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The fundamental concept of superfluidity gives rise to fascinating effects and collective behaviour such as vortex creation and second sound. Using quantum gases in optical lattices, superfluids can be realized over a wide range of tunable parameters, with a continuous connection to the regime of strong correlation. However, for full experimental access and a comprehensive comparison with condensed-matter systems, there is a need for new detection techniques to probe their essential physics. Here we report on a comprehensive study of superfluids in optical lattices by Bragg spectroscopy. We present fully momentum-resolved measurements of the band structure and associated interaction effects at several lattice depths. In addition, we directly study the composition of excitations and observe strong indications for Bogoliubov backscattering. Our measurements demonstrate the applicability and limits of the Bogoliubov theory to describe excitation properties of superfluids in periodic potentials and should pave the way for detailed studies of strongly correlated phases. A spectroscopic technique that enables momentum-resolved probing of excitations of atomic gases in optical lattices allows the full band structure of such systems to be measured for the first time. The method should facilitate the comparison of quantum-gas phases with their condensed-matter counterparts.

Ustilago maydis, a member of the Ustilaginaceae family, is a promising host for the production of several metabolites including itaconic acid. This dicarboxylate has great potential as a bio-based building block in the polymer industry, and is of special interest for pharmaceutical applications. Several itaconate overproducing Ustilago strains have been generated by metabolic and morphology engineering. This yielded stabilized unicellular morphology through fuz7 deletion, reduction of by-product formation through deletion of genes responsible for itaconate oxidation and (glyco)lipid production, and the overexpression of the regulator of the itaconate cluster ria1 and the mitochondrial tricarboxylate transporter encoded by mttA from Aspergillusterreus. In this study, itaconate production was further optimized by consolidating these different optimizations into one strain. The combined modifications resulted in itaconic acid production at theoretical maximal yield, which was achieved under biotechnologically relevant fed-batch fermentations with continuous feed.

Ponatinib, a third-generation tyrosine kinase inhibitor, is effective in patients with chronic myeloid leukemia (CML), particularly in cases of resistance or BCR::ABL1 T315I mutation. However, arterial occlusive events (AOEs) remain an important safety concern. The PONDEROSA registry evaluated ponatinib use under routine clinical conditions in Germany and the Czech Republic. This observational cohort study included 99 adult CML patients treated with ponatinib; patient recruitment took place between 2015 and 2022 at 31 centers. The median follow-up was 22 months (range: 1–83). Among the 99 patients (median age 54 years at CML diagnosis), 91.9% were in chronic phase, 4.0% in accelerated phase, and 4.0% in blast phase. The T315I BCR::ABL1 mutation was detected in 19.2%. Ponatinib starting doses were 45 mg/day (32.3%), 30 mg/day (37.3%), or 15 mg/day (29.3%). Adverse events (AEs) were recorded in 64.6% of patients. Severe cardiovascular or cerebrovascular events occurred in 12.1% of patients, with no fatal events observed. Ponatinib was discontinued in 31.3% of patients, mainly due to intolerance or lack of response. 58.6% of patients achieved or maintained at least a major molecular response (MMR), compared to 19.0% at baseline. Disease progression was observed in 14.1% of patients, and 8.1% underwent allogeneic stem cell transplantation. The estimated 2-year progression-free survival and overall survival rates were 84.4% and 85.7%, respectively. The PONDEROSA study confirms the clinical effectiveness of ponatinib in routine practice. Individualized dosing strategies are essential to balance efficacy and cardiovascular safety. Ponatinib remains a valuable bridging therapy for patients requiring allogeneic transplantation.

Background Currently, Aspergillus terreus is used for the industrial production of itaconic acid. Although, alternative feedstock use in fermentations is crucial for cost-efficient and sustainable itaconic acid production, their utilisation with A. terreus most often requires expensive pretreatment. Ustilaginacea are robust alternatives for itaconic acid production, evading the challenges, including the pretreatment of crude feedstocks regarding reduction of manganese concentration, that A. terreus poses. Results In this study, five different Ustilago strains were screened for their growth and production of itaconic acid on defined media. The most promising strains were then used to find a suitable alternative feedstock, based on the local food industry. U. cynodontis ITA Max pH, a highly engineered production strain, was selected to determine the biologically available nitrogen concentration in thick juice and molasses. Based on these findings, thick juice was chosen as feedstock to ensure the necessary nitrogen limitation for itaconic acid production. U. cynodontis ITA Max pH was further characterised regarding osmotolerance and product inhibition and a successful scale-up to a 2 L stirred tank reactor was accomplished. A titer of 106.4 g itaconic acid /L with a theoretical yield of 0.50 g itaconic acid /g sucrose and a space-time yield of 0.72 g itaconic acid /L/h was reached. Conclusions This study demonstrates the utilisation of alternative feedstocks to produce ITA with Ustilaginaceae, without drawbacks in either titer or yield, compared to glucose fermentations.

Background Industrial by-products accrue in most agricultural or food-related production processes, but additional value chains have already been established for many of them. Crude glycerol has a 60% lower market value than commercial glucose, as large quantities are produced in the biodiesel industry, but its valorisation is still underutilized. Due to its high carbon content and the natural ability of many microorganisms to metabolise it, microbial upcycling is a suitable option for this waste product. Results In this work, the use of crude glycerol for the production of the value-added compound itaconate is demonstrated using the smut fungus Ustilago maydis . Starting with a highly engineered strain, itaconate production from an industrial glycerol waste stream was quickly established on a small scale, and the resulting yields were already competitive with processes using commercial sugars. Adaptive laboratory evolution resulted in an evolved strain with a 72% increased growth rate on glycerol. In the subsequent development and optimisation of a fed-batch process on a 1.5-2 L scale, the use of molasses, a side stream of sugar beet processing, eliminated the need for other expensive media components such as nitrogen or vitamins for biomass growth. The optimised process was scaled up to 150 L, achieving an overall titre of 72 g L − 1 , a yield of 0.34 g g − 1 , and a productivity of 0.54 g L − 1 h − 1 . Conclusions Pilot-scale itaconate production from the complementary waste streams molasses and glycerol has been successfully established. In addition to achieving competitive performance indicators, the proposed dual feedstock strategy offers lower process costs and carbon footprint for the production of bio-based itaconate.

Background Itaconic acid is a promising bio-based building block for the synthesis of polymers, plastics, fibers and other materials. In recent years, Ustilago cynodontis has emerged as an additional itaconate producing non-conventional yeast, mainly due to its high acid tolerance, which significantly reduces saline waste coproduction during fermentation and downstream processing. As a result, this could likely improve the economic viability of the itaconic acid production process with Ustilaginaceae. Results In this study, we characterized a previously engineered itaconate hyper-producing Ustilago cynodontis strain in controlled fed-batch fermentations to determine the minimal and optimal pH for itaconate production. Under optimal fermentation conditions, the hyper-producing strain can achieve the theoretical maximal itaconate yield during the production phase in a fermentation at pH 3.6, but at the expense of considerable base addition. Base consumption is strongly reduced at the pH of 2.8, but at cost of production yield, titer, and rate. A techno-economic analysis based on the entire process demonstrated that savings due to an additional decrease in pH control reagents and saline waste costs cannot compensate the yield loss observed at the highly acidic pH value 2.8. Conclusions Overall, this work provides novel data regarding the balancing of yield, titer, and rate in the context of pH, thereby contributing to a better understanding of the itaconic acid production process with Ustilago cynodontis , especially from an economic perspective.

Bio-based bulk chemicals such as carboxylic acids continue to struggle to compete with their fossil counterparts on an economic basis. One possibility to improve the economic feasibility is the use of crude substrates in biorefineries. However, impurities in these substrates pose challenges in fermentation and purification, requiring interdisciplinary research. This work demonstrates a holistic approach to biorefinery process development, using itaconic acid production on thick juice based on sugar beets with Ustilago sp. as an example. A conceptual process design with data from artificially prepared solutions and literature data from fermentation on glucose guides the simultaneous development of the upstream and downstream processes up to a 100 L scale. Techno-economic analysis reveals substrate consumption as the main constituent of production costs and therefore, the product yield is the driver of process economics. Aligning pH-adjusting agents in the fermentation and the downstream process is a central lever for product recovery. Experiments show that fermentation can be transferred from glucose to thick juice by changing the feeding profile. In downstream processing, an additional decolorization step is necessary to remove impurities accompanying the crude substrate. Moreover, we observe an increased use of pH-adjusting agents compared to process simulations.

The use of structured reports (SR) has been shown to improve report completeness, time efficiency and interrater reliability in head and neck sonography (HNS). However, no data exists to date on the influence on report accuracy in terms of correct interpretation of findings. The aim of this study was to evaluate report accuracy as well as completeness using SR and free text reports (FTR). 128 participants of certified HNS courses were randomly assigned to create either SRs or FTR of predefined clinical cases. Demographic data, clinical training level and ultrasound experience of participants were documented prior to randomization. Each case included ultrasound images and clinical histories representing typical pathologies in HNS. Reports were independently evaluated by DEGUM-certified otorhinolaryngologists using standardized templates with respect to accuracy and completeness. SR demonstrated significantly higher accuracy ( p  < 0.001) as well as completeness ( p  < 0.001) compared to FTR. A strong positive correlation was found between completeness and accuracy using SR ( r  = 0.30, p  < 0.01) only. Additionally, use of SR was the only significant predictor of improved report accuracy ( p  < 0.01) and completeness ( p  < 0.01). Structured reporting significantly improves both completeness and accuracy in head and neck ultrasound reports. The use of SR may contribute to more consistent reporting quality in clinical and educational settings.

Even today, surgical reports are usually dictated in a free text form (FTR), leading to a wide range in report-quality. This study investigated the use of a fully structured panendoscopy report (SR) compared to FTRs. 64 panendoscopies were performed by three experienced head and neck surgeons. The surgical reports were created as both FTRs and SRs, which were examined regarding time to completion and content using a multilevel regression analysis. User satisfaction was evaluated using a questionnaire. There was no significant difference in time to complete the SRs compared to FTRs. The completeness ratings of SRs were significantly higher than for FTRs (81% vs. 66%, p  < 0.001), leading to increased report quality. Overall user satisfaction was higher for SRs than for conventional FTRs (VAS 8.1 vs. 3.5, p  < 0.001). The SRs proved to be fast to complete and more comprehensive with a higher completeness of content. Participating surgeons indicated that they preferred SRs over FTRs because of their advantages in terms of structure, guidance for inexperienced residents and non-native speakers. The data stratification also enables secondary data use to further develop deep learning algorithms in patient care and research.