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Introduction: Survival data reported by randomised controlled trials are collected in a highly selected patient population and can thus only be transferred to a limited extent to real-world patients: the patients in routine care are mostly older, present with more comorbidities and a worse general state of health. This so-called efficacy-effectiveness gap typically results in inferior survival data in routine healthcare.
Methods: Six prospective clinical tumour registries recruited a total of 11,679 patients receiving systemic therapy in haemato-oncological practices in Germany between 2006 and 2020. For these patients with advanced colorectal cancer, breast cancer, lung cancer, pancreatic cancer, renal cell cancer, and lymphatic neoplasms, overall survival was analysed. A comprehensive literature search was performed to identify suitable pivotal randomised controlled trials.
Results: Median overall survival of patients treated in German routine care, with advanced colorectal, breast, lung, and pancreatic cancer, as well as with diffuse large B-cell lymphoma and multiple myeloma, is not shorter than the respective survival data reported in trials. Patients with advanced renal cell carcinoma, chronic lymphocytic leukaemia, or indolent non-Hodgkin lymphoma showed slightly lower survival rates compared to clinical trials.
Conclusions: Despite less favourable patient characteristics, survival data from patients with cancer treated in ambulatory routine care in Germany are in range with results from randomised controlled studies.
High-resolution mapping of cell cycle dynamics during T-cell development and regeneration in vivo
(2024)
Control of cell proliferation is critical for the lymphocyte life cycle. However, little is known on how stage-specific alterations in cell cycle behavior drive proliferation dynamics during T-cell development. Here, we employed in vivo dual-nucleoside pulse labeling combined with determination of DNA replication over time as well as fluorescent ubiquitination-based cell cycle indicator mice to establish a quantitative high-resolution map of cell cycle kinetics of thymocytes. We developed an agent-based mathematical model of T-cell developmental dynamics. To generate the capacity for proliferative bursts, cell cycle acceleration followed a ‘stretch model’, characterized by simultaneous and proportional contraction of both G1 and S phase. Analysis of cell cycle phase dynamics during regeneration showed tailored adjustments of cell cycle phase dynamics. Taken together, our results highlight intrathymic cell cycle regulation as an adjustable system to maintain physiologic tissue homeostasis and foster our understanding of dysregulation of the T-cell developmental program.
Agility, as the ability to react rapidly to unforeseen events, is an essential component of football performance. However, existing agility diagnostics often do not reflect the complex motor–cognitive interaction required on the field. Therefore, this study evaluates the criterion and ecological validity of a newly developed motor–cognitive dual-task agility approach in elite youth football players and compare it to a traditional reactive agility test. Twenty-one male youth elite football players (age:17.4 ±0 .6; BMI:23.2 ± 1.8) performed two agility tests (reactive agility, reactive agility with integrated multiple-object-tracking (Dual-Task Agility)) on the SKILLCOURT system. Performance was correlated to motor (sprint, jump), cognitive (executive functions, attention, reaction speed) and football specific tests (Loughborough soccer passing test (LSPT)) as well as indirect game metrics (coaches' rating, playing time). Reactive agility performance showed moderate correlations to attention and choice reaction times (r = 0.48−0.63), as well as to the LSPT (r = 0.51). The dual-task agility test revealed moderate relationships with attention and reaction speed (r = 0.47−0.58), executive functions (r = 0.45−0.63), as well as the game metrics (r = 0.51−0.61). Finally, the dual-task agility test significantly differentiated players based on their coaches' rating and playing time using a median split (p < 0.05; d = 0.8–1.28). Motor–cognitive agility performance in elite youth football players seems to be primarily determined by cognitive functions. The integration of multiple object tracking into reactive agility testing seems to be an ecologically valid approach for performance diagnostics in youth football.
Highlights
* The study introduces a novel motor–cognitive dual-task agility approach (incorporation of multiple-object-tracking in agility testing), evaluating its criterion and ecological validity in elite youth football players compared to a standard agility test.
* The standard agility test was shown to have moderate correlations with attention and choice reaction times, while the dual-task agility approach additionally incorporates executive functions
* While the agility test correlates to football-specific test performance, the dual-task agility test significantly discriminates players based on their potential ratings and in-season playing time, highlighting its potential as a valuable tool for assessing performance in youth football.
* The findings suggest that agility performance in elite youth football is primarily determined by cognitive functions
* Incorporating more complex cognitive elements such as multiple-object-tracking in agility testing may improve ecological validity and therefore the predictive value of the testing procedure.
Using electron-positron annihilation data samples corresponding to an integrated luminosity of 4.5 fb−1, collected by the BESIII detector in the energy region between 4600 MeV and 4699 MeV, we report the first observations of the Cabibbo-suppressed decays Λ+c→nπ+π0, Λ+c→nπ+π−π+, and the Cabibbo-favored decay Λ+c→nK−π+π+ with statistical significances of 7.9σ, 7.8σ, and >10σ, respectively. The branching fractions of these decays are measured to be B(Λ+c→nπ+π0)=(0.64±0.09±0.02)%, B(Λ+c→nπ+π−π+)=(0.45±0.07±0.03)%, and B(Λ+c→nK−π+π+)=(1.90±0.08±0.09)%, where the first uncertainties are statistical and the second are systematic. We find that the branching fraction of the decay Λ+c→nπ+π0 is about one order of magnitude higher than that of Λ+c→nπ+.
In this paper we develop an HPSG syntax-semantics of negative concord in Romanian. We show that n-words in Romanian can best be treated as negative quantifiers which may combine by resumption to form polyadic negative quantifiers. Optionality of resumption explains the existence of simple sentential negation readings alongside double negation readings. We solve the well-known problem of defining general semantic composition rules for translations of natural language expressions in a logical language with polyadic quantifiers by integrating our higher-order logic in Lexical Resource Semantics, whose constraint-based composition mechanisms directly support a systematic syntax-semantics for negative concord with polyadic quantification.
The energy-dependent cross section for e+e−→ηψ(2S) is measured at eighteen center of mass energies from 4.288 GeV to 4.951 GeV using the BESIII detector. Using the same data samples, we also perform the first search for the reaction e+e−→ηX~(3872), but no evidence is found for the X~(3872) in the π+π−J/ψ mass distribution. At each of the eighteen center of mass energies, upper limits at the 90\% confidence level on the cross section for e+e−→ηψ(2S) and on the product of the e+e−→ηX~(3872) cross section with the branching fraction of X~(3872)→π+π−J/ψ are reported.
The main goal of this work is to contribute to the existing knowledge of soil micro-fungi in Panama and Germany. Studies about soil degradation and its influents in the soil fungi diversity have not been investigated as extensively in these countries. This is an extensive and challenging topic to examine since there is an immense phenotypic and genetic diversity in the soil fungal community and relating this community together with factors of soil degradation is an extensive task. For this reason, the present thesis studies the species identified in the study areas, in other words, the soil fungal diversity in relation to environmental factors in the Taunus Mountain range in Frankfurt, Germany, and in the Majagua valley in Chiriquí, Panama. Two complementary objectives were achieved, the first was the development of a theoretical irrigation model for degraded soils. The second was the development of a mobile application to facilitate laboratory work in the cultivation of soil micro-fungi.
The design of the methodology was based on identifying the species and relating the diversity found to soil factors. Soil samples were taken in both countries: the Taunus Mountain range was sampled eight times from January to November 2012 and the Majagua valley was sampled on three occasions between February and July 2012. In both studies, the areas included three different vegetation types (forest, grassland, and bare soil). Samples were separated for two purposes: the assessment of fungal diversity by molecular and morphological methods and soil characterization.
Soil samples used in the methodology of pyrosequencing were related to global climatic factors. Morphological identification was achieved with identification keys. Micro-fungi were cultivated in different media until obtaining pure cultures. Molecular identification was performed by getting the DNA sequences using the ITS1 and ITS4 primers and comparing the sequences with other reference sequences from GenBank. This was done considering the BLAST algorithm, which considered sequences that matched 98 % or more of maximum identity as reliable identifications.
Soil characterization was carried out to measure the soil's Physico-chemical properties; those abiotic factors were compaction, temperature, pH, moisture, and soil composition.
Species richness was calculated in each study area with the estimators Chao, Jackknife, and Bootstrap. Furthermore, the species accumulation curves were performed to observe the species discovery rate and estimate sample completeness. Estimate linear regression models correlated the influence between the soil factors (temperature, moisture, pH, soil compaction, and soil composition) and the species richness. In the same way, an analysis of ecological distance was undertaken based on the similarity in the species composition, compared across samples, and correlated with soil factors, using non-metric multidimensional scaling (NMDs).
Study of abundance showed differences between the bare soil abundances and the forest abundances in Germany and Panama; the grasslands in both countries work as transitional areas in the fungi abundance. The key stone species in Germany were Penicillium daleae, and Pochonia bulbillosa, whereas in Panama were Purpureocillium lilacinum and Trichoderma harzianum. Based on Pareto analysis, a theoretical irrigation model was developed to counteract the degradation effects on the abundance of micro-fungi in the soil.
Applications for mobile devices dealing with the cultivation of soil micro fungi were sought. Due to the small number of existing applications, a new App called Soil-Fungi-Cultures (SFC) was developed to facilitate data collection of cultivated soil micro fungi. App Inventor was the program used to design, program, test, and publish the application developed. The developed application was compared with other applications used in identifying bacteria cultures. The results showed that the new application needed more time to capture the records because it saves more information, the navigation flow was acceptable, the number of clicks was high, but it is due to the usefulness in data capture, and finally, the users rated it as a good application with an eight out of ten rating.
Pyrosequencing resulted in 204 Operational Taxonomic Units (OTUs) considering the two study areas (the Taunus Mountain range and the Majagua valley). The Pyrosequencing database was used to contribute to the most important study of fungal diversity globally based on OTUs, which surpasses any study of molecular and taxonomic diversity previously conducted. The principal result in this study was that the climatic factor is the best predictor of fungal richness and community composition on a global scale. However, the part of the research that focused on the local scale, that is to say, on the correlation patterns between the distribution of fungal species and abiotic factors, showed that the soil properties and degradation levels were not associated with fungal richness, diversity or soil composition in the study areas in Germany or Panama. The above confirms that there are exceptions to the way relationships between soil factors with fungal diversity are established at the local level.
In the case of soil samples used for morphological identification, 71 fungal species were obtained, 47 from Germany, and 32 from Panama.
The expanding field of epitranscriptomics might rival the epigenome in the diversity of biological processes impacted. In recent years, the development of new high-throughput experimental and computational techniques has been a key driving force in discovering the properties of RNA modifications. Machine learning applications, such as for classification, clustering or de novo identification, have been critical in these advances. Nonetheless, various challenges remain before the full potential of machine learning for epitranscriptomics can be leveraged. In this review, we provide a comprehensive survey of machine learning methods to detect RNA modifications using diverse input data sources. We describe strategies to train and test machine learning methods and to encode and interpret features that are relevant for epitranscriptomics. Finally, we identify some of the current challenges and open questions about RNA modification analysis, including the ambiguity in predicting RNA modifications in transcript isoforms or in single nucleotides, or the lack of complete ground truth sets to test RNA modifications. We believe this review will inspire and benefit the rapidly developing field of epitranscriptomics in addressing the current limitations through the effective use of machine learning.
Based on electron positron collision data collected with the BESIII detector operating at the BEPCII storage rings, the differential cross sections of inclusive π0 and K0S production as a function of hadron momentum, normalized by the total cross section of the e+e−→ hadrons process, are measured at six center-of-mass energies from 2.2324 to 3.6710 GeV. Our results with a relative hadron energy coverage from 0.1 to 0.9 significantly deviate from several theoretical calculations based on existing fragmentation functions, especially at lower energies.
Using 7.93 fb−1 of e+e− collision data collected at the center-of-mass energy of 3.773 GeV with the BESIII detector, we measure the absolute branching fractions of D0→K−e+νe, D0→K−μ+νμ, D+→K¯0e+νe, and D+→K¯0μ+νμ to be (3.509±0.009stat.±0.013syst.)%, (3.408±0.011stat.±0.013syst.)%, (8.856±0.039stat.±0.078syst.)%, and (8.661±0.046stat.±0.080syst.)%, respectively. By performing a simultaneous fit to the partial decay rates of these four decays, the product of the hadronic form factor fK+(0) and the modulus of the c→s CKM matrix element |Vcs| is determined to be fK+(0)|Vcs|=0.7162±0.0011stat.±0.0012syst.. Taking the value of |Vcs|=0.97349±0.00016 from the standard model global fit or that of fK+(0)=0.7452±0.0031 from the LQCD calculation as input, we derive the results fK+(0)=0.7357±0.0011stat.±0.0012syst. and |Vcs|=0.9611±0.0015stat.±0.0016syst.±0.0040LQCD.
The decay 𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂 is searched for through the radiative transition 𝜓(3686)→𝛾𝜂𝑐(2𝑆) using 448 million 𝜓(3686) events accumulated at the BESIII detector. The first evidence of 𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂 is found with a statistical significance of 3.5𝜎. The product of the branching fractions of 𝜓(3686)→𝛾𝜂𝑐(2𝑆) and 𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂 is measured to be Br(𝜓(3686)→𝛾𝜂𝑐(2𝑆))×Br(𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂)=(2.97±0.81±0.26)×10−6, where the first uncertainty is statistical and the second one is systematic. The branching fraction of the decay 𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂 is determined to be Br(𝜂𝑐(2𝑆)→𝜋+𝜋−𝜂)=(42.4±11.6±3.8±30.3)×10−4, where the third uncertainty is transferred from the uncertainty of the branching fraction of 𝜓(3686)→𝛾𝜂𝑐(2𝑆).
The decay $\eta_c(2S)\to\pipieta$ is searched for through the radiative transition ψ(3686)→γηc(2S) using 448 million ψ(3686) events accumulated at the BESIII detector. The first evidence of ηc(2S)→π+π−η is found with a statistical significance of 3.5σ. The product of the branching fractions of ψ(3686)→γηc(2S) and $\eta_c(2S)\to\pipieta$ is measured to be $Br(\psi(3686)\to\gamma\eta_c(2S))\times Br(\eta_c(2S)\to\pipieta)=(2.97\pm0.81\pm0.26)\times10^{-6}$, where the first uncertainty is statistical and the second one is systematic. The branching fraction of the decay $\eta_c(2S)\to\pipieta$ is determined to be $Br(\eta_c(2S)\to\pipieta)=(42.4\pm11.6\pm3.8\pm30.3)\times10^{-4}$, where the third uncertainty is transferred from the uncertainty of the branching fraction of ψ(3686)→γηc(2S).
The decay $\eta_c(2S)\to\pipieta$ is searched for through the radiative transition ψ(3686)→γηc(2S) using 448 million ψ(3686) events accumulated at the BESIII detector. The first evidence of ηc(2S)→π+π−η is found with a statistical significance of 3.5σ. The product of the branching fractions of ψ(3686)→γηc(2S) and $\eta_c(2S)\to\pipieta$ is measured to be $Br(\psi(3686)\to\gamma\eta_c(2S))\times Br(\eta_c(2S)\to\pipieta)=(2.97\pm0.81\pm0.26)\times10^{-6}$, where the first uncertainty is statistical and the second one is systematic. The branching fraction of the decay $\eta_c(2S)\to\pipieta$ is determined to be $Br(\eta_c(2S)\to\pipieta)=(42.4\pm11.6\pm3.8\pm30.3)\times10^{-4}$, where the third uncertainty is transferred from the uncertainty of the branching fraction of ψ(3686)→γηc(2S).
Based on data samples collected with the BESIII detector at the BEPCII collider, the process e+e−→Σ+Σ¯− is studied at center-of-mass energies s√ = 2.3960, 2.6454, and 2.9000~GeV. Using a fully differential angular description of the final state particles, the complete information of the Σ+ electromagnetic form factors in the time-like region is extracted. The relative phase between the electric and magnetic form factors is determined to be sinΔΦ = -0.67~±~0.29~(stat.)~±~0.18~(syst.) at s√ = 2.3960~GeV, ΔΦ = 55∘~±~19∘~(stat.) ±~14∘~(syst.) at s√ = 2.6454~GeV, and 78∘~±~22∘~(stat.) ±~9∘~(syst.) at s√ = 2.9000~GeV. For the first time, the phase of the hyperon electromagnetic form factors is explored in a wide range of four-momentum transfer. The evolution of the phase along with four-momentum transfer is an important input for understanding its asymptotic behavior and the dynamics of baryons.
Based on data samples collected with the BESIII detector at the BEPCII collider, the process e+e−→Σ+Σ¯− is studied at center-of-mass energies s√ = 2.3960, 2.6454, and 2.9000~GeV. Using a fully differential angular description of the final state particles, the complete information of the Σ+ electromagnetic form factors in the time-like region is extracted. The relative phase between the electric and magnetic form factors is determined to be sinΔΦ = -0.67~±~0.29~(stat.)~±~0.18~(syst.) at s√ = 2.3960~GeV, ΔΦ = 55∘~±~19∘~(stat.) ±~14∘~(syst.) at s√ = 2.6454~GeV, and 78∘~±~22∘~(stat.) ±~9∘~(syst.) at s√ = 2.9000~GeV. For the first time, the phase of the hyperon electromagnetic form factors is explored in a wide range of four-momentum transfer. The evolution of the phase along with four-momentum transfer is an important input for understanding its asymptotic behavior and the dynamics of baryons.
Based on data samples collected with the BESIII detector at the BEPCII collider, the process e+e−→Σ+Σ¯− is studied at center-of-mass energies s√ = 2.3960, 2.6454, and 2.9000 GeV. Using a fully differential angular description of the final state particles, both the relative magnitude and phase information of the Σ+ electromagnetic form factors in the timelike region are extracted. The relative phase between the electric and magnetic form factors is determined to be sinΔΦ = -0.67~±~0.29~(stat)~±~0.18~(syst) at s√ = 2.3960 GeV, ΔΦ = 55∘~±~19∘~(stat) ±~14∘~(syst) at s√ = 2.6454 GeV, and 78∘~±~22∘~(stat) ±~9∘~(syst) at s√ = 2.9000 GeV. For the first time, the phase of the hyperon electromagnetic form factors is explored in a wide range of four-momentum transfer. The evolution of the phase along with four-momentum transfer is an important input for understanding its asymptotic behavior and the dynamics of baryons.
Using a data sample of (10087±44)×106 J/ψ events collected by the BESIII detector in 2009, 2012, 2018 and 2019, the electromagnetic Dalitz process J/ψ→e+e−η(1405) is observed via the decay η(1405)→π0f0(980), f0(980)→π+π−, with a significance of about 9.6σ. The branching fraction of this decay is measured to be B(J/ψ→e+e−π0η(1405)→e+e−π0f0(980)→e+e−π0π+π−)=(2.02±0.24(stat.)±0.09(syst.))×10−7. The branching-fraction ratio B(J/ψ→e+e−η(1405))/B(J/ψ→γη(1405)) is determined to be (1.35±0.19(stat.)±0.06(syst.))×10−2. Furthermore, an e+e− invariant-mass dependent transition form factor of J/ψ→e+e−η(1405) is presented for the first time. The obtained result provides input for different theoretical models, and is valuable for the improved understanding the intrinsic structure of the η(1405) meson.
The high collision energies reached at the LHC lead to significant production yields of light (anti)hypernuclei in proton–proton (pp), proton–lead (p–Pb) and, in particular, Pb–Pb collisions. The lightest known hypernucleus is the hypertriton, which is a bound state of a proton, a neutron, and a Λ hyperon. It decays weakly with a decay length of a few centimeters. The excellent tracking and particle identification capabilities of the ALICE detector, exploiting the energy loss measurement of the Time Projection Chamber (TPC) and using the Inner Tracking System (ITS) to distinguish between primary and secondary (decay) vertices, allow for the determination of the hypertriton yield across different collision systems, its lifetime, and its binding energy. The latest hypertriton lifetime measurement in Pb–Pb collisions performed in the 2-body decay channel will be presented. This measurement contributes to the solution of the hypertriton lifetime puzzle. In addition, the hypertriton production in different collision systems and at different energies will be compared to model predictions. Due to its low binding energy, and hence to its large size, the hypertriton is the ideal candidate to distinguish between statistical hadronization and coalescence models. With the precision of the presented yield measurements some variants of the aforementioned models can be excluded.
Introduction: Due to an inhibited tryptophan resorption, patients with fructose malabsorption are expected to experience decreased serotonin synthesis. A deficiency of serotonin may cause internalizing mental disorders like depression and anxiety, and a fructose-oriented eating behavior may affect these symptoms.
Methods: The parents of 24 children and adolescents with a currently diagnosed fructose malabsorption aged 4;00–13;02 years (M = 8.10, SD = 2.05), the parents of 12 patients with a currently confirmed combination of fructose and lactose malabsorption aged 4;00–12;11 years (M = 8.07, SD = 2.11) and the parents of a comparative sample of 19 healthy participants aged 5;00 to 17;07 years (M = 9.06, SD = 3.04) were interviewed. The interviews were conducted using a screening questionnaire of the German “Diagnostic System of Mental Disorders in children and adolescents based on the ICD-10 and DSM-5 DISYPS-III” and a self-developed questionnaire on eating, leisure and sleeping behavior.
Results: On standardized scales parents of children with fructose malabsorption reported higher levels of Depression compared to symptoms of Attention-Deficit/Hyperactivity Disorders (ADHD) and Oppositional Defiant and Conduct Disorders (ODD/CD). Compared to healthy controls, for patients with fructose malabsorption, higher symptom levels of Depression and Anxiety were reported. With regard to eating behavior, within the group with a combination of fructose and lactose malabsorption, a strong positive association between an increased fruit sugar consumption and higher levels of Anxiety and Obsessive-Compulsive Disorders/Tics were found.
Discussion: These results suggest a close association between fructose malabsorption and elevated internalizing psychological symptoms in children and adolescents.
Clinical trial registration: https://drks.de/search/en/trial/DRKS00031047, DRKS-ID [DRKS00031047].