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Using 448 million ψ(2S) events, the spin-singlet P-wave charmonium state hc(11P1) is studied via the ψ(2S)→π0hc decay followed by the hc→γηc transition. The branching fractions are measured to be BInc(ψ(2S)→π0hc)×BTag(hc→γηc)=(4.22+0.27−0.26±0.19)×10−4 , BInc(ψ(2S)→π0hc)=(7.32±0.34±0.41)×10−4, and BTag(hc→γηc)=(57.66+3.62−3.50±0.58)%, where the uncertainties are statistical and systematic, respectively. The hc(11P1) mass and width are determined to be M=(3525.32±0.06±0.15) MeV/c2 and Γ=(0.78+0.27−0.24±0.12) MeV. Using the center of gravity mass of the three χcJ(13PJ) mesons (M(c.o.g.)), the 1P hyperfine mass splitting is estimated to be Δhyp=M(hc)−M(c.o.g.)=(0.03±0.06±0.15) MeV/c2, which is consistent with the expectation that the 1P hyperfine splitting is zero at the lowest-order.
Using 448 million ψ(2S) events, the spin-singlet P-wave charmonium state hc(11P1) is studied via the ψ(2S)→π0hc decay followed by the hc→γηc transition. The branching fractions are measured to be BInc(ψ(2S)→π0hc)×BTag(hc→γηc)=(4.17+0.27−0.25±0.19)×10−4 , BInc(ψ(2S)→π0hc)=(7.23±0.33±0.38)×10−4, and BTag(hc→γηc)=(57.66+3.62−3.50±0.58)%, where the uncertainties are statistical and systematic, respectively. The hc(11P1) mass and width are determined to be M=(3525.32±0.06±0.15) MeV/c2 and Γ=(0.78+0.27−0.24±0.12) MeV. Using the center of gravity mass of the three χcJ(13PJ) mesons (M(c.o.g.)), the 1P hyperfine mass splitting is estimated to be Δhyp=M(hc)−M(c.o.g.)=(0.03±0.06±0.15) MeV/c2, which is consistent with the expectation that the 1P hyperfine splitting is zero at the lowest-order.
Using 448 million ψ(2S) events, the spin-singlet P-wave charmonium state hc(11P1) is studied via the ψ(2S)→π0hc decay followed by the hc→γηc transition. The branching fractions are measured to be BInc(ψ(2S)→π0hc)×BTag(hc→γηc)=(4.22+0.27−0.26±0.19)×10−4 , BInc(ψ(2S)→π0hc)=(7.32±0.34±0.41)×10−4, and BTag(hc→γηc)=(57.66+3.62−3.50±0.58)%, where the uncertainties are statistical and systematic, respectively. The hc(11P1) mass and width are determined to be M=(3525.32±0.06±0.15) MeV/c2 and Γ=(0.78+0.27−0.24±0.12) MeV. Using the center of gravity mass of the three χcJ(13PJ) mesons (M(c.o.g.)), the 1P hyperfine mass splitting is estimated to be Δhyp=M(hc)−M(c.o.g.)=(0.03±0.06±0.15) MeV/c2, which is consistent with the expectation that the 1P hyperfine splitting is zero at the lowest-order.
Nowadays, teachers are facing a more and more digitized world, as digital tools are being used by their students on a daily basis. This requires digital competencies in order to react in a professional manner to individual and societal challenges and to teach the students a purposeful use of those tools. Regarding the subject (e.g., STEM), this purpose includes specific content aspects, like data processing, or modeling and simulations of complex scientific phenomena. Yet, both pre-service and experienced teachers often consider their digital teaching competencies insufficient and wish for guidance in this field. Especially regarding immersive tools like augmented reality (AR), they do not have a lot of experience, although their willingness to use those modern tools in their lessons is high. The digital tool AR can target another problem in science lessons: students and teachers often have difficulties with understanding and creating scientific models. However, these are a main part of the scientific way of acquiring knowledge and are therefore embedded in curricula. With AR, virtual visualizations of model aspects can be superimposed on real experimental backgrounds in real time. It can help link models and experiments, which usually are not part of the same lesson and are perceived differently by students. Within the project diMEx (digital competencies in modeling and experimenting), a continuing professional development (CPD) for physics teachers was planned and conducted. Secondary school physics educators were guided in using AR in their lessons and their digital and modeling competencies for a purposeful use of AR experiments were promoted. To measure those competencies, various instruments with mixed methods were developed and evaluated. Among others, the teachers’ digital competencies have been assessed by four experts with an evaluation matrix based on the TPACK model. Technological, technical and design aspects as well as the didactical use of an AR experiment were assessed. The teachers generally demonstrate a high level of competency, especially in the first-mentioned aspects, and have successfully implemented their learnings from the CPD in the (re)design of their AR experiments.
Based on 586 pb−1 of e+e− annihilation data collected at a center-of-mass energy of s√=4.6 GeV with the BESIII detector at the BEPCII collider, the absolute branching fraction of Λ+c→pK0Sη decays is measured for the first time to be B(Λ+c→pK0Sη)=(0.414±0.084±0.028)%, where the first uncertainty is statistical and the second is systematic. The result is compatible with a previous CLEO result on the relative branching fraction B(Λ+c→pK0Sη)B(Λ+c→pK−π+), and consistent with theoretical predictions of SU(3) flavor symmetry.
Focused electron-beam-induced deposition (FEBID) is a highly versatile direct-write approach with particular strengths in the 3D nanofabrication of functional materials. Despite its apparent similarity to other 3D printing approaches, non-local effects related to precursor depletion, electron scattering and sample heating during the 3D growth process complicate the shape-true transfer from a target 3D model to the actual deposit. Here, we describe an efficient and fast numerical approach to simulate the growth process, which allows for a systematic study of the influence of the most important growth parameters on the resulting shape of the 3D structures. The precursor parameter set derived in this work for the precursor Me3PtCpMe enables a detailed replication of the experimentally fabricated nanostructure, taking beam-induced heating into account. The modular character of the simulation approach allows for additional future performance increases using parallelization or drawing on the use of graphics cards. Ultimately, beam-control pattern generation for 3D FEBID will profit from being routinely combined with this fast simulation approach for optimized shape transfer.
The correction of valgus leg malalignment in children using implant-mediated growth guidance is widely used and effective. Despite the minimal invasive character of the procedure, a relevant number of patients sustain prolonged pain and limited mobility after temporary hemiepiphysiodesis. Our aim was to investigate implant-associated risk factors (such as implant position and screw angulation), surgical- or anesthesia-related risk factors (such as type of anesthesia, use, and duration), and pressure of tourniquet or duration of surgery for these complications. Thirty-four skeletally immature patients with idiopathic valgus deformities undergoing hemiepiphysiodesis plating from October 2018–July 2022 were enrolled in this retrospective study. Participants were divided into groups with and without prolonged complications (persistent pain, limited mobility of the operated knee between five weeks and six months) after surgery. Twenty-two patients (65%) had no notable complications, while twelve patients (35%) had prolonged complications. Both groups differed significantly in plate position relative to physis (p = 0.049). In addition, both groups showed significant differences in the distribution of implant location (p = 0.016). Group 1 had a shorter duration of surgery than group 2 (32 min vs. 38 min, p = 0.032) and a lower tourniquet pressure (250 mmHg vs. 270 mmHg, p = 0.019). In conclusion, simultaneous plate implantation at the femur and tibia and metaphyseal plate positioning resulted in prolonged pain and a delay of function. In addition, the amplitude of tourniquet pressure or duration of surgery could play a factor.
We derive an expression for the tensor polarization of a system of massive spin-1 particles in a hydrodynamic framework. Starting from quantum kinetic theory based on the Wigner-function formalism, we employ a modified method of moments which also takes into account all spin degrees of freedom. It is shown that the tensor polarization of an uncharged fluid is determined by the shear-stress tensor. In order to quantify this novel polarization effect, we provide a formula which can be used for numerical calculations of vector-meson spin alignment in relativistic heavy-ion collisions.
Background: Malalignments of the lower extremity are common reasons for orthopedic consultation because it may lead to osteoarthritis in adulthood. An accurate and reliable radiological assessment of lower limb alignment in children and adolescents is essential for clinical decision-making on treatment of limb deformities and for regular control after a surgical intervention.
Objective: First, does the analysis of full-length standing anteroposterior radiographs show a good intra- and interobserver reliability? Second, which parameter is most susceptible to observer-dependent errors? Third, what is the Standard Error of Measurement (SEM95%) of the absolute femoral and tibial length?
Methods: Two observers evaluated digital radiographs of 144 legs from 36 children and adolescents with pathological valgus alignment before a temporary hemiepiphysiodesis and before implant removal. Parameters included Mechanical Femorotibial Angle (MFA), Mechanical Axis Deviation (MAD), mechanical Lateral Distal Femoral Angle (mLDFA), mechanical Medial Proximal Tibial Angle (mMPTA), mechanical Lateral Proximal Femoral Angle (mLPFA), mechanical Lateral Distal Tibial Angle (mLDTA), Joint Line Convergence Angle (JLCA), femur length, tibial length. Intra- and interobserver reliability (ICC2,1), SEM95% and proportional errors were calculated.
Results: The intra- and interobserver reliability for almost all measurements was found to be good to excellent (Intra-ICC2,1: 0.849–0.999; Inter-ICC2,1: 0.864–0.996). The SEM95% of both observers was found to be ± 1.39° (MFA), ± 3.31 mm (MAD), ± 1.06° (mLDFA) and ± 1.29° (mMPTA). The proportional error of MAD and MFA is comparable (47.29% vs. 46.33%). The relevant knee joint surface angles show a lower proportional error for mLDFA (42.40%) than for mMPTA (51.60%). JLCA has a proportional error of 138%. Furthermore, the SEM95% for the absolute values of the femoral and tibial length was 4.53 mm for the femur and 3.12 mm for the tibia.
Conclusions: In conclusion, a precise malalignment measurement and the knowledge about SEM95% of the respective parameters are crucial for correct surgical or nonsurgical treatment. The susceptibility to error must be considered when interpreting malalignment analysis and must be considered when planning a surgical intervention. The results of the present study elucidate that MAD and MFA are equally susceptible to observer-dependent errors. This study shows good to excellent intra- and interobserver ICCs for all leg alignment parameters and joint surface angles, except for JLCA.
Trial registration: This study was registered with DRKS (German Clinical Trials Register) under the number DRKS00015053.
Level of evidence
I, Diagnostic Study.
Background: Lennox–Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant epilepsy with multiple seizure types starting in childhood, a typical slow spike-wave pattern on electroencephalogram, and cognitive dysfunction.
Methods: We performed a systematic literature review according to the PRISMA guidelines to identify, synthesize and appraise the burden of illness in LGS (including “probable” LGS). Studies were identified by searching MEDLINE, Embase and APA PsychInfo, Cochrane’s database of systematic reviews, and Epistemonikos. The outcomes were epidemiology (incidence, prevalence or mortality), direct and indirect costs, healthcare resource utilization, and patient and caregiver health-related quality of life (HRQoL).
Results: The search identified 22 publications evaluating the epidemiology (n = 10), direct costs and resource (n = 10) and/or HRQoL (n = 5). No studies reporting on indirect costs were identified. With no specific ICD code for LGS in many regions, several studies had to rely upon indirect methods to identify their patient populations (e.g., algorithms to search insurance claims databases to identify “probable” LGS). There was heterogeneity between studies in how LGS was defined, the size of the populations, ages of the patients and length of the follow-up period. The prevalence varied from 4.2 to 60.8 per 100,000 people across studies for probable LGS and 2.9–28 per 100,000 for a confirmed/narrow definition of LGS. LGS was associated with high mortality rates compared to the general population and epilepsy population. Healthcare resource utilization and direct costs were substantial across all studies. Mean annual direct costs per person varied from $24,048 to $80,545 across studies, and home-based care and inpatient care were significant cost drivers. Studies showed that the HRQoL of patients and caregivers was adversely affected, although only a few studies were identified. In addition, studies suggested that seizure events were associated with higher costs and worse HRQoL. The risk of bias was low or moderate in most studies.
Conclusions: LGS is associated with a significant burden of illness featuring resistant seizures associated with higher costs and worse HRQoL. More research is needed, especially in evaluating indirect costs and caregiver burden, where there is a notable lack of studies.
Cone photoreceptor cells are wavelength-sensitive neurons in the retinas of vertebrate eyes and are responsible for color vision. The spatial distribution of these nerve cells is commonly referred to as the cone photoreceptor mosaic. By applying the principle of maximum entropy, we demonstrate the universality of retinal cone mosaics in vertebrate eyes by examining various species, namely, rodent, dog, monkey, human, fish, and bird. We introduce a parameter called retinal temperature, which is conserved across the retinas of vertebrates. The virial equation of state for two-dimensional cellular networks, known as Lemaître’s law, is also obtained as a special case of our formalism. We investigate the behavior of several artificially generated networks and the natural one of the retina concerning this universal, topological law.
Rationale: Attention deficit/hyperactivity disorder (ADHD) is common in alcohol use disorder (AUD). Continuous performance tests (CPTs) allow to measure ADHD related deficits in a laboratory setting. Most studies on this topic focused on CPTs measuring inattention or impulsivity, disregarding hyperactivity as one of the core symptoms of ADHD.
Methods: We examined N = 47 in three groups (ADHD N = 19; AUD N = 16; ADHD + AUD N = 12) with questionnaires on ADHD core symptoms, executive functioning (EF), mind wandering, and quality of life (QoL). N = 46 (ADHD N = 16; AUD N = 16; ADHD + AUD N = 14) were examined with a CPT (QbTest®) that also measures motor activity objectively.
Results: Inattention and impulsivity were significantly increased in AUD vs. ADHD and in AUD vs. ADHD + AUD. Hyperactivity was significantly higher in ADHD + AUD vs. ADHD and ADHD + AUD vs. AUD, but not in ADHD vs. AUD. EF was lower in both ADHD groups vs. AUD. Mind wandering was increased in both ADHD groups vs. AUD. QoL was significantly lower in ADHD + AUD compared to AUD. In contrast, results of the QbTest were not significantly different between groups.
Conclusion: Questionnaires are more useful in assessing ADHD core symptoms than the QbTest®. Hyperactivity appears to be a relevant symptom in ADHD + AUD, suggesting a possible pathway from ADHD to AUD. The lower QoL in ADHD + AUD emphasizes the need for routine screening, diagnostic procedures and treatment strategies for this patient group.
The Cabibbo-allowed weak radiative decay Λ+c→Σ+γ has been searched for in a sample of Λ+cΛ¯−c pairs produced in e+e− annihilations, corresponding to an integrated luminosity of 4.5fb−1 collected with the BESIII detector at center-of-mass energies between 4.60 and 4.70 GeV. No excess of signal above background is observed, and we set an upper limit on the branching fraction of this decay to be B(Λ+c→Σ+γ)<4.4×10−4 at a confidence level of 90\%, which is in agreement with Standard Model expectations.
The Cabibbo-allowed weak radiative decay Λ+c→Σ+γ has been searched for in a sample of Λ+cΛ¯−c pairs produced in e+e− annihilations, corresponding to an integrated luminosity of 4.5fb−1 collected with the BESIII detector at center-of-mass energies between 4.60 and 4.70 GeV. No excess of signal above background is observed, and we set an upper limit on the branching fraction of this decay to be B(Λ+c→Σ+γ)<4.4×10−4 at a confidence level of 90\%, which is in agreement with Standard Model expectations.
The Cabibbo-allowed weak radiative decay Λ+c→Σ+γ has been searched for in a sample of Λ+cΛ¯−c pairs produced in e+e− annihilations, corresponding to an integrated luminosity of 4.5fb−1 collected with the BESIII detector at center-of-mass energies between 4.60 and 4.70 GeV. No excess of signal above background is observed, and we set an upper limit on the branching fraction of this decay to be B(Λ+c→Σ+γ)<4.4×10−4 at a confidence level of 90\%, which is in agreement with Standard Model expectations.
Using a data sample collected with the BESIII detector operating at the BEPCII storage ring, the Born cross section of the process 𝑒+𝑒−→𝜂𝐽/𝜓 at a center-of-mass energy √𝑠=3.773 GeV is measured to be (8.88±0.87±0.42) pb. We fit the cross section line shape before correcting for the initial state radiation from √𝑠=3.773 to 4.600 GeV to obtain the branching fraction ℬ(𝜓(3770)→𝜂𝐽/𝜓). We obtain ℬ(𝜓(3770)→𝜂𝐽/𝜓)=(11.3±5.9±1.1)×10−4 when the 𝜓(3770) decay amplitude is added coherently to the other contributions, and (8.7±1.0±0.8)×10−4 when it is added incoherently. Here the quoted uncertainties are statistical and systematic, respectively. In both cases, the statistical significance of 𝜓(3770) resonance is above 7𝜎. This is the first time the decay 𝜓(3770)→𝜂𝐽/𝜓 is observed with a statistical significance greater than 5𝜎.
The Born cross section of the process e+e−→ηJ/ψ at a center-of-mass energy s√=3.773 GeV is measured to be (8.89±0.88±0.42) pb, using a data sample collected with the BESIII detector operating at the BEPCII storage ring. The decay ψ(3770)→ηJ/ψ is observed for the first time with a statistical significance of 7.4σ. From a fit to the dressed cross-section line-shape of e+e−→ηJ/ψ from s√=3.773 to 4.600 GeV we obtain the branching fraction of the decay ψ(3770)→ηJ/ψ to be (11.6±6.1±1.0)×10−4 when the ψ(3770) decay amplitude is added coherently to the other contributions, and (7.9±1.0±0.7)×10−4 when it is added incoherently. Here the first uncertainties are statistical and the second are systematic.
Observation of a vector charmoniumlike state at 4.7 GeV/c² and search for Zcₛ in e⁺e⁻ → K⁺K⁻J/ψ
(2023)
Using data samples with an integrated luminosity of 5.85~fb−1 collected at center-of-mass energies from 4.61 to 4.95 GeV with the BESIII detector operating at the BEPCII storage ring, we measure the cross section for the process e+e−→K+K−J/ψ. A new resonance with a mass of M=4708+17−15±21 MeV/c2 and a width of Γ=126+27−23±30 MeV is observed in the energy-dependent line shape of the e+e−→K+K−J/ψ cross section with a significance over 5σ. The K+J/ψ system is also investigated to search for charged charmoniumlike states, but no significant Z+cs states are observed. Upper limits on the Born cross sections for e+e−→K−Zcs(3985)+/K−Zcs(4000)++c.c. with Zcs(3985)±/Zcs(4000)±→K±J/ψ are reported at 90\% confidence levels. The ratio of branching fractions B(Zcs(3985)+→K+J/ψ)B(Zcs(3985) +→ (D¯0D∗+s+D¯∗0D+s)) is measured to be less than 0.03 at 90\% confidence level.
Cross sections for the process e+e−→K0SK0SJ/ψ at center-of-mass energies from 4.128 to 4.950 GeV are measured using data samples with a total integrated luminosity of 21.2 fb−1 collected by the BESIII detector operating at the BEPCII storage ring. The Y(4230) state is observed in the energy dependence of the e+e−→K0SK0SJ/ψ cross section for the first time with a statistical significance of 26.0σ. In addition, an enhancement around 4.710 GeV, called the Y(4710), is seen with a statistical significance of 4.2σ. There is no clear structure around 4.484 GeV. Using a fit with a coherent sum of three Breit-Wigner functions, we determine the mass and width of the Y(4230) state to be 4226.9±6.6±21.9 MeV/c2 and 71.7±16.2±31.4 MeV, respectively, and the mass and width of the Y(4710) state to be 4704.0±52.3±69.5 MeV/c2 and 183.2±114.0±90.8 MeV, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the average Born cross section ratio of e+e−→K0SK0SJ/ψ to e+e−→K+K−J/ψ is measured to be 0.388+0.035−0.028±0.016, or 0.426+0.038−0.031±0.018 if three-body phase space is considered.
Cross sections for the process e+e−→K0SK0SJ/ψ at center-of-mass energies from 4.128 to 4.950 GeV are measured using data samples with a total integrated luminosity of 21.2 fb−1 collected by the BESIII detector operating at the BEPCII storage ring. The Y(4230) state is observed in the energy dependence of the e+e−→K0SK0SJ/ψ cross section for the first time with a statistical significance of 26.0σ. In addition, an enhancement around 4.710 GeV, called the Y(4710), is seen with a statistical significance of 4.2σ. There is no clear structure around 4.484 GeV. Using a fit with a coherent sum of three Breit-Wigner functions, we determine the mass and width of the Y(4230) state to be 4226.9±6.6±21.9 MeV/c2 and 71.7±16.2±31.4 MeV, respectively, and the mass and width of the Y(4710) state to be 4704.0±52.3±69.5 MeV/c2 and 183.2±114.0±90.8 MeV, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the average Born cross section ratio of e+e−→K0SK0SJ/ψ to e+e−→K+K−J/ψ is measured to be 0.388+0.035−0.028±0.016, or 0.426+0.038−0.031±0.018 if three-body phase space is considered.
Cross sections for the process e+e−→K0SK0SJ/ψ at center-of-mass energies from 4.128 to 4.950 GeV are measured using data samples with a total integrated luminosity of 21.2 fb−1 collected by the BESIII detector operating at the BEPCII storage ring. The Y(4230) state is observed in the energy dependence of the e+e−→K0SK0SJ/ψ cross section for the first time with a statistical significance of 26.0σ. In addition, an enhancement around 4.710 GeV, called the Y(4710), is seen with a statistical significance of 4.2σ. There is no clear structure around 4.484 GeV. Using a fit with a coherent sum of three Breit-Wigner functions, we determine the mass and width of the Y(4230) state to be 4226.9±6.6±21.9 MeV/c2 and 71.7±16.2±31.4 MeV, respectively, and the mass and width of the Y(4710) state to be 4704.0±52.3±69.5 MeV/c2 and 183.2±114.0±90.8 MeV, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the average Born cross section ratio of e+e−→K0SK0SJ/ψ to e+e−→K+K−J/ψ is measured to be 0.388+0.035−0.028±0.016, or 0.426+0.038−0.031±0.018 if three-body phase space is considered.
Using 4.5fb−1 of e+e− annihilation data samples collected at center-of-mass energies ranging from 4.600 to 4.698 GeV with the BESIII detector at the BEPCII collider, we measured the absolute branching fraction for the inclusive semileptonic decay Λ+c→Xe+νe, where X refers to any possible particle system. The branching fraction of the decay is determined to be B(Λ+c→Xe+νe)=(4.06±0.10stat.±0.09syst.)%. Our result improves the precision of previous measurement of B(Λ+c→Xe+νe) by more than threefold. Using the known Λ+c lifetime and the charge-averaged semileptonic decay width of nonstrange charmed mesons, we measure the ratio of inclusive semileptonic decay widths Γ(Λ+c→Xe+νe)/Γ¯(D→Xe+νe)=1.28±0.05, where statistical and systematic uncertainties are combined.
Highlights:
• Assessment of body composition parameters in a large cohort of patients with HCC undergoing TACE.
• Fully automated artificial intelligence-based quantitative 3D volumetry of abdominal cavity tissue composition.
• Skeletal muscle volume and related parameters were independent prognostic factors in patients with HCC undergoing TACE.
Background & Aims: Body composition assessment (BCA) parameters have recently been identified as relevant prognostic factors for patients with hepatocellular carcinoma (HCC). Herein, we aimed to investigate the role of BCA parameters for prognosis prediction in patients with HCC undergoing transarterial chemoembolization (TACE).
Methods: This retrospective multicenter study included a total of 754 treatment-naïve patients with HCC who underwent TACE at six tertiary care centers between 2010–2020. Fully automated artificial intelligence-based quantitative 3D volumetry of abdominal cavity tissue composition was performed to assess skeletal muscle volume (SM), total adipose tissue (TAT), intra- and intermuscular adipose tissue, visceral adipose tissue, and subcutaneous adipose tissue (SAT) on pre-intervention computed tomography scans. BCA parameters were normalized to the slice number of the abdominal cavity. We assessed the influence of BCA parameters on median overall survival and performed multivariate analysis including established estimates of survival.
Results: Univariate survival analysis revealed that impaired median overall survival was predicted by low SM (p <0.001), high TAT volume (p = 0.013), and high SAT volume (p = 0.006). In multivariate survival analysis, SM remained an independent prognostic factor (p = 0.039), while TAT and SAT volumes no longer showed predictive ability. This predictive role of SM was confirmed in a subgroup analysis of patients with BCLC stage B.
Conclusions: SM is an independent prognostic factor for survival prediction. Thus, the integration of SM into novel scoring systems could potentially improve survival prediction and clinical decision-making. Fully automated approaches are needed to foster the implementation of this imaging biomarker into daily routine.
Impact and implications: Body composition assessment parameters, especially skeletal muscle volume, have been identified as relevant prognostic factors for many diseases and treatments. In this study, skeletal muscle volume has been identified as an independent prognostic factor for patients with hepatocellular carcinoma undergoing transarterial chemoembolization. Therefore, skeletal muscle volume as a metaparameter could play a role as an opportunistic biomarker in holistic patient assessment and be integrated into decision support systems. Workflow integration with artificial intelligence is essential for automated, quantitative body composition assessment, enabling broad availability in multidisciplinary case discussions.
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±0.6stat±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.
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.
Highlights
• A proteomic analysis of the mandibular glands of Shinisaurius crocodilurus and Corucia zebrata, was performed.
• Scanning electron microscopy of S. crocodilurus' teeth revealed a sharp ridge on the anterior surface, but no grooves.
• Scanning electron microscopy of C. zebrata teeth showed a flattened crown with a pointed cusp.
• Proteomic analysis of gland extracts of S. crocodilurus and C. zebrata showed absence of venom-derived peptides or proteins.
• Our results strongly support the non-venomous character of both S. crocodilurus and C. zebrata.
Abstract
Based on its phylogenetic relationship to monitor lizards (Varanidae), Gila monsters (Heloderma spp.), and the earless monitor Lanthanotus borneesis, the Chinese crocodile lizard, Shinisaurus crocodilurus, has been assigned to the Toxicofera clade, which comprises venomous reptiles. However, no data about composition and biological activities of its oral secretion have been reported. In the present study, a proteomic analysis of the mandibular gland of S. crocodilurus and, for comparison, of the herbivorous Solomon Island skink Corucia zebrata, was performed. Scanning electron microscopy (SEM) of the teeth from S. crocodilurus revealed a sharp ridge on the anterior surface, but no grooves, whereas those of C. zebrata possess a flattened crown with a pointed cusp. Proteomic analysis of their gland extracts provided no evidence of venom-derived peptides or proteins, strongly supporting the non-venomous character of these lizards. Data are available via ProteomeXchange with identifier PXD039424.
Highlights
• Proteomic analyses of submandibular gland extracts of two alligator lizards of the Anguidae family are reported.
• A conserved set of putative toxins was found in the submandibular gland extracts of Abronia lythrochila and A. graminea.
• Toxins evolved in oral secretions of paleo- and neoanguimorpha over more than 100 million years of Anguimorpha cladogenesis.
• Electron microscopy of pleurodont teeth of A. lythrochila showed no sign of groove, external opening or striations.
• Assessing the role toxins play in the ecology of extant anguimorph lizards deserves functional studies in natural prey.
Abstract
A useful approach to deepen our knowledge about the origin and evolution of venom systems in Reptilia has been exploring the vast biodiversity of this clade of vertebrates in search of orally produced proteins with toxic actions, as well as their corresponding delivery systems. The occurrence of toxins in anguimorph lizards has been demonstrated experimentally or inferred from reports of the toxic effects of the oral secretions of taxa within the Varanidae and Helodermatidae families. In the present study, we have focused on two alligator lizards of the Anguidae family, the Mexican alligator lizard, Abronia graminea, and the red-lipped arboreal alligator lizard, A. lythrochila. In addition, the fine morphology of teeth of the latter species is described. The presence of a conserved set of proteins, including B-type natriuretic peptides, cysteine-rich secretory proteins, group III phospholipase A2, and kallikrein, in submandibular gland extracts was demonstrated for both Abronia species. These proteins belong to toxin families found in oral gland secretions of venomous reptile species. This finding, along with previous demonstration of toxin-producing taxa in both paleo- and neoanguimorpha clades, provides further support for the existence of a handful of conserved toxin families in oral secretions across the 100+ million years of Anguimorpha cladogenesis.
Introduction: Patients undergoing left atrial appendage closure (LAAC) are often severly anemic and close to the transfusion threshold. The aim was to investigate the prevalence of severe anemia in this cohort and if procedural safety is compromised compared with non-anemic patients.
Methods and results: Comparison of severly anemic patients (Hb < 80 g/l) vs. non-severly anemic patients in the prospective, multicentre observational LAARGE registry of patients undergoing LAAC. A total of 638 patients (anemia 22.3% vs non-anemic 77.7%) were included. Anemic patients were older (77.1 years ± 7.9 vs 75.6 years ± 7.9, p = 0.014), had more comorbidities, higher CHA2DS2-VASc (4.8 vs 4.4, p = 0.017) and higher HAS-BLED (4.3 vs 3.8, p < 0.001) scores. Implant success was not influenced by anemia (99.3% vs 97.2%). Severe in-hospital (0.7% vs 5.6%, p = 0.01) and overall complications (8.5% vs 13.7%, p = 0.11) were less common in patients with anemia, driven by fewer pericardial effusions. Mortality was higher in anemic patients and associated with an increased hazard ratio, albeit not significantly (16.0% vs 10.3%, HR 1.61 (95%-CI: 0.97–2.67), p = 0.06). In the one-year follow-up, composite outcome of death, stroke or systemic embolism occurred in 22/142 anemic and in 54/496 non-anemic patients with an adjusted HR of 1.04 (95%-CI 0.62–1.73, p = 0.89).
Conclusion: Severe anemia close to the transfusion threshold is common in patients undergoing LAAC. However, this does not influence in-hospital complications or implant success. One-year mortality is higher in anemic patients, mainly driven by co-morbidities.
Key Teaching Points
• Wearables such as smartwatches can monitor beyond heart rate and heart rhythm.
• Specific smartwatches provide reliable measurements of electrocardiographic intervals (eg, QT interval).
• Correct analysis and interpretation of the QT interval in an individual with previously unknown long QT syndrome facilitated the diagnosis.
Aim: The aim of this study was to evaluate the relationship between coronary artery calcification (CAC) assessed by multi-detector computed tomography (MDCT) and myocardial perfusion assessed by cardiac magnetic resonance imaging (CMR) in a group of symptomatic patients.
Method: Retrospective analysis of 120 patients (age 65.1 ± 8.9 years, 88 males) who presented with atypical chest pain to Bethanien Hospital, Frankfurt, Germany, between 2007 and 2010 and who underwent CAC scoring using MDCT, CMR, and conventional coronary angiography. Patients were divided into those with high-grade (HG) stenosis (n = 67, age 65.1 ± 9.4 years) and those with no-HG stenosis (n = 53, age 65.1 ± 8.6 years).
Results: There were more males with HG stenosis (82.1% vs. 62.3%, p = 0.015), in whom the percentage and number of abnormal perfusion segments were higher at rest (37.3% vs. 17%, p = 0.014) but not different with stress (p = 0.83) from those with no-HG stenosis. Thirty-four patients had myocardial perfusion abnormalities at rest and 26 patients developed perfusion defects with stress. Stress-induced myocardial perfusion defects were 22.4% sensitive and 79.2% specific for detecting HG stenosis. The CAC score was lower in patients with no-HG stenosis compared to those with HG stenosis (p < 0.0001). On the ROC curve, a CAC score of 293 had a sensitivity of 71.6% and specificity of 83% in predicting HG stenosis [(AUC 0.80 (p < 0.0001)]. A CAC score of 293 or the presence of at least 1 segment myocardial perfusion abnormality was 74.6% sensitive and 71.7% specific in detecting HG stenosis, the respective values for the 2 abnormalities combined being 19.4% and 90.6%. The severity of CAC correlated with the extent of myocardial perfusion in the patient group as a whole with stress (r = 0.22, p = 0.015), particularly in those with no-HG stenosis (r = 0.31, p = 0.022). A CAC score of 293 was 31.6% sensitive and 87.3% specific in detecting myocardial perfusion abnormalities.
Conclusion: In a group of patients with exertional angina, coronary calcification is more accurate in detecting high-grade luminal stenosis than myocardial perfusion defects. In addition, in patients with no stenosis, the incremental relationship between coronary calcium score and the extent of myocardial perfusion suggests coronary wall hardening as an additional mechanism for stress-induced angina other than luminal narrowing. These preliminary findings might have a clinical impact on management strategies of these patients other than conventional therapy.
Rationale and Objectives: Lumbar disk degeneration is a common condition contributing significantly to back pain. The objective of the study was to evaluate the potential of dual-energy CT (DECT)-derived collagen maps for the assessment of lumbar disk degeneration.
Patients and Methods: We conducted a retrospective analysis of 127 patients who underwent dual-source DECT and MRI of the lumbar spine between 07/2019 and 10/2022. The level of lumbar disk degeneration was categorized by three radiologists as follows: no/mild (Pfirrmann 1&2), moderate (Pfirrmann 3&4), and severe (Pfirrmann 5). Recall (sensitivity) and accuracy of DECT collagen maps were calculated. Intraclass correlation coefficient (ICC) was used to evaluate inter-reader reliability. Subjective evaluations were performed using 5-point Likert scales for diagnostic confidence and image quality.
Results: We evaluated a total of 762 intervertebral disks from 127 patients (median age, 69.7 (range, 23.0–93.7), female, 56). MRI identified 230 non/mildly degenerated disks (30.2%), 484 moderately degenerated disks (63.5%), and 48 severely degenerated disks (6.3%). DECT collagen maps yielded an overall accuracy of 85.5% (1955/2286). Recall (sensitivity) was 79.3% (547/690) for the detection of no/mild lumbar disk degeneration, 88.7% (1288/1452) for the detection of moderate disk degeneration, and 83.3% (120/144) for the detection of severe disk degeneration (ICC = 0.9). Subjective evaluations of DECT collagen maps showed high diagnostic confidence (median 4) and good image quality (median 4).
Conclusion: The use of DECT collagen maps to distinguish different stages of lumbar disk degeneration may have clinical significance in the early diagnosis of disk-related pathologies in patients with contraindications for MRI or in cases of unavailability of MRI.
Highlights
• Early reconstruction of injured cruciate ligaments improves functional outcomes.
• Modern CT imaging can be used to rapidly identify patients with injury to the cruciate ligaments and streamline therapeutic pathways.
• Dual-energy CT demonstrates superior diagnostic accuracy compared to single-energy CT.
Abstract
Background: This study aimed to evaluate the clinical utility of modern single and dual-energy computed tomography (CT) for assessing the integrity of the cruciate ligaments in patients that sustained acute trauma.
Methods: Patients who underwent single- or dual-energy CT followed by 3 Tesla magnetic resonance imaging (MRI) or knee joint arthroscopy between 01/2016 and 12/2022 were included in this retrospective, monocentric study. Three radiologists specialized in musculoskeletal imaging independently evaluated all CT images for the presence of injury to the cruciate ligaments. An MRI consensus reading of two experienced readers and arthroscopy provided the reference standard. Diagnostic accuracy parameters and area under the receiver operator characteristic curve (AUC) were the primary metrics for diagnostic performance.
Results: CT images of 204 patients (median age, 49 years; IQR 36 – 64; 113 males) were evaluated. Dual-energy CT yielded significantly higher diagnostic accuracy and AUC for the detection of injury to the anterior (94% [240/255] vs 75% [266/357] and 0.89 vs 0.66) and posterior cruciate ligaments (95% [243/255] vs 87% [311/357] and 0.90 vs 0.61) compared to single-energy CT (all parameters, p <.005). Diagnostic confidence and image quality were significantly higher in dual-energy CT compared to single-energy CT (all parameters, p <.005).
Conclusions: Modern dual-energy CT is readily available and can serve as a screening tool for detecting or excluding cruciate ligament injuries in patients with acute trauma. Accurate diagnosis of cruciate ligament injuries is crucial to prevent adverse outcomes, including delayed treatment, chronic instability, or long-term functional limitations.
Highlights
• Assessment of coronary artery plaque burden according to the CAC-DRS Score correlated well with pulmonary involvement of SARS-CoV-2 pneumonia (min. r=0.81, 95% CI 0.76 to 0.86).
• Visual and quantitative CAC-DRS Score of coronary artery plaque burden provided independent prognostic information on all-cause mortality in patients with SARS-CoV-2 pneumonia (p=0.0016 and p<0.0001, respectively).
• Incorporating CAC-DRS Score and pulmonary involvement into clinical decision making revealed great potential to discriminate patients with fatal outcomes from a mild course of disease (AUC 0.938, 95% CI 0.89 to 0.97) and the need for intensive care treatment (AUC 0.801, 95% CI 0.77 to 0.83).
Purpose: To assess and correlate pulmonary involvement and outcome of SARS-CoV-2 pneumonia with the degree of coronary plaque burden based on the CAC-DRS classification (Coronary Artery Calcium Data and Reporting System).
Methods: This retrospective study included 142 patients with confirmed SARS-CoV-2 pneumonia (58 ± 16 years; 57 women) who underwent non-contrast CT between January 2020 and August 2021 and were followed up for 129 ± 72 days. One experienced blinded radiologist analyzed CT series for the presence and extent of calcified plaque burden according to the visual and quantitative HU-based CAC-DRS Score. Pulmonary involvement was automatically evaluated with a dedicated software prototype by another two experienced radiologists and expressed as Opacity Score.
Results: CAC-DRS Scores derived from visual and quantitative image evaluation correlated well with the Opacity Score (r=0.81, 95% CI 0.76-0.86, and r=0.83, 95% CI 0.77-0.89, respectively; p<0.0001) with higher correlation in severe than in mild stage SARS-CoV-2 pneumonia (p<0.0001). Combined, CAC-DRS and Opacity Scores revealed great potential to discriminate fatal outcomes from a mild course of disease (AUC 0.938, 95% CI 0.89-0.97), and the need for intensive care treatment (AUC 0.801, 95% CI 0.77-0.83). Visual and quantitative CAC-DRS Scores provided independent prognostic information on all-cause mortality (p=0.0016 and p<0.0001, respectively), both in univariate and multivariate analysis.
Conclusions: Coronary plaque burden is strongly correlated to pulmonary involvement, adverse outcome, and death due to respiratory failure in patients with SARS-CoV-2 pneumonia, offering great potential to identify individuals at high risk.
Background: Dual-energy CT (DECT)-derived bone mineral density (BMD) of the distal radius and other CT-derived metrics related to bone health have been suggested for opportunistic osteoporosis screening and risk evaluation for sustaining distal radius fractures (DRFs).
Methods: The distal radius of patients who underwent DECT between 01/2016 and 08/2021 was retrospectively analyzed. Cortical Hounsfield Unit (HU), trabecular HU, cortical thickness, and DECT-based BMD were acquired from a non-fractured, metaphyseal area in all examinations. Receiver-operating characteristic (ROC) analysis was conducted to determine the area under the curve (AUC) values for predicting DRFs based on DECT-derived BMD, HU values, and cortical thickness. Logistic regression models were then employed to assess the associations of these parameters with the occurrence of DRFs.
Results: In this study, 263 patients (median age: 52 years; interquartile range: 36–64; 132 women; 192 fractures) were included. ROC curve analysis revealed a higher area under the curve (AUC) value for DECT-derived BMD compared to cortical HU, trabecular HU, and cortical thickness (0.91 vs. 0.61, 0.64, and 0.69, respectively; p <.001). Logistic regression models confirmed the association between lower DECT-derived BMD and the occurrence of DRFs (Odds Ratio, 0.83; p <.001); however, no influence was observed for cortical HU, trabecular HU, or cortical thickness.
Conclusions: DECT can be used to assess the BMD of the distal radius without dedicated equipment such as calibration phantoms to increase the detection rates of osteoporosis and stratify the individual risk to sustain DRFs. In contrast, assessing HU-based values and cortical thickness does not provide clinical benefit.
Rationale and Objectives: Bone non-union is a serious complication of distal radius fractures (DRF) that can result in functional limitations and persistent pain. However, no accepted method has been established to identify patients at risk of developing bone non-union yet. This study aimed to compare various CT-derived metrics for bone mineral density (BMD) assessment to identify predictive values for the development of bone non-union.
Materials and Methods: CT images of 192 patients with DRFs who underwent unenhanced dual-energy CT (DECT) of the distal radius between 03/2016 and 12/2020 were retrospectively identified. Available follow-up imaging and medical health records were evaluated to determine the occurrence of bone non-union. DECT-based BMD, trabecular Hounsfield unit (HU), cortical HU and cortical thickness ratio were measured in normalized non-fractured segments of the distal radius.
Results: Patients who developed bone non-union were significantly older (median age 72 years vs. 54 years) and had a significantly lower DECT-based BMD (median 68.1 mg/cm3 vs. 94.6 mg/cm3, p < 0.001). Other metrics (cortical thickness ratio, cortical HU, trabecular HU) showed no significant differences. ROC and PR curve analyses confirmed the highest diagnostic accuracy for DECT-based BMD with an area under the curve (AUC) of 0.83 for the ROC curve and an AUC of 0.46 for the PR curve. In logistic regression models, DECT-based BMD was the sole metric significantly associated with bone non-union.
Conclusion: DECT-derived metrics can accurately predict bone non-union in patients who sustained DRF. The diagnostic performance of DECT-based BMD is superior to that of HU-based metrics and cortical thickness ratio.
We can see an increasing consumption of meat together with the corresponding behavioral adaptations in early hominins, such as Homo erectus. This new development was driven by one or more behavioral adaptations, such as a shift to a higher-quality diet, increased social interactions and/or changes in the life history strategies. The methods by which these hominins obtained meat—through scavenging the carcasses of large herbivores or hunting themselves—remain a topic of debate. They seem to have thrived in expanding grasslands, which offered few resources except for herds of large, gregarious mammals. In our study, we developed an agent-based model that simulates the behavior of a group of hunter-gatherers foraging in a reconstructed tropical grassland environment. The environmental parameters, including plant availability and prey population densities, are derived from the Serengeti National Park. In this model, agents gather or hunt various species either alone or as a group, using strategies early hominins may already have access to. The basic behavior and the implemented hunting strategies are based on data from recent hunter-gatherer societies living in tropical grasslands. Our model demonstrates how foragers may have thrived in tropical grasslands by either adopting fast hunting strategies, which often require access to sophisticated hunting tools, or by cooperating extensively, which would rely on an enhanced social structure to promote cooperative behavior. Our model can be used to study other scenarios by offering the option to change the environmental conditions and aspects of the agent behavior.
Abstract
In serial dependence, perceptual decisions are biased towards stimuli encountered in the recent past. Here, we investigate whether and how serial dependence is affected by the availability of visual working memory (VWM) resources. In two experiments, participants reproduced the orientation of a series of stimuli. On alternating trials, we included an additional VWM task with randomly varying levels of load. Serial dependence was not only affected by the additional load task but also clearly modulated by the level of load: a high load in the previous trial reduced serial dependence while a high load in the present increased it. These results were independent of the effects of VWM load on the precision of reproduction responses. Our findings provide new insights into the mechanisms that may regulate serial dependence, revealing its intimate link with VWM resources.
Significance statement
Our perception, thoughts, and behavior are continuously influenced by recent events. For instance, the way we process and understand current visual information depends on what we have seen in the preceding seconds, a phenomenon known as serial dependence. The precise mechanisms and factors involved in serial dependence are still unclear. Here, we demonstrated that working memory resources are a crucial component. Specifically, when we are currently experiencing a heavy memory load, the influence of prior stimuli becomes stronger. Conversely, when prior stimuli were shown under a high memory load, their influence was reduced. These findings highlight the importance of working memory resources in shaping our interpretation of the present based on the recent past.
The branching fraction of D+→K0Sπ0e+νe is measured for the first time using 7.93 fb−1 of e+e− annihilation data collected at the center-of-mass energy s√=3.773~GeV with the BESIII detector operating at the BEPCII collider, and is determined to be B(D+→K0Sπ0e+νe) = (0.881 ± 0.017stat. ± 0.016syst.)\%. Based on an analysis of the D+→K0Sπ0e+νe decay dynamics, we observe the S-wave and P-wave components with fractions of fS-wave = (6.13 ± 0.27stat. ± 0.30syst.)% and fK¯∗(892)0 = (93.88 ± 0.27stat. ± 0.29syst.)\%, respectively. From these results, we obtain the branching fractions B(D+→(K0Sπ0)S-wave e+νe) = (5.41 ± 0.35stat. ± 0.37syst.)×10−4 and B(D+→K¯∗(892)0e+νe) = (4.97 ± 0.11stat. ± 0.12syst.)\%. In addition, the hadronic form-factor ratios of D+→K¯∗(892)0e+νe at q2=0, assuming a single-pole dominance parameterization, are determined to be rV=V(0)A1(0)=1.43 ± 0.07stat. ± 0.03syst. and r2=A2(0)A1(0)=0.72 ± 0.06stat. ± 0.02syst.
In this paper, we construct a Dynamic Stochastic General Equilibrium (DSGE) model to examine the implications of dual rates for green lending. We demonstrate that implementing a distinct interest rate for banks engaged in green lending can effectively mitigate transition risks while channeling more capital towards green production sectors and firms for an immediate cut of emissions and net zero emission economy targets.
Biological drug substance (DS) is typically stored frozen to increase stability. However, freezing and thawing (F/T) of DS can impact product quality and therefore F/T processes need to be controlled. Because active F/T systems for DS bottles are lacking, freezing is often performed uncontrolled in conventional freezers, and thawing at ambient temperature or using water baths.
In this study, we evaluated a novel device for F/T of DS in bottles, which can be operated in conventional freezers, generating a directed air stream around bottles. We characterized the F/T geometry and process performance in comparison to passive F/T using temperature mapping and analysis of concentration gradients. The device was able to better control the F/T process by inducing directional bottom-up F/T. As a result, it reduced cryo-concentration during freezing as well as ice mound formation. However, freezing with the device was dependent on freezer performance, i.e. prolonged process times in a highly loaded freezer were accompanied by increased cryo-concentrations. Thawing was faster compared to without the device, but had no impact on concentration gradients and was slower compared to thawing in a water bath.
High-performance freezers might be required to fully exploit the potential of directional freezing with this device and allow F/T process harmonization and scaling across sites.
Using (2712±14) × 106 ψ(2S) events collected with the BESIII detector at the BEPCII collider, we search for the decays ηc(2S)→ωω and ηc(2S)→ωϕ via the process ψ(2S)→γηc(2S). Evidence of ηc(2S)→ωω is found with a statistical significance of 3.2σ. The branching fraction is measured to be B(ηc(2S)→ωω)=(5.65±3.77(stat.)±5.32(syst.))×10−4. No statistically significant signal is observed for the decay ηc(2S)→ωϕ. The upper limit of the branching fraction at the 90\% confidence level is determined to be B(ψ(2S)→γηc(2S),ηc(2S)→ωϕ)<2.24×10−7. We also update the branching fractions of χcJ→ωω and χcJ→ωϕ decays via the ψ(2S)→γχcJ transition. The branching fractions are determined to be B(χc0→ωω)=(10.63±0.11±0.46)×10−4, B(χc1→ωω)=(6.39±0.07±0.29)×10−4, B(χc2→ωω)=(8.50±0.08±0.38)×10−4, B(χc0→ωϕ)=(1.18±0.03±0.05)×10−4, B(χc1→ωϕ)=(2.03±0.15±0.12)×10−5, and B(χc2→ωϕ)=(9.37±1.07±0.59)×10−6, where the first uncertainties are statistical and the second are systematic.
Highlights
• Piriform cortex and amgydala can be separated based on their distinct structural connectivity.
• Similar to histological findings, the connectivity of the piriform cortex suggests posterior frontal and temporal subregions.
• Subregions of the piriform cortex have distinct connectivity profiles.
• Anterior PC extended into ventrotemporal PC posteriorly, which has not been described before, requiring further investigation.
• All parcellations were made publicly available.
Abstract
The anatomy of the human piriform cortex (PC) is poorly understood. We used a bimodal connectivity-based-parcellation approach to investigate subregions of the PC and its connectional differentiation from the amygdala.
One hundred (55 % female) genetically unrelated subjects from the Human Connectome Project were included. A region of interest (ROI) was delineated bilaterally covering PC and amygdala, and functional and structural connectivity of this ROI with the whole gray matter was computed. Spectral clustering was performed to obtain bilateral parcellations at granularities of k = 2–10 clusters and combined bimodal parcellations were computed. Validity of parcellations was assessed via their mean individual-to-group similarity per adjusted rand index (ARI).
Individual-to-group similarity was higher than chance in both modalities and in all clustering solutions. The amygdala was clearly distinguished from PC in structural parcellations, and olfactory amygdala was connectionally more similar to amygdala than to PC. At higher granularities, an anterior and ventrotemporal and a posterior frontal cluster emerged within PC, as well as an additional temporal cluster at their boundary. Functional parcellations also showed a frontal piriform cluster, and similar temporal clusters were observed with less consistency. Results from bimodal parcellations were similar to the structural parcellations. Consistent results were obtained in a validation cohort.
Distinction of the human PC from the amygdala, including its olfactory subregions, is possible based on its structural connectivity alone. The canonical fronto-temporal boundary within PC was reproduced in both modalities and with consistency. All obtained parcellations are freely available.
Highlights
• Northern and eastern grassland-savanna boundary defined by minimum temperature.
• Dynamics of fire, frost and growing season temperatures combine to produce this limit.
• Western limit is related to moisture availability.
• Modern, high-resolution climate data enables refinement of bioclimatic limits.
• Reparameterisation improves global model performance at regional scale.
Abstract
Understanding the controls of biome distributions is crucial for assessing terrestrial ecosystem functioning and its response to climate change. We analysed to what extent differences in climate factors (minimum temperatures, water availability, and growing season temperatures (degree days above 5 °C (GDD5)) might explain the poorly understood borders between grasslands, savannas and shrublands in eastern South Africa. The results were used to improve bioclimatic limits in the dynamic global vegetation model (DGVM) LPJ-GUESS. The vegetation model was also used to explore the role of fire in the biome borders. Results show no clear differences between the adjacent biomes in water availability. Treeless grasslands primarily occur in areas with minimum temperatures and GDD5 values below that of savannas. The standard fire module in LPJ-GUESS is not able to reproduce observed burned area patterns in the study region, but simulations with prescribed fire return intervals show that a combination of low temperatures and fire can explain the treeless state of the grassland biome. These results confirm earlier hypotheses that a combination of low winter temperatures, causing frost damage to trees, and low growing season temperatures that impede tree sapling growth and recruitment, particularly under re-occurring fires, drive the grassland-savanna border. With these insights implemented, the LPJ-GUESS simulation results substantially improved grass distribution in the grassland biome, but challenges remain concerning the grassland-shrubland boundary, tree-grass competition and prognostic fire modelling.
Purpose: To describe a novel surgical technique of a combined implantation of an artificial iris and a scleral fixated intraocular lens (IOL) using flanged IOL haptics (“Yamane” technique).
Observations: The suturelessly implanted artificial iris-IOL-sandwich was stable with good functional as well as aesthetic results. However, our case showed a postoperative intraocular pressure rise.
Conclusions: The presented case demonstrates that a visual as well as cosmetical rehabilitation seems to be possible even after severe, penetrating ocular trauma with profound iris defects.
Importance: The sutureless IOL scleral fixation technique can also be used in combination with a sutureless artificial iris implantation. Further studies are needed to evaluate the long-term safety profile and rates of postoperative complications.
Purpose: The IC-8® Apthera™ (AcuFocus Inc.™, Irvine, California, USA) is the first small aperture intraocular lens (IOL) to receive FDA approval for presbyopia correction in the summer of 2022. It is a single-piece hydrophobic acrylic monofocal lens, which is placed in the capsular bag. In its center it carries a black circular mask (FilterRing™) with a diameter of 3.23 mm consisting of polyvinylidene fluoride and carbon black nanoparticles. In the center of this mask sits a 1.36 mm wide aperture. Thanks to this pinhole effect the IC-8® serves as an extended-depth-of-focus (EDOF) IOL and can be used in presbyopia correction.
This report describes the case of a patient with an IC-8® implant who underwent Nd:YAG laser capsulotomy for posterior capsule opacification (PCO). The post laser checkup showed a dark central optical change within the IOL and the patient described optical phenomena as well as blurred central vision, which is why he received IOL exchange. The explanted IC-8® was sent to the Intermountain Ocular Research Center at the University of Utah for further analysis.
Observations: A 56-year-old male underwent cataract surgery with implantation of a non-diffractive EDOF-IOL on the right and the IC-8® small aperture IOL on the left eye. On the left eye, the patient had received penetrating keratoplasty seven years prior to the cataract operation due to posttraumatic corneal scarring. The early checkups after cataract surgery showed a corrected distance visual acuity (CDVA) in the left eye of +0.1 logMAR in the first month. About 5 months after the operation, PCO was first described on the left eye leading to a decrease in visual acuity to +0.4 logMAR (CDVA). Due to PCO, Nd:YAG laser capsulotomy was conducted 5 months after the cataract operation on the left eye. 12 shots were applied at 2.7 mJ. The following appointments showed a continuously reduced visual acuity of +1.3 logMAR (uncorrected) on the left eye and the patient described blurry and ‘swirled’ central vision. By slightly tilting his head and thus not using the center of his optic axis, he would be able to see sharper. Slit lamp examination showed a small optical change inside the IC-8® IOL not resembling a pit but believed to be a small pocket of air. Due to the ongoing symptoms as well as the reduced VA, the seemingly damaged small aperture IOL was exchanged for a three-piece hydrophobic acrylic monofocal lens, which was also placed in the posterior chamber. The explanted IC-8® was sent to the Intermountain Ocular Research Center at the University of Utah for further analysis. Results from gross and light microscopic analysis showed that the change caused by the Nd:YAG laser application consisted of a localized optical area containing carbon black nanoparticles used for the circular mask within the IOL.
Conclusions and importance: When dealing with PCO and performing Nd:YAG laser capsulotomy in eyes with an IC-8® IOL implant, the laser shots should be applied either inside the aperture or outside of the black circular mask of the IOL. Otherwise, the Nd:YAG laser can lead to bursts of carbon nanoparticles within the IOL which may cause optical phenomena as well as decreased visual acuity possibly resulting in an IOL exchange.
Using 𝑒+𝑒− collision data with an integrated luminosity of 7.33 fb−1 collected at center-of-mass energies between 4.128 and 4.226 GeV with the BESIII detector operating at the BEPCII collider, the branching fraction of the leptonic decay 𝐷+ 𝑠→𝜇+𝜈𝜇 is measured to be (0.5294±0.0108stat±0.0085syst)%. Based on this, the product of the 𝐷+ 𝑠 decay constant 𝑓𝐷+ 𝑠 and the magnitude of the 𝑐→𝑠 quark mixing matrix element |𝑉𝑐𝑠| is determined to be 𝑓𝐷+ 𝑠|𝑉𝑐𝑠| = 241.8±2.5stat±2.2syst MeV. Using the value of |𝑉𝑐𝑠| given by the global standard model fit, 𝑓𝐷+ 𝑠 is found to be 248.4±2.5stat±2.2syst MeV. Alternatively, using the value of 𝑓𝐷+ 𝑠 from a recent lattice quantum chromodynamics calculation, |𝑉𝑐𝑠| is determined to be 0.968±0.010stat±0.009syst.
The processes hc→γP(P=η′, η, π0) are studied with a sample of (27.12±0.14)×108 ψ(3686) events collected by the BESIII detector at the BEPCII collider. The decay hc→γη is observed for the first time with the significance of 9.0σ, and the branching fraction is determined to be (3.77±0.55±0.13±0.26)×10−4, while B(hc→γη′) is measured to be (1.40±0.11±0.04±0.10)×10−3, where the first uncertainties are statistical, the second systematic, and the third from the branching fraction of ψ(3686)→π0hc. The combination of these results allows for a precise determination of Rhc=B(hc→γη)B(hc→γη′), which is calculated to be (27.0±4.4±1.0)%. The results are valuable for gaining a deeper understanding of η−η′ mixing, and its manifestation within quantum chromodynamics. No significant signal is found for the decay hc→γπ0, and an upper limit is placed on its branching fraction of B(hc→γπ0)<5.0×10−5, at the 90% confidence level.
Based on 368.5 pb−1 of 𝑒+𝑒− collision data collected at center-of-mass energies 4.914 and 4.946 GeV by the BESIII detector, the 𝑒+𝑒−→𝜙𝜒𝑐1(3872) process is searched for the first time. No significant signal is observed and the upper limits at the 90% confidence level on the product of the Born cross section 𝜎(𝑒+𝑒−→𝜙𝜒𝑐1(3872)) and the branching fraction ℬ[𝜒𝑐1(3872)→𝜋+𝜋−𝐽/𝜓] at 4.914 and 4.946 GeV are set to be 0.85 and 0.96 pb, respectively. These measurements provide useful information for the production of the 𝜒𝑐1(3872) at 𝑒+𝑒− colliders and deepen our understanding about the nature of this particle.
Using data samples collected with the BESIII detector operating at the BEPCII storage ring, the cross section of the inclusive process e+e−→η+X, normalized by the total cross section of e+e−→hadrons, is measured at eight center-of-mass energy points from 2.0000 GeV to 3.6710 GeV. These are the first measurements with momentum dependence in this energy region. Our measurement shows a significant discrepancy from calculations with the existing fragmentation functions. To address this discrepancy, a new QCD analysis is performed at the next-to-next-to-leading order with hadron mass corrections and higher twist effects, which can explain both the established high-energy data and our measurements reasonably well.
Using data samples collected with the BESIII detector operating at the BEPCII storage ring, the cross section of the inclusive process e+e−→η+X, normalized by the total cross section of e+e−→hadrons, is measured at eight center-of-mass energy points from 2.0000 GeV to 3.6710 GeV. These are the first measurements with momentum dependence in this energy region. Our measurement shows a significant discrepancy from calculations with the existing fragmentation functions. To address this discrepancy, a new QCD analysis is performed at the next-to-next-to-leading order with hadron mass corrections and higher twist effects, which can explain both the established high-energy data and our measurements reasonably well.
We search for the di-photon decay of a light pseudoscalar axion-like particle, a, in radiative J/ψ decays, using 10 billion J/ψ events collected with the BESIII detector. We find no evidence of a signal and set upper limits at the 95% confidence level on the product branching fraction B(J/ψ→γa)×B(a→γγ) and the axion-like particle photon coupling constant gaγγ in the ranges of (3.7−48.5)×10−8 and (2.2−101.8)×10−4 GeV−1, respectively, for 0.18≤ma≤2.85 GeV/c2. These are the most stringent limits to date in this mass region.
We search for the di-photon decay of a light pseudoscalar axion-like particle, a, in radiative J/ψ decays, using 10 billion J/ψ events collected with the BESIII detector. We find no evidence of a signal and set upper limits at the 95% confidence level on the product branching fraction B(J/ψ→γa)×B(a→γγ) and the axion-like particle photon coupling constant gaγγ in the ranges of (3.7−48.5)×10−8 and (2.2−101.8)×10−4 GeV−1, respectively, for 0.18≤ma≤2.85 GeV/c2. These are the most stringent limits to date in this mass region.
We search for the di-photon decay of a light pseudoscalar axion-like particle, a, in radiative J/ψ decays, using 10 billion J/ψ events collected with the BESIII detector. We find no evidence of a signal and set upper limits at the 95% confidence level on the product branching fraction B(J/ψ→γa)×B(a→γγ) and the axion-like particle photon coupling constant gaγγ in the ranges of (3.7−48.5)×10−8 and (2.2−101.8)×10−4 GeV−1, respectively, for 0.18≤ma≤2.85 GeV/c2. These are the most stringent limits to date in this mass region.
Using 6.32 fb−1 of electron-positron collision data recorded by the BESIII detector at center-of-mass energies between 4.178 and 4.226~GeV, we present the first search for the decay D+s→a0(980)0e+νe, a0(980)0→π0η, which could proceed via a0(980)-f0(980) mixing. No significant signal is observed. An upper limit of 1.2×10−4 at the 90% confidence level is set on the product of the branching fractions of D+s→a0(980)0e+νe and a0(980)0→π0η decays.
We measure the inclusive semielectronic decay branching fraction of the D+s meson. A double-tag technique is applied to e+e− annihilation data collected by the BESIII experiment at the BEPCII collider, operating in the center-of-mass energy range 4.178−4.230 GeV. We select positrons from D+s→Xe+νe with momenta greater than 200 MeV/c, and determine the laboratory momentum spectrum, accounting for the effects of detector efficiency and resolution. The total positron yield and semielectronic branching fraction are determined by extrapolating this spectrum below the momentum cutoff. We measure the D+s semielectronic branching fraction to be B(D+s→Xe+νe)=(6.30±0.13(stat.)±0.10(syst.))%, showing no evidence for unobserved exclusive semielectronic modes. We combine this result with external data taken from literature to determine the ratio of the D+s and D0 semielectronic widths, Γ(D+s→Xe+νe)Γ(D0→Xe+νe)=0.790±0.016(stat.)±0.020(syst.). Our results are consistent with and more precise than previous measurements.
Using 2.93 fb−1 of e+e− collision data collected with the BESIII detector at a center-of-mass energy of 3.773 GeV, we measure the absolute branching fractions of the decays D0→K−e+νe and D+→K¯0e+νe to be (3.567±0.031stat±0.025syst)% and (8.68±0.14stat±0.16syst)%, respectively. Starting with the process e+e−→DD¯, a new reconstruction method is employed to select events that contain candidates for both D→K¯e+νe and D¯→Ke−ν¯e decays. The branching fractions reported in this work are consistent within uncertainties with previous BESIII measurements that selected events containing D→K¯e+νe and hadronic D¯ decays. Combining our results with the lifetimes of the D0 and D+ mesons and the previous BESIII measurements leads to a ratio of the two decay partial widths of Γ¯D0→K−e+νeΓ¯D+→K¯0e+νe=1.039±0.021. This ratio supports isospin symmetry in the D0→K−e+νe and D+→K¯0e+νe decays within 1.9σ.
Using 2.93 fb−1 of e+e− collision data collected with the BESIII detector at a center-of-mass energy of 3.773 GeV, we measure the absolute branching fractions of the decays D0→K−e+νe and D+→K¯0e+νe to be (3.567±0.031stat±0.025syst)% and (8.68±0.14stat±0.16syst)%, respectively. Starting with the process e+e−→DD¯, a new reconstruction method is employed to select events that contain candidates for both D→K¯e+νe and D¯→Ke−ν¯e decays. The branching fractions reported in this work are consistent within uncertainties with previous BESIII measurements that selected events containing D→K¯e+νe and hadronic D¯ decays. Combining our results with the lifetimes of the D0 and D+ mesons and the previous BESIII measurements leads to a ratio of the two decay partial widths of Γ¯D0→K−e+νeΓ¯D+→K¯0e+νe=1.039±0.021. This ratio supports isospin symmetry in the D0→K−e+νe and D+→K¯0e+νe decays within 1.9σ.
Using 2.93 fb−1 of e+e− collision data collected with the BESIII detector at a center-of-mass energy of 3.773~GeV, we measure the absolute branching fractions of the decays D0→K−e+νe and D+→K¯0e+νe to be (3.574±0.031stat±0.025syst)% and (8.70±0.14stat±0.16syst)%, respectively. Starting with the process e+e−→DD¯, a new reconstruction method is employed to select events that contain candidates for both D→K¯e+νe and D¯→Ke−ν¯e decays. The branching fractions reported in this work are consistent within uncertainties with previous BESIII measurements that selected events containing D→K¯e+νe and inclusive hadronic D¯ decays. Combining our results with the lifetimes of the D0 and D+ mesons and the previous BESIII measurements leads to a ratio of the two decay partial widths of Γ¯D0→K−e+νeΓ¯D+→K¯0e+νe=1.040±0.021. This ratio supports isospin symmetry in the D0→K−e+νe and D+→K¯0e+νe decays within 1.9σ.
Using e+e− collision data at ten center-of-mass energies between 2.644 and 3.080 GeV collected with the BESIII detector at BEPCII and corresponding to an integrated luminosity of about 500 pb−1, we measure the cross sections and effective form factors for the process e+e−→Ξ0Ξ¯0 utilizing a single-tag method. A fit to the cross section of e+e−→Ξ0Ξ¯0 with a pQCD-driven power function is performed, from which no significant resonance or threshold enhancement is observed. In addition, the ratio of cross sections for the processes e+e−→Ξ−Ξ¯+ and Ξ0Ξ¯0 is calculated using recent BESIII measurement and is found to be compatible with expectation from isospin symmetry.
Using e+e− collision data at ten center-of-mass energies between 2.644 and 3.080 GeV collected with the BESIII detector at BEPCII and corresponding to an integrated luminosity of about 500 pb−1, we measure the cross sections and effective form factors for the process e+e−→Ξ0Ξ¯0 utilizing a single-tag method. A fit to the cross section of e+e−→Ξ0Ξ¯0 with a pQCD-driven power function is performed, from which no significant resonance or threshold enhancement is observed. In addition, the ratio of cross sections for the processes e+e−→Ξ−Ξ¯+ and Ξ0Ξ¯0 is calculated using recent BESIII measurement and is found to be compatible with expectation from isospin symmetry.
Using e+e− collision data at ten center-of-mass energies between 2.644 and 3.080 GeV collected with the BESIII detector at BEPCII and corresponding to an integrated luminosity of 500.0 pb−1, we measure the cross sections and effective form factors for the process e+e−→Ξ0Ξ¯0 utilizing a single-tag method. A fit to the cross section of e+e−→Ξ0Ξ¯0 with a pQCD-driven power function is performed, from which no significant resonance or threshold enhancement is observed. In addition, the ratio of cross sections for the processes e+e−→Ξ−Ξ¯+ and Ξ0Ξ¯0 is calculated using recent BESIII measurement and is found to be compatible with expectation from isospin symmetry.
We evaluate the influence of a forest parametrization on the simulation of the boundary layer flow over moderate complex terrain in the context of the Perdigão 2017 field campaign. The numerical simulations are performed using the Weather Research and Forecasting model in large eddy simulation mode (WRF-LES). The short-term, high-resolution (40 m horizontal grid spacing) and long-term (200 m horizontal grid spacing) WRF-LES are evaluated for an integration time of 12 h and 1.5 months, respectively, with and without forest parameterization. The short-term simulations focus on low-level jet events over the valley, while the long-term simulations cover the whole intensive observation period (IOP) of the field campaign. The results are validated using lidar and meteorological tower observations. The mean diurnal cycle during the IOP shows a significant improvement of the along-valley wind speed and the wind direction when using the forest parametrization. However, the drag imposed by the parametrization results in an underestimation of the cross-valley wind speed, which can be attributed to a poor representation of the land surface characteristics. The evaluation of the high-resolution WRF-LES shows a positive influence of the forest parametrization on the simulated winds in the first 500 m above the surface.
We evaluate the influence of a forest parametrization on the simulation of the boundary layer flow over moderate complex terrain in the context of the Perdigão 2017 field campaign. The numerical simulations are performed using the Weather Research and Forecasting model in large eddy simulation mode (WRF-LES). The short-term, high-resolution (40 m horizontal grid spacing) and long-term (200 m horizontal grid spacing) WRF-LES are evaluated for an integration time of 12 h and 1.5 months, respectively, with and without forest parameterization. The short-term simulations focus on low-level jet events over the valley, while the long-term simulations cover the whole intensive observation period (IOP) of the field campaign. The results are validated using lidar and meteorological tower observations. The mean diurnal cycle during the IOP shows a significant improvement of the along-valley wind speed and the wind direction when using the forest parametrization. However, the drag imposed by the parametrization results in an underestimation of the cross-valley wind speed, which can be attributed to a poor representation of the land surface characteristics. The evaluation of the high-resolution WRF-LES shows a positive influence of the forest parametrization on the simulated winds in the first 500 m above the surface.
Marine stratocumuli are the most dominant cloud type by area coverage in the Southern Ocean (SO). They can be divided into different self-organized cellular morphological regimes known as open and closed mesoscale-cellular convective (MCC) clouds. Open and closed cells are the two most frequent types of organizational regimes in the SO. Using the liDAR-raDAR (DARDAR) version 2 retrievals, we quantify 59 % of all MCC clouds in this region as mixed-phase clouds (MPCs) during a 4-year time period from 2007 to 2010. The net radiative effect of SO MCC clouds is governed by changes in cloud albedo. Both cloud morphology and phase have previously been shown to impact cloud albedo individually, but their interactions and their combined impact on cloud albedo remain unclear.
Here, we investigate the relationships between cloud phase, organizational patterns, and their differences regarding their cloud radiative properties in the SO. The mixed-phase fraction, which is defined as the number of MPCs divided by the sum of MPC and supercooled liquid cloud (SLC) pixels, of all MCC clouds at a given cloud-top temperature (CTT) varies considerably between austral summer and winter. We further find that seasonal changes in cloud phase at a given CTT across all latitudes are largely independent of cloud morphology and are thus seemingly constrained by other external factors. Overall, our results show a stronger dependence of cloud phase on cloud-top height (CTH) than CTT for clouds below 2.5 km in altitude.
Preconditioning through ice-phase processes in MPCs has been observed to accelerate individual closed-to-open cell transitions in extratropical stratocumuli. The hypothesis of preconditioning has been further substantiated in large-eddy simulations of open and closed MPCs. In this study, we do not find preconditioning to primarily impact climatological cloud morphology statistics in the SO. Meanwhile, in-cloud albedo analysis reveals stronger changes in open and closed cell albedo in SLCs than in MPCs. In particular, few optically thick (cloud optical thickness >10) open cell stratocumuli are characterized as ice-free SLCs. These differences in in-cloud albedo are found to alter the cloud radiative effect in the SO by 21 to 39 W m−2 depending on season and cloud phase.
Ferroptosis is a regulated form of cell death which is considered an oxidative iron-dependent process. The lipid hydroperoxidase glutathione peroxidase 4 prevents the iron (Fe2+)-dependent formation of toxic lipid reactive oxygen species. While emerging evidence indicates that inhibition of glutathione peroxidase 4 as a hallmark of ferroptosis in many cancer cell lines, the involvement of this biochemical pathway in neuronal death remains largely unclear. Here, we investigate, first whether the ferroptosis key players are involved in the neuronal cell death induced by erastin. The second objective was to examine whether there is a cross talk between ferroptosis and autophagy. The third main was to address neuron response to erastin, with a special focus on ferritin and nuclear receptor coactivator 4-mediated ferritinophagy. To test this in neurons, erastin (0.5–8 µM) was applied to hippocampal HT22 neurons for 16 hours. In addition, cells were cultured with the autophagy inhibitor, 3-methyladenin (10 mM) and/or ferroptosis inhibitors, ferrostatin 1 (10–20 µM) or deferoxamine (10–200 µM) before exposure to erastin. In this study, we demonstrated by immunofluorescence and western blot analysis, that erastin downregulates dramatically the expression of glutathione peroxidase 4, the sodium-independent cystine-glutamate antiporter and nuclear receptor coactivator 4. The protein levels of ferritin and mitochondrial ferritin in HT22 hippocampal neurons did not remarkably change following erastin treatment. In addition, we demonstrated that not only the ferroptosis inhibitor, ferrostatin1/deferoxamine abrogated the ferroptotic cell death induced by erastin in hippocampal HT22 neurons, but also the potent autophagy inhibitor, 3-methyladenin. We conclude that (1) erastin-induced ferroptosis in hippocampal HT22 neurons, despite reduced nuclear receptor coactivator 4 levels, (2) that either nuclear receptor coactivator 4-mediated ferritinophagy does not occur or is of secondary importance in this model, (3) that ferroptosis seems to share some features of the autophagic cell death process.
In the basal, proliferative layer of healthy skin, the mTOR complex 1 (mTORC1) is activated, thus regulating proliferation while preventing differentiation. When cells leave the proliferative, basal compartment, mTORC1 signaling is turned off, which allows differentiation. Under inflammatory conditions, this switch is hijacked by cytokines and prevents proper differentiation. It is currently unknown how mTORC1 is regulated to mediate these effects on keratinocyte differentiation. In other tissues, mTORC1 activity is controlled through various pathways via the tuberous sclerosis complex (TSC). Thus, we investigated whether the TS complex is regulated by proinflammatory cytokines and contributes to the pathogenesis of psoriasis. TNF-α as well as IL-1β induced the phosphorylation of TSC2, especially on S939 via the PI3-K/AKT and MAPK pathway. Surprisingly, increased TSC2 phosphorylation could not be detected in psoriasis patients. Instead, TSC2 was strongly downregulated in lesional psoriatic skin compared to non-lesional skin of the same patients or healthy skin. In vitro inflammatory cytokines induced dissociation of TSC2 from the lysosome, followed by destabilization of the TS complex and degradation. Thus, we assume that in psoriasis, inflammatory cytokines induce strong TSC2 phosphorylation, which in turn leads to its degradation. Consequently, chronic mTORC1 activity impairs ordered keratinocyte differentiation and contributes to the phenotypical changes seen in the psoriatic epidermis.
The culture of primary intestinal epithelia cells is not possible in a normal culture system. In 2009 a three-dimensional culture system of intestinal stem cells was established that shows many of the physiological features of the small intestine, such as crypt-villus structure, stem cell niche and all types of differentiated intestinal epithelial cells. These enteroids can be used to analyze biology of intestinal stem cells, gut homeostasis and the development of diseases. They also give the possibility to reduce animal numbers, as enteroids can be cryo-conserved and cultivated for many passages. To investigate the influence of genes such as NADPH oxidases on the gut homeostasis, transgenic approached are the method of choice. The generation of enteroids from knockout mice allows real-time observations of knockout effects. Often conditional knockout or overexpression strategies using inducible Cre recombinase are applied to avoid effects of adaption to the knockout. However, the Cre recombinase has many known caveats from unspecific binding and its endonuclease activity. In this study, we show that although NADPH oxidases are important for in vivo differentiation and proliferation of the intestine, their expression is drastically reduced in the organoid system. Activation of Cre recombinase by 4-hydroxy tamoxifen in freshly isolated enteroids, independently of floxed genes, leads to decreased diameter of organoids. This effect is concentration-dependent and is caused by reduced cell proliferation and induction of apoptosis and DNA damage. In contrast, constitutive expression of Cre has no impact on the enteroids. Therefore, reduction of tamoxifen concentration and treatment duration should be carefully titrated, and appropriate controls are necessary.
Using a sample of about 1010 𝐽/𝜓 events collected at a center-of-mass energy √𝑠=3.097 GeV with the BESIII detector, the electromagnetic Dalitz decays 𝐽/𝜓→𝑒+𝑒−𝜋+𝜋−𝜂′, with 𝜂′→𝛾𝜋+𝜋− and 𝜂′→𝜋+𝜋−𝜂, have been studied. The decay 𝐽/𝜓→𝑒+𝑒−𝑋(1835) is observed with a significance of 15𝜎, and also an 𝑒+𝑒− invariant-mass dependent transition form factor of 𝐽/𝜓→𝑒+𝑒−𝑋(1835) is presented for the first time. The intermediate states 𝑋(2120) and 𝑋(2370) are also observed in the 𝜋+𝜋−𝜂′ invariant-mass spectrum with significances of 5.3𝜎 and 7.3𝜎. The corresponding product branching fractions for 𝐽/𝜓→𝑒+𝑒−𝑋, 𝑋→𝜋+𝜋−𝜂′ [𝑋=𝑋(1835), 𝑋(2120), and 𝑋(2370)] are reported.
Four different structural models, which all fit the same X-ray powder pattern, were obtained in the structure determination of 4,11-difluoroquinacridone (C20H10N2O2F2) from unindexed X-ray powder data by a global fit. The models differ in their lattice parameters, space groups, Z, Z′, molecular packing and hydrogen bond patterns. The molecules form a criss-cross pattern in models A and B, a layer structure built from chains in model C and a criss-cross arrangement of dimers in model D. Nevertheless, all models give a good Rietveld fit to the experimental powder pattern with acceptable R-values. All molecular geometries are reliable, except for model D, which is slightly distorted. All structures are crystallochemically plausible, concerning density, hydrogen bonds, intermolecular distances etc. All models passed the checkCIF test without major problems; only in model A a missed symmetry was detected. All structures could have probably been published, although 3 of the 4 structures were wrong. The investigation, which of the four structures is actually the correct one, was challenging. Six methods were used: (1) Rietveld refinements, (2) fit of the crystal structures to the pair distribution function (PDF) including the refinement of lattice parameters and atomic coordinates, (3) evaluation of the colour, (4) lattice-energy minimizations with force fields, (5) lattice-energy minimizations by two dispersion-corrected density functional theory methods, and (6) multinuclear CPMAS solid-state NMR spectroscopy (1H, 13C, 19F) including the comparison of calculated and experimental chemical shifts. All in all, model B (perhaps with some disorder) can probably be considered to be the correct one. This work shows that a structure determination from limited-quality powder data may result in totally different structural models, which all may be correct or wrong, even if they are chemically sensible and give a good Rietveld refinement. Additionally, the work is an excellent example that the refinement of an organic crystal structure can be successfully performed by a fit to the PDF, and the combination of computed and experimental solid-state NMR chemical shifts can provide further information for the selection of the most reliable structure among several possibilities.
Mexico’s role in the US-Central American migration regime is threefold: not only is it a country of origin, and a transit country, but also increasingly becoming a receiving country for migrants who flee from violence, insecurity and poverty. The Mexican state responds with detention enforcement. Clinical research usually puts emphasise on the negative impact of detention enforcement on the detainees‘ mental health. Yet, it often disregards the spatial configurations of detention centres and their socio-political context. This study aims to fill this gap by analysing how such factors create harmful environments that affect both the detainees‘ mental health and their social life in Mexico’s migration detention centres. The study’s mixed method approach builds on semi-structured interviews with a sample of N = 56 migrants of diverse nationalities and varying socioeconomic status of whom 22 were still detained while 34 had been released. The interviews include the Torturing Environment Scale (TES), a novel instrument for the analysis of detention environments, as well as clinical psychological measures of emotional distress. Additional n = 10 in-depth interviews with human rights advocates to explore the interconnections between the detention environments, their impact on mental health, and Mexican migration politics. Facultative counter-mappings of the detention centres complement the interviews. Without exception, all interviews of detainees underline that the manipulation of detention conditions creates torturing environments that cause harm to basic physiological and psychological needs. A comparison between detained vs. released interviewees revealed lasting feelings of fear and shame. The study emphasises that immigration detention immobilises migrants in a necropolitical limbo, which destroys hope as much as human integrity. It indicates that detention is part of deterrence politics, which perpetuates harm and inequality through detention and deportation. Highlighting structural human rights violations, the findings stress the need to review current migration policies.
Diurnal and nocturnal behaviour of cheetahs (Acinonyx jubatus) and lions (Panthera leo) in zoos
(2022)
Mammals are constantly exposed to exogenous and endogenous influences that affect their behaviour and daily activity. Light and temperature, as well as anthropogenic factors such as husbandry routines, visitors, and feeding schedules are potential influences on animals in zoological gardens. In order to investigate the effects of some of these factors on animal behaviour, observational studies based on the analyses of activity budgets can be used. In this study, the daily and nightly activity budgets of six lions (Panthera leo) and five cheetahs (Acinonyx jubatus) from four EAZA institutions were investigated. Focused on the influencing factor light and feeding, we analysed these activity budgets descriptively. Behaviour was recorded and analysed during the winter months over an observation period of 14 days and 14 nights using infrared-sensitive cameras. Our results show that lions and cheetahs exhibit activity peaks at crepuscular and feeding times, regardless of husbandry. Thus, lions in captivity shift nocturnal behaviour familiar from the wild to crepuscular and diurnal times. In cheetahs, in contrast, captive and wild individuals show similar 24 h behavioural rhythms. The resting behaviour of both species is more pronounced at night, with cheetahs having a shorter overall sleep duration than lions. This study describes the results of the examined animals and is not predictive. Nevertheless, the results of this study make an important contribution to gaining knowledge about possible factors influencing the behaviour of lions and cheetahs in zoos and offer implications that could be useful for improving husbandry and management.
Magnetoencephalography (MEG) and Electroencephalography (EEG) provide direct electrophysiological measures at an excellent temporal resolution, but the spatial resolution of source-reconstructed current activity is limited to several millimetres. Here we show, using simulations of MEG signals and Bayesian model comparison, that non-invasive myelin estimates from high-resolution quantitative magnetic resonance imaging (MRI) can enhance MEG/EEG source reconstruction. Our approach assumes that MEG/EEG signals primarily arise from the synchronised activity of pyramidal cells, and since most of the myelin in the cortical sheet originates from these cells, myelin density can predict the strength of cortical sources measured by MEG/EEG. Leveraging recent advances in quantitative MRI, we exploit this structure-function relationship and scale the leadfields of the forward model according to the local myelin density estimates from in vivo quantitative MRI to inform MEG/EEG source reconstruction. Using Bayesian model comparison and dipole localisation errors (DLEs), we demonstrate that adapting local forward fields to reflect increased local myelination at the site of a simulated source explains the simulated data better than models without such leadfield scaling. Our model comparison framework proves sensitive to myelin changes in simulations with exact coregistration and moderate-to-high sensor-level signal-to-noise ratios (≥10 dB) for the multiple sparse priors (MSP) and empirical Bayesian beamformer (EBB) approaches. Furthermore, we sought to infer the microstructure giving rise to specific functional activation patterns by comparing the myelin-informed model which was used to generate the activation with a set of test forward models incorporating different myelination patterns. We found that the direction of myelin changes, however not their magnitude, can be inferred by Bayesian model comparison. Finally, we apply myelin-informed forward models to MEG data from a visuo-motor experiment. We demonstrate improved source reconstruction accuracy using myelin estimates from a quantitative longitudinal relaxation (R1) map and discuss the limitations of our approach.
Highlights
We use quantitative MRI to implement myelin-informed forward models for M/EEG
Local myelin density was modelled by adapting the local leadfields
Myelin-informed forward models can improve source reconstruction accuracy
We can infer the directionality of myelination patterns, but not their strength
We apply our approach to MEG data from a visuo-motor experiment
Purpose
To assess the diagnostic value of different imaging modalities in distinguishing systemic vasculitis from other internal and immunological diseases.
Methods
This retrospective study included 134 patients with suspected vasculitis who underwent ultrasound, magnetic resonance imaging (MRI), or 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) between 01/2010 and 01/2019, finally consisting of 70 individuals with vasculitis. The main study parameter was the confirmation of the diagnosis using one of the three different imaging modalities, with the adjudicated clinical and histopathological diagnosis as the gold standard. A secondary parameter was the morphological appearance of the vessel affected by vasculitis.
Results
Patients with systemic vasculitis had myriad clinical manifestations with joint pain as the most common symptom. We found significant correlations between different imaging findings suggestive of vasculitis and the final adjudicated clinical diagnosis. In this context, on MRI, vessel wall thickening, edema, and diameter differed significantly between vasculitis and non-vasculitis groups (p < 0.05). Ultrasound revealed different findings that may serve as red flags in identifying patients with vasculitis, such as vascular occlusion or halo sign (p = 0.02 vs. non-vasculitis group). Interestingly, comparing maximal standardized uptake values from PET/CT examinations with vessel wall thickening or vessel diameter did not result in significant differences (p > 0.05).
Conclusions
We observed significant correlations between different imaging findings suggestive of vasculitis on ultrasound or MRI and the final adjudicated diagnosis. While ultrasound and MRI were considered suitable imaging methods for detecting and discriminating typical vascular changes, 18F-FDG PET/CT requires careful timing and patient selection given its moderate diagnostic accuracy.
The success of the increasing use of technology in education is highly dependent on learner acceptance. Although the Technology Acceptance Model (TAM) is dominant in research for surveying acceptance of technology, it does not allow the prediction of a successful first time use of technology. The successful first time use can be determined with the survey of technology affinity, as it corresponds to the expression of certain personality traits of users and is thus detached from the specific technology. Since there are no measurement instruments for the educational sector so far and existing instruments for measuring technology affinity do not meet the specific requirements for use in the educational context (e.g., limited time for questioning), we present the single item Inclusion of Technology Affinity in Self-Scale (ITAS). In study 1 we provide evidence of convergent and discriminant validity within the general population so that a generalization of its applicability is possible. In study 2 we subsequently tested ITAS in the actual target group, the educational sector. The high correlations of the ITAS with the ATI and the control instrument TA-EG (ranging from rs = 0.679 to rs = 0.440) show that ITAS is suitable for use in research. Furthermore, the newly developed instrument convinces with its low complexity, the graphical component, which requires little text understanding and the high time saving. This research thus can contribute to the investigation of technology affinity in the educational sector helping educators to conduct technical activities with their learning group, to predict possible difficulties and adjust their planning accordingly.
During winter 2015/2016, the Arctic stratosphere was characterized by extraordinarily low temperatures in connection with a very strong polar vortex and with the occurrence of extensive polar stratospheric clouds. From mid-December 2015 until mid-March 2016, the German research aircraft HALO (High Altitude and Long-Range Research Aircraft) was deployed to probe the lowermost stratosphere in the Arctic region within the POLSTRACC (Polar Stratosphere in a Changing Climate) mission. More than 20 flights have been conducted out of Kiruna, Sweden, and Oberpfaffenhofen, Germany, covering the whole winter period. Besides total reactive nitrogen (NOy), observations of nitrous oxide, nitric acid, ozone, and water were used for this study. Total reactive nitrogen and its partitioning between the gas and particle phases are key parameters for understanding processes controlling the ozone budget in the polar winter stratosphere. The vertical redistribution of total reactive nitrogen was evaluated by using tracer–tracer correlations (NOy–N2O and NOy–O3). The trace gases are well correlated as long as the NOy distribution is controlled by its gas-phase production from N2O. Deviations of the observed NOy from this correlation indicate the influence of heterogeneous processes. In early winter no such deviations have been observed. In January, however, air masses with extensive nitrification were encountered at altitudes between 12 and 15 km. The excess NOy amounted to about 6 ppb. During several flights, along with gas-phase nitrification, indications for extensive occurrence of nitric acid containing particles at flight altitude were found. These observations support the assumption of sedimentation and subsequent evaporation of nitric acid-containing particles, leading to redistribution of total reactive nitrogen at lower altitudes. Remnants of nitrified air masses have been observed until mid-March. Between the end of February and mid-March, denitrified air masses have also been observed in connection with high potential temperatures. This indicates the downward transport of air masses that have been denitrified during the earlier winter phase. Using tracer–tracer correlations, missing total reactive nitrogen was estimated to amount to 6 ppb. Further, indications of transport and mixing of these processed air masses outside the vortex have been found, contributing to the chemical budget of the winter lowermost stratosphere. Observations within POLSTRACC, at the bottom of the vortex, reflect heterogeneous processes from the overlying Arctic winter stratosphere. The comparison of the observations with CLaMS model simulations confirm and complete the picture arising from the present measurements. The simulations confirm that the ensemble of all observations is representative of the vortex-wide vertical NOy redistribution.
Uniform sampling from the set G(d) of graphs with a given degree-sequence d=(d1,…,dn)∈Nn is a classical problem in the study of random graphs. We consider an analogue for temporal graphs in which the edges are labeled with integer timestamps. The input to this generation problem is a tuple D=(d,T)∈Nn×N>0 and the task is to output a uniform random sample from the set G(D) of temporal graphs with degree-sequence d and timestamps in the interval [1,T]. By allowing repeated edges with distinct timestamps, G(D) can be non-empty even if G(d) is, and as a consequence, existing algorithms are difficult to apply.
We describe an algorithm for this generation problem which runs in expected time O(M) if Δ2+ϵ=O(M) for some constant ϵ>0 and T−Δ=Ω(T) where M=∑idi and Δ=maxidi. Our algorithm applies the switching method of McKay and Wormald [1] to temporal graphs: we first generate a random temporal multigraph and then remove self-loops and duplicated edges with switching operations which rewire the edges in a degree-preserving manner.
Purpose:
The purpose of the study was to provide a consensus definition of the infrarenal sealing zone and develop an algorithm to determine when and if adjunctive procedure(s) or reintervention should be considered in managing patients undergoing endovascular aortic repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA).
Methods:
A European Advisory Board (AB), made up of 11 vascular surgeons with expertise in EVAR for AAA, was assembled to share their opinion regarding the definition of preoperative and postoperative infrarenal sealing zone. Information on their current clinical practice and level of agreement on proposed reintervention paths was used to develop an algorithm. The process included 2 virtual meetings and 2 rounds of online surveys completed by the AB (Delphi method). Consensus was defined as reached when ≥ 8 of 11 (73%) respondents agreed or were neutral.
Results:
The AB reached complete consensus on definitions and measurement of the pre-EVAR target anticipated sealing zone (TASZ) and the post-EVAR real achieved sealing zone (RASZ), namely, the shortest length between the proximal and distal reference points as defined by the AB, in case of patients with challenging anatomies. Also, agreement was achieved on a list of 4 anatomic parameters and 3 prosthesis-/procedure-related parameters, considered to have the most significant impact on preoperative and postoperative sealing zones. Furthermore, the agreement was reached that in the presence of visible neck-related complications, both adjunctive procedure(s) and reintervention should be contemplated (100% consensus). In addition, adjunctive procedure(s) or reintervention can be considered in the following cases (% consensus): insufficient sealing zone on completion imaging (91%) or on the first postoperative computed tomography (CT) scan (91%), suboptimal sealing zone on completion imaging (73%) or postoperative CT scan (82%), and negative evolution of the actual sealing zone over time (91%), even in the absence of visible complications.
Conclusions:
AB members agreed on definitions of the pre- and post-EVAR infrarenal sealing zone, as well as factors of influence. Furthermore, a clinical decision algorithm was proposed to determine the timing and necessity of adjunctive procedure(s) and reinterventions.
Uniform sampling from the set G(d) of graphs with a given degree-sequence d=(d1,…,dn)∈Nn is a classical problem in the study of random graphs. We consider an analogue for temporal graphs in which the edges are labeled with integer timestamps. The input to this generation problem is a tuple D=(d,T)∈Nn×N>0 and the task is to output a uniform random sample from the set G(D) of temporal graphs with degree-sequence d and timestamps in the interval [1,T]. By allowing repeated edges with distinct timestamps, G(D) can be non-empty even if G(d) is, and as a consequence, existing algorithms are difficult to apply.
We describe an algorithm for this generation problem which runs in expected time O(M) if Δ2+ϵ=O(M) for some constant ϵ>0 and T−Δ=Ω(T) where M=∑idi and Δ=maxidi. Our algorithm applies the switching method of McKay and Wormald [1] to temporal graphs: we first generate a random temporal multigraph and then remove self-loops and duplicated edges with switching operations which rewire the edges in a degree-preserving manner.
Background
Musclin is an activity‐stimulated and cardioprotective myokine that attenuates pathological cardiac remodeling. Musclin deficiency, in turn, results in reduced physical endurance. The aim of this study was to assess the prognostic value of circulating musclin as a novel, putative biomarker to identify patients undergoing transcatheter aortic valve implantation (TAVI) who are at a higher risk of death.
Methods and Results
In this study, we measured systemic musclin levels in 368 patients undergoing TAVI who were at low to intermediate clinical risk (median EuroSCORE [European System for Cardiac Operative Risk Evaluation] II: 3.5; quartile 1–quartile, 2.2%–5.3%), whereby 209 (56.8%) patients were at low and 159 (43.2%) were at intermediate risk. Median preprocedural musclin levels were 2.7 ng/mL (quartile 1–quartile 3, 1.5–4.6 ng/mL). Musclin levels were dichotomized in low (<2.862 ng/mL, n=199 [54.1%]) or high (≥ 2.862 ng/mL, n=169 [45.9%]) groups using cutoff values determined by classification and regression tree analysis. The primary end point was 1‐year overall survival. Patients with low circulating musclin levels exhibited a significantly higher prevalence of frailty, low albumin values, hypertension, and history of stroke as well as higher N‐terminal pro‐B‐type natriuretic peptide. Low musclin levels significantly predicted risk of death in univariable (hazard ratio, 1.81; 95% CI, 1.00–3.53 [P=0.049]) and multivariable (adjusted hazard ratio, 2.45; 95% CI, 1.06–5.69 [P=0.037]) Cox regression analyses. Additionally, low musclin levels in combination with conventional EuroSCORE II suggested improved risk stratification in patients undergoing TAVI who were at low to intermediate clinical risk into subgroups with reduced 1‐year survival rates by log‐rank test (P for trend=0.003).
Conclusions
Circulating musclin is an independent predictor of 1‐year overall survival in patients undergoing TAVI. Combined with EuroSCORE II, circulating musclin might help to improve prediction of mortality in patients undergoing TAVI who are at low to intermediate clinical risk.
In this dissertation, we look at environmental effects in extreme and intermediate mass ratio inspirals into massive black holes. In these systems, stellar mass compact objects orbit massive black holes and lose orbital energy due to gravitational wave emission and other dissipative forces. We explore environmental interactions with dark matter spikes, stellar distributions, accretion disks, and combine and compare them. We discuss the existence and properties of dark matter spikes in the presence of these environmental effects. The signatures of the environmental effects, such as the phase space flow, dephasing, deshifting of the periapse, and alignment with accretion disks, are examined. These signatures are quantified in isolated spike systems, in dry, and in wet inspirals. We generally find dark matter effects to be subdominant to the other environmental effects, but their impact on the waveform is still observable and identifiable. Lastly, the rates of inspirals and the impact of spikes are estimated. All of these results are obtained with the help of a code imripy that is published alongside. If dark matter spikes exist, they should be observable with space-based gravitational wave observatories.
Emissions of the potent greenhouse gas perfluorocyclobutane (c-C4F8, PFC-318, octafluorocyclobutane) into the global atmosphere inferred from atmospheric measurements have been increasing sharply since the early 2000s. We find that these inferred emissions are highly correlated with the production of hydrochlorofluorocarbon-22 (HCFC-22, CHClF2) for feedstock (FS) uses, because almost all HCFC-22 FS is pyrolyzed to produce (poly)tetrafluoroethylene ((P)TFE) and hexafluoropropylene (HFP), a process in which c-C4F8 is a known by-product, causing a significant fraction of global c-C4F8 emissions. We find a global emission factor of ∼0.003 kg c-C4F8 per kilogram of HCFC-22 FS pyrolyzed. Mitigation of these c-C4F8 emissions, e.g., through process optimization, abatement, or different manufacturing processes, such as refined methods of electrochemical fluorination and waste recycling, could reduce the climate impact of this industry. While it has been shown that c-C4F8 emissions from developing countries dominate global emissions, more atmospheric measurements and/or detailed process statistics are needed to quantify c-C4F8 emissions at country to facility levels.
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.
Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematode Caenorhabditis elegans and its microbiota isolate Pseudomonas fluorescens MYb115 that is known to protect against Bacillus thuringiensis (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids that are derived from an iterative type I polyketide synthase (PKS), thereby describing a noncanonical pathway of bacterial sphingolipid production. We provide evidence that MYb115-derived sphingolipids affect C. elegans tolerance to Bt infection by altering host sphingolipid metabolism. This work establishes sphingolipids as structural outputs of bacterial PKS and highlights the role of microbiota-derived sphingolipids in host protection against pathogens.
Infection with the SARS (Severe Acute Respiratory Syndrome)-associated coronavirus results in respiratory failure probably by immunological mechanisms in 10% of patients. Laboratory markers that predict subsequent respiratory failure would therefore be useful in patient management.
We describe the clinical course, hematologic parameters, lymphocyte subpopulations and markers of inflammation in two patients with SARS, i.e., one man with diabetes mellitus and one pregnant woman, infected by the same viral isolate.
The patient with underlying diabetes mellitus developed respiratory failure after admission in the second week of the illness while the second patient developed only a mild disease without respiratory failure. Subsequent respiratory dysfunction was associated with lown umbers of Natural Killer (NK) cells at presentation and elevated CRP levels during the illness.
NK cells and CRP levels at the end of the first week of the disease might be related to subsequent respiratory dysfunction and may link underlying conditions to disease severity.
The transcription factor hypoxia-inducible factor 1 (HIF1) is an important driver of cancer and is therefore an attractive drug target. Acriflavine (ACF) has been suggested to inhibit HIF1, but its mechanism of action is unknown. Here we investigated the interaction of ACF with DNA and long non-coding RNAs (lncRNAs) and its function in human endothelial cells. ACF promoted apoptosis and reduced proliferation, network formation, and angiogenic capacity. It also induced changes in gene expression, as determined by RNA sequencing (RNA-seq), which could not be attributed to specific inhibition of HIF1. A similar response was observed in murine lung endothelial cells. Although ACF increased and decreased a similar number of protein-coding genes, lncRNAs were preferentially upregulated under normoxic and hypoxic conditions. An assay for transposase accessibility with subsequent DNA sequencing (ATAC-seq) demonstrated that ACF induced strong changes in chromatin accessibility at lncRNA promoters. Immunofluorescence showed displacement of DNA:RNA hybrids. Such effects might be due to ACF-mediated topoisomerase inhibition, which was indeed the case, as reflected by DNA unwinding assays. Comparison with other acridine derivatives and topoisomerase inhibitors suggested that the specific function of ACF is an effect of acridinium-class compounds. This study demonstrates that ACF inhibits topoisomerases rather than HIF specifically and that it elicits a unique expression response of lncRNAs.
Objectives
To identify the main problem areas in the applicability of the current TNM staging system (8th ed.) for the radiological staging and reporting of rectal cancer and provide practice recommendations on how to handle them.
Methods
A global case-based online survey was conducted including 41 image-based rectal cancer cases focusing on various items included in the TNM system. Cases reaching < 80% agreement among survey respondents were identified as problem areas and discussed among an international expert panel, including 5 radiologists, 6 colorectal surgeons, 4 radiation oncologists, and 3 pathologists.
Results
Three hundred twenty-one respondents (from 32 countries) completed the survey. Sixteen problem areas were identified, related to cT staging in low-rectal cancers, definitions for cT4b and cM1a disease, definitions for mesorectal fascia (MRF) involvement, evaluation of lymph nodes versus tumor deposits, and staging of lateral lymph nodes. The expert panel recommended strategies on how to handle these, including advice on cT-stage categorization in case of involvement of different layers of the anal canal, specifications on which structures to include in the definition of cT4b disease, how to define MRF involvement by the primary tumor and other tumor-bearing structures, how to differentiate and report lymph nodes and tumor deposits on MRI, and how to anatomically localize and stage lateral lymph nodes.
Conclusions
The recommendations derived from this global survey and expert panel discussion may serve as a practice guide and support tool for radiologists (and other clinicians) involved in the staging of rectal cancer and may contribute to improved consistency in radiological staging and reporting.
Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine.
While in large clinical laboratories the implementation of total laboratory automation is continuously proceeding, this concept is mostly not suitable for small- and middle-sized laboratories or for testing laboratories of blood donation services due to costs and required space. For these facilities, however, a rational level of automation can be achieved by the installation of stand-alone work cells for pre-analytical and selected analytical processes. In this review, the features of some automated pre-analytical sample processing systems and automated systems for the serological testing for infectious diseases are described exemplarily and compared with each other. The major advantages of automated systems, compared to a solely manual workflow, are described. Essential factors which have to be considered for making the choice for an appropriate automated system are pointed out.
Purpose: Discordance between pre-operative biopsy and final pathology for Upper Tract Urothelial Carcinoma (UTUC) is high and optimal management remains controversial. The aim of this study is to evaluate the accuracy of pre-operative biopsy, to identify prognostic factors and to evaluate the effect of adjuvant chemotherapy on survival and oncologic outcome in UTUC.
Methods: We analyzed records of patients receiving surgical treatment for UTUC. Pathology of pre-operative biopsy was compared to surgical specimen. We used Kaplan-Meier method to estimate survival probabilities and Cox's proportional hazards models to estimate the association between covariates and event times. Primary endpoint was overall survival (OS). A matched-pair analysis was performed to evaluate the effect of adjuvant chemotherapy.
Results: 151 patients underwent surgical treatment (28% open, 36% laparoscopic, 17% robotic radical nephroureterectomy; 14% segmental ureteral resections and 5% palliative nephrectomy) for UTUC and were included in the analysis. Upstaging from <pT1 in endoscopic biopsy to ≥pT1 in final pathology occurred in 61% of patients and upgrading from low-grade to high-grade occurred in 30% of patients. Five-year OS was 59.5%. In the univariate Cox-regression model pathological stage, grade, lymphovascular invasion and positive surgical margins were associated with OS. Matched pair analysis for stage (<pT3; ≥pT3; pN+) and age revealed a significant survival benefit for adjuvant chemotherapy (HR 0.40, 0.14–0.77, p < 0.018) in this cohort.
Conclusion: UTUC is often underestimated in pre-operative biopsy, and it is associated with significant mortality. Pathological stage and grade, lymphovascular invasion and lymph node metastases are predictors of oncologic outcome and survival.
Congenital diaphragmatic hernia (CDH) is a relatively common and life-threatening birth defect, characterized by an abnormal opening in the primordial diaphragm that interferes with normal lung development. As a result, CDH is accompanied by immature and hypoplastic lungs, being the leading cause of morbidity and mortality in patients with this condition. In recent decades, various animal models have contributed novel insights into the pathogenic mechanisms underlying CDH and associated pulmonary hypoplasia. In particular, the generation of genetically modified mouse models, which show both diaphragm and lung abnormalities, has resulted in the discovery of multiple genes and signaling pathways involved in the pathogenesis of CDH. This article aims to offer an up-to-date overview on CDH-implicated transcription factors, molecules regulating cell migration and signal transduction as well as components contributing to the formation of extracellular matrix, whilst also discussing the significance of these genetic models for studying altered lung development with regard to the human situation.
Background: Photochemical internalization (PCI) is a novel technology for light-induced enhancement of the local therapeutic effect of cancer drugs, utilizing a specially designed photosensitizing molecule (fimaporfin). The photosensitizing molecules are trapped in endosomes along with macromolecules or drugs. Photoactivation of fimaporfin disrupts the endosomal membranes so that drug molecules are released from endosomes inside cells and can reach their therapeutic target in the cell cytosol or nucleus. Compared with photodynamic therapy, the main cytotoxic effect with PCI is disruption of the endosomal membrane resulting in delivery of chemotherapy drug, and not to the photochemical reactions per se. In this study we investigated the effect of PCI with gemcitabine in patients with inoperable perihilar cholangiocarcinoma (CCA).
Methods: The in vitro cytotoxic effect of PCI with gemcitabine was studied on two CCA-derived cell lines. In a fimaporfin dose-escalation phase I clinical study, we administered PCI with gemcitabine in patients with perihilar CCA (n = 16) to establish a safe and tolerable fimaporfin dose and to get early signals of efficacy. The patients enrolled in the study had tumors in which the whole length of the tumor could be illuminated from the inside of the bile duct, using an optical fiber inserted via an endoscope (Fig. 1). Fimaporfin was administered intravenously at day 0; gemcitabine (i.v.) and intraluminal biliary endoscopic laser light application on day 4; followed by standard gemcitabine/cisplatin chemotherapy.
Results: Preclinical experiments showed that PCI enhanced the effect of gemcitabine. In patients with CCA, PCI with gemcitabine was well tolerated with no dose-limiting toxicities, and no unexpected safety signals. Disease control was achieved in 10 of 11 evaluable patients, with a clearly superior effect in the two highest dose groups. The objective response rate (ORR) was 42%, including two complete responses, while ORR at the highest dose was 60%. Progression-free survival at 6 months was 75%, and median overall survival (mOS) was 15.4 months, with 22.8 months at the highest fimaporfin dose.
Conclusion: Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA.
We study a relativistic fluid with longitudinal boost invariance in a quantum-statistical framework as an example of a solvable nonequilibrium problem. For the free quantum field, we calculate the exact form of the expectation values of the stress-energy tensor and the entropy current. For the stress-energy tensor, we find that a finite value can be obtained only by subtracting the vacuum of the density operator at some fixed proper time τ0. As a consequence, the stress-energy tensor acquires nontrivial quantum corrections to the classical free-streaming form.
Microplastics are small plastic fragments that are widely distributed in marine and terrestrial environments. While the soil ecosystem represents a large reservoir for plastic, research so far has focused mainly on the impact on aquatic ecosystems and there is a lack of information on the potentially adverse effects of microplastics on soil biota. Earthworms are key organisms of the soil ecosystem and are due to their crucial role in soil quality and fertility a suitable and popular model organism in soil ecotoxicology.
Therefore, the aim of this study was to gain insight into the effects of environmentally relevant concentrations of microplastics on the earthworm Eisenia andrei on multiple levels of biological organization after different exposure periods. Earthworms were exposed to two types of microplastics: (1) polystyrene-HBCD and (2) car tire abrasion in natural soil for 2, 7, 14 and 28 d. Acute and chronic toxicity and all subcellular investigations were conducted for all exposure times, avoidance behavior assessed after 48 h and reproduction after 28 d. Subcellular endpoints included enzymatic biomarker responses, namely, carboxylesterase, glutathione peroxidase, acetylcholinesterase, glutathione reductase, glutathione S-transferase and catalase activities, as well as fluorescence-based measurements of oxidative stress-related markers and multixenobiotic resistance activity. Multiple biomarkers showed significant changes in activity, but a recovery of most enzymatic activities could be observed after 28 d. Overall, only minor effects could be observed on a subcellular level, showing that in this exposure scenario with environmentally relevant concentrations based on German pollution levels the threat to soil biota is minimal. However, in areas with higher concentrations of microplastics in the environment, these results can be interpreted as an early warning signal for more adverse effects. In conclusion, these findings provide new insights regarding the ecotoxicological effects of environmentally relevant concentrations of microplastics on soil organisms.