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Utilizing the data set corresponding to an integrated luminosity of 3.19 fb−1 collected by the BESIII detector at a center-of-mass energy of 4.178 GeV, we perform an amplitude analysis of the D+s→π+π−π+ decay. The sample contains 13,797 candidates with a signal purity of ∼80%. The amplitude and phase of the contributing ππ S wave are measured based on a quasi-model-independent approach, along with the amplitudes and phases of the P and D waves parametrized by Breit-Wigner models. The fit fractions of different intermediate decay channels are also reported.
Using a data sample of (1.0087±0.0044)×1010 J/ψ decay events collected with the BESIII detector at the center-of-mass energy of s√=3.097 GeV, we present a search for the hyperon semileptonic decay Ξ0→Σ−e+νe which violates the ΔS=ΔQ rule. No significant signal is observed, and the upper limit on the branching fraction B(Ξ0→Σ−e+νe) is determined to be 1.6×10−4 at the 90% confidence level. This result improves the previous upper limit result by about one order of magnitude.
Using a data sample of (1.0087±0.0044)×1010 J/ψ decay events collected with the BESIII detector at the center-of-mass energy of s√=3.097 GeV, we present a search for the hyperon semileptonic decay Ξ0→Σ−e+νe which violates the ΔS=ΔQ rule. No significant signal is observed, and the upper limit on the branching fraction B(Ξ0→Σ−e+νe) is determined to be 1.6×10−4 at the 90% confidence level. This result improves the previous upper limit result by about one order of magnitude.
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.
Using 2.93 fb−1 of 𝑒+𝑒− annihilation data collected at a center-of-mass energy √𝑠=3.773 GeV with the BESIII detector operating at the BEPCII collider, we search for the semileptonic 𝐷0(+) decays into a 𝑏1(1235)−(0) axial-vector meson for the first time. No significant signal is observed for either charge combination. The upper limits on the product branching fractions are ℬ𝐷0→𝑏1(1235)−𝑒+𝜈𝑒·ℬ𝑏1(1235) −→ 𝜔𝜋−<1.12×10−4 and ℬ𝐷+→𝑏1(1235)0𝑒+𝜈𝑒·ℬ𝑏1(1235)0→𝜔𝜋0<1.75×10−4 at the 90% confidence level.
Using 6.32~fb−1 of e+e− collision data recorded by the BESIII detector at center-of-mass energies between 4.178 to 4.226 GeV, we present the first measurement of the decay D+s→f0(980)e+νe,f0(980)→π0π0. The product branching fraction of D+s→f0(980)e+νe,f0(980)→π0π0 is measured to be (7.9±1.4stat±0.3syst)×10−4, with a statistical significance of 7.8σ. Furthermore, the upper limits on the product branching fractions of D+s→f0(500)e+νe with f0(500)→π0π0 and the branching fraction of D+s→K0SK0Se+νe are set to be 7.3×10−4 and 3.8×10−4 at 90\% confidence level, respectively. Our results provide valuable inputs to the understanding of the structures of light scalar mesons.
A search for invisible decays of the Λ baryon is carried out in the process 𝐽/𝜓→Λ¯Λ based on (1.0087±0.0044)×1010 𝐽/𝜓 events collected with the BESIII detector located at the BEPCII storage ring. No signals are found for the invisible decays of Λ baryon, and the upper limit of the branching fraction is determined to be 7.4×10−5 at the 90% confidence level. This is the first search for invisible decays of baryons; such searches will play an important role in constraining dark sector models related to the baryon asymmetry.
By analyzing e+e− annihilation data corresponding to an integrated luminosity of 2.93fb−1 collected at the center-of-mass energy of 3.773\,GeV with the BESIII detector, we report the first observations of the doubly Cabibbo-suppressed decays D+→K+π0π0 and D+→K+π0η. The branching fractions of D+→K+π0π0 and D+→K+π0η are measured to be (2.1±0.4stat±0.1syst)×10−4 and (2.1±0.5stat±0.1syst)×10−4 with statistical significances of 8.8σ and 5.5σ, respectively. In addition, we search for the subprocesses D+→K∗(892)+π0 and D+→K∗(892)+η with K∗(892)+→K+π0. The branching fraction of D+→K∗(892)+η is determined to be (4.4+1.8−1.5stat±0.2syst)×10−4, with a statistical significance of 3.2σ. No significant signal for D+→K∗(892)+π0 is found and we set an upper limit on the branching fraction of this decay at the 90\% confidence level to be 5.4×10−4.
By analyzing e+e− annihilation data corresponding to an integrated luminosity of 2.93fb−1 collected at the center-of-mass energy of 3.773\,GeV with the BESIII detector, we report the first observations of the doubly Cabibbo-suppressed decays D+→K+π0π0 and D+→K+π0η. The branching fractions of D+→K+π0π0 and D+→K+π0η are measured to be (2.1±0.4stat±0.1syst)×10−4 and (2.1±0.5stat±0.1syst)×10−4 with statistical significances of 8.8σ and 5.5σ, respectively. In addition, we search for the subprocesses D+→K∗(892)+π0 and D+→K∗(892)+η with K∗(892)+→K+π0. The branching fraction of D+→K∗(892)+η is determined to be (4.4+1.8−1.5stat±0.2syst)×10−4, with a statistical significance of 3.2σ. No significant signal for D+→K∗(892)+π0 is found and we set an upper limit on the branching fraction of this decay at the 90\% confidence level to be 5.4×10−4.
By analyzing e+e− annihilation data corresponding to an integrated luminosity of 2.93fb−1 collected at the center-of-mass energy of 3.773\,GeV with the BESIII detector, we report the first observations of the doubly Cabibbo-suppressed decays D+→K+π0π0 and D+→K+π0η. The branching fractions of D+→K+π0π0 and D+→K+π0η are measured to be (2.1±0.4stat±0.1syst)×10−4 and (2.1±0.6stat±0.1syst)×10−4 with statistical significances of 8.0σ and 5.0σ, respectively. In addition, we search for the subprocesses D+→K∗(892)+π0 and D+→K∗(892)+η with K∗(892)+→K+π0. The branching fraction of D+→K∗(892)+η is determined to be (4.7+1.9−1.6stat±0.2syst)×10−4, with a statistical significance of 3.3σ. No significant signal for D+→K∗(892)+π0 is found and we set an upper limit on the branching fraction of this decay at the 90\% confidence level to be 4.5×10−4.
Schon vor Mitte des 19. Jahrhunderts war mit der Romantik auch der frühromantische, von Friedrich Schlegel vorgebrachte Grundsatz, Poesie kann nur durch Poesie kritisiert werden, zusamt der ihn begleitenden Konzentration auf Dichtungskritik obsolet geworden. Heine prägte 1831 die berühmte - Romantik und Klassik umgreifende - Formel vom Ende der Kunstperiode. Der konstatierte Paradigmenwechsel von einer autonomen, alltagsabgehobenen Dichtung hin zu einer politisch lebensbezogenen Literatur bedeutete aber nicht, dass poetische Ansprüche aufgegeben worden wären. Dies war, was keines neuerlichen Nachweises bedarf, weder bei Heine selbst der Fall, noch bei einer Vielzahl seiner gleichfalls innovativen literarischen Zeitgenossen im Vor- und Nachmärz. Es ist ferner geläufig, dass sie zumeist darin übereinkamen, eine neue Poesie, eine mehr oder weniger zukünftige Poesie des Lebens zu fordern und zu suchen - im einzelnen freilich auf unterschiedlichen Wegen. Vernachlässigt hingegen hat man die Rolle der Literaturkritik bei diesen Bemühungen. Zu fragen ist nicht nur nach dem Verhältnis von politischen und poetologischen Schriftstellerkonzepten, sondern insbesondere nach der ästhetischen Fundierung politisierter literaturkritischer Feststellungen, Wertungen und Forderungen der Zeit um 1850. Es geht um die Praxis damaliger Literaturkritik, die bisher hinter einem Forschungsinteresse an der Theorie und an programmatischen Selbstbekundungen der Kritiker zurückstand. Versucht wird deshalb zunächst ein Umriss am Beispiel dreier exponierter Autoren: Ludolf Wienbarg, Friedrich Theodor Vischer und Julian Schmidt - Literaturkritiker alle drei, die beiden erstgenannten zudem Schriftsteller und Ästhetiker.
Traditional chinese medicine and herbal hepatotoxicity: a tabular compilation of reported cases
(2015)
Traditional Chinese Medicine (TCM) with its focus on herbal use became popular worldwide. Treatment was perceived as safe, with neglect of rare adverse reactions including liver injury. To compile worldwide cases of liver injury by herbal TCM, we undertook a selective literature search in the PubMed database and searched for the items Traditional Chinese Medicine, TCM, Traditional Asian Medicine, and Traditional Oriental Medicine, also combined with the terms herbal hepatotoxicity or herb induced liver injury. The search focused primarily on English-language case reports, case series, and clinical reviews. We identified reported hepatotoxicity cases in 77 relevant publications with 57 different herbs and herbal mixtures of TCM, which were further analyzed for causality by the Council for International Organizations of Medical Sciences (CIOMS) scale, positive reexposure test results, or both. Causality was established for 28/57 different herbs or herbal mixtures, Bai Xian Pi, Bo He, Ci Wu Jia, Chuan Lian Zi, Da Huang, Gan Cao, Ge Gen, Ho Shou Wu, Huang Qin, Hwang Geun Cho, Ji Gu Cao, Ji Xue Cao, Jin Bu Huan, Jue Ming Zi, Jiguja, Kudzu, Ling Yang Qing Fei Keli, Lu Cha, Rhen Shen, Ma Huang, Shou Wu Pian, Shan Chi, Shen Min, Syo Saiko To, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, and Zhen Chu Cao. In conclusion, this compilation of liver injury cases establishes causality for 28/57 different TCM herbs and herbal mixtures, aiding diagnosis for physicians who care for patients with liver disease possibly related to herbal TCM.
Objectives: An increasing number of treatment-determining biomarkers has been identified in non-small cell lung cancer (NSCLC) and molecular testing is recommended to enable optimal individualized treatment. However, data on implementation of these recommendations in the “real-world” setting are scarce. This study presents comprehensive details on the frequency, methodology and results of biomarker testing of advanced NSCLC in Germany.
Patients and methods: This analysis included 3,717 patients with advanced NSCLC (2,921 non-squamous; 796 squamous), recruited into the CRISP registry at start of systemic therapy by 150 German sites between December 2015 and June 2019. Evaluated were the molecular biomarkers EGFR, ALK, ROS1, BRAF, KRAS, MET, TP53, RET, HER2, as well as expression of PD-L1.
Results: In total, 90.5 % of the patients were tested for biomarkers. Testing rates were 92.2 % (non-squamous), 70.7 % (squamous) and increased from 83.2 % in 2015/16 to 94.2% in 2019. Overall testing rates for EGFR, ALK, ROS1, and BRAF were 72.5 %, 74.5 %, 66.1 %, and 53.0 %, respectively (non-squamous). Testing rates for PD-L1 expression were 64.5 % (non-squamous), and 58.5 % (squamous). The most common testing methods were immunohistochemistry (68.5 % non-squamous, 58.3 % squamous), and next-generation sequencing (38.7 % non-squamous, 14.4 % squamous). Reasons for not testing were insufficient tumor material or lack of guideline recommendations (squamous). No alteration was found in 37.8 % (non-squamous), and 57.9 % (squamous), respectively. Most common alterations in non-squamous tumors (all patients/all patients tested for the respective biomarker): KRAS (17.3 %/39.2 %), TP53 (14.1 %/51.4 %), and EGFR (11.0 %/15.1 %); in squamous tumors: TP53 (7.0 %/69.1 %), MET (1.5 %/11.1 %), and EGFR (1.1 %/4.4 %). Median PFS (non-squamous) was 8.7 months (95 % CI 7.4–10.4) with druggable EGFR mutation, and 8.0 months (95 % CI 3.9–9.2) with druggable ALK alterations.
Conclusion: Testing rates in Germany are high nationwide and acceptable in international comparison, but still leave out a significant portion of patients, who could potentially benefit. Thus, specific measures are needed to increase implementation.
Herb induced liver injury (HILI) is a particular challenge that also applies to purported cases presumably caused by black cohosh (BC), an herb commonly used to treat menopausal symptoms. We analyzed and reviewed all published case reports and spontaneous reports of initially alleged BC hepatotoxicity regarding quality of case details and causality assessments. Shortcomings of data quality were more evident in spontaneous reports of regulatory agencies compared to published case reports, but assessments with the scale of CIOMS (Council for the International Organizations of Sciences) or its updated version revealed lack of causality for BC in all cases. The applied causality methods are structured, quantitative, and liver specific with clear preference over an ad hoc causality method or the liver unspecific Naranjo scale. Reviewing the case data and the reports dealing with quality specifications of herbal BC products, there is general lack of analysis with respect to authentication of BC in the BC products used by the patients. However, in one single regulatory study, there was a problem of BC authentication in the analysed BC products, and other reports addressed the question of impurities and adulterants in a few BC products. It is concluded that the use of BC may not exert an overt hepatotoxicity risk, but quality problems in a few BC products were evident that require additional regulatory quality specifications.
Background: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure.
Methods: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated.
Discussion: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment.
Trial registration: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
This paper reports on Monte Carlo simulation results for future measurements of the moduli of time-like proton electromagnetic form factors, |GE | and |GM|, using the ¯pp → μ+μ− reaction at PANDA (FAIR). The electromagnetic form factors are fundamental quantities parameterizing the electric and magnetic structure of hadrons. This work estimates the statistical and total accuracy with which the form factors can be measured at PANDA, using an analysis of simulated data within the PandaRoot software framework. The most crucial background channel is ¯pp → π+π−,due to the very similar behavior of muons and pions in the detector. The suppression factors are evaluated for this and all other relevant background channels at different values of antiproton beam momentum. The signal/background separation is based on a multivariate analysis, using the Boosted Decision Trees method. An expected background subtraction is included in this study, based on realistic angular distribuations of the background contribution. Systematic uncertainties are considered and the relative total uncertainties of the form factor measurements are presented.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematopoietic malignancy characterized by dismal prognosis and overall poor therapeutic response. Since the biology of BPDCN is barely understood, our study aims to shed light on the genetic make-up of these highly malignant tumors. Using targeted high-coverage massive parallel sequencing, we investigated 50 common cancer genes in 33 BPDCN samples. We detected point mutations in NRAS (27.3% of cases), ATM (21.2%), MET, KRAS, IDH2, KIT (9.1% each), APC and RB1 (6.1% each), as well as in VHL, BRAF, MLH1, TP53 and RET (3% each). Moreover, NRAS, KRAS and ATM mutations were found to be mutually exclusive and we observed recurrent mutations in NRAS, IDH2, APC and ATM. CDKN2A deletions were detected in 27.3% of the cases followed by deletions of RB1 (9.1%), PTEN and TP53 (3% each). The mutual exclusive distribution of some mutations may point to different subgroups of BPDCN whose biological significance remains to be explored.