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Using a data sample corresponding to an integrated luminosity of 2.93 fb−1 collected at a center-of-mass energy √𝑠=3.773 GeV by the BESIII detector, the decay 𝐷0→𝜔𝜙 is observed for the first time. The branching fraction is measured to be (6.48±0.96±0.40)×10−4 with a significance of 6.3𝜎, where the first and second uncertainties are statistical and systematic, respectively. An angular analysis reveals that the 𝜙 and 𝜔 mesons from the 𝐷0→𝜔𝜙 decay are transversely polarized. The 95% confidence level upper limit on longitudinal polarization fraction is set to be less than 0.24, which is inconsistent with current theoretical expectations and challenges our understanding of the underlying dynamics in charm meson decays.
Using data samples with a total integrated luminosity of 20.1 fb−1 collected by the BESIII detector operating at the BEPCII collider, the cross section of the process 𝑒+𝑒−→𝜋+𝜋−𝜓(3686) is measured at center-of-mass energies between 4.0076 and 4.6984 GeV. The measured cross section is consistent with previous results, and with much improved precision. A fit to the measured energy-dependent cross section, which includes three Breit-Wigner functions and a nonresonant contribution, confirms the existence of the charmonium-like states 𝑌(4220), 𝑌(4390), and 𝑌(4660). This is the first observation of the 𝑌(4660) at the BESIII experiment.
Using (10.087±0.044)×109 𝐽/𝜓 events collected by the Beijing Spectrum III (BESIII) detector at the Beijing Electron Positron Collider II (BEPCII) collider, we search for the hyperon semileptonic decay Ξ−→Ξ0𝑒−¯𝜈𝑒. No significant signal is observed and the upper limit on the branching fraction ℬ(Ξ−→Ξ0𝑒−¯𝜈𝑒) is set to be 2.59×10−4 at 90% confidence level. This result is one order of magnitude more strict than the previous best limit.
Using 2.93 fb−1 of e+e− collision data collected with the BESIII detector at the center-of-mass energy 3.773 GeV, we perform the first amplitude analysis of the decay D+ → π+π0π0 and determine the relative magnitudes and phases of different intermediate processes. The absolute branching fraction of D+ → π+π0π0 is measured to be (2.888 ± 0.058stat. ± 0.069syst.)%. The dominant intermediate processes are D+ → a1(1260)+(→ ρ+π0) and D+ → *0ρ+, with branching fractions of (8.66 ± 1.04stat. ± 1.39syst.) × 10−3 and (9.70 ± 0.81stat. ± 0.53syst.) × 10−3, respectively.
The singly Cabibbo-suppressed decay D+s → K+π+π−π0 is observed by using a data set corresponding to an integrated luminosity of 6.32 fb−1 recorded by the BESIII detector at the centre-of-mass energies between 4.178 and 4.226 GeV. The first amplitude analysis of D+s → K+π+π−π0 reveals the sub-structures in this decay and determines the fractions and relative phases of different intermediate processes. The dominant intermediate process is D+s → K∗0ρ+, with a fit fraction of (40.5 ± 2.8stat. ± 1.5syst.)%. With the detection efficiency based on our amplitude analysis, the absolute branching fraction forD+s → K+π+π−π0 is measured to be (9.75 ± 0.54stat. ± 0.17syst.) × 10−3.
Using inclusive decays of the J/ψ, a precise determination of the number of J/ψ events collected with the BESIII detector is performed. For the two data sets taken in 2009 and 2012, the numbers of J/ψ events are recalculated to be (224.0±1.3)×106 and (1088.5±4.4)×106 respectively, which are in good agreement with the previous measurements. For the J/ψ sample taken in 2017--2019, the number of events is determined to be (8774.0±39.4)×106. The total number of J/ψ events collected with the BESIII detector is determined to be (10087±44)×106, where the uncertainty is dominated by systematic effects and the statistical uncertainty is negligible.
Using a data sample of 4.481×108 𝜓(3686) events collected with the BESIII detector, we report the first observation of the four-lepton-decays 𝐽/𝜓→𝑒+𝑒−𝑒+𝑒− and 𝐽/𝜓→𝑒+𝑒−𝜇+𝜇− utilizing the process 𝜓(3686)→𝜋+𝜋−𝐽/𝜓. The branching fractions are determined to be [5.48±0.31(stat)±0.45(syst)]×10−5 and [3.53±0.22(stat)±0.13(syst)]×10−5, respectively. The results are consistent with theoretical predictions. No significant signal is observed for 𝐽/𝜓→𝜇+𝜇−𝜇+𝜇−, and an upper limit on the branching fraction is set at 1.6×10−6 at the 90% confidence level. A 𝐶𝑃 asymmetry observable is constructed for the first two channels, which is measured to be (−0.012±0.054±0.010) and (0.062±0.059±0.006), respectively. No evidence for 𝐶𝑃 violation is observed in this process.
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.
Whereas the lack of biomarkers in penile cancer (PeCa) impedes the development of efficacious treatment protocols, preliminary evidence suggests that c-MET and associated signaling elements may be dysregulated in this disorder. In the following study, we investigated whether c-MET and associated key molecular elements may have prognostic and therapeutic utility in PeCa. Formalin-fixed, paraffin-embedded tumor tissue from therapy-naïve patients with invasive PeCa was used for tissue microarray (TMA) analysis. Immunohistochemical staining was performed to determine the expression of the proteins c-MET, PPARg, β-catenin, snail, survivin, and n-MYC. In total, 94 PeCa patients with available tumor tissue were included. The median age was 64.9 years. High-grade tumors were present in 23.4%, and high-risk HPV was detected in 25.5%. The median follow-up was 32.5 months. High expression of snail was associated with HPV-positive tumors. Expression of β-catenin was inversely associated with grading. In both univariate COX regression analysis and the log-rank test, an increased expression of PPARg and c-MET was predictive of inferior disease-specific survival (DSS). Moreover, in multivariate analysis, a higher expression of c-MET was independently associated with worse DSS. Blocking c-MET with cabozantinib and tivantinib induced a significant decrease in viability in the primary PeCa cell line UKF-PeC3 isolated from the tumor tissue as well as in cisplatin- and osimertinib-resistant sublines. Strikingly, a higher sensitivity to tivantinib could be detected in the latter, pointing to the promising option of utilizing this agent in the second-line treatment setting.
The cellular composition of the tumor microenvironment, including tumor, immune, stromal, and endothelial cells, significantly influences responses to cancer therapies. In this study, we analyzed the impact of oxidative stress, induced by cold atmospheric plasma (CAP), on tumor cells, T cells, and macrophages, which comprise part of the melanoma microenvironment. To accomplish this, cells were grown in different in vitro cell culture models and were treated with varying amounts of CAP. Subsequent alterations in viability, proliferation, and phenotype were analyzed via flow cytometry and metabolic alterations by Seahorse Cell Mito Stress Tests. It was found that cells generally exhibited reduced viability and proliferation, stemming from CAP induced G2/M cell cycle arrest and subsequent apoptosis, as well as increased mitochondrial stress following CAP treatment. Overall, sensitivity to CAP treatment was found to be cell type dependent with T cells being the most affected. Interestingly, CAP influenced the polarization of M0 macrophages to a “M0/M2-like” phenotype, and M1 macrophages were found to display a heightened sensitivity to CAP induced mitochondrial stress. CAP also inhibited the growth and killed melanoma cells in 2D and 3D in vitro cell culture models in a dose-dependent manner. Improving our understanding of oxidative stress, mechanisms to manipulate it, and its implications for the tumor microenvironment may help in the discovery of new therapeutic targets.
In this review article, we will first provide a brief overview of the ErbB receptor–ligand system and its importance in developmental and physiological processes. We will then review the literature regarding the role of ErbB receptors and their ligands in the maladaptive remodeling of lung tissue, with special emphasis on idiopathic pulmonary fibrosis (IPF). Here we will focus on the pathways and cellular processes contributing to epithelial–mesenchymal miscommunication seen in this pathology. We will also provide an overview of the in vivo studies addressing the efficacy of different ErbB signaling inhibitors in experimental models of lung injury and highlight how such studies may contribute to our understanding of ErbB biology in the lung. Finally, we will discuss what we learned from clinical applications of the ErbB1 signaling inhibitors in cancer in order to advance clinical trials in IPF.
Children’s and adolescents’ lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017–2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85–1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93–1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57–1.02 and 0.26 (0.05–0.75)), whereas household and leisure accidents increased (1.33 (1.06–1.66) and 1.34 (1.06–1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38–1.16) and 2.09 (1.19–3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42–1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51–3.02)), but decreased in adolescent girls (0.56 (0.32–0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation.
Unified probabilistic deep continual learning through generative replay and open set recognition
(2022)
Modern deep neural networks are well known to be brittle in the face of unknown data instances and recognition of the latter remains a challenge. Although it is inevitable for continual-learning systems to encounter such unseen concepts, the corresponding literature appears to nonetheless focus primarily on alleviating catastrophic interference with learned representations. In this work, we introduce a probabilistic approach that connects these perspectives based on variational inference in a single deep autoencoder model. Specifically, we propose to bound the approximate posterior by fitting regions of high density on the basis of correctly classified data points. These bounds are shown to serve a dual purpose: unseen unknown out-of-distribution data can be distinguished from already trained known tasks towards robust application. Simultaneously, to retain already acquired knowledge, a generative replay process can be narrowed to strictly in-distribution samples, in order to significantly alleviate catastrophic interference.
Mucormycosis is an invasive fungal infection associated with high mortality, partly due to delayed diagnosis and inadequate empiric therapy. As fungal cultures often fail to grow Mucorales, identification of respective hyphae in tissue is frequently needed for diagnosis but may be challenging. We studied fluorescence in situ hybridization (FISH) targeting specific regions of the fungal ribosomal RNA (rRNA) of Mucorales to improve diagnosis of mucormycosis from tissue samples. We generated a probe combination specifically targeting Mucorales. Probe specificity was verified in silico and using cultivated fungi. Mucorales hyphae in tissue of a mouse model demonstrated a bright cytoplasmatic hybridization signal. In tissue samples of patients with mucormycosis, a positive signal was seen in 7 of 12 (58.3%) samples. However, autofluorescence in 3 of 7 (42.9%) samples impaired the diagnostic yield. Subsequent experiments suggested that availability of nutrients and antifungal therapy may impact on the FISH signal obtained with Mucorales hyphae. Diagnosis of mucormycosis from tissue might be improved by rRNA FISH in a limited number of cases only. FISH signals may reflect different wphysiological states of fungi in tissue. Further studies are needed to define the value of FISH to diagnose mucormycosis from other clinical samples.
The cross sections of the 𝑒+𝑒−→𝜙𝜂′ process at center-of-mass energies from 3.508 to 4.951 GeV are measured with high precision using 26.1 fb−1 data collected with the BESIII detector operating at the BEPCII storage ring. The cross sections are of the order of a few picobarn and decrease as the center-of-mass energy increases as 𝑠−𝑛/2 with 𝑛=4.35±0.14. This result is in agreement with the Nambu-Jona-Lasinio model prediction of 𝑛=3.5±0.9. In addition, the charmless decay 𝜓(3770)→𝜙𝜂′ is searched for by fitting the measured cross sections, yet no significant signal is observed. The upper limit of ℬ(𝜓(3770)→𝜙𝜂′) at the 90% confidence level is determined to be 2.3×10−5.
With data samples collected with the BESIII detector at seven energy points at √s = 3.68 − 3.71 GeV, corresponding to an integrated luminosity of 333 pb−1, we present a study of the Λ transverse polarization in the e+e− → ΛΛ¯ reaction. The signifcance of polarization by combining the seven energy points is found to be 2.6σ including the systematic uncertainty, which implies a non-zero phase between the transition amplitudes of the ΛΛ¯ helicity states. The modulus ratio and the relative phase of EM-psionic form factors combined with all energy points are measured to be RΨ = 0.71+0.10−0.10 ± 0.03 and ∆ΦΨ = 23+8.8−8.0 ± 1.6◦, where the frst uncertainties are statistical and the second systematic.
There has recently been a dramatic renewal of interest in hadron spectroscopy and charm physics. This renaissance has been driven in part by the discovery of a plethora of charmonium-like XYZ states at BESIII and B factories, and the observation of an intriguing proton-antiproton threshold enhancement and the possibly related X(1835) meson state at BESIII, as well as the threshold measurements of charm mesons and charm baryons.
We present a detailed survey of the important topics in tau-charm physics and hadron physics that can be further explored at BESIII during the remaining operation period of BEPCII. This survey will help in the optimization of the data-taking plan over the coming years, and provides physics motivation for the possible upgrade of BEPCII to higher luminosity.
Using data samples collected with the BESIII detector at the BEPCII collider at six center-of-mass energies between 4.008 and 4.600 GeV, we observe the processes e+e− → φφω and e+e− → φφφ. The Born cross sections are measured and the ratio of the cross sections σ(e+e− → φφω)/σ(e+e− → φφφ) is estimated to be 1.75 ± 0.22 ± 0.19 averaged over six energy points, where the first uncertainty is statistical and the second is systematic. The results represent first measurements of these interactions.
The integrated luminosities of data samples collected in the BESIII experiment in 2016–2017 at center-of-mass energies between 4.19 and 4.28 GeV are measured with a precision better than 1% by analyzing large-angle Bhabha scattering events. The integrated luminosities of old datasets collected in 2010–2014 are updated by considering corrections related to detector performance, offsetting the effect of newly discovered readout errors in the electromagnetic calorimeter, which can haphazardly occur.