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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.
We introduce a top-down stylized model to analyse the impact of a transition to a European power system based only on wind and solar power. Wind and solar power generation is calculated from high-resolution weather data and based on the country specific electricity demand alone, we introduce a model of the conventional power system that facilitates simple spatio-temporal modelling of its macroscopic behavior without direct reference to the underlying technological, economical, and political development in the system. Using this model, we find that wind and solar power generation can replace conventional power generation and power capacity to a large degree if power transmission across the continent is made possible.
During the co-translational assembly of protein complexes, a fully synthesized subunit engages with the nascent chain of a newly synthesized interaction partner. Such events are thought to contribute to productive assembly, but their exact physiological relevance remains underexplored. Here, we examine structural motifs contained in nucleoporins for their potential to facilitate co-translational assembly. We experimentally test candidate structural motifs and identify several previously unknown co-translational interactions. We demonstrate by selective ribosome profiling that domain invasion motifs of beta-propellers, coiled-coils, and short linear motifs may act as co-translational assembly domains. Such motifs are often contained in proteins that are members of multiple complexes (moonlighters) and engage with closely related paralogs. Surprisingly, moonlighters and paralogs assemble co-translationally in only some but not all of the relevant biogenesis pathways. Our results highlight the regulatory complexity of assembly pathways.
Using 9.9 fb−1 of e+e− collision data collected by the BESIII detector at center-of-mass energies between 4.15 and 4.30 GeV, we search for the processes e+e−→γX(3872) with X(3872)→π0χc0 and X(3872)→ππχc0. Depending on the fitting model, the statistical significance for X(3872)→π0χc0 ranges from 1.3σ to 2.8σ. We set upper limits (at 90\% C.L.) of B(X(3872)→π0χc0)B(X(3872)→π+π−J/ψ)<3.6, B(X(3872)→π+π−χc0)B(X(3872)→π+π−J/ψ)<0.68, and B(X(3872)→π0π0χc0)B(X(3872)→π+π−J/ψ)<1.7. Combined with the BESIII measurement of X(3872)→π0χc1, we also set an upper limit of B(X(3872)→π0χc0)B(X(3872)→π0χc1)<4.4.
Using 9.9 fb−1 of e+e− collision data collected by the BESIII detector at center-of-mass energies between 4.15 and 4.30 GeV, we search for the processes e+e−→γX(3872) with X(3872)→π0χc0 and X(3872)→ππχc0. Depending on the fitting model, the statistical significance for X(3872)→π0χc0 ranges from 1.3σ to 2.8σ. We set upper limits (at 90\% C.L.) of B(X(3872)→π0χc0)B(X(3872)→π+π−J/ψ)<3.6, B(X(3872)→π+π−χc0)B(X(3872)→π+π−J/ψ)<0.68, and B(X(3872)→π0π0χc0)B(X(3872)→π+π−J/ψ)<1.7. Combined with the BESIII measurement of X(3872)→π0χc1, we also set an upper limit of B(X(3872)→π0χc0)B(X(3872)→π0χc1)<4.4.
Using 9.9 fb−1 of e+e− collision data collected by the BESIII detector at center-of-mass energies between 4.15 and 4.30 GeV, we search for the processes e+e−→γX(3872) with X(3872)→π0χc0 and X(3872)→ππχc0. Depending on the fitting model, the statistical significance for X(3872)→π0χc0 ranges from 1.3σ to 2.8σ. We set upper limits (at 90\% C.L.) of B(X(3872)→π0χc0)B(X(3872)→π+π−J/ψ)<3.6, B(X(3872)→π+π−χc0)B(X(3872)→π+π−J/ψ)<0.68, and B(X(3872)→π0π0χc0)B(X(3872)→π+π−J/ψ)<1.7. Combined with the BESIII measurement of X(3872)→π0χc1, we also set an upper limit of B(X(3872)→π0χc0)B(X(3872)→π0χc1)<4.4.
Background Microdeletions are known to confer risk to epilepsy, particularly at genomic rearrangement “hotspot” loci. However, deciphering their role outside hotspots and risk assessment by epilepsy sub-type has not been conducted.
Methods We assessed the burden, frequency and genomic content of rare, large microdeletions found in a previously published cohort of 1,366 patients with Genetic Generalized Epilepsy (GGE) plus two sets of additional unpublished genome-wide microdeletions found in 281 Rolandic Epilepsy (RE) and 807 Adult Focal Epilepsy (AFE) patients, totaling 2,454 cases. These microdeletion sets were assessed in a combined analysis and in sub-type specific approaches against 6,746 ethnically matched controls.
Results When hotspots are considered, we detected an enrichment of microdeletions in the combined epilepsy analysis (adjusted-P= 2.00×10-7; OR = 1.89; 95%-CI: 1.51-2.35), where the implicated microdeletions overlapped with rarely deleted genes and those involved in neurodevelopmental processes. Sub-type specific analyses showed that hotspot deletions in the GGE subgroup contribute most of the signal (adjusted-P = 1.22×10-12; OR = 7.45; 95%-CI = 4.20-11.97). Outside hotspot loci, microdeletions were enriched in the GGE cohort for neurodevelopmental genes (adjusted-P = 4.78×10-3; OR = 2.30; 95%-CI = 1.42-3.70), whereas no additional signal was observed for RE and AFE. Still, gene content analysis was able to identify known (NRXN1, RBFOX1 and PCDH7) and novel (LOC102723362) candidate genes affected in more than one epilepsy sub-type but not in controls.
Conclusions Our results show a heterogeneous effect of recurrent and non-recurrent microdeletions as part of the genetic architecture of GGE and a minor to negligible contribution in the etiology of RE and AFE.
Der Beitrag stellt am Beispiel der dritten Phase der Lehrer:innenbildung den Professionalisierungsansatz vor, der in dem Forschungs- und Entwicklungsprojekt „Reflexion, Leistung und Inklusion“ (ReLInk) konzipiert und in Fortbildungsworkshops für Lehrkräfte der Sekundarstufe I erprobt wurde. Nach einer Projektdarstellung (Abschnitt 1) werden ausgewählte Ergebnisse der im Rahmen von ReLInk durchgeführten qualitativen Studie vorgestellt (Abschnitt 2). Diese Ergebnisse bildeten den Ausgangspunkt für die Entwicklung kasuistischer Materialien für die Aus- und Fortbildung von (angehenden) Lehrkräften. Für die Gestaltung der Fortbildungsworkshops stellte die Arbeit mit der Methode der sequenzanalytischen praxisreflexiven Kasuistik den Kern des Professionalisierungsansatzes von ReLInk dar. Die Materialien stehen online in einem Open-Access-Themenheft zur Verfügung (Abschnitt 3). Hierzu werden Erfahrungen aus den Workshops und Ergebnisse einer qualitativen Evaluation dieses Ansatzes präsentiert (Abschnitt 4). Am Ende werden anschließende Fragen sowohl für die Professionalisierung sowie für die Forschung aufgeworfen (Abschnitt 5).
The induction of apoptosis is a direct way to eliminate tumor cells and improve cancer therapy. Apoptosis is tightly controlled by the balance of pro- and antiapoptotic Bcl-2 proteins. BH3 mimetics neutralize the antiapoptotic function of Bcl-2 proteins and are highly promising compounds inducing apoptosis in several cancer entities including pediatric malignancies. However, the clinical application of BH3 mimetics in solid tumors is impeded by the frequent resistance to single BH3 mimetics and the anticipated toxicity of high concentrations or combination treatments. One potential avenue to increase the potency of BH3 mimetics is the development of immune cell-based therapies to counteract the intrinsic apoptosis resistance of tumor cells and sensitize them to immune attack. Here, we describe spheroid cultures of pediatric cancer cells that can serve as models for drug testing. In these 3D models, we were able to demonstrate that activated allogeneic Natural Killer (NK) cells migrated into tumor spheroids and displayed cytotoxicity against a wide range of pediatric cancer spheroids, highlighting their potential as anti-tumor effector cells. Next, we investigated whether treatment of tumor spheroids with subtoxic concentrations of BH3 mimetics can increase the cytotoxicity of NK cells. Notably, the cytotoxic effects of NK cells were enhanced by the addition of BH3 mimetics. Treatment with either the Bcl-XL inhibitor A1331852 or the Mcl-1 inhibitor S63845 increased the cytotoxicity of NK cells and reduced spheroid size, while the Bcl-2 inhibitor ABT-199 had no effect on NK cell-mediated killing. Taken together, this is the first study to describe the combination of BH3 mimetics targeting Bcl-XL or Mcl-1 with NK cell-based immunotherapy, highlighting the potential of BH3 mimetics in immunotherapy.
Using 7.33 fb−1 of e+e− collision data collected by the BESIII detector at center-of-mass energies between 4.128 and 4.226~GeV, we observe for the first time the decay D±s→ωπ±η with a statistical significance of 7.6σ. The measured branching fraction of this decay is (0.54±0.12±0.04)%, where the first uncertainty is statistical and the second is systematic.
Measurement of e⁺e⁻ → π⁺π⁻D⁺D⁻ cross sections at center-of-mass energies from 4.190 to 4.946 GeV
(2022)
Using data samples collected with the BESIII detector operating at the BEPCII storage ring, we measure the cross sections of the e+e−→π+π−D+D− process at center-of-mass energies from 4.190 to 4.946 GeV with a partial reconstruction method. Two resonance structures are seen and the resonance parameters are determined from a fit to the cross section line shape. The first resonance we observe has a mass of (4373.1 ± 4.0 ± 2.2) MeV/c2 and a width of (146.5 ± 7.4 ± 1.3) MeV, in agreement with those of the Y(4390) state; the other resonance has a mass of (4706 ± 11 ± 4) MeV/c2, a width of (45 ± 28 ± 9) MeV, and a statistical significance of 4.1 standard deviations (σ). This is the first evidence for a vector state at this mass value. The spin-3 D-wave charmonium state X(3842) is searched for through the e+e−→π+π−X(3842)→π+π−D+D− process, and evidence with a significance of 4.2σ is found in the data samples with center-of-mass energies from 4.600 to 4.700 GeV.
Zoos attract millions of visitors every year, many of whom are schoolchildren. For this reason, zoos are important institutions for the environmental education of future generations. Empirical studies on the educational impact of environmental education programs in zoos are still rare. To address this issue, we conducted two studies: In study 1, we investigated students’ interests in different biological topics, including zoos (n = 1,587). Data analysis of individual topics revealed large differences of interest, with advanced students showing less interest in zoos. In study 2, we invited school classes of this age group to visit different guided tours at the zoo and tested connection to nature before and after each educational intervention (n = 608). The results showed that the guided tours are an effective tool to raise students’ connection to nature. Add-on components have the potential to further promote connection to nature. The education programs are most effective with students with a low initial nature connection.
The decays J/ψ→ηΣ+Σ¯− and ψ(3686)→ηΣ+Σ¯− are observed for the first time, using (10087±44)×106 J/ψ and (448.1±2.9)×106 ψ(3686) events collected with the BESIII detector at the BEPCII collider. We determine the branching fractions of these two decays to be B(J/ψ→ηΣ+Σ¯−)=(6.34±0.21±0.37)×10−5 and B(ψ(3686)→ηΣ+Σ¯−)=(9.59±2.37±0.61)×10−6, where the first uncertainties are statistical and the second are systematic. The ratio of these two branching fractions is determined to be B(ψ(3686)→ηΣ+Σ¯−)B(J/ψ→ηΣ+Σ¯−)=(15.1±3.8)%, which is in agreement with the "12\% rule."
he decay D→K−π+ is studied in a sample of quantum-correlated DD¯ pairs, based on a data set corresponding to an integrated luminosity of 2.93\,fb−1 collected at the ψ(3770) resonance by the BESIII experiment. The asymmetry between CP-odd and CP-even eigenstate decays into K−π+ is determined to be AKπ=0.132±0.011±0.007, where the first uncertainty is statistical and the second is systematic. This measurement is an update of an earlier study exploiting additional tagging modes, including several decay modes involving a K0L meson. The branching fractions of the K0L modes are determined as input to the analysis in a manner that is independent of any strong phase uncertainty. Using the predominantly CP-even tag D→π+π−π0 and the ensemble of CP-odd eigenstate tags, the observable Aπππ0Kπ is measured to be 0.130±0.012±0.008. The two asymmetries are sensitive to rKπDcosδKπD, where rKπD and δKπD are the ratio of amplitudes and phase difference, respectively, between the doubly Cabibbo-suppressed and Cabibbo-favoured decays. In addition, events containing D→K−π+ tagged by D→K0S,Lπ+π− are studied in bins of phase space of the three-body decays. This analysis has sensitivity to both rKπDcosδKπD and rKπDsinδKπD. A fit to AKπ, Aπππ0Kπ and the phase-space distribution of the D→K0S,Lπ+π− tags yields δKπD=(187.5+8.9−9.7+5.4−6.4) degrees, where external constraints are applied for rKπD and other relevant parameters. This is the most precise measurement of δKπD in quantum-correlated DD¯ decays.
The decay D→K−π+ is studied in a sample of quantum-correlated DD¯ pairs, based on a data set corresponding to an integrated luminosity of 2.93\,fb−1 collected at the ψ(3770) resonance by the BESIII experiment. The asymmetry between CP-odd and CP-even eigenstate decays into K−π+ is determined to be AKπ=0.132±0.011±0.007, where the first uncertainty is statistical and the second is systematic. This measurement is an update of an earlier study exploiting additional tagging modes, including several decay modes involving a K0L meson. The branching fractions of the K0L modes are determined as input to the analysis in a manner that is independent of any strong phase uncertainty. Using the predominantly CP-even tag D→π+π−π0 and the ensemble of CP-odd eigenstate tags, the observable Aπππ0Kπ is measured to be 0.130±0.012±0.008. The two asymmetries are sensitive to rKπDcosδKπD, where rKπD and δKπD are the ratio of amplitudes and phase difference, respectively, between the doubly Cabibbo-suppressed and Cabibbo-favoured decays. In addition, events containing D→K−π+ tagged by D→K0S,Lπ+π− are studied in bins of phase space of the three-body decays. This analysis has sensitivity to both rKπDcosδKπD and rKπDsinδKπD. A fit to AKπ, Aπππ0Kπ and the phase-space distribution of the D→K0S,Lπ+π− tags yields δKπD=(187.6+8.9−9.7+5.4−6.4) degrees, where external constraints are applied for rKπD and other relevant parameters. This is the most precise measurement of δKπD in quantum-correlated DD¯ decays.
Based on a sample of 448.1×106 ψ(3686) events collected with the BESIII detector, a study of ψ(3686)→ΛΛ¯π0 and ψ(3686)→ΛΛ¯η is performed. Evidence of the isospin-violating decay ψ(3686)→ΛΛ¯π0 is found for the first time with a statistical significance of 3.7σ, the branching fraction B(ψ(3686)→ΛΛ¯π0) is measured to be (1.42±0.39±0.59)×10−6, and its corresponding upper limit is determined to be 2.47×10−6 at 90\% confidence level. A partial wave analysis of ψ(3686)→ΛΛ¯η shows that the peak around Λη invariant mass threshold favors a Λ∗ resonance with mass and width in agreement with the Λ(1670). The branching fraction of the ψ(3686)→ΛΛ¯η is measured to be (2.34±0.18±0.52)×10−5. The first uncertainties are statistical and the second are systematic.
Based on e+e− collision data corresponding to an integrated luminosity of 4.5 fb−1 collected at the center-of-mass energies between 4.600 and 4.699 GeV with the BESIII detector at BEPCII, the absolute branching fraction of the inclusive decay Λ+c→n+X, where X refers to any possible final state particles, is measured. The absolute branching fraction is determined to be B(Λ+c→n+X)=(32.4±0.7±1.5)%, where the first uncertainty is statistical and the second systematic. Assuming CP symmetry, the measurement indicates that about one-fourth of Λ+c (Λ¯−c) decay modes with a neutron (an anti-neutron) in the final state have not been observed.
Based on e+e− collision data corresponding to an integrated luminosity of 4.5 fb−1 collected at the center-of-mass energies between 4.600 and 4.699 Gev with the BESIII detector at BEPCII, the absolute branching fraction of the inclusive decay Λ¯−c→n¯+X, where X refers to any possible final state particles, is measured. The absolute branching fraction is determined to be B(Λ¯−c→n¯+X)=(33.5±0.7±1.2)%, where the first uncertainty is statistical and the second systematic. Neglecting the effect of CP violation, the measurement indicates that about one-fourth of Λ+c decay modes with a neutron in the final state have not been observed.
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 to be (0.832±0.038stat±0.054syst)×10−3, which is a factor of 2.1 lower and 5.6 standard deviations different than the previous measurement. 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±0.10stat±0.05syst.
Measurement of e⁺e⁻ → π⁺π⁻D⁺D⁻ cross sections at center-of-mass energies from 4.190 to 4.946 GeV
(2022)
Using data samples collected with the BESIII detector operating at the BEPCII storage ring, we measure the cross sections of the e+e−→π+π−D+D− process at center-of-mass energies from 4.190 to 4.946 GeV with a partial reconstruction method. Two resonance structures are seen and the resonance parameters are determined from a fit to the cross section line shape. The first resonance we observe has a mass of (4373.1 ± 4.0 ± 2.2) MeV/c2 and a width of (146.5 ± 7.4 ± 1.3) MeV, in agreement with those of the Y(4390) state; the other resonance has a mass of (4706 ± 11 ± 4) MeV/c2, a width of (45 ± 28 ± 9) MeV, and a statistical significance of 4.1 standard deviations (σ). This is the first evidence for a vector state at this mass value. The spin-3 D-wave charmonium state X(3842) is searched for through the e+e−→π+π−X(3842)→π+π−D+D− process, and evidence with a significance of 4.2σ is found in the data samples with center-of-mass energies from 4.600 to 4.700 GeV.