annotated methylation machinery genes but also with new candidates. Variation in DNA methylation was also significantly associated with climate of origin, with methylation levels being lower in colder regions and in more variable climates. Finally, we used variance decomposition to assess genetic versus environmental associations with differentially methylated regions (DMRs). We found that while genetic variation was generally the strongest predictor of DMRs, the strength of environmental associations increased from CG to CHG and CHH, with climate-of-origin as the strongest predictor in about one third of the CHH DMRs. In summary, our data show that natural epigenetic variation in Thlaspi arvense is significantly associated with both DNA sequence and environment of origin, and that the relative importance of the two factors strongly depends on the sequence context of DNA methylation. T. arvense is an emerging biofuel and winter cover crop; our results may hence be relevant for breeding efforts and agricultural practices in the context of rapidly changing environmental conditions.
Author summary
Variation within species is an important level of biodiversity, and it is key for future adaptation. Besides variation in DNA sequence, plants also harbour heritable variation in DNA methylation, and we want to understand the evolutionary significance of this epigenetic variation, in particular how much of it is under genetic control, and how much is associated with the environment. We addressed these questions in a high-resolution molecular analysis of 207 lines of the common plant field pennycress (Thlaspi arvense), which we collected across Europe, propagated under standardized conditions, and sequenced for their genetic and epigenetic variation. We found large geographic variation in DNA methylation, associated with both DNA sequence and climate of origin. Genetic variation was generally the stronger predictor of DNA methylation variation, but the strength of environmental association varied between different sequence contexts. Climate-of-origin was the strongest predictor in about one third of the differentially methylated regions in the CHH context, which suggests that epigenetic variation may play a role in the short-term climate adaptation of pennycress. As pennycress is currently being domesticated as a new biofuel and winter cover crop, our results may be relevant also for agriculture, particularly in changing environments.
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
Introduction and Objective: Identifying patients that benefit from cisplatin-based adjuvant chemotherapy is a major issue in the management of muscle-invasive bladder cancer (MIBC). The purpose of this study is to correlate “luminal” and “basal” type protein expression with histological subtypes, to investigate the prognostic impact on survival after adjuvant chemotherapy and to define molecular consensus subtypes of “double negative” patients (i.e., without expression of CK5/6 or GATA3).
Materials and Methods: We performed immunohistochemical (IHC) analysis of CK5/6 and GATA3 for surrogate molecular subtyping in 181 MIBC samples. The mRNA expression profiles for molecular consensus classification were determined in CK5/6 and GATA3 (double) negative cases using a transcriptome panel with 19.398 mRNA targets (HTG Molecular Diagnostics). Data of 110 patients undergoing radical cystectomy were available for survival analysis.
Results: The expression of CK5/6 correlated with squamous histological subtype (96%) and expression of GATA3 was associated with micropapillary histology (100%). In the multivariate Cox-regression model, patients receiving adjuvant chemotherapy had a significant survival benefit (hazard ratio [HR]: 0.19 95% confidence interval [CI]: 0.1–0.4, p < 0.001) and double-negative cases had decreased OS (HR: 4.07; 95% CI: 1.5–10.9, p = 0.005). Double negative cases were classified as NE-like (30%), stroma-rich (30%), and Ba/Sq (40%) consensus molecular subtypes and displaying different histological subtypes.
Using (448.1 ± 2.9) × 106 ψ(3686) events collected with the BESIII detector at the BEPCII collider, the decay ψ(3686) → Σ⁻Σ‾⁺ is observed for the first time with a branching fraction of (2.82 ± 0.04stat. ± 0.08syst.) × 10−4, and the angular parameter αΣ− is measured to be 0.96 ± 0.09stat. ± 0.03syst..
Based on (10087±44)×106 𝐽/𝜓 events collected with the BESIII detector at BEPCII, the double Dalitz decay 𝜂′→𝑒+𝑒−𝑒+𝑒− is observed for the first time via the 𝐽/𝜓→𝛾𝜂′ decay process. The significance is found to be 5.7𝜎 with systematic uncertainties taken into consideration. Its branching fraction is determined to be ℬ(𝜂′→𝑒+𝑒−𝑒+𝑒−)=(4.5±1.0(stat)±0.5(sys))×10−6.
Using a data sample of (448.1±2.9)×106 𝜓(3686) decays collected at an 𝑒+𝑒− center-of-mass energy of 3.686 GeV by the BESIII detector at Beijing Electron Positron Collider II, we report an observation of the hindered electromagnetic Dalitz decay 𝜓(3686)→𝑒+𝑒−𝜂𝑐 with a significance of 7.9𝜎. The branching fraction is determined to be ℬ(𝜓(3686)→𝑒+𝑒−𝜂𝑐)=(3.77±0.40stat±0.18syst)×10−5, agreeing well with the prediction of the vector meson dominance model. This is the first measurement of the electromagnetic Dalitz transition between the 𝜓(3686) and the 𝜂𝑐, which provides new insight into the electromagnetic properties of this decay, and offers new opportunities to measure the absolute branching fractions of 𝜂𝑐 decays.
A measurement of the 𝐶𝑃-even fraction of the decay 𝐷0→𝜋+𝜋−𝜋+𝜋− is performed with a quantum-correlated 𝜓(3770)→𝐷¯𝐷 data sample collected by the BESIII experiment, corresponding to an integrated luminosity of 2.93 fb−1. Using a combination of 𝐶𝑃 eigenstates, 𝐷→𝜋+𝜋−𝜋0 and 𝐷→𝐾0𝑆,𝐿𝜋+𝜋− as tagging modes, the 𝐶𝑃-even fraction is measured to be 𝐹4𝜋+=0.735±0.015±0.005, where the first uncertainty is statistical and the second is systematic. This is the most precise determination of this quantity to date. It provides valuable model-independent input for the measurement of the angle 𝛾 of the Cabibbo-Kobayashi-Maskawa matrix with 𝐵±→𝐷𝐾± decays, and for time-dependent studies of 𝐶𝑃 violation and mixing in the 𝐷0−¯𝐷0 system.
A measurement of the CP-even fraction of the decay D0→π+π−π+π− is performed with a quantum-correlated ψ(3770)→DD¯ data sample collected by the BESIII experiment, corresponding to an integrated luminosity of 2.93 fb−1. Using a combination of CP eigenstates, D→π+π−π0 and D→K0S,Lπ+π− as tagging modes, the CP-even fraction is measured to be F4π+=0.735±0.015±0.005, where the first uncertainty is statistical and the second is systematic. This is the most precise determination of this quantity to date. It provides valuable model-independent input for the measurement of the CKM angle γ with B±→DK± decays, and for time-dependent studies of CP violation and mixing in the D0-D¯0 system.