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Distal humeral coronal shear fractures in children and adolescents: need for cross-sectional imaging and a revised classification
No full textCharacterization of elements of gene expression and production of virus-like particles in the moss Physcomitrium (Physcomitrella) patens
No full textThe demand for recombinant proteins in medicine continues to grow, driving advancements in biopharmaceutical production. While microbial and mammalian systems are widely used, plants are increasingly being explored as expression hosts for producing eukaryotic proteins. The moss Physcomitrella (Physcomitrium patens) is an emerging and promising platform for the production of recombinant proteins for medicinal use. This study focuses on optimizing Physcomitrella as an expression system by characterizing endogenous terminators and on extending its repertoire of biopharmaceuticals by establishing proof of concept for virus like particle (VLP) production in Physcomitrella. Terminators play a crucial role in transcription and translation, however, their potential to increase recombinant protein yields was long overlooked. Here, 14 novel terminators were selected and characterized for their effects on heterologous gene expression using a Dual Luciferase assay. A subset of endogenous terminators performed comparably to the established terminators CaMV35S, AtHSP90, and NOS. Analysis of terminator characteristics revealed that motifs associated with polyadenylation during pre-mRNA processing are key predictors of terminator efficiency. It was found that even though terminators are crucial for transcription and translation, promoters exhibit a stronger impact on overall gene expression levels. Notably, this data diverges from findings in vascular plant systems, indicating evolutionary differences in gene regulation. Human papillomavirus (HPV) infections are a leading cause of cervical and other cancers. Current HPV vaccines utilize VLPs, which are self-assembling nanoparticles formed from viral structural proteins. Here, Physcomitrella was used to produce HPV-16 VLPs by expressing the major structural protein L1. Physcomitrella chloroplast transit peptides were characterized and used for L1 chloroplast targeting, resulting in higher protein accumulation compared to nuclear or cytoplasmic localization. Production was upscaled to 5 L photobioreactors and a purification protocol using ammonium sulphate precipitation and cation exchange chromatography was established. Final assembly of purified L1 was confirmed via transmission electron microscopy. Overall, our results enhance the versatility of the biotechnology platform Physcomitrella by making available a set of newly characterized terminator sequences and demonstrating, for the first time, production of VLPs in a non-vascular plant
High rate of inappropriate utilization of an ophthalmic emergency department: a prospective analysis of patient perceptions and contributing factors
No full textBackground and Objectives: In Germany, access to medical care is often hindered by long wait times for specialist appointments and emergency department care. Inappropriate utilization of emergency services further exacerbates delays for truly urgent cases. To evaluate the utilization of the statutory ophthalmic emergency service in Freiburg and identify patient- and system-level factors contributing to inappropriate use. Materials and Methods: A paper-based, anonymous questionnaire was distributed to patients attending the ophthalmologic emergency practice (Notfallpraxis) of the Association of Statutory Health Insurance Physicians (Kassenärztliche Vereinigung), which is located within the premises of the Eye Center of the University Hospital Freiburg, Germany, at selected periods between July and September 2020, alongside a short physician assessment. Standardized instruments were used to assess symptom severity, urgency perception, and healthcare-seeking behavior. Statistical analyses were performed using R and Excel. Results: A total of 157 questionnaires were included (response rate: 63%). Most visits occurred on weekends (47%) and before 10 p.m. (83%). While 68% of patients believed their symptoms required same-day treatment, physicians assessed only 30% of cases as clinically urgent. A total of 60% of patients did not attempt to contact an outpatient ophthalmologist beforehand, and only 38% reported having a regular ophthalmologist. Patients’ perceived urgency was significantly associated with symptom severity and older age, whereas physician-assessed urgency was strongly linked to symptom duration. Conclusions: A substantial proportion of ophthalmic emergency visits in Freiburg are for non-urgent conditions. These findings underscore the need for improved coordination with outpatient care providers, better patient education, and structural reforms to reduce inappropriate utilization and ensure timely access for truly urgent cases
Dissecting forest transition: contribution of mature forests, second-growth forests and tree plantations to tree cover dynamics in the tropics
No full textForest Transition (FT) is a theoretical framework for understanding tree cover changes but often overlooks differences within countries, across forest types (e.g., second-growth forests, tree plantations replacing natural forests), regions, and climates. We quantified tropical tree cover dynamics across eight regions in four tropical countries, examining how these patterns relate to FT and how they vary between climates and forest types. Each country represented a different stage in the FT trajectory. We combined Landsat-derived time-series from 1990 to 2020 with Sentinel-2-based land cover classification to distinguish between mature natural forests (MF), second-growth forests (SF), tree plantations (TP), and their dynamics. During this period, 50 % of MF was lost, while tree cover gains averaged 16 % across regions; SF contributed 23 % and TP 12 % of total tree cover by 2020. SF steadily increased, yet its average lifespan was only 10 years, limiting its ecological contributions compared to MF. The studied regions followed the theoretical FT trajectory: the Ghanaian regions were in early transition (pre-inflection), Mexican regions were in late transition (pre-inflection), and the Australian and Brazilian (São Paulo state) regions were in post-transition (post-inflection). Evaluating FT while including or excluding TP results in different conclusions about the FT trajectory of a region or country. MF was lower in dry (from 55 % in the 1990s to 23 % in 2020) than in wet (from 73 % in the 1990s to 35 % in 2020) forest regions. SF gains were higher in dry (31 %) than in wet (23 %) regions, though SF increases did not compensate for MF loss, resulting in reduced biodiversity and ecological functioning. Hence, halting deforestation and protecting young forests are equally crucial. Evaluating FT excluding TP and quantifying SF persistence may have far-reaching consequences for how to evaluate tree cover by not only evaluating tree cover quantity, but also tree cover quality. Our findings can inform policymakers to design smart policy mixes that sequence the right policy instruments at the right time. Local people must participate in forest restoration strategies and issues of equity, justice and power imbalances must be addressed to facilitate FT. Dissecting FT increases our understanding of the underlying forest cover dynamics, which can lead to better policies for protecting local people`s livelihoods, halt deforestation, and facilitate FT to restore the natural world upon which people`s lives and society depend
Investigating the characteristics of yellow stimulated luminescence from potassium feldspar
No full textWe investigate the characteristics of low-temperature yellow stimulated luminescence (YSL), to assess its utility for dating with infrared stimulated luminescence (IRSL) stimulated at 50 °C (IR50), post-IR50 yellow stimulated luminescence (pIR-YSL) and pIRIR290. Altogether, eleven samples from a range of depositional environments and with a wide range of known ages were tested. Bleaching tests show that the pIR-YSL signal bleaches at a rate and extent that is similar to the IR50 signal. Dose recovery tests on four of the young intermediate samples illustrate that the pIR-YSL signal can be both recovered and fully reset. Equivalent dose estimations of the modern samples indicate that the YSL50 signal more consistently returns a result close to 0 Gy than the IR50 signal in fluvial samples. The saturated samples show that the IR50, IR-YSL and YSL50 signals significantly underestimate relative to the pIRIR290 signal and independent age control. Fading tests show that all three signals suffer from significant fading, with the largest fading effect on the YSL50 signal, whereas the IR50 and pIR YSL signals have similar fading rates. We note however, that the De values of the YSL50 signal for the young intermediate samples are largely in agreement with independent age control, while the IR50 signal underestimates and the pIRIR290 results overestimate. We propose that low temperature YSL has the potential to be suitable for dating samples spanning from the last glacial maximum to the Holocene
Insights into the redox chemistry and structural evolution of a P2-type cathode material in sodium-ion batteries
No full textThe causal impact of body mass index on metabolic biomarkers and nonalcoholic fatty liver disease risk
No full textBackgroundNonalcoholic fatty liver disease (NAFLD) is a growing global health concern linked to obesity.MethodsThis study employed a Mendelian randomization approach to explore the causal influence of BMI on metabolic biomarkers and the subsequent risk of NAFLD. We analyzed data from multiple sources, including 249 metabolic traits, to establish direct and mediating relationships among BMI, metabolic factors, and NAFLD risk.ResultsOur findings revealed a significant positive correlation between BMI and NAFLD across various datasets. We identified 176 metabolites associated with BMI, of which 106 were also linked to NAFLD. Importantly, 86 metabolites were found to mediate the relationship between BMI and NAFLD risk. Specifically, elevated levels of branched-chain amino acids, triglycerides, and certain cholesterol esters were notably associated with increased NAFLD risk, whereas changes in free cholesterol and phospholipid levels also played critical roles.ConclusionThis study highlights the complex interactions between BMI, metabolic biomarkers, and NAFLD risk. By elucidating these relationships, we highlight potential targets for interventions aimed at reducing NAFLD incidence in populations with elevated BMI, ultimately contributing to improved metabolic health
CDK4/6 inhibition - therapy sequences and the quest to find the best biomarkers - an overview of current programs
No full textFür Patientinnen wie auch Patienten mit hormonrezeptorpositivem (HRpos)/Human epidermal growth factor receptor 2- negativem (HER2neg) Mammakarzinom wurden in den letzten Jahren einige neue, zielgerichtete Therapien eingeführt. Einige dieser Behandlungen konnten sich nicht nur als neuer Therapiestandard etablieren, sondern führten auch zu einem signifikant verlängerten Gesamtüberleben. Insbesondere die Cyclin-dependent Kinase 4 and 6 Inhibitors (CDK4/6i) haben sich als Therapiestandard in der ersten Therapielinie etabliert. Insgesamt 70–80 % der Patientinnen werden mit einem CDK4/6i behandelt. Sowohl für die CDK4/6i als auch für die endokrinen Kombinationspartner wurden in den letzten Jahren zunehmend Biomarker beschrieben, die mit einem Progress oder einer klonalen Selektion oder Evolution assoziiert sind. Vor diesem Hintergrund ist die Kenntnis um Effektivitäts- und Resistenzmechanismen von besonderer Bedeutung. Dieses Wissen könnte wegweisend sein, um die effektivsten Sequenzen zu planen und molekulare Grundlagen für das Überwinden der endokrinen Resistenz zu nutzen. Eine der Studien, die mit einer großen Fallzahl dazu beitragen soll, diese Mechanismen zu erforschen, ist die Comprehensive Analysis of sPatial, TempORal and molecular patterns of ribociclib efficacy and resistance in advanced Breast Cancer patients (CAPTOR BC)-Studie. Diese Übersichtsarbeit fasst den aktuellen Stand der klinischen Forschung zur Resistenz gegen endokrine Therapien mit Fokus auf CDK4/6-Inhibitoren zusammen und erörtert aktuelle Studienkonzepte.In recent years, new targeted therapies have been developed to treat patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−)breast cancer. Some of these therapies have not just become the new therapy standard but also led to significantly longer overall survival rates. The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the therapeutic standard for first-line therapy. Around 70–80 % of patients are treated with a CDK4/6i. In recent years, a number of biomarkers associated with progression, clonal selection or evolution have been reported for CDK4/6i and their endocrine combination partners. Understanding the mechanisms behind treatment efficacy and resistance is important. A better understanding could contribute to planning the most effective therapeutic sequences and utilizing basic molecular information to overcome endocrine resistance. One study with large numbers of patients which aims to elucidate these mechanisms is the Comprehensive Analysis of sPatial, TempORal and molecular patterns of ribociclib efficacy and resistance in advanced Breast Cancer patients (CAPTOR BC) trial. This overview summarizes the latest clinical research on resistance to endocrine therapies, focusing on CDK4/6 inhibitors and discussing current study concepts
